Clinical Neurology

IVANO-FRANKIVSK NATIONAL MEDICAL UNIVERSITY
Bibliotechka praktykuyuchoho likarya
CLINICAL NEUROLOGY
Edited by
Gryb V.A., MD, PhD,
Professor, Head of the Department of
Neurology and Neurosurgery in
Ivano-Frankivsk National Medical University
Publishing house Medknyha

Kyiv
2017
УДК 616.8 (02)
ББК 56.1
К 49
Recommended by Commission of therapeutic disciplines of Ivano-Frankivsk National Medical

University (protocol № 22 of June 22, 2016) and decision of the Ivano-Frankivsk National
Medical University Academic Council (protocol № 15 of August 30, 2016)
Authors:
Gryb V.A., MD, PhD, professor, Head of the Department of Neurology and Neurosurgery IFNMU;
Doroshenko O.O., MD, PhD, associate professor;
Genyk S.I., MD, PhD, assistant professor;
Hrytsiuk T.D., assistant professor;
Kupnovytska-Sabadosh M.Y., MD, PhD, associate professor;
Liskevich I.I., MD, PhD, assistant professor;
Maksymchuk L.T., MD, PhD, associate professor;
Mykhaloiko O.Y., MD, PhD, assistant professor;
Tkachuk N.P., assistant professor.
Reviewers:
Moskovko S.P. — MD, PhD, professor, Head of the Department of Nervous Diseases with
Neurosurgery course, Vinnitsa National Medical University named after M.I. Pirogov
Pashkovskyi V.M. — MD, PhD, professor, Head of the Department of Neurology, Psychiatry and
Medical Psychology, Bukovinian State Medical University
Special acknowledgement to scientists-neurologists for the relevant corrections and

recommendations:
Mariienko L.B., MD, PhD, Professor of the Department of Neurology in Danylo Halytsky Lviv National
Medical University
Nehrych T.I., MD, PhD, Vice Rector for Research, Professor of the Department of Neurology in
Danylo Halytsky Lviv National Medical University
Muratova T.M., MD, PhD, Head of the Department of Neurology in Odesa National Medical University
Matviienko Yu.O., MD, PhD, Associate Professor of the Department of Neurology in Danylo Halytsky
Lviv National Medical University
К 49 Clinical Neurology / Edited by Gryb V.A. — К.: Publishing house Medknyha, 2017. —
288 с.
ISBN 978-966-1597-42-5
This manual highlights the key areas of clinical neurology, which are represented
in the program for the maintenance of educational process on discipline «Neurology»,
specialty 7.12010001 Medicine of the Medical Faculty.
Essential for university students, interns, doctors, neurologists.
© Gryb V.A., Doroshenko O.O., Genyk S.I., Hrytsiuk T.D.,

Kupnovytska-Sabadosh M.Y., Liskevich I.I.,
Maksymchuk L.T., Mykhaloiko O.Y., Tkachuk N.P., 2017
ISBN 978-966-1597-42-5 © Publishing house Medknyha, 2017
Medications used in neurology 3
Topic 1
MEDICATIONS USED IN NEUROLOGY
Topic questions:
1. Neuroprotective and neurotrophic drugs
2. Drugs improved brain microcirculation
3. Drugs used for Parkinson’s disease treatment
4. Antiepileptic drugs
5. Antihypertensive drugs
6. Drugs used for treating migraine headaches
7. Lipid-lowering drugs
8. Psychotropic drugs
9. Stabilized autonomic nervous system drugs
10. Drugs that affect coagulation system of blood
11. Acetylcholinesterase inhibitors (AChEI)
12. Drugs used in Multiple Sclerosis
13. Drugs used in Myasthenia gravis
14. Antiviral drugs
15. Antispastic drugs (muscle relaxants)
16. Treatment of pain
1. Neuroprotective and neurotrophic drugs

The dose applied
Active Name of the (daily dosage;
Orally Infusion
substance drug route of adminis-
tration)
low molecular Cerebrolysin - 1, 5, 10, 20, 5-50 ml;
weight biolo 30 ml/ampule i/m, i/v
gically active
neuropeptides
citicoline Ceraxon 500, 4 ml (500 mg) 500-2000 mg;
sodium 1000 mg 4 ml (1000 mg)/ orally, i/v
ampule
piracetam Lucetam, 400, 800, 20% 5ml, 1200 mg — 12 g;
Nootropil 1200 mg 20% 15ml/ am- orally, i/m, i/v
pule
www.medkniga.kiev.ua
4 Clinical Neurology
choline alfos- Gliatilin 400 mg 4 ml 1000 mg;

cerat (1000 mg) orally, i/v
deproteinized Actovegin 200 mg 2 (80 mg), 5 1200-2400 mg;
calve blood (200 mg), orally, i/m, i/v
extract 10 (400 mg) ml/ 1200 mg; orally
ampule 80-2000 mg; i/m, i/v
2. Drugs improved brain microcirculation

The dose applied
Active Name of the
Orally Infusion (daily dosage; admin-
substance drug
istration route)
nicergoline Sermion 5, 10, 4 ml (4 mg)/ 15-60 mg; orally
30 mg ampule 4-8 mg; i/m, i/v
vincamine Oxybral 30 mg - 60 mg
vinpocetin Cavinton 5 mg 2 ml (10 mg)/ 15-30 g;orally
Cavinton 10 mg ampule 2-4 ml; i/v
forte
pentoxifylline Trental 100 mg 2% 5 ml 300-1200 mg; orally
(100 mg)/ am- 100-300 mg; i/v
pule
50 ml/10 mg
Nimotop 30 mg vial 360 mg; orally, 10 mg;
calcium-chan- i/v
nel blocker Cinnarizine 25, - 75-150 mg; orally
75 mg
standardized Tanakan, 40 mg - 120-240 mg; orally
gingko leaf Memoplant
extract
betagistine / Betaserc 8, 16, - 48 mg; orally
affect the inner 24 mg
ear microcircu-
lation/
3. Drugs used for Parkinson’s disease treatment

The dose ap-
Active Name of plied (daily
Orally Infusion
substance the drug dosage; route of
administration)
selegiline hydro- Jumex, 5 mg - 5-10 mg;
chloride /type B Eldepryl 1-2 t/d; orally
monoamine oxi-
dase inhibitor/
amantadine Neomi- 100 mg - 100-200 mg;
hydrochloride / dantan 1-2 t/d; orally
NMDA-receptor
inhibitor/
amantadine PK-Merz 100 mg 500 ml 100-600 mg;
sulfate (200 mg)/ orally
vial 200-600 mg;
i/v
pramipexole di- Mirapex 0.25, 1 mg - 0.375-4.5 mg
hydrochloride 3 t/d; orally
/dopamine re- Mirapex 0.375, 0.750, 1.5, - 0.375-4.5 mg
ceptor agonist/ ER 3, 4.5 mg 1 t/d; orally
levodopa + car- Nakom 250 mg + 25 mg - 1-12 tab; 3-12 t/d;
bidopa /levodopa orally
combined drug/
levodopa + Madopar 200 mg + 50 mg - 1-12 tab; 3-12 t/d;
benserazide orally
trihexyphenidyl / Parko- 2, 5 mg - 1-16 mg;
anticholinergiс pan 1-3 t/d; orally
levodopa + Stalevo 50+12.5+200 mg - 1-10 tab; orally for
carbidopa + en- 100+25+200 mg 200+50+
tacapone 150+37.5+200 mg 200 mg — 1-7 tab;
/levodopa com- 200+50+200 mg orally
bined drug/
4. Antiepileptic drugs
The dose applied
Active Name of the (daily dosage;
Orally Infusion
substance drug route of adminis-
tration)
valproic acid de- Depakine 300 - - 20-30 mg/kg;
rivatives / sodium chrono 500 mg 1-2 t/d; orally
valproate, Convulex re- 300 - 5 ml (1ml= 20-30 mg/kg;
valproic acid/ tard 500 mg 100 mg)/am- 1-2 t/d; orally
pule 25 ml; i/v
carbamazepine Finlepsin 200 mg 10-20 mg/kg;
Finlepsinretard
200, - 1-3 t/d; orally
400 mg
Tegretol 200, -
400 mg
lamotrigine Lamictal 25, 50, - 1-5 — (10) mg/kg;
100 mg 1-3 t/d
topiramate Topamax 25, - 3-6 — (9) mg/kg;
100 mg 1-2 t/d; orally
levetiracetamum Keppra 250, 500, - 500-3000 mg;
barbiturates Benzonal 50, - 2-4 mg/kg;
100 mg
Phenobarbital 5, 50, - 1-3 t/d; orally
100 mg
5. Antihypertensive drugs
The dose applied
Active Name of
Orally Infusion (daily dosage; route of
substance the drug
administration)
selective Ebrantil 30 mg 5 ml 30-60 mg; orally
Alpha-block- (25 mg), 9 mg/h, i.e. 250 mg in
ers/ urapidil 10 ml sodium chloride 0.9%
(50mg)/ 500 ml (1 mg = 44 drops =
ampule 2.2 ml); i/v using perfusion
pump
selective Esmolol - 10 ml/ am- 0,25-0,5 mg/kg/min; i/v
Beta-blockers pule
ACE Inhibi- Captopril 25 mg - 25-100 mg; 1-4 t/d;

tors./ Enalapril orally
Enalapril 5, 10, 1 ml 5-40 mg; orally
20 mg (1,25 mg)/ 1 ml; i/v
ampule
clonidine Clophelin 0.15, 1, 10 ml 0.075-1.5 mg;
0.075 mg 0.01%/ 1-3 t/d; orally
ampule 0.5-1.5 ml;
i/m, i/v
6. Drugs used for treating migraine headaches

The dose applied
Active Name of
Orally Infusion (daily dosage; route
substance the drug
of administration)
ergotamine Ergotamin 1 mg 1 ml 0.05%/ 1-4 mg; orally
hydrotartrat 0.1% ampule 15-20 drops; orally
solution 0.5-1.0 ml; i/m
sumatriptan / sero- Suma 50, - 100-300 mg; orally
tonin 5-HT1 recep- triptan 100 mg
tor agonist/
zolmitriptan Rapimig 2.5, - 2.5-20 mg; orally
5 mg
7. Lipid-lowering drugs
The dose applied
Active Name of
substance the drug
administration)
atorvastatin Atoris 10, 20, 40, - 10-80 mg;
80 mg 1 t/d; orally
lovastatin Lovacor 20 mg - 20-80 mg;
1 t/d; orally
provastatin Lipostat 20 mg - 10-40 mg;
1 t/d; orally
rosuvastatin Crestor 10, 20, - 10-40 mg;
40 mg 1 t/d; orally
8. Psychotropic drugs
The dose applied
Active Name of
substance the drug
of administration)
Tranquillizers / anxiolytics
benzodiazepine Diazepam 2 mg, 1 ml 5-60 mg; orally
derivative 5 mg, 0.5%/ 10-70 mg; i/m, i/v
10 mg ampule
phenibuti /derivatives Noophen 250, - 0.75-2.5 g;
of GABA and phenyl- 500 mg 2-3 t/d; orally
ethylamine/
Antidepressants
amitriptyline hydro- Amitripty- 10, 25 mg, 2 ml 1%/ 25-300 mg;
chloride /non-se- line ampule 1-3 t/d; orally
lective inhibitors of 2-12 ml i/m, i/v
monoamine oxidase/
noradrenergic and Mirtazap- 15 mg, - 15-45 mg;
serotoninergic drug ine 30 mg, 1 t/d; orally
45 mg
selective serotonin Venlafax- 75 mg - 37.5-225 mg;
and norepinephrine ine 1 t/d; orally
reuptake
inhibitor
selective serotonin
reuptake inhibitors:
-fluoxetine Prozac 20 mg - 20-80 mg; 1 t/d; orally
hydrochloridi
-sertralin Zoloft 50, 100 mg - 50-200 mg; 1 t/d; orally
-paroxetine Rexetin 20, 30 mg - 20-60 mg; 1 t/d; orally
-escitalopram Ezopram 20 mg - 10-20 mg; 1 t/d; orally
agomelatin Melitor 25 mg - 25-50 mg; 1 t/d; orally
Hypnotics
melatonin Melatonin 3 mg - 3-6 mg; 1 t/d; orally
zopiclon Imovane 7.5 mg - 3.75-7.5 mg;
1 t/d; orally
zolpidem Stilnox, 10 mg - 10-20 mg;
Ivadal 1 t/d; orally
9. Drugs that stabilize autonomic activity

The dose applied
Active Name of the
Orally
Infusion (daily dosage; route
substance drug
of administration)
propranolol / adre- Propranolol 10, 2 ml 20-320 mg;
nal-blockers 40 mg 0.25%/ 2-3 t/d; orally
ampule
herbal adaptogens: agents containing Rhodiola rosea, Valerian root, Ginseng,
Eleutherococcus, Aralia, Astragalus, Centaurium erythraea, Schisandra
chinensis, Hippophae, Ginger
antidepressants
(see item 8)
tranquillizers / anx-
iolytics
(see item 8)
10. Drugs that affect coagulation system of blood

The dose applied
Active Name of
substance the drug
administration)
Thrombolytics
alteplase or re- Actilyse - 50 0.9 mg/kg (max — 90 mg)
combinant tissue mg/vial is administered for infusion
plasminogen dripwise during 60 min;
activator /rt-PA/ 10% of the total dose is
administered initially for i/v
stream infusion
Disaggregation (antiplatelet) drugs
acetilsalycicylic Aspi- 100 mg - 100-300 mg;
acid rin-Cardio 1 t/d; orally
acetilsalycicylic Cardioma- 75, -
acid + gnyl 150 mg
magnesium
hydroxide
Clopidogrel Plavix 75 mg - 75 mg;
1 t/d; orally
Anticoagulants
- Direct
unfractionated Heparin - 5 ml/vial 7500-22500 U; s/c

heparin: (1 ml=5000 25000-80000 U; i/v
Units)
enoxaparin Clexan - 20-40-60- 0.5-1.5 mg/kg;
80-100mg/ s/c
syringe
pen: 0,2;
0,4; 0,6;
0.8; 1 ml
nadroparinum Fraxi- - 0.3, 0.4, 0.3-1 ml;
parine 0.6, 0.8 ml/ 1-2 t/d; s/c, i/v
syringe pen
rivaroxabanum / Xarelto 10, 15, - 10-30 mg;
selective inhibi- 20 mg 1 t/d; orally
tors of factor Xa
dabigatran / se- Pradaxa 110, - 220-300 mg;
lective inhibitors 150 mg 2 t/d; orally
of factor IIa
- Indirect
warfarin sodium Warfarin 2.5, - 2.5-10 mg;
5 mg 1 t/d; orally
needs control of INR = 2-3
Hemostatic agents
etamsylate Dycinone 250 mg 12.5% 2 ml 750-1500 mg;
3-4 t/d; orally
2 ml; 1-5 t/d; i/m
11. Acetylcholinesterase inhibitors (AChEI)

The dose applied
Active Name of the
substance drug
of administration)
pyridostigmini Kalymin 60 mg - 60-720 mg;
bromidum 3-4 t/d; orally
Kalymin forte - 1 ml 1 ml; 5 t/d; s/c
0.5%/
ampule
neostigmine Proserinum 15 mg 1 ml - 15-50 mg;
methylsul- 0.5%/ 3-6 t/d; orally
phate ampule - 1 ml 5 t/d; s/c
galantamine Galantamine, 5, 10 mg 1 ml - 5-40 mg;

Nivalin 0.25%/ 1-2 t/d; orally
ampule - 10-20 mg;
1-2 t/d; s/c
Galantamine
4, 8, - 4-32 mg;
Teva 16 mg 1-2 t/d; orally
rivastigmine Exelon 1.5, 3, - 1.5-12 mg; 1-2 t/d;
4.5, 6 mg orally
donepezil hy- Donepezil, Almer, 5, 10 mg - 5-10 mg;
drochloride Aricept 1-2 t/d; orally
12. Drugs used in Multiple Sclerosis

The dose applied
Active Name of
Orally Infusion
(daily dosage; route
substance the drug
of administration)
Treatment of Multiple sclerosis exacerbations
methylpredniso- Metypred, 4, 16, 250, 500, 1000 - 24-96 mg;
lone Solupred, 32 mg mg/vial 1 t/d; orally
Solu- - 500-1000 mg; 1 t/d;
medrol i/v
normal human Octagam - 10% 0.4-0.8 g/kg (100-
immunoglobulin 50 ml/vial 200 ml);
(IVIG) 1 t/d; i/v
Preventive therapy
interferons:
interferon beta-1a Rebif, - 22, 44 mсg / 22, 44 mcg;
Avonex lyophilisate for 3 t/week; s/c
solution for injec-
tion /vial
interferon beta-1b Betaferon - 250 mcg/ lyophi- 250 mcg;
lisate for solution every other day; s/c
for injection / vial
monoclonal anti- Tisabri - 300 mg / concen- 300 mg;
bodies: trate for solution once a month; i/v
natalizumab for infusion / vial
glatiramer acetate Copaxone - 1 ml (20 mg)/ 20 mg;
syringe pen daily; s/c
13. Drugs used in Myasthenia gravis

The dose applied
Active Infu-
Name of the drug Orally (daily dosage; route
substance sion
of administration)
acetylcholines- Kalymin, Proserini,
terase inhibitors Galantamine, Nivalin,
(see item 11) Galantamine Teva
potassium Kalii Orotas 100, - 750-1500 mg;
Kaldyum 600 mg - 1200-1800 mg;
1-2 t/d; orally
immuneglobulin Octagam
therapy
(see item 12)
corticosteroids Prednisone 5 mg - 60-100 mg (1-1.5 mg/
(see item 12) kg) per day; after 2 to
4 weeks change to a
dose of 60-100 mg
every other day; orally
14. Antiviral drugs

The dose applied
Active Name of
substance the drug
of administration)
acyclovir Zovirax, 200 mg 250 mg / - 1000-4000 mg;
Acyclovir for solution for 4-5 t/d; orally
injection / vial - 5 mg/kg; i/v
valacyclovir Valtrex 500 mg - 1000-3000 mg; 2-3 t/d;
orally
15. Antispastic drugs (muscle relaxants)

The dose applied
Active Name of
substance the drug
administration)
tolperisone Mydo- 50, 1 ml/ 150, 450 mg;
calm 150 mg ampule 3 t/d; orally 1 ml;
1-2 t/d; i/m
baclofen Baclofen 10, - 15-75 mg;

tizanidinum Sirdalud 2, 4 mg - 2-24 mg; 2-3 t/d; orally
flupirtine Katado- 100 mg - 100-600 mg;
lon 1-6 t/d; orally
Katado- 400 mg - 400 mg;
lon retard 1 t/d; orally
botulinum toxin Disport 300, 500 250-1000 mg in cer-
type A / clostridium units / vial tain muscles; once per
botulinum toxin 3-4 month
type A haemagluti-
nin complex
16. Treatment of pain

The dose applied
Active Name of the
substance drug
administration)
Nociceptive pain
non-steroidal
anti-inflammato-
ry drugs
- diclofenac Diclofenac 100 mg 3 ml - 100 mg;
(75 mg) 1 t/d; orally
- 3 ml; 1 t/d; i/m
- meloxicam Meloxicam, 7.5, 1.5 ml - 7.5, 15 mg;
Movalis 15 mg (15 mg) 1 t/d; orally
- 1.5 ml;
1 t/d; i/m
antispastic drugs
(see item 15)
Neuropathic pain
gabapentin Gabapentin 100, - 300-3600 mg;
Tebantin, 300, 1-3 t/d; orally
Neuralgin 400 mg
pregabalin Lyrica 25, 75, - 75-600 mg;
150, 1-2 t/d; orally
300 mg
Antidepressants
(see item 8)
TESTS
1. First-line treatment for epilepsy (according to the AAN Epilepsy Guidelines)

is valproate. What drug belongs to this pharmacological group?
1) Cavinton
2) Betaserc
3) Noophen
4) Depakine
5) Tegretol
2. Specify the anti-epileptic drug.
1) Cerebrolysin
2) Tanakan
3) Lamotrigine
4) Cavinton
5) Warfarin
3. Which drug belongs to antidepressants — selective serotonin reuptake
inhibitors?
1) Cavinton
2) Clexane
3) Paroxetine
4) Depakine
5) Krestor
4. Which of the following drug is used to treat Myasthenia gravis?
1) Lucetam
2) Depakine
3) Kalymin
4) Topiramat
5) Clexane
5. Antiviral drug should be prescribed in case of herpes ganglionitis. Specify it.
1) Kalymin
2) Clexane
3) Valtrex
4) Lamotrigine
5) Rosuvastatin
Epilepsy 15
Topic 2
EPILEPSY
Topic questions:
1. Definitions
2. Etiology
3. Pathogenesis of epilepsy
4. International classification of
- epilepsy, epileptic syndromes
- seizures
5. Characteristics of seizures
6. Definition of the types of seizures
7. Status epilepticus
8. Sudden unexpected death in epilepsy (SUDEP)
9. Diagnosis of epilepsy
10. Differential diagnosis
11. Treatment of epilepsy
1. Definitions
The International League Against Epilepsy (ILAE) (2014) proposed that
Epilepsy is considered to be a disease of the brain defined by any of the
following conditions:
1) at least two unprovoked (or reflex) seizures occurring >24 h apart;
2) one unprovoked (or reflex) seizure and a probability of further seizures
similar to the general recurrence risk (at least 60%) after two unprovoked
seizures, occurring over the next 10 years;
3) diagnosis of an epilepsy syndrome.
Epileptic focus is a pathological group of neurons that is capable of spon-
taneous periodic self-excitation and is almost independent from external con-
ditions. It is caused by a decrease of the membrane charge, namely its depo-
larization in a limited number of neurons (locally) or distributed throughout the
cortex (generalized).
Epileptic seizure is a brief sudden episode of signs or symptoms of motor,
sensory, autonomic-visceral, mental disorders due to abnormal excessive or
synchronous neuronal activity in the brain.
Epilepsy does not include the isolated attacks or attacks in acute brain
diseases (acute stroke, meningitis, encephalitis, etc.) or epileptic reaction.
Acute symptomatic seizure is a seizure that occur at the time of a systemic

pathological state or in close temporal association with a documented brain
disease. That is within 1 week of an acute CNS insult, which may be metabol-
ic, toxic, structural, infectious, or due to inflammation: stroke, CNS infection,
brain trauma, cerebral hemorrhage, medication toxicity, autoimmune diseas-
es, multiple sclerosis relapse, alcohol withdrawal, or drug withdrawal. The
term acute symptomatic seizure should be used instead of provoked seizure,
reactive seizure, or situation-related seizure.
An epilepsy syndrome refers to a cluster of features incorporating seizure
types, EEG, and imaging features that tend to occur together. It often has
age-dependent features such as age at onset and remission (where applica-
ble), seizure triggers, diurnal variation, and sometimes prognosis.
2. Etiology (1989)
Idiopathic epilepsy usually with age-related onset tends to appear during
childhood or adolescence. There is often a family history of epilepsy.
Symptomatic epilepsy forms result from organic brain damage: traumatic
brain injury, stroke, meningitis, Multiple sclerosis, alcoholism (one in ten alco-
holic suffers from seizures), drug addiction and many other reasons.
Cryptogenic form is epilepsy with undetected, hidden etiology.
Very soon this classification will be revised.
3. Pathogenesis of epilepsy
The basis of the occurrence of spontaneous seizures is local or general-
ized cortical neuronal membrane instability associated with inherited or ac-
quired secondary features of metabolic processes.
4. International classification of epilepsies, epileptic syndromes
The modern international classification of epilepsy and epileptic syn-
dromes (the International League Against Epilepsy (ILAE), 1989) is based on
two fundamental principles: due to etiology and localization of epileptic focus.
1. Due to etiology, there are:
- idiopathic epilepsy and epileptic syndromes are characterized as the
disease that is not caused by known factors, with the exception of existing
genetic predisposition.
- symptomatic epilepsy and epileptic syndromes are considered to be a
result of known or possible diseases of the central nervous system.
- cryptogenic epilepsy and epileptic syndromes. The term «cryptogenic
epilepsy» defines the disease with unidentified hidden cause in many cases.
2. Due to localization of epileptic focus there are:
- localized epilepsy and epileptic syndromes (focal, partial), characterized
by seizures with focal onset.
Epilepsy 17
- generalized epilepsy and epileptic syndromes are characterized by dif-

fuse bilateral involvement of the cerebral hemispheres.
- epilepsy and epileptic syndromes that cannot be defined as partial or
generalized.
Special syndromes. They are distinguished separately; there are following
situations caused seizures (epileptic reactions): febrile convulsions, seizures
in the case of metabolic and toxic disorders etc.
According to the clinical characteristics, the seizures are divided into:
- partial (localization-related)
- generalized.
5. Characteristics of seizures
- spontaneity (low dependence on external factors)
- frequency of repetition
- attachment to a period of day
- stereotype
- characterized by short-time seizures (duration is up to 10 minutes)
- satisfactory condition after attack
- progressive nature (with complications, increase the frequency of sei-
zures, the appearance of the emotional and cognitive changes).
There are following periods of epileptic attack
- pre-ictal refers to the state immediately before the actual seizure
- ictal state — is a very period of seizure
- post-ictal refers to the state shortly after the event
- interictal refers to the period between seizures.
6. Definition of seizures
A. Partial (focal) seizures occur in case of epileptic focus stimulation in one
limited area of the brain. There are:
- motor epilepsy (simple motor seizure, adversive (the head and eyes turn
away from the side of the focus), phonatory, operculary (licking and clicking);
- sensory (somatosensory (simple sensory seizure), visual, auditory, olfac-
tory, gustatory, attacks of dizziness) epilepsy is the elementary hallucinations
and related to the discharges in primary projection areas of the cortex;
- autonomic epilepsy (respiratory, cardiac, abdominal etc) belongs to the
old cortex of parietal, Sylvian area, insula, temporal lobe with limbic system
irritation in particular;
- psychic epilepsy with mental disorders are the result of the discharge of
the secondary and tertiary associative cortical areas, accompanied by twilight
state: dysphoric, illusory, hallucinatory complex attacks, automatism. Automa
tism is manifested in automatic movements (scratching, stroking, search or
Fig. 1. Partial seizures, simple and complex, are controlled by the function
of the brain in which they occur
other gestures). The attacks of fear, happiness, and a sense of unreality of

surrounding environment «deja-vu» (the phenomenon of having the strong
sensation that an event currently being experienced) are possible.
Simple partial seizure
- consciousness is saved, the patient remembers attack
Complex partial seizure occurs as
1. as simple partial onset followed by impairment of consciousness
2. with impairment of consciousness at onset.
Automatism is possible.
General features of partial seizures:
- EEG shows epileptic focus.
- possible focal changes on MRI (CT scan).
- in case of spread of the excitation beyond the epileptic focus, the focal
manifestations complete with a consciousness loss and generalized seizures
that are secondary generalized. The partial part of the attack is called an aura,
which the patient remembers.
The main difference between simple partial and generalized attacks is pre-
serving memories of the attack due to the lack of complete loss of consciousness.
B. Generalized seizures are the result of sudden diffuse coverage of brain
by epileptic excitation due to pathological activation of central brain struc-
tures, especially the thalamo-cortical system, which leads to a momentary
consciousness loss. There are no focal changes on EEG.
Epilepsy 19
There are following types of generalized seizures:

Tonic-clonic seizures (grand mal seizure). A patient falls with a scream.
Apnea occurs due to contraction of the muscles of diaphragm and glottis.
It starts with the tonic phase of the attack, which lasts 30 seconds: body is
tense, limbs are straighten, hands are clenched in a fist, head is thrown back,
eyeballs are turned up, jaws are clenched, tongue can be biten, pupils are
dilated without reaction to light. Clonic phase lasts 1-5 minutes: rhythmic jerk-
ing of the limbs, trunk, eyeballs, facial muscles, salivation. It may be ended
with involuntary urination. This phase turns into a coma, followed by a nap or
consciousness restoration.
Myoclonic (klonos — chaotic movements) seizures are characterized by
fast (fulminant) symmetric twitching of muscle bundles and their groups.
Generalized atonic seizures are characterized by sudden loss of postural tone
(tone that supports one’s pose), therefore one suddenly falls, loses conscious-
ness; no seizures, while the patient is lying unconscious. The attack is brief.
General features of primary generalized seizures:
- primary total loss of consciousness.
- there is no focal activity, but presence of a generalized epileptiform dis-
charges activity on EEG and no focal changes on MRI (CT scan).
- irritation occurs simultaneously in both hemispheres and/or brainstem;
the patient does not remember the attack.
Absences (Absence (French) — petit mal) are typical for children and ad-
olescents. A person has a brief loss of consciousness (an absence) for a few
seconds. He does not fall, but may pause in what he is doing. His face often
looks pale with a blank expression. He can look dazed, the eyes stare, and
the eyelids can flutter a little. Sometimes his head falls down a little, or arms
shake once or twice. Each seizure usually starts and finishes abruptly. The
person is not aware of the one’s absence, and typically that any activity stops.
7. Status epilepticus is an epileptic seizure of greater than five minutes
or more than one seizure without the person returning to normal condition be-
tween them. The seizures can either be of the tonic-clonic type with a regular
pattern of contraction and extension of the arms and legs or of types that do
not involve contractions such as absence seizures or complex partial sei-
zures. Status epilepticus is a life-threatening condition particularly if treatment
is delayed.
Factors of status epilepticus may be:
• sudden termination at taking antiepileptic drugs
• withdrawal syndrome
• sleep deprivation and others.
This is mortally dangerous, as the patient stops breathing, and death can
occur due to suffocation.
8. Sudden unexpected death in epilepsy (SUDEP)
The risk of SUDEP can be minimized by:
- optimizing control of seizures
- information on the potential consequences of nocturnal seizures.
9. Epilepsy diagnosis: EEG, EEG expanded by spectral-compression
analysis, mapping of bioelectrical activity, determining three-dimensional im-
aging of localized epileptic activity, video and TV-EEG monitoring, MRI, CT
scan of the brain.
Neurologist and/or psychiatrist set final diagnosis of «epilepsy» after two
unprovoked seizures.
10. Differential diagnosis — See the topic «paroxysmal non-epileptic
states».
11. Treatment of epilepsy
A. What to do during an attack!!!!!
- Do not try to restrain forcibly the convulsive movements.
- Do not try to decompress teeth.
- Do not initiate an artificial respiration and cardiac massage.
- Lay a person with seizures on a flat surface and put something soft under
his head.
- Do not move the person from the place where the attack occurred, unless
this place is a life threatening.
- Turn the head of the lying patient aside to prevent retraction of the tongue
and saliva getting into the respiratory tract, and in cases of vomiting gently
return aside the entire body.
After the attack, you can leave the patient in rest and, if necessary, let him
sleep. Often at the end of the attack, a confusion and weakness may occur,
and usually after 5-30 minutes, the one can stand on one’s own.
B. Treatment of seizures
If the patient has two or more seizures, using antiepileptic drugs (AEDs) is
required. Treatment of patients with epilepsy begins with the first-line choice
monotherapy. Effectiveness is assessed for a period of at least 3 months after
reaching the therapeutic dose. In case of efficiency, it is recommended to use
the therapeutic doses of AEDs and continue for at least 2-3 years.
The basic principles of treatment of epilepsy and epileptic syndromes in-
clude: individuality, comprehensiveness, continuity, duration and heredity.
The main groups of AEDs (daily dosage):
1. Carbamazepine — 10-20 mg/kg;
Epilepsy 21
2. Valproate — 20-30 mg/kg;
3. Ethosuximide — 15-20 mg/kg;
4. Topiramate — 3-6 — (9) mg/kg;
5. Lamotrigine — 1-5 — (10) mg/kg;
6. Gabapentin — 5/10/30 mg/kg;
7. Benzodiazepines — 0.03-0.1 mg/kg;
8. Barbiturates — 2-4 mg/kg;
9. Phenytoin — 5-7 mg/kg.
The Antiepileptic International League (ILAE) in modern conditions recom-
mended choice AED conducted not only for the type of attack and forms of
epilepsy, but also from the standpoint of evidence based medicine. In accor-
dance with the recommendations of ILAE (2013):
1. Partial epilepsy:
- Monotherapy: first-line drugs — carbamazepine or topiramate, valproate,
benzodiazepines, lamotrigine (level of evidence A);
- Combined therapy with first-line drugs, and the second line — gabapen-
tin, phenobarbital, phenytoin, oxcarbazepine (level of evidence B and C).
2. Generalized epilepsy and syndromes
2.1. Idiopathic
Absence form:
- First line: succinimide or valproate (level of evidence A);
- Second line: lamotrigine (level of evidence B).
Myoclonic form:
- First line: valproate, topiramate (level of evidence B)
- Second line: lamotrigine or levetiracetam (level of evidence B).
Epilepsy with generalized tonic-clonic seizures:
- First line: topiramate or valproate, carbamazepine (level of evidence B)
- Second line: lamotrigine (level of evidence B), phenytoin (level of evidence C).
C. In case of pharmacological resistance to drugs, the incidence of which
is 20-40% of all patients with epilepsy, it should be considered the possibility
of surgery. The ketogenic diet, vagus nerve stimulation and epilepsy surgery
are alternative therapeutic options.
D. Preventing attacks. Restful sleep, active lifestyle (activity is the antag-
onist of attacks) are required. Alcohol, electrical phisiotherapy are contrain-
dicated. To avoid rhythmic foto-stimulation (disco), trauma, hyperventilation,
watching TV for a long time, a work with a computer.
E. Treatment of status epilepticus.
Relieve the airways; turn the patient aside. Initiate ECG monitoring.
5-20 Minutes Initial Therapy Phase
Benzodiazepine is the initial therapy of choice (Level A):

Choose one of the following 3 equivalent first line options with dosing and
frequency:
• i/m midazolam (10 mg for > 40 kg, 5 mg for 13-40 kg, single dose) or
• i/v lorazepam (0.1 mg/kg/dose, max: 4 mg/dose, may repeat dose once) or
• i/v diazepam (0.15-0.2 mg/kg/dose, max: 10 mg/dose, may repeat dose once)
If none of the 3 options above are available, choose one of the following:
• i/v phenobarbital (15 mg/kg/dose, single dose) or
• Rectal diazepam (0.2-0.5 mg/kg, max: 20 mg/dose, single dose) or
• Intranasal midazolam, buccal midazolam.
20-40 Minutes Second Therapy Phase
There is no evidence based preferred second therapy of choice (Level U):
Choose one of the following second line options and give as a single dose
• i/v fosphenytoin (20 mg PE/kg, max: 1500 mg PE/dose, single dose) or
• i/v valproic acid (40 mg/kg, max: 3000 mg/dose, single dose) or
• i/v levetiracetam (60 mg/kg, max: 4500 mg/dose, single dose)
If none of the options above are available, choose one of the following (if
not given already) — i/v phenobarbital (15 mg/kg, single dose)
40-60 Minutes Second Third Phase
There is no clear evidence to guide therapy in this phase (Level U):
Choices include: repeat second line therapy or anesthetic doses of either
thiopental, midazolam, pentobarbital, or propofol (all with continuous EEG
monitoring).
TESTS
1. A seizure that occurs due to a lesion of a limited portion of the brain, and
causes localized dysfunction, is:
1) partial
2) tonic
3) petit mal
4) absence
5) grand mal
2. A patient tells you that she experienced an episode of involuntary «shak-
ing» in her arm. She describes a 1- to 2-minutes-long episode of muscular
jerking and contracting of her entire left arm. She preserved consciousness,
and had no pain associated with the episode. This is:
Epilepsy 23
1) petit mal
2) psychosomatic seizure
3) absence
4) simple partial seizure
5) complex partial seizure
3. What is a name of a very period of seizure?
1) ictal phase
2) aura
3) post-ictal phase
4) unconsciousness phase
5) interictal phase
4. A 35-year-old patient complained of attacks that had started with pares-
thesia in the left extremities. Then he lost consciousness, bit his tongue, ton-
ic-clonic seizures and involuntary urination appeared, then he fell asleep. He
was prescribed anticonvulsants, but ceased to take them suddenly, which
caused tonic-clonic seizures, followed one another repeatedly in short time.
What treatment is applied first?
1) general anesthesia
2) decongestant drugs
3) antiepileptic drugs
4) corticosteroids
5) lumbar puncture
5. A 7-year-old schoolboy was inattentive during lessons, smacking move-
ments of lips his appeared. During the brief attack, he was not responding to
his name. The falling and seizures were not observed at that time. His mother
had noticed such events before, but ignored them, considering that the child
was fooling around. What is the most likely epilepsy form?
1) absence
2) generalized myoclonic attack
3) adversive seizure
4) complex partial seizure
5) simple motor seizure
Topic 3
PAROXYSMAL NON-EPILEPTIC STATES
Topic questions:
1. The states with seizures:
1) spasmophilia (infantile tetany)
2) febrile and toxic seizures
3) psychogenic nonepileptic seizures (PNES)
2. The states without seizures:
1) autonomic paroxysms
2) syncope:
- vasovagal syncope
- Morgagni–Adams–Stokes attacks
- cough syncope
- hypoglycemic state
- drop attack
- transient global amnesia.
Non-epileptic seizures disorders are events superficially resembling an ep-

ileptic seizure, but without the characteristic electrical discharges associated
with epilepsy. Recall that epileptic generalized convulsions are characterized
by phasing paroxysm; there are not only dilated pupils, but also loss of their
reactions to light, involuntary urination, high blood pressure and cyanosis.
1. The states with seizures:
1) spasmophilia (infantile tetany) is characterized by the predisposition
of children to seizures, spastic conditions arising as a result of increased ex-
citability of the nervous system (especially the neuromuscular system) and
are caused by violation of calcium and phosphorus metabolism.
It usually occurs in children aged three months to two years, most often in
children suffering from rickets.
Pathogenesis. At low levels of calcium in the blood the level of K+ and
Na+ increase; the acid-base imbalance with alkalosis occurs. K+ and Na+ ions
increase the excitability of the neuromuscular system, and calcium and mag-
nesium ions reduce it. Such conditions as fever, prolonged crying, frequent
vomiting etc. can cause the rapid shifting of the acid-base balance toward
alkalosis and provoke an attack of cramps.
Clinic. The course can be latent (hidden) and manifest (explicit).
Paroxysmal non-epileptic states 25
Obvious spasmophilia clinical picture:

- spasmodic contraction of the larynx muscles (laryngospasm). There are
cyanosis, exophthalmia; a child gets covered with sticky sweat, is frightened.
A loud breath («cockish cry») occurs immediately after spasm. The attack
lasts from a few seconds up to 1-2 minutes, may repeat.
- tonic contractions of muscles of the foot (horse’s foot) and hand («obste-
trician’s hand»). It lasts from several hours to several days.
- general convulsions (eclampsia). Severe attack begins with twitching of
facial muscles, involving other muscle groups along with breathing. The child
loses consciousness, there are involuntary urination and defecation. The at-
tack lasts from few seconds up to 20-30 minutes.
2) febrile and toxic seizures
Hyperthermia (febrile) convulsions are typical for children. Hyperthermia
is defined as a temperature more than 38 °C. There are clonic-tonic seizures,
lasting from a few seconds up to 15-20 minutes. Prophylactic anticonvulsants
are not recommended after an uncomplicated febrile seizure. If febrile sei-
zures are complicated or prolonged, or if medical reassurance fails to relieve
family anxiety, anticonvulsant (phenobarbital and valproic acid) prophylaxis
may be indicated and can reduce the incidence of recurrent febrile seizures.
Seizures of infectious origin (toxic) associated with toxic-infectious effects
on the nervous system. Manifestations of neuro-intoxication are usually as-
sociated with the occurrence of generalized seizures, preceded by the weak-
ness of the child and muscular hypotonia. Seizures may be one of the major
symptoms of neuro-infections (meningitis or encephalitis).
3) psychogenic nonepileptic seizures (PNES), earlier known as hyster-
ical paroxysms
Table 3.1.
Differential diagnosis of seizures and psychogenic seizures
Seizures Psychogenic seizures
Start at any age Does not occur in early childhood
Occurs in any conditions, even at night In the presence of the observer,
doesn’t occur at night
During the attack injury, bite of tongue Traumatic injuries are absent, but the
is possible tongue can be bitten
Attack is intermittent The long-term attack
Stereotyped synchronous movements A variety of chaotic motion. Often accom-
panied by weeping, and mourning
Seizures Psychogenic seizures

There is no resistance when doctor is Obvious resistance
trying to open the eyes of patient
Possible involuntary urination No urination disorders
Often amnesia No amnesia
Mydriasis with the lack of reaction of The reaction of pupils to light is pre-
pupils to light served
Fig. 1. Psychogenic nonepileptic seizures in woman
2. The states without seizures:

1) autonomic paroxysms (panic attack)
Usually it occurs at the age of 20-40 years and 2 times more common
for women. Is expressed by growing of anxiety for several minutes and by a
complex of autonomic disorders: feeling lack of breath, palpitations, pain or
discomfort in the left half of the chest, tremor, hyperhidrosis, waves of heat
or cold, nausea, dizziness, presyncope, or discomfortable abdominal pain,
frequent urination, increased blood pressure. It can be marked by functional
symptoms (lump in throat, weakness or numbness in the extremities, mutism,
and loss of vision), a kind of psychic phenomena such as depersonalization
(alienation from himself) and derealization (feeling of unreality). Sometimes
dizziness and other vestibular symptoms appear during the attack. During a
crisis, an anxiety is diffuse, but sometimes it becomes focus on fear of death,
fear of losing control etc. The duration of the attack is 20-40 minutes.
Panic in mildly ill patients often requires no medication and can be managed
with psychotherapy alone. Medications (antidepressants, including paroxetine,
sertraline, venlafaxine) in combination with psychotherapy (behavioral or
cognitive-behavioral therapy) should be reserved for more severely ill patients.
2) syncope (neurogenic unconsciousness)
Syncope (fainting) is a brief loss of consciousness and falling down be-
cause of the sudden decrease brain metabolism. Most often, this decrease
occurs as a result of short lasting disturbance of cerebral blood flow and,

consequently, insufficient oxygen level in the brain.
Possible causes include:
I. Syncope
1. Neurally mediated syncope (reflex syncope):
- vasovagal syncope (common faint)
- situational syncope — cough, sneeze, gastrointestinal stimulation
(swallowing, defecation, visceral pain), micturition
- carotid sinus hypersensitivity
2. Orthostatic hypotension (postural hypotension).
3. Autonomic failure in case of:
- some diseases, e.g. Parkinson’s disease, Diabetes Melitus, amy-
loidosis etc
- medication taking, e.g. antihypertensive
- hypovolaemia due to heamorrhage, vomiting, diarrhea, Addison’s
disease etc
- post-exercise period
- postprandial period
4. Cerebrovascular:
- drop attack
- transient global amnesia
5. Substance abuse, alcohol intoxication.
6. Psychogenic: factitiousness, anxiety, panic attacks, hyperventilation.
Vasovagal syncope, which is mediated by the vagus nerve, is the most
common type of fainting.
Episodes of vasovagal response are recurrent typically, and usually occur
when the predisposed person is exposed to a specific trigger. Before losing
consciousness, the individual frequently experiences early signs or symptoms
such as lightheadedness, nausea, the feeling of being extremely hot or cold
(accompanied by sweating), ringing in the ears (tinnitus), an uncomfortable
feeling in the heart, fuzzy thoughts, confusion, weakness and visual distur-
bances such as lights seeming too bright, as dark clouds before the eyes,
and a feeling of anxiety can occur as well. The symptoms last for few seconds
before the possible consciousness (losing), which typically happens when
the person is sitting or standing up. When sufferers pass out, they fall down
(unless it is impeded) and, when in this position, effective blood flow to the
brain is immediately restored, allowing the person to regain consciousness; if
the person does not fall into a fully flat, supine position, and the head remains
elevated above the trunk, a state similar to a seizure; it may be the result of
the blood’s inability to return quickly to the brain, the neurons in the body fire
off leading to reduction of muscles contractile ability, but mostly remain very
tense. Fainting occurs due to decreased oxygen supply to the brain.
The autonomic nervous system’s physiologic state leading to loss of con-
sciousness may persist for several minutes, so
• if sufferers try to sit or stand when they regain consciousness, they may
pass out again
• the person may be nauseated, pale, and sweaty for several minutes or hours.
Vasovagal syncope occurs in response to a trigger, with a corresponding
malfunction in the parts of the nervous system that regulate heart rate and
blood pressure. When heart rate slows, blood pressure drops, which result in
lack of blood flow to the brain causes fainting and confusion.
Typical triggers for vasovagal episodes include:
• prolonged standing or upright sitting
• after or during urination (micturition syncope)
• standing up very quickly (orthostatic hypotension)
• during or post-biopsy procedures
• stress directly related to trauma
• stress
• postural orthostatic tachycardia syndrome. Multiple chronic episodes
are experienced daily by many patients diagnosed with this syndrome.
Episodes are most commonly manifested upon standing up
• any painful or unpleasant stimuli, such as:
♦ trauma (such as hitting one’s funny bone)
♦ watching or experiencing medical procedures (such as venipunc-
ture or injection)
♦ severe menstrual cramps
♦ sensitivity to pain
♦ sudden onset of extreme emotions
• lack of sleep
• dehydration
• hunger
• being exposed to high temperatures
• in health care, such as nursing care, digital rectal procedures
• pressing on certain areas on the throat, sinuses, and eyes (also known
as vagal reflex stimulation when performed clinically)
• use of certain drugs that affect blood pressure, such as cocaine, alco-
hol, marijuana, inhalants, and opiates
• the sight of blood
• swallowing
• (less commonly) low blood sugar
• time varying magnetic field (e.g., transcranial magnetic stimulation)
Pathogenesis
Regardless of the trigger, the mechanism of syncope is similar in the vari-
ous vasovagal syncope syndromes. The nucleus tractus solitarii of the brain-
stem is activated directly or indirectly by the triggering stimulus, resulting in
simultaneous enhancement of parasympathetic nervous system (vagal) tone
and withdrawal of sympathetic nervous system tone.
This results in a spectrum of hemodynamic responses:
1. On one end of the spectrum is the cardioinhibitory response, charac-
terized by a drop in heart rate (negative chronotropic effect) and contractili-
ty (negative inotropic effect) leading to a decrease in cardiac output that is
significant enough to result in a loss of consciousness. It is thought that this
response results primarily from enhancement in parasympathetic tone.
2. On the other end of the spectrum is the vasodepressor response,
caused by a drop in blood pressure (to as low as 80/20) without much change
in heart rate. This phenomenon occurs due to vasodilation, probably as a
result of withdrawal of sympathetic nervous system tone.
3. The majority of people with vasovagal syncope have a mixed response
somewhere between these two ends of the spectrum.
Table 3.2.
Differential diagnosis of neurogenic syncope and seixures
Neurogenic syncope Seizures
External factors (fear, long vertical position) There is no external factor
Starts gradually Begins with aura or arises suddenly
Falling slowly, there may be some clonic Falling is rapid
jerking
After syncope the condition worsens Sleep or good condition after attack
Does not occur in a horizontal position, Occurs during sleep
during sleep
During the attack blood pressure decreases, Increased blood pressure, tachy-
bradycardia, pallor, sweating cardia, flushing of the skin
Epileptic activity on EEG is not detected Epileptic activity on EEG is detected
Diagnosis
In addition to the mechanism described above, a number of other medical
conditions may cause syncope. Setting the correct diagnosis for loss of con-
sciousness is one of the most difficult challenges that a physician can face.
The core of the diagnosis of vasovagal syncope rests upon a clear description
by the patient of a typical pattern of triggers, symptoms, and time course. It
is also pertinent to differentiate lightheadedness, seizures, vertigo, and hypo-
glycemia as other causes.
In patients with recurrent vasovagal syncope, diagnostic accuracy can of-
ten be improved with one of the following diagnostic tests:
1. tilt table test (to measure one’s blood pressure and heart rate with
changes in posture)
2. Holter monitor
3. echocardiogram
4. electrophysiology study
Treatment
• The cornerstone of treatment is avoidance of triggers known to cause
syncope in that person. However, a new development in psychological
research has shown that patients show great reductions in vasovagal
syncope through exposure-based exercises with therapists if the trig-
ger is mental or emotional, e.g. sight of blood. However, if the trigger is
a specific drug, then avoidance is the only treatment.
• As vasovagal syncope causes a decrease in blood pressure, relaxing
the entire body as a mode of avoidance is not favorable. A patient can
move or cross his/her legs and tighten leg muscles to keep blood pres-
sure from dropping so drastically before an injection.
• Before known triggering events, the patient may increase consumption
of salt and fluids to increase blood volume. Sports drinks or drinks with
electrolytes may be particularly helpful.
• Discontinuation of medications known to lower blood pressure may be
helpful, but terminating antihypertensive drugs can also be dangerous
in some people. Taking antihypertensive drugs may worsen the synco-
pe, as the hypertension may have been the body’s way to compensate
for the low blood pressure.
• There are certain orthostatic training exercises, which have been prov-
en to improve symptoms in people with recurrent vasovagal syncope.
• Certain medications may also be helpful: beta-blockers, CNS stimu-
lants, fludrocortisone, midodrine, paroxetine or sertraline.
The San Francisco Syncope Rule (SFSR) was proposed for evaluating
the risk of adverse outcomes in patient who present with fainting or syncope.
The mnemonic for parameters of the rule is CHESS:
• C — History of congestive heart failure
• H — Hematocrit < 30%
• E — Abnormal ECG

• S — Shortness of breath
• S — Triage systolic blood pressure < 90
If patient has any of criteria listed above he/she is considered to be at high
risk for a serious outcome (death, myocardial infarction, arrhythmia, pulmo-
nary embolism, stroke, subarachnoid hemorrhage, significant hemorrhage, or
any other condition causing hospitalization for a related event.
- Morgagni–Adams–Stokes attacks (sick sinus syndrome, atrioventricu-
lar conduction system disease, long QT syndrome, malfunction of pacemaker
or implantable cardioverter defibrillator, drug-induced arrhythmias) and cardi-
ac syncope due to arrhythmias or structural cardiac or cardiopulmonary dis-
ease (paroxysmal supraventricular tachycardia, obstructive cardiac valvular
disease, acute coronary syndrome, hypertrophic obstructive cardiomyopathy,
atrial myxoma, pericardial disease or tamponade, pulmonary embolus or pul-
monary hypertension etc).
Morgagni–Adams–Stokes attack is a life-threatening type of syncope that
develops as a result of the decrease in blood flow of the brain during sinus
brady-arrhythmias, sinoatrial blockade, cardiac sinus node, atrioventricular
block, tachy-arrhythmias paroxysm with acute decrease of propulsive activity
of the heart.
Clinical picture. A person suddenly becomes pale, loses consciousness,
neck veins swell. There are deep breathing movements, twitching of facial mus-
cles, limbs, which pass into general epileptic seizures. Pulse is very slow, and
often not defined. Normalization of heart rate leads to recovery of conscious-
ness. The end of attack is accompanied by a sharp redness of the patient. Such
attacks may be repeated at different time intervals. Prolongation of any attack
of asystole may result in a deep coma and death. Syndrome differs from epi-
leptic seizure by the following features: no aura, there is no bite of tongue with
the release of blood stained saliva. The attack begins with the blanching of skin,
and ends with its redness. In epilepsy, a face is cyanotic at the beginning and it
is pale after the attack, reduction of heart rate does not occur.
- Cough syncope. It is situational syncope episode that occurs in patients
with chronic lung disease with prolonged cough. It may be accompanied by
fainting and convulsions with or without face cyanosis, mydriasis, and dilata-
tion of neck veins.
- Hypoglycemic state. Low concentration of glucose in the blood at pan-
creas insuloma or overdose of insulin in patients with diabetes may be ac-
companied by sweating, weakness, hunger, tachycardia, agitation, and rarely
by drowsiness, loss of consciousness and convulsions.
- Epileptic atonic seizures should be differentiated from a sudden drop,

that is drop attack, which occurs after a sharp turn or tilt head back in
the elderly and are accompanied by quadriplegia, falling down without loss
of consciousness due to blood supplying disorders of C1-C4 spinal cord
segments.
- Transient global amnesia is caused by blood flow impaired in the verte-
bral-basilar region. It occurs in old age and is characterized by sudden mem-
ory impairment, disorientation in space and time, speech and motor automa-
tisms with no more than 1-hour duration with subsequent amnesia episode.
TESTS
1. A generalized epileptic seizure occurred in a 6-month child on the back-

ground of acute respiratory infection. It was lasting for 2 minutes with sud-
den stopping. Objectively: t — 38.5 C, redness of face, focal neurological
symptoms were absent. EEG — without changes. Blood test: Hb-135 g/l,
Ca-5 mmol/l , glucose-6.1 mmol/l . What is the most likely diagnosis?
1) spasmophilia
2) epilepsy
3) febrile seizures
4) meningitis
5) hypoglycemia
2. A 16-years-old girl complains of poor memory and attention. Mother noticed
that last month she repeatedly passed out, lost the subject, did not respond
when addressed. This situation was continuing for 5-10 seconds. What is the
firstly suspected diagnosis?
1) epileptic seizure
2) vasovagal paroxysm
3) syncope
4) neurotic condition
5) transient blood circulation disorder
3. A 45-years-old patient addressed to the doctor complaining of intermittent
spasmodic muscle twitching of his arms, similar to electric shock, which last-
ed about 1 sec. What is the most likely diagnosis?
1) myoclonic absences
2) syncope
3) vasovagal paroxysm
5) simple absences
4. A 45-years-old woman addressed to the doctor complaining of paresthesia
attacks in the right foot that often occur during the day, slowly spread through-
out the whole half of the body, from bottom to top. Examination shows no focal
neurological deficits and no changes at EEG and MRI. What is the most likely
diagnosis?
1) simple sensory seizure
3) panic attack
4) hysterical attack
5) vasovagal attack
5. A 24-year-old emotionally labile woman, began to feel weakness, dizzi-
ness, darkening of the eyes, nausea and loss of consciousness without sei-
zures, being in a stuffy room. Objectively: unconscious, skin is pale, sweaty,
distal extremities are cold. BP — 200/110 mm Hg, PR 78-100 bpm, shallow
breathing. Pupillary and tendon reflexes are preserved. What is the most like-
ly diagnosis?
2) panic attack
3) syncope
4) seizures
5) hysterical neurosis
Topic 4
LESIONS OF THE NERVOUS SYSTEM UNDER THE INFLUENCE

OF PROFESSIONAL AND DOMESTIC TOXINS; AND PHYSICAL
FACTORS IMPACT
Topic questions
1. Intoxication with industrial poisons of neurotropic action
1.1. Lead intoxication (saturnism)
1.2. Metallic mercury intoxication (mercurialism)
1.3. Intoxication with manganese (manganism)
1.4. Tetraethyl lead intoxication
1.5. Carbon monoxide intoxication
1.6. Arsenic compounds intoxication
1.7. Methanol intoxication
1.8. Organophosphate compounds intoxication
2. Food intoxication, botulism
3. Wernicke–Korsakoff syndrome and other neurological manifestations of
alcoholism
4. Barbiturates intoxication
5. Vibration disease
6. Ionising radiation damage of the nervous system
7. Electrical injury of the nervous system
8. Lesions of the nervous system in the heat and sunstroke

1. Intoxication with industrial poisons of neurotropic action
1.1. Lead intoxication (saturnism)
Lead poisoning occurs by its ingestion, by inhalation or via digestive tract.
Acute poisoning. Symptoms:
1) abdominal pain - moderate-to-severe, usually diffuse but can be colic,
vomiting;
2) headache, weakness, dizziness, bradycardia, hypotension, sweating,
salivation, itching, paresthesia, tremor of limbs, insomnia, ataxia, seizures,
hallucinations, psychomotor agitation;
3) jaundice due to hepatitis, lethargy due to haemolytic anaemia.
Chronic poisoning. Symptoms:
1) anemia due to disorders of biosynthesis of porphyrin and hemе;
2) mild abdominal pain, constipation;
Lesions of the nervous system under the influence of professional and domestic toxins 35
3) subfertility;
4) aggression, antisocial behavior;
4) headaches, hearing loss, foot drop or wrist drop due to motor peripheral
neuropathy, carpal tunnel syndrome, autonomic dysfunctions.
Laboratory tests.
- Full blood count: features of a microcytic hypochromic anaemia such as
a low mean corpuscular volume may be present. Sideroblasts may be seen.
- Radio imaging: plain X-ray can show transverse lines on tubular bones,
CT or MRI scan of brain shows the signs of encephalopathy of encephalopathy;
- Level of serum iron is high or normal; Level of erythrocyte protopor-
phyrin and/or zinc protoporphyrin);
- Blood lead level;
- Urine level of delta-aminolevulinic acid (DALA); and
- Uroporphirins in urine.
Treatment. Chelators such as calcium disodium edetate (EDTA) are used
parenteral. Dimercaptosuccinic acid (DMSA - succimer, Chemet) is an alter-
native oral agent. D-penicillamine is occasionally used.
1.2. Metallic mercury intoxication (mercurialism)
Elemental mercury toxicity can occur in people who work with equipment
containing mercury. In case of accidental ingestion of mercury it transits via
the gastrointestinal tract. Inhalation of mercury vapor can cause mood swings,
nervousness, irritability, and other emotional changes, erethism including anx-
iety, strong emotion in presence of the strangers. There are insomnia, head-
ache, abnormal sensations, muscle twitching, tremors, weakness, and de-
creased cognitive functions, mercurial stomatitis, hair and nails brittle.
Organic mercury toxicity arises in application of organic mercury com-
pounds in agriculture. It causes peripheral vision impairment, stinging or nee-
dle-like sensations in the extremities and mouth, loss of coordination, muscle
weakness, and impairments of speech and hearing.
Treatment involves applying chelating agents that bind most toxic forms
by competing for sulfhydryl groups that toxic mercury forms bind to in tissue
cells. The often-used agent is dimercaprol (Unithiol) (BAL in Oil). Mercury
forms chelated with dimercaprol can also be removed from the blood with he-
modialysis. Dimercaprol should not be used with methylmercury exposure as
it may increase toxicity for brain and spinal cord. Another chelating agent used
for both organic and inorganic forms of mercury exposure (chronic and mild
exposures) is DMSA (succimer, Chemet). Other treatments are neostigmine
(Prostigmin Bromide) to help motor function and polythiol to bind methylmercury
in bile secretions.
1.3. Intoxication with manganese (manganism)

Poisoning occurs by ingestion of manganese, by inhalation, via digestive
tract or skin.
In initial stages of manganism, neurological symptoms consist of reduced
response speed, irritability, mood changes, and compulsive behaviors. Upon
protracted exposure symptoms are more prominent and resemble those
of idiopathic Parkinson’s disease, as which it is often misdiagnosed, although
there are particular differences in both the symptoms (for example, nature of
tremors, response to drugs such as levodopa, and affected portion of the bas-
al ganglia. Long-term accumulation of manganese affects fertility).
Treatment. The current mainstay of manganism treatment is chelation with
EDTA and administration of cholinolytic drugs. Both have limited and at best
transient efficacy. However, the symptoms remain largely unchanged.
1.4. Tetraethyl lead (TEL) intoxication
Poisoning can occur in manufacturing TEL; pouring, mixing it with fuel, gas-
oline storage cleaning. It can get into the human body by inhalation and via
skin. It is excreted from the body very slowly through the lungs, urine and feces.
TEL metabolites accumulate in parenchymal organs and nervous system.
The first indications in acute TEL poisoning are severe headache, weak-
ness, and euphoria. Sleep is interrupted by nightmares. Characteristic fea-
tures of TEL poisoning are the disorders of the autonomic nervous system,
such as drop in blood pressure and body temperature, a slowing of the pulse,
and hypersalivation. Difficulty in walking, impairment of memory, emotional
instability and tactile hallucinations («hair on the tongue», «ants crawling over
the body») are also possible.
Chronic poisoning remains latent for a long period. Symptoms of mild cas-
es are asthenia and disorders of the autonomic nervous system; severe cas-
es are manifested by toxic psychoses. There may be cognitive dysfunction.
In severe cases there can be delirium, auditory, visual and tactile halluci-
nations, vital phobias, psychomotor agitation, death.
Treatment for acute TEL poisoning involves gastric lavage and the adminis-
tration of soporifics, sedatives, and cardiovascular agents; for chronic cases the
general restorative treatment is also indicated. Detoxification agents (5% glu-
cose, ascorbic acid and glutamic acid), sedatives, hypnotics, neuroprotective
agents, vasoactive agents, biogenic stimulators, vitamins B group are used.
1.5. Carbon monoxide intoxication
This gas is colorless and odorless. In addition, poisoning occurs slowly,
signs of intoxication appear when 30% of hemoglobin is converted to car-
boxyhemoglobin (COHb), leading to red blood cells hemolysis.
A headache is the most common symptom of mild carbon monoxide poi-

soning. Other symptoms include: dizziness and nausea (feeling sick), vomit-
ing (being sick), tiredness and confusion, stomach pain, shortness of breath
and difficulty breathing. Symptoms of carbon monoxide poisoning can be sim-
ilar to those of food poisoning and the flu. However, unlike flu, carbon mon-
oxide poisoning does not cause a high temperature (fever). Skin and mucous
membranes become cherry red. Death occurs when more than 60% COHb is
accumulated in blood.
Treatment. First Aid: to remove victim to fresh air, to provide tranquil-
ity and warm, inhalation of ammonia, to rub the body, to give a strong
sweet tea.
Exposure to a high amount of CO gas is treated with oxygen therapy: 100%
oxygen through a tight fitting mask (normal air contains around 21% oxygen).
Hyperbaric oxygen therapy (HBOT) floods the body with pure oxygen, helping
it to overcome the oxygen shortage caused by carbon monoxide poisoning.
A long-term complications such as damage to the brain or heart develop in
10-15% of people who have severe carbon monoxide poisoning.
P.S. (!) Carbon monoxide is lighter than air, thus being in smoky room
during a fire, one should move, bent to the floor.
1.6. Arsenic compounds intoxication
Arsenic is a part of the insecticides, antirodents poisons, is used in the man-
ufacture of glass. It is ingested by inhalation, via the digestive tract and skin.
Body organs that are usually affected by arsenic poisoning include skin, lungs,
kidneys, and liver. Initial symptoms include the following: headache, confusion,
drowsiness, severe diarrhea, pallor, rashes, swelling. As the poisoning increases,
convulsions and fingernail pigmentation changes (leukonychia) occur.
Symptoms of acute arsenic poisoning are diarrhea, vomiting, cramping
muscles, blood in the urine (he-
maturia), stomach pain, hair loss,
breath that smells like garlic, me-
tallic off-flavor, convulsions.
Chronic poisoning: paresis
of small vessels, first of all gas-
trointestinal vessels that leads
to anorexia, nausea, diarrhea or
constipation; pigmented spots
on the skin; nails lesion (white
bands going across the nails —
Mees’ lines); headache, pares- Fig. 1. Mees’ lines
thesia of the extremities, paralysis of muscles (extensor muscles are affected

more than flexors), their atrophy.
If arsenic poisoning is not treated properly, the patient can enter into a
coma and eventually die.
Treatment. Usе a drug, which has monoisomyl succimer as its base, along
with aloe vera. The drug has a better ability to penetrate cell membranes, get
attached to the arsenic content and to excrete it from the body. Other steps to
counter the arsenic poisoning is to remove the contaminated clothes and wash
them. Wash skin thoroughly; use a bowel irrigation (passing large quantities of
polyethylene solution through the GI tract to flush out arsenic), blood transfu-
sions, supportive treatment for complications like heart failure and seizures.
1.7. Methanol intoxication
Formaldehyde and formic acid, which are metabolites of methanol oxida-
tion in the liver, are highly toxic.
Initially, the symptoms of methanol intoxication are similar to those of eth-
anol intoxication, often with disinhibition and ataxia. Following a latent period,
patients may develop headache, nausea, vomiting, or epigastric pain. In later
stages, drowsiness may rapidly progress to obtundation and coma. Seizures
may occur, generally as a complication of the metabolic derangement or as
a result of damage to the brain parenchyma. It is likely that neuropathies and
spinal cord dysfunction are underestimated.
Patients may present with diminished visual acuity, which can progress to sco-
toma and scintillations. The frank blindness that develops sometimes responds to
immediate therapy; however, complete loss of vision is a common sequela.
Treatment. Metabolic acidosis in methanol poisoning may necessitate the
administration of bicarbonate and assisted ventilation. Bicarbonate potentially
may reverse visual deficits. In addition, bicarbonate may help to decrease the
amount of active formic acid. Antidote therapy, such as ethanol or fomepizole,
is directed towards delaying methanol metabolism until the methanol is elimi-
nated from the patient’s system either naturally or via dialysis. Ethanol is pre-
scribed at a rate of 1-2 g of 96° alcohol per 1 kg/day for 3-4 days per os or i/v.
Hemodialysis can easily remove methanol and formic acid.
1.8. Organophosphate compounds intoxication
Organophosphorus compounds (OPhC) are widely used in industry and
agriculture, for example, to combat pests. OPhC are absorbed through the
skin or ingested via the respiratory and digestive tracts. OPhC belong to an-
ticholinesterase agents that block cholinesterase, resulting in acetylcholine
excess accumulation in synapses that lead to disruption of the nerve impulses
transmission.
Signs and symptoms of organophosphate poisoning:

1) Muscarinic effects: pale skin, hypersalivation, sweating, increase of mo-
tor and secretory functions of digestive tract, nausea, vomiting, stomach pain,
diarrhea, miosis, bradycardia, bronchorrhea, bronchospasm; laryngeal spasm
can lead to airway compromise. Respiratory failure is the most life-threaten-
ing effect and requires immediate intervention.
2) Nicotinic effects: twitching of facial and tongue muscles, nystagmus.
3) CNS effects: headache, anxiety, mental disorders and dyssomnia (sleep
disorders), seizures, dystonia, cogwheel rigidity and other parkinsonian fea-
tures; paralysis are possible.
Treatment. Remove all clothing and gently cleanse patient suspected of
organophosphate exposure with soap and water because organophosphates
are hydrolysed readily in aqueous solutions with a high pH. Gastric lavage is
carried out 2-3 times. Then give to drink half a cup of 2% solution of bicarb
and 1-2 tablespoons of activated carbon. Atropine is an antidote.
2. Food intoxication, botulism

Botulism is a rare but serious paralytic illness caused by a nerve toxin that
is produced by the bacterium Clostridium botulinum. Botulinum inhibits the
release of acetylcholine in synapse, thus leading to disorders of the nervous
transmission.
The incubation period is 18-48 hours. There are weakness, dizziness, epi-
gastric pain, sometimes vomiting and diarrhea, which further is changed by
constipation. Patients complain on dry mouth, dyspnoea, persistent consti-
pation, anxiety, poor sleep, dry skin, hypo- or anuria, hypothermia (35-36 °),
tachycardia (HR — 140-160 bpm), accommodation disorders occur due to
disruptions in the autonomic nervous system.
Severe muscle weakness simulates the paralysis. Double vision, drooping
of both eyelids (ptosis), loss of facial expression and swallowing problems may
occur, as well as difficulty with talking. The weakness then spreads to the arms
(starting in the shoulders and proceeding to the forearms) and legs (again from
the thighs down to the feet). In severe cases, death occurs within a few days.
Severe botulism leads to reduced movement of the muscles of respiration that
can lead to respiratory failure and require a patient to be on a breathing ma-
chine (ventilator) for weeks or months, plus intensive medical and nursing care.
The differential diagnosis: atropine, methanol, mushroom poisoning; diph-
theria, myasthenia gravis, encephalitis.
Treatment. Botulism can be treated with an antitoxin, which blocks the
action of toxin circulating in the blood. If antitoxin is given before a paralysis
is complete, worsening can be prevented and recovery time can be shorten.

Physicians may try to remove contaminated food still in the gut by inducing
vomiting or by using enemas.
Prevention. Supervision of the canning manufacture. In sealed cans toxin
is destroyed by boiling for half an hour. In the manufacture of salted food, salt
concentration should be at least 10%. Do not eat products with the smell of
rancid oils and products from swollen canned tins.
3. Wernicke–Korsakoff syndrome and other neurological manifesta-

tions of alcoholism
Wernicke–Korsakoff syndrome is caused by deficiency of the vitamin B1
(Thiamine) in alcohol abuse. Patients with this condition have marked con-
fusion, delirium, disorientation, inattention, memory loss, and drowsiness.
Examination reveals abnormalities of eye movement, including nystagmus
and double vision. Problems with balance make walking difficult. People may
have trouble coordinating their leg movements, but usually not their arms.
If thiamine is not given promptly, Wernicke encephalopathy may progress to
stupor, coma, and death.
Severe alcoholism can cause cerebellar degeneration, a slowly progres-
sive condition affecting portions of the brain called the anterior and superior
cerebellar vermis, causing a wide-based gait, leg incoordination, and an in-
ability to walk in a straight line. The gait disturbance usually develops over
several weeks, but may be relatively mild for some time, and then suddenly
worsen after binge drinking or an unrelated illness.
When a chronic alcoholic suddenly stops drinking, such withdrawal of al-
cohol leads to a syndrome of increased excitability of the central nervous sys-
tem, called delirium tremens or «DTs». Symptoms begin in six to eight hours
after abstinence, and are most pronounced in 24-72 hours after abstinence.
They include body shaking (tremulousness), insomnia, agitation, confusion,
hearing voices or seeing images that are not really there, seizures, rapid
heartbeat, profuse sweating, high blood pressure, and fever. Alcohol-related
seizures may also occur without withdrawal, but during active heavy drinking.
Epileptic seizures occur mainly after prolonged drinking bout in 3-4% of
cases. The majority (90%) of attacks occur during 7 to 48 hours after with-
drawal alcohol. In 2% of cases status epilepticus develops. Almost 30% of pa-
tients have alcoholic psychosis after seizures (delirium). EEG does not detect
epileptic activity between seizures.
Prevention of attacks is the avoiding alcohol abuse; it is not required to
prescribe the antiepileptic drugs.
Alcohol intake can trigger epileptic seizure and various neurological dis-
eases (epilepsy, brain tumors, subdural hematoma, etc). Therefore, the de-
velopment of attack after alcohol consumption requires exclusion of other dis-
eases. Partial seizures are not typical for alcoholism. Data of CT or MRI scan
of brain play leading role in the differential diagnosis.
Alcoholic myopathy, or weakness secondary to breakdown of muscle tis-
sue, is also known as alcoholic rhabdomyolysis or alcoholic myoglobinuria.
Breakdown of muscle tissue (myonecrosis) can come on suddenly during
drinking bout or in the first days of alcohol withdrawal.
In patients who abuse alcohol over many years, chronic alcoholic myop-
athy may develop. Symptoms include painless weakness of the limb mus-
cles closest to the trunk and the girdle muscles, including the thighs, hips,
shoulders, and upper arms. This weakness develops gradually, over weeks
or months, without symptoms of acute muscle injury. Muscle atrophy, or de-
crease of their volume, may be striking.
Although alcoholic peripheral neuropathy may contribute to muscle weak-
ness and atrophy by injuring the motor nerves controlling muscle movement, al-
coholic neuropathy more commonly affects sensory fibres. Injury to these fibres
can cause tingling or burning pain in the feet, which may be severe enough to
interfere with walking. As the condition worsens, pain decreases but numbness
increases. Due to loss of proprioception, sensory ataxia occurs.
Treatment. Recovery is possible in case of maintaining a healthy diet and
taking vitamin supplements. Chronic alcoholic myopathy and other chronic
conditions are treated by correcting associated nutritional deficiencies and
maintaining a diet adequate in protein and carbohydrate. The key to treating
any alcohol-related disease is helping the patient to overcome alcohol addic-
tion. People with walking disturbances may benefit from physical therapy and
assistive devices. Doctors may also prescribe drugs to treat the pain associ-
ated with peripheral neuropathy (gabapentin, pregabalin).
Fetal alcohol syndrome occurs in children whose mothers frequently con-
sumed alcohol during pregnancy. It is manifested by low birth weight, skull and
joints deformities. One of the six infants dies; half of the survivors has back-
wardness in mental and physical development. There is no effective treatment.
4. Barbiturate intoxication
Depending on the duration of hypnotic effect, barbiturates are divided into
following groups:
1. Long acting — Phenobarbitone
2. Short acting — Butobarbitone, Pentobarbitone
3. Ultra short acting — Thiopentone, Methohexitone

There are four stages of acute poisoning.
Sleep stage is characterized by drowsiness, decreased reaction to external
stimuli. Patients are still contact. There are ptosis, moderate miosis, reaction to
light is preserved. There may be muscle hypotonia, bradycardia, hypersalivation.
Stage of superficial coma is characterized by sopor, miosis. There are
Babinski reflex, slight stiff neck, muscle hypotonia, hypersalivation, bronchor-
rhoea, falling back of the tongue, aspiration of vomit. Significant hemodyna
mic disorders are absent.
Stage of deep coma is characterized by the complete inhibition of reflex-
es, muscular atonia, constricted or dilated pupils, respiratory disorders. He-
modynamic disorders are manifested with significant arterial hypotension or
collapse, paroxysmal tachycardia. Pulmonary edema may develop due to the
acute left ventricular failure.
Stage of waking up (after comatose state) is characterized by a gradual
restoration of normal functioning of the central nervous system. Neurological
symptoms are similar to those which are at sleep stage.
Treatment. Stages of intoxication should be considered when treating in
intensive care department. A patient may receive a medicine called naloxone
(Narcan). This medicine will often rapidly restore consciousness and breathing.
There is no direct antidote for this type of overdose. Breathing support, such as
a breathing machine, may be needed until all the drug is removed from the body.
5. Vibration disease
Vibration disease results from the long-term use of vibrating tools. Initially
only the vascular component was recognised but it is now clear that it is a
complex disease with sensor neural, vascular and musculoskeletal deficits.
The sensor neural deficits precedes vascular elements leading to a second-
ary Raunaud’s phenomenon. Disability is not limited to time at work but can
interfere with hobbies and recreation.
The main clinic features are neurological and vascular symptoms.
• Neurological features responsible for the subjective numbness, tingling
and pain and the neurological signs of sensory deficits, especially to
fine touch discrimination and temperature. There is also reduced man-
ual dexterity and muscle weakness.
• Vascular features are blanching of the fingers, especially after expo-
sure to cold and with delayed or poor recovery thereafter. This is a
secondary Raynaud’s phenomenon and patients report white fingers in
the morning or after outdoor activity.
• There may be other manifestations from damage to bone and muscles.

Dupuytren’s contracture can result from cumulative trauma to the palm
of the hand. Other effects include exostoses and cysts in carpal bones,
carpal tunnel syndrome and osteoarthritis.
Treatment:
Medical therapy. Nifedipine or another calcium-channel blocker may be useful.
Alternative medicine. Eliminate the source of vibration if possible or con-
sider redeployment, keeping the body warm, and stopping smoking.
6. Ionising radiation damage of the nervous system

Ionising radiation can cause two main types of biological effects:
- somatic effects (acute and chronic), in which the damage appears in
the irradiated person;
- genetic effects, which arise only in the offspring of the irradiated persons
as a result of radiation damage to the germ cells in the reproductive organs.
Acute effects of irradiation at different doses
Dose (Sv) Effect
1,000 Spastic seizures; death in minutes
100 Damage to the central nervous system; death in hours
10 Circulating changes; death in days
1 Radiation sickness (nausea, vomiting, fatigue; following a short la-
tent period epilation, loss of appetite, fever, diarrhoea, rapid emaci-
ation, and possible death); decrease in life expectancy and disease
resistance; sterility, erythema — reddening of the skin)
0.1 No obvious injury
Some Chronic Effects of Radiation
Effect Mean Latent Period Evidence for Effect
Leukaemia 8-10 years Atomic bomb casualties, Medical X-ray
treatment
Bone Cancer 15 years Radium luminous dial painters
Thyroid Cancer 15-30 years Atomic bomb casualties, Medical treatment
Lung Cancer 10-20 years Mine workers
Life shortening - Experiments with mice
Cataract 5-10 years Atomic bomb casualties
The first medical aid includes: in case of vomiting — Atropine sulfate
(0.01% 1 ml subcutaneously), in case of dehydration — isotonic sodium chlo-
ride i/v, in case of cardiovascular disease — caffeine, Cordiamine, Mezatone;
in case of convulsions — diazepam i/v; in case of the digestive tract dysfunc-

tion — Ftalazol, chelators, in case of increased bleeding — ascorbic acid,
Etamsylate. A patient should drink plenty of fluid.
7. Electrical injury of the nervous system

Electrical injury occurs under the action of electrical current or lightning
(discharge of atmospheric electricity) action. It causes local and general dis-
orders in humans.
Local injuries are skin and tissues burns at points of electric current entry
and exit. Such burns often resemble thermal III- or IV-degree burns. It is pos-
sible a tissue rupture surrounding the lesion.
The most dangerous is general damage. As the nervous system works
on the principle of electrical phenomena, it suffers first. The victim loses con-
sciousness; muscle spasm, paralysis of the respiratory system, inhibition of
cardiovascular activity occur.
In case of lightning stroke, victim condition is severe. Onset paralysis,
deafness, respiratory arrest are typical.
Immediate hospitalization is required
8. Lesions of the nervous system in the heat and sunstroke

When a person’s body temperature is more than 40.6 °C (105.1°F), and
this is caused by environmental heat exposure with poor thermoregulation
(temperature control), one has heat stroke. Heat stroke is not a fever, where
the body deliberately raises its temperature in response to, for example,
infection.
There are three levels of heat emergencies — heat cramps, heat ex-
haustion, heat syncope and heat stroke, with heat stroke being the most se-
vere and life-threatening. Heat stroke may be diagnosed at lower tempera-
tures. In addition, some people may reach these temperatures and never
develop heat stroke.
The signs and symptoms of heat stroke may include:
• high temperature
• profuse sweating that abruptly stops — when the body cannot sweat
any more, as may happen in cases of severe dehydration, the skin be-
comes dry. Without perspiration, the body has no way of cooling itself
• accelerated (weak) heartbeat
• hyperventilation — rapid and shallow breath
• muscle cramps
• skin becomes hot, dry and red
• nausea
• vomiting
• dark urine.
As the nervous system becomes affected, the following symptoms may
emerge: confusion, coordination problems, seizures, headache, vertigo, diz-
ziness, light-headedness — a sensation of spinning or moving when stand-
ing (vertigo), anxiety, restlessness, hallucinations, irrational behaviour, loss of
consciousness
Treatment. Move the patient to a cool place, preferably air-conditioned. If
it is not available, go to a shady area. Make sure the place is ventilated. Use
a fan or open the windows. Give a person to drink water. Do not give any
painkilling medications, such as ibuprofen, paracetamol or acetaminophen.
If you can, place him in a cool (not cold) shower. Partly fill a bathtub with
cool (not cold) water, sit the person in there and hydrate his skin. Do not fully
immerse the person in the water until the paramedics arrive. To encourage
blood circulation, gently massage his skin. If the person has seizures, do not
place anything in his mouth. Move nearby objects out of the way. If the person
vomits, make sure there is no blockage for breathing.
TESTS
1. Why does a patient with botulism require artificial respiration?

1) respiratory failure due to toxic pneumonia
2) paralysis of respiratory muscles
3) heart failure
4) seizures
5) coma
2. Cholinesterase blockage is observed in the following cases of poisoning:
1) botulism
2) organophosphate compounds intoxication
3) mercurialismus
4) lead intoxication
5) all of the above
3. Diminished visual acuity can occur in case of:
1) botulism
2) methanol poisoning
3) manganese intoxication
4) arsenic poisoning
5) Wernicke–Korsakoff syndrome
4. Symptoms of which substance poisoning are similar to idiopathic Parkin-
son’s disease?
1) lead intoxication
2) mercury intoxication
3) manganese intoxication
4) tetraethyl lead intoxication
5) arsenic intoxication
5. Fingernail pigmentation changes (leukonychia) can occur in case of poi-
soning by:
1) lead
2) mercury
3) manganese
4) tetraethyl lead
5) arsenic compounds
Гриб В.А.
Діагностичні
алгоритми в неврології
В.А. Гриб, Н.П. Яворська,
В.В. Смілевська, С.І. Геник;
за ред. проф. В.А. Гриб та доц.
Н.П. Яворської. — 3-є видання,
виправлене й доповнене. — К.:
Видавничий дім Медкнига,
2017. — 48 с.
ISBN 978-966-1597-31-9
Дивовижно швидко розійшлись два перших видання цієї книги. І хоча обидва
тиражі були стандартними, автори переконались в актуальності й необхідності по-
сібника. На суд читача подаємо третє видання, виправлене та доповнене, оскільки
на початку кар’єри лікаря надзвичайно важливо мати під рукою книгу з дуже ко-
ротким викладом основних моментів, які б охоплювали весь спектр можливих ви-
падків, що зустрічаються на практиці. Саме для цього створена ця книга, яку можна
використовувати як під час прийому пацієнтів у поліклініці, так і біля ліжка хворого
в стаціонарах. У ній у вигляді зручних схем зображено алгоритми диференціаль-
ної діагностики різноманітних неврологічних патологій, що може знадобитися як
молодим сімейним лікарям, так і досвідченим невропатологам. Компоновка мате-
ріалів дозволяє швидко зорієнтуватися в проблемі та призначити необхідні обсте-
ження, а, отже вчасно діагностувати захворювання, що збільшує ймовірність його
ефективного лікування.
Кожному поколінню потрібен свій підручник, який включає сучасні знання для
практичної роботи лікаря. Ця книга відповідає таким вимогам та рекомендується
для широкого кола лікарів, які прагнуть удосконалити якість надання медичної до-
помоги пацієнтам.
Видання розраховане на терапевтів, лікарів загальної практики – сімейної
медицини, ревматологів, ортопед-травматологів, слухачів курсів спеціалізації та
передатестаційних циклів, лікарів-інтернів та студентів старших курсів вищих ме-
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Замовити книги можна за телефоном (044) 485-15-86,

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Cerebral vascular diseases. The blood supply of the brain and spinal cord. Cerebral autoregulation 49
Topic 5
CEREBRAL VASCULAR DISEASES. THE BLOOD SUPPLY OF THE

BRAIN AND SPINAL CORD. CEREBRAL AUTOREGULATION
Topic questions:
I. Blood supply of the brain
1. Cerebral circulation
a) anterior cerebral artery circulation;
b) posterior cerebral artery circulation.
2. Cerebral autoregulation
II. Blood supply of the spinal cord
III. The venous system of:
1. Brain
2. Spinal cord
I. Blood supply of the brain

Cerebral blood flow (CBF) is the
blood supply to the brain in a given
time. In adult, CBF is typically 750 ml
per min or 15% of the cardiac output.
This equates to an average perfusion
of 55 to 58 ml of blood per 100 g of
brain tissue per min. The brain only
extracts about 20% of the delivered
oxygen, and about 10% of the
delivered glucose.
Extracranial arteries are shown in
Fig. 1.
1. Cerebral circulation
a) Anterior cerebral artery Fig. 1. Arteries of the neck
circulation
It is the blood supply to the anterior portion of the brain, and is supplied by
the following arteries (Fig. 2):
Internal carotid arteries. These large arteries are the left and right branches
of the common carotid arteries in the neck, which enter the skull, as opposed
to the external carotid branches, which supply the facial tissues.
The internal carotid artery

branches into:
- ophthalmic artery;
- anterior choroidal artery;
- anterior cerebral artery;
- middle cerebral artery;
- posterior communicating artery.
Anterior communicating artery
connects both anterior cerebral
arteries, within and along the floor
of the cerebral vault.
Ophthalmic artery is the first
large branch, which supplies all the
structures in the orbit. Its branch,
a. dorsalis nasi, connects with
a. angularis (facial branch of the
external carotid artery) and forms
supratrochlear anastomosis.
Anterior cerebral artery supplies
parasagittal cortex, including front
and back areas of the central
gyri that control the opposite leg,
centers of urination and defecation
(Fig 3).
Middle cerebral artery supplies Fig. 2. Schematic representation of the
the most of the cerebral cortex Circle of Willis, arteries of the brain and
and subcortical white and gray brain stem
Fig. 3. Blood supply regions of brain convex and medial surface of the brain
matter (basal ganglia and internal capsule are supplied by its branches — the
lenticulostriate arteries).
Posterior communicating artery connects the three cerebral arteries of the
same side. Anteriorly, it connects to the internal carotid artery that is to the
anterior cerebral artery and middle cerebral artery. Posteriorly, it communicates
with the posterior cerebral artery.
b) Posterior cerebral artery circulation
The following arteries supply the posterior cerebral circulation (Fig. 2):
- Vertebral arteries
- Posterior inferior cerebellar artery
- Basilar artery
- Anterior inferior cerebellar artery
- Pontine branches
- Superior cerebellar artery
- Posterior cerebral artery
Vertebral artery originates from the subclavian artery follows through holes in
the transverse processes of vertebrae C1-C6 and enters into the cranial cavity
through the foramen magnum. Within the cranium, the two vertebral arteries
fuse into the basilar artery and a complex called the vertebrobasilar system.
Basilar artery ascends in the central gutter (sulcus basilaris) superior to
the pons and divides into the posterior cerebral arteries and the superior
cerebellar arteries.
Posterior cerebral circulation supplies lower internal part of temporal lobes,
occipital lobe, and thalamus, brain stem, giving branches to the vascular
plexus of the third and lateral ventricles.
2. Cerebral autoregulation refers to the physiological mechanisms
that maintain cerebral blood flow during changes in systemic blood flow,
metabolism and blood chemistry.
The brain is very sensitive to increased or decreased blood flow, and
several mechanisms (metabolic, myogenic, and neurogenic) are involved
in maintaining an appropriate cerebral blood pressure. The mechanisms of
autoregulation in the brain are not completely understood.
The limits of autoregulation are 50-150 mm Hg (it is mean arterial pressure
(MAP) = diastolic pressure +1/3(systolic pressure — diastolic pressure).
In case of increased blood pressure the small vessels (arterioles) constrict, in
case of decreased blood pressure they dilate. When MAP is over the upper limit
the vascular wall is stretched, plasma gets through the wall leading to cerebral
edema. In case of MAP lower limit the vessels deflate and ischemia occurs.
Therefore, above and below this limit, autoregulation is lost and cerebral blood
flow becomes dependent on mean

arterial pressure in a linear fashion.
Autoregulation also activates in
response to an abnormal level of
CO2 partial pressure: the cerebral
blood flow decreases at its low levels
(hyperventilation) and increases in
response to increased CO2 pressure.
II. Blood supply of the spinal
cord is quite variable. But in general at
the level of the medulla, the vertebral
arteries give off branches that merge to
form a single anterior spinal artery and
two posterior spinal arteries (Fig. 5,
6). Approximately 6 to 12 segmental
arteries known as radiculo-medullary
arteries join the anterior spinal artery
along its course. These segmental
arteries arise from various branches
of the aorta and one of them — from
iliac artery. Therefore, a single anterior
median spinal artery and two posterior
spinal arteries perfuse the spinal cord. Fig. 4. Blood supply of the spinal cord
Fig. 5. Blood supply of the spinal cord. View of the ventral (anterior) and dorsal
(posterior) surfaces of the spinal cord. Cross section through the spinal cord
Fig. 6. Cerebral veins

The anterior spinal arteries give rise to numerous sulcal branches that
supply the anterior two-thirds of the spinal cord. The posterior spinal arteries
supply most of the dorsal horns and the dorsal columns.
In the cervical region, the anterior median artery is collateralized at several
levels by medullary arteries derived from the vertebral and some branches of
subclavian arteries; this blood supply is rich in collateral branches.
In the thoracic region, only a few branches of the thoracic aorta join the
anterior median and posterior spinal arteries, and blood supply is relatively
sparse, especially in the lower segments.
Lumbar and sacral spinal areas with conus and cauda equina are supplied by
the largest and most constant of radiculo-medullary arteries, the «great anterior
radicular artery» of Adamkiewicz. This is usually found at Th12 to L4 level. In 50% of
cases conus and cauda equina are also can be supplied by radicular lumbosacral
arteries known as Deproges-Gotteron arteries ascending from the iliac arteries.
ІІІ. The venous system of

1. Brain
Venous net is filled deep in the brain and brings blood up to the surface. Superficial
veins lie in the subarachnoid space partition and form a winding net. After that, the
blood is flowing in «reservoirs» of the dura mater (sinuses) (Fig 6). In the sinuses
blood flows from the top and front towards the back and down, supplemented with
the liquor and flows into the Galen`s great vein, and further to the straight sinus.
Blood enters the transverse and sigmoid sinuses from the upper sagittal and direct
sinus. The sigmoid sinus is a major collector that carries blood into the internal
jugular vein and vertebral venous lace and deeper — into the superior vena cava.
The total venous chanel diameter is always bigger than the arterial, what
makes the blood flow slower. The veins do not have valves in their wall
(muscle layer is absent). They are not able to active constriction.
2. Spinal cord
The plexiform venous system interconnects freely with the radicular
arteries within subarachnoid space. The radicular veins empty into the
epidural venous plexus, which in turn communicates with the inferior vena
cava and azygos system through the perivertebral plexus.
TESTS
1. Most of the brain lateral surface is supplied by this artery:

1) anterior cerebral artery
2) middle cerebral artery

3) posterior cerebral artery
4) vertebral artery
5) anterior choroidal artery
2. One of the following artery is a branch of the basilar artery:
1) anterior inferior cerebellar artery
2) posterior inferior cerebellar artery
3) anterior spinal artery
4) posterior spinal artery
5) radicular arteries to the cervical part of the spinal cord
3. Regarding the cerebral arteries, one of the following is incorrect:
1) they are present in the subarachnoid space
2) occlusion of the right anterior cerebral artery may cause paralysis of
the left upper limb
3) anterior cerebral artery supplies the centers of urination and defecation
4) vertebral artery originates from the subclavian artery
5) basal ganglia and internal capsule are supplied by the lenticulostriate arteries
4. This spinal artery runs in the ventral midline from foramen magnum to
the filum terminale, is supplied by series of 5-10 unpaired radicular arteries
that originate from vertebral arteries and aorta and its branches, arises from
the vertebral artery caudal to the basilar artery.
1) anterior spinal artery
2) posterior spinal artery
3) Adamkiewicz artery
4) Deproges-Gotteron artery
5) medullary artery
5. What happens when mean arterial pressure increases above the upper
limit of cerebral blood flow autoregulation?
1) increased permeability of cerebral vasculature leading to cerebral
edema and increased intracranial pressure
2) decreased permeability of cerebral vasculature leading to cerebral
edema and increased intracranial pressure
3) increased permeability of cerebral vasculature leading to decreased
intracranial pressure
4) decreased permeability of cerebral vasculature leading to decreased
intracranial pressure
5) vessels deflate and ischemia occurs
Topic 6
TRANSIENT ISCHEMIC ATTACK. ISCHEMIC STROKE, ITS

DIAGNOSTICS. TREATMENT. PREVENTION
Topic questions:
1. Risk factors of cerebral circulation disorders
a) which can be treated.
b) which cannot be treated.
2. Classification of acute disturbances of cerebral circulation
3. Transient ischemic attack
a) definition
b) clinical picture
c) the underlying causes of the TIA
d) diagnosis
e) prevention of stroke.
4. Acute hypertensive encephalopathy.
5. Ischemic stroke.
a) definition
b) pathogenesis
c) main signs of ischemic stroke
d) clinical neurological picture depending on the vessel lesion
e) diagnosis.
6. Treatment of ischemic stroke
a) definition of the term «therapeutic window»
b) thrombolysis
c) providing vital functions
d) prevention of complications during acute period
e) stroke prevention (primary, secondary)
f) medicines for secondary prevention of ischemic stroke.
1. Risk factors of cerebral circulation disorders

1) which can be treated:
a) arterial hypertension;
b) hyperlipidemia;
c) atherosclerosis;
d) diabetes mellitus;
e) obesity;
Transient ischemic attack. Ischemic stroke, its diagnostics. Treatment. Prevention 57
f) smoking;
g) atrial fibrillation, artificial heart valves, bacterial endocarditis etc;
h) carotid stenosis;
i) anemia;
j) traumatic brain injury;
k) high levels of homocysteine can cause one’s arteries to thicken and
scar, which makes them to be more susceptible to clots;
l) previous stroke or transient ischemic attack;
m) congenital and acquired arterial and arterio-venous malformations;
n) combinations of several factors.
2) which cannot be treated:
a) age over 55 years;
b) gender (males);
c) family history of stroke;
d) dark-skinned are at greater risk of dying of a stroke, partly because of
the higher prevalence of high blood pressure and diabetes among them;
e) neuroleukemia, hemophilia etc.
2. Classification of acute disturbances of cerebral circulation

1. Transient ischemic attack (TIA)
2. Stroke:
2.1. Ischemic stroke. Pathogenetic subtypes of ischemic stroke are de-
fined due to TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria
- large-artery atherosclerosis
- cardioembolism
- small-vessel occlusion (lacune)
- stroke of other determined etiology
- stroke of undetermined etiology
2.2. Hemorrhagic stroke:
- parenchymal hemorrhage
- subarachnoid hemorrhage
3. Transient ischemic attack (TIA)

a) definition. TIA is an acute episode of temporary neurologic dysfunction
that may last less than an hour; results from focal cerebral, spinal cord, or
retinal ischemia; and is not associated with acute tissue infarction that is ver-
ificated using CT scanning or MRI.
b) clinical picture. TIA usually lasts a few minutes. Most signs and symp-
toms disappear within an hour. The signs and symptoms of TIA resemble
those found early in a stroke and may include sudden onset of:
- weakness, numbness or paralysis of face, arm or leg, typically on one
side of the body;
- slurred or garbled speech or difficulty of understanding the interlocutors;
- amaurosis fugas (dynamic blindness): loss of vision in ipsilateral eye
that lasts a few seconds or minutes;
- dizziness or loss of balance or coordination.
c) the underlying causes of the
TIA often are following. Atherosclerotic
plaque leads to vessel stenosis and can
decrease the blood flow through an ar-
tery (Fig. 1). In people with atrial fibrilla-
tion the small blood clots (emboli) can be
formed within the heart and float down-
stream to cause the occlusion. There is
another way of embolus forming. Plaque
in the vessel wall can rupture and oc-
clude the blood vessel by its thrombotic
material or piece of plaque.
d) diagnosis of a TIA is based just
on the medical history of the event
rather than on anything found during a
general physical and neurological ex-
amination. Fig. 1. Carotid bifurcation plaque
Diagnosis of the TIA causes:
- lipoprotein profile (total cholesterol, low-density lipoprotein cholesterol,
high-density lipoprotein cholesterol, triglycerides);
- screening for hypercoagulable states (particularly in younger patients
with unknown vascular risk factors);
- carotid ultrasonography, mainly of neck vessels;
- CT scanning or MRI to exclude a brain tissue lesion;
- 12-lead electrocardiogram with rhythm strip;
- echocardiography, which visualizes blood clots.
e) prevention of stroke.
The medication of choice depends on the location, cause, severity and
type of TIA. Two frequently prescribed types of drugs are:
- Anti-platelet drugs to prevent clot formation in injured blood vessels (see
below);
- Anticoagulants in case of atrial fibrillation (see below).
In case of severely narrowed neck (carotid) artery (50-99%), a patient is

suggested to undergo carotid endarterectomy or angioplasty (stenting) using
a balloon device to open a clogged artery and placing a small wire tube (stent)
into the artery to keep it open.
Knowing one’s risk factors and living a healthy life are the best things a
patient can do to prevent a TIA.
4. Acute hypertensive encephalopathy

It`s an acute cerebral circulation disorder with the increase of intracranial pres-
sure. It occurs on the background of high arterial blood pressure. The pathogenesis
of this state is cerebral angiospasm, diffuse edema of the brain and its membranes
during a hypertensive crisis and disruption of cerebral autoregulation.
The clinical picture shows the increase of blood pressure, severe head-
ache, photo- and phono-phobia, vomiting, dizziness. The patient may be
stunned. There are no rough focal neurologic symptoms. Only anisoreflexia
can be observed. Seizures, body temperature increase, tachycardia or brady-
cardia are possible. Moreover, the main feature is a meningeal syndrome.
The CSF changes are minimal: increase of CSF pressure, protein-cell dissociation.
Treatment includes antihypertensive therapy, diuretics.
5. Ischemic stroke
a) definition
Ischemic stroke (defined by WHO): clinical syndrome of rapid develop-
ment of focal or global cerebral function signs, lasting 24 hours and longer,
or leading to death in the absence of other (non-vascular) causes. It is the
consequence of cerebral perfusion disorder.
Pathogenetic subtypes of ischemic stroke are defined due to TOAST cri-
teria (Trial of ORG 10172 in Acute Stroke Treatment): atherosclerosis type
(large-artery) (approximately 35%), cardioembolic type (20%), lacunar type
(small-vessel occlusion) (15-20%), the stroke of other determined etiology
(vessel dissection, coagulopathy, 5%), and the stroke of undetermined etiolo-
gy (cases when a patient has factors of atherothrombotic, cardioembolic and/
or lacunar subtypes altogether, and it is not possible to determine the true
mechanism; prevalence is 20-25%).
b) pathogenesis
It’s worth mentioning that an average cerebral perfusion of 55 to 58 ml of
blood per 100 g of brain tissue per min. At focal cerebral ischemia, when cere-
bral blood flow drops below the functional threshold (18-22 mL/100g/min), the
electrical activity disappears (evoked potentials, EEG). If blood supply is re-
stored, brain function is restored also (both clinical and electrical). If the blood
flow drops below the infarction threshold (8-10 mL/100 g/min), then irreversible
structural changes occur. The degree of lesion depends on hypoperfusion du-
ration. The area of the brain, in which regional cerebral blood flow occurs be-
tween two thresholds (functional and ischemic) is called ischemic penumbra.
Typically, cerebral infarction consists of irreversibly damaged central zone,
surrounded by penumbra, cells survival in which depends on the time and
level of blood circulation in it (Fig. 2). Therefore, they say: «brain is time!».
Fig. 2. Formation of cerebral infarction
Ischemic injury is an active biochemical process. Due to depletion of ener-

gy opportunities, cells cannot maintain membrane potential and ion gradients.
Potassium leaves the cells and sodium is absorbed by the cells, carrying
water into them. This causes acute swelling of the cells (cytotoxic edema).
Membrane depolarization stimulates the release of a large number of excit-
atory amino acids (glutamate etc), leading to excessive entry of calcium into
the cell. The latter activates protease, lipase and nuclease that together with
a big number of free oxygen radicals destroy the plasma membranes and
cytoskeleton, thus leading to cell death. This sequence of events is called a
glutamate cascade or excitotoxicity.
The blood-brain barrier disruption leads to the output of blood plasma
components outside the cells in the infarct zone, which have high osmotic
feature. It increases water volume in extracellular space, causing a vasogen-
ic cerebral edema. The latter increases intracranial pressure which worsens
blood supply in the penumbra area and leads to an expasion of the infarct
zone. Swelling can lead to a shift of brain tissues, ventricular compression

and brain herniation (transtentorial herniation or herniation of the cerebellum
tonsils in foramen magnum). In the penumbra area, cell death can be devel-
oped either by necrosis scenario described above, or by the mechanisms of
apoptosis. Apoptosis is a slow, programmed cell death that is associated with
the synthesis of new proteins, chromatin condensation, relative survival of
membranes and mitochondria, etc.
c) the main signs of ischemic stroke:
- relatively slow development of symptoms (excluding cardiogenic embolism);
- predominance of focal neurological symptoms over the cerebral (head-
ache is not typical except basilar artery thrombosis, thrombosis of veins and
sinuses);
- in most cases consciousness is preserved (deterioration of conscious-
ness can occur afterwards when cerebral edema is progressing, and in case
of large lesions);
- no meningeal signs (stiff neck can be present in case of cerebellum isch-
emia and its edema).
d) clinical neurological picture depending on the vessel lesion:
Anterior cerebral artery lesion is followed by paresis and sensory lesion in
the opposite leg or hemi-syndrome, but mainly affecting the leg. There may
be ataxia, mental disorders (apathy, euphoria).
Middle cerebral artery: contralateral hemiparesis dominant in hand, hemi-
hyperesthesia, homonym contralateral hemianopsia and cortical paresis of
gaze (the patient «looks» at the brain focus). Motor, sensory, amnestic or total
aphasia in case of the dominant hemisphere damage.
Posterior cerebral artery: contralateral hemianopsia. The defeat of the
dominant hemisphere may be accompanied by neuropsychological deficits,
«alexia without agraphia», Gerstmann’s syndrome (agraphia, acalculia, finger
agnosia and inability to distinguish between the right and left sides of one’s
body), sensory aphasia, color agnosia. Defeat of subdominant hemisphere
includes violation of spatial orientation, anosognosia and neglection of oppo-
site side phenomenon (space and body). Bilateral occlusion causes bilateral
thalamic and medial-basal temporal lobe lesions.
Basilar artery: severe headache, dizziness, vomiting, disorders of con-
sciousness and tetraplegia with severe pseudo bulbar and bulbar disorders,
seizures. Occlusion of the basilar artery branches leads to formation of lesions
in brainstem — alternating paralysis (Weber, Miyar-Hubler, Foville`s, Jackson,
Wallenberg etc.), which are characterized by cross symptoms of cranial nerve
nuclei lesion and contralateral hemiparesis or unilateral cerebellar ataxia.
Internal carotid artery: its blockage often occurs due to stenosis. Recurrent
TIAs precede stroke. There are hemiparesis (with speech disorders and lesions
of the dominant hemisphere), including symptoms of the middle cerebral artery
blockage. Thrombosis of the internal carotid artery may be asymptomatic when
the blood supply is well compensated by Circle of Willis. In case of artery throm-
bosis, before separation of eye artery, ocular-pyramidal syndrome arises, clini-
cally manifested by ipsilateral vision reduction or loss (blindness), contralateral
hemiparesis or hemiplegia and contralateral hemihypoesthesia.
When there is a blockage of large arteries, ischemia of small cells may
occur, sized to 1.5 cm, which manifest themselves clinically as lacunar infarc-
tions — mainly monosymptomatic (hemi- or monoparesis, hemihypoesthe
siya, isolated aphasia, etc.).
e) diagnosis.
CT-scan or MRI are the world gold standard for stroke diagnosis. Isch-
emic stroke can be seen on CT after 24-48 hours. CT scan is performed
after stroke as soon as possible to exclude hemorrhagic stroke, which can be
diagnosed immediately.
The Glasgow Coma Scale (GCS) has been the gold standard for assessing a
patient's level of consciousness and acute changes in neurological status (Fig. 3).
Fig. 3. Glasgow Coma Scale

A 3- to 15-point scale used to assess a patient’s level of consciousness

and neurologic functioning; scoring is based on best motor response, best
verbal response, and eye opening (eg, eyes open to pain, open to command).
It consists of 3 sections, each of which is scored: best motor response, best
verbal response, and eye opening. A total score of 3-8 for the 3 sections indi-
cates severe state, a score of 9-12 indicates moderate state, and a score of
13-15 indicates mild state.
6. Treatment of ischemic stroke
a) definition of the term «therapeutic window»
Medical management of stroke consists in the urgency actions (brain is
time!): The patient must be delivered to the stroke unit as soon as possible.
The diagnosis of stroke test is conducted as FAST (face – arm – speech –
time): face — lowered corner of the mouth on one side, arm — weakness in
limbs on one side («hand drop») and speech – aphasia, dysarthria, time —
the duration of symptoms. Any healthcare worker can do this and he must call
an ambulance. The department conducts general and neurological examina-
tion and execute the CT scan to exclude hemorrhagic stroke.
b) thrombolysis
If ischemic stroke is proven, and there is a confidence that from the be-
ginning of symptoms not more than 4,5 hours has been passed («therapeu-
tic window»), then the patient is a candidate for thrombolysis. Recombi-
nant tissue plasminogen activator (rTPA, actilyse) is applied, that dissolves
the clot, leading to the restoration of blood flow and regression of stroke
symptoms. The use of the drug after 4.5 hours dramatically increases the
risk of bleeding in the area of ischemia and therefore is not recommended.
If the patient was delivered after this time or if the start of symptoms can-
not be set, then only aspirin (160-325 mg) is used. This is the treatment of
ischemic stroke.
All other measures are aimed at ensuring vital functions, prevention of
complications of acute period and prevention of recurrent cerebrovascular
events.
c) ensuring vital functions
1. Providing a free breathing with the oxygen addition.
2. Control and correction of blood pressure. When the blood pressure in-
creases, which is a physiological response to brain catastrophe, for patients
with ischemic stroke, blood pressure reducing is not recommended, if systolic
blood pressure is < 200-220 mm Hg and diastolic blood pressure is < 120 mm
Hg. Exceptions are the patients who will be carried thrombolysis. They need
to reduce the blood pressure by 10-15% of the original.
Ways for reducing blood pressure:

- Urapidil (ebrantil) (selective alpha-blocker) 12,5-25 mg i/v bolus, fol-
lowed by infusion of 2-5 mg/min);
- Captopril (angiotensin converting enzyme inhibitor) 6.25-12,5 mg per os.
- Labetalol (alfa-beta-blocker): 5-20 mg i/v bolus;
- Metoprolol succinate (beta-blocker) 5 mg i/v bolus with a break of 5 min
three times.
3. Temperature control. Hyperthermia increases the mortality of patients.
In case of hyperthermia is above 37.5 C, Paracetamol (1 g every 3 hours,
3-6 g per day) is injected or physical cooling is applied.
4. Glucose control. The use of insulin is recommended in case blood glu-
cose level is > 10 mmol/L. Infusion of 40 ml 20% glucose solution is recom-
mended in case blood glucose level < 2.8 mmol.
5. Correction of fluid and electrolyte balance.
The patient must be provided with proper nutrition and the use of the liquid
daily (per os, through a tube or intra venous: infusion of sodium chloride 0.9% or
Ringer’s solution 1500-1000 ml, parenteral nutrition, but avoid glucose solution).
d) prevention of complications during acute period
1. Prevention of thrombosis and thromboembolism. Heparin and low mo-
lecular weight heparins (Clexane, Fraxiparine) are used for prophylaxis in
patients at high risk (predictable long stay in bed, obesity, varicose of veins,
thrombophlebitis, disorders of consciousness, flickering arrhythmia). For the
same purpose, bandaging of legs is used, as well as early physical activities
of patients and early physiotherapy.
2. Prevention of pneumonia and urinary infections. Patients in a conscious
state, might be activated as early as on the first day (sitting in bed, rotate, put
on the feet). Catheterization of the bladder. Antibiotics are used when needed.
3. Prevention and treatment of cerebral edema
- Prevention:
1. Blood pressure stabilization.
2. Hematocrit is no more than 40%.
3. Each hour urine output must be 60 ml/h.
4. Keep the head elevated in bed up to 30 degrees.
- Treatment:
Osmotherapy
a) mannitol 25-50 g every 3-6 h (0.25-0.5 g/kg i/v);
b) furosemide 2 ml i/m in 15 min after mannitol.
In сase of seizures diazepam 10-20 mg (2-4ml) i/v, Magnesium Sulfate
25% 10 ml i/v are injected.
c) Decompressive hemicraniectomy prevents death and may improve out-

come in patients with massive hemispheric ischemic stroke complicated with
edema.
e) prevention of stroke
Primary prevention of stroke involves a «mass strategy» that includes a
wide range of sanitary and educational work aimed at increasing the knowl-
edge of the population about the risk factors for stroke (smoking, high blood
pressure, diabetes mellitus, hypercholesterolemia, hyperglycemia, excessive
consumption of salt, alcohol abuse, stress, hypodynamia, sleep apnea syn-
drome), and about measures of their correction; and «strategy of high-risk
groups», which includes the identification of groups of people at high risk of
developing a stroke based on a special algorithm. Such patients are under the
supervision of a family doctor.
Secondary prevention of stroke. All stroke patients should receive an edu-
cational program on the risk of developing a recurrent stroke, signs and symp-
toms of the disease onset, and the actions to be taken; as well as recommen-
dations about modification of lifestyle, correction of risk factors for stroke.
f) medicines for secondary prevention of ischemic stroke
Medicines for secondary prevention are prescribed as soon as possible
and are recommended to use continuously after discharge from the hospi-
tal. They include: antiplatelet agents (aspirin 75-100 mg/day or Plavix 75 mg
daily), individually selected antihypertensive medications and statins, and
dose of which have to be chosen regardless of blood pressure and blood
cholesterol. In case of atrial fibrillation or heart valve lesions, indirect antico-
agulant warfarin is prescribed under permanent control of INR (international
normalized ratio) or direct anticoagulants, Dabigatran (Pradaxa) 110-150 mg
2 times/day. In case of therapy failure, antiplatelet agents are used.
For patients with symptomatic carotid stenosis (ie, patients who have had
a stroke or TIA presumed secondary to carotid disease), the benefit of end-
arterectomy for stroke prevention is robust. In patients who have suffered
a stroke or TIA secondary to a high-grade (>70%) carotid stenosis, endar-
terectomy significantly reduces the risk of subsequent stroke and should be
considered in all patients.
Carotid artery angioplasty and stent implantation has become an alterna-
tive therapeutic option for extracranial carotid artery atherosclerotic disease.
Particular attention should be given to modifying risk factors and lifestyle
of a patient: weight loss, giving up smoking and alcohol, diabetes treatment,
increased physical activity etc.
TESTS
1. Name the type of cerebral circulation disorder, which is characterized by

the meningeal syndrome and absence of neurological deficit:
1) small-vessel occlusion (lacune)
2) transient ischemic attack
3) cardioembolic ischemic stroke
4) acute hypertensive encephalopathy
5) progressive vascular leukoencephalopathy
2. Name cerebral artery, which lesion can lead to alternating paralysis:
1) internal carotid artery
2) basilar artery
3) middle cerebral artery
4) posterior cerebral artery
5) anterior cerebral artery
3. Name the signs of ischemic stroke in the blood supplying area of the right
middle cerebral artery:
1) left-side hemiplegia
2) alternating paralysis
3) visual agnosia
4) motor aphasia
5) dysarthria
4. What is the duration of «therapeutic window» in ischemic stroke?
1) 1 hour
2) up to 2 hours
3) 2 days
4) up to 4,5 hours
5) 24 hours
5. What are the main ischemic stroke diagnosis methods?
1) CTscan
2) lumbar punction
3) carotid ultrasonography
4) electroencephalography
5) electroneuromyography
Hemorrhagic stroke, the differential diagnosis. Treatment. Prevention 67
Topic 7
HEMORRHAGIC STROKE, THE DIFFERENTIAL DIAGNOSIS.

TREATMENT. PREVENTION
Topic questions:
1. Definition.
2. Etiology and risk factors.
3. Classification of hemorrhagic strokes.
4. Parenchymal hemorrhage:
a) etiology;
b) mechanisms of hemorrhage;
c) hemorrhage location;
d) pathomorphology;
e) clinical picture;
f) diagnosis;
g) differential diagnosis;
h) treatment.
5. Subarachnoid hemorrhage (brain membrane hemorrhage):
a) etiology;
b) clinical picture;
c) diagnosis;
d) differential diagnosis;
e) treatment.
6. Complications of hemorrhagic stroke.
7. Medicines for secondary prevention of hemorrhagic stroke.
8. Binswanger's disease.
1. Definition.
Hemorrhagic stroke (HS) is an acute brain blood circulatory disorder as
a result of spontaneous violation of the vascular wall integrity and output of
blood outside a vessel. Hemorrhagic strokes account for about 15 % of all
strokes, yet responsible for more than 30 % of all stroke deaths.
2. Etiology and risk factors for HS: arterial hypertension, symptomatic
hypertension, vasculitis, hematological diseases (leukemia), using of
anticoagulants and antiplatelet drugs (platelet antiaggregants), congenital
malformation of blood vessels (arteriovenous malformations, aneurysms,
caverns, fistulas), Moya-moya disease (genetically determined obliteration of
both ICA and compensatory proliferation of defective vascular network in the

basal parts of the brain), narcotic drug addiction (often with the use of cocaine
and amphetamine). In addition to congenital aneurysms, acquired aneurysms,
which are formed in malignant hypertension may cause the hemorrhage.
3. Classification of hemorrhagic strokes.
Hemorrhagic stroke (blood stroke):
a) Parenchymal hemorrhage.
b) Subarachnoid hemorrhage (brain membrane hemorrhage).
There are also epi- and subdural hematoma; parenchymatous and
subarachnoid hemorrhage; parenchymatous and ventricular hemorrhage.
4. Parenchymal hemorrhage
a) etiology
Cerebral hemorrhage is often the result of artery rupture (microaneurysms
Charcot-Bouchard in hypertensive disease and vascular amyloidosis in
people older than 70 years).
b) mechanisms of hemorrhage
The main mechanism is per rhexis (rupture) of vessels (1), which occurs
in 85 %. Another hemorrhage mechanism is per diapedesis (2) (Fig. 1), which
occurs in 15% as a result of the increasing of vascular wall penetrance.
1 2
Fig. 1. Hemorrhage into the cerebral hemispheres substance
1) per rhexia mechanism, 2) per diapedesis mechanism.
c) hemorrhage location
Depending on the location relative to the internal capsule, the hemorrhages
may be distinguished on (Fig. 2):
1) lateral hemorrhage (hematoma), located laterally from the internal capsule;
2) medial hematoma, which is located in thalamus;

3) mixed hemorrhages that extends to the
subcortical nodes.
There are:
a) lobar hemorrhage. Lobar hemorrhage
is localized in the cerebral hemispheres,
but does not cover the basal ganglia and
thalamus. This occurs due to the rupture of
aneurysm or malformation as well as amyloid
angiopathy; or hemorrhagic diathesis because
of the application of anticoagulants, cocaine
or amphetamine addiction; and intravenous
use of heroin, often complicated by bacterial Fig. 2. Hemorrhage location
endocarditis with the development of septic
embolism and mycosis brain aneurysms (Fig. 3);
b) hemorrhage in capsula interna (Fig. 4);
c) hemorrhage in cerebellum (Fig. 5).
Fig. 3. Lobar hemorrhage Fig. 4. Hemorrhage Fig. 5. Hemorrhage

(CT scan) in capsula interna in cerebellar
(CT scan) (CT scan)
c) pathomorphology
The lesions mostly occur in the region of MCA blood supplying, which are
localized in the subcortex and capsule area: deep striatal arteries origin from
MCA at a direct angle, they don’t have anastomosis, collateral circulation, so
there is no amortization to sudden blood pressure increasing.
d) clinical picture
Parenchymal hemorrhage starts as an acute attack without warnings,
often during the daytime, during the patient activity, after emotional or physical
overload, sometimes during the rest or sleep. It is characterized by:
1) the prevalence of cerebral symptoms (sudden and severe headache,

vomiting) with:
- consciousness disorder (from mild stupor to deep coma);
- autonomic disorders: severe sweating, flushing of the skin and mucous
membranes cyanosis, intense pulse, accelerated or slowed increased blood
pressure. Breathing becomes hoarse, such as Cheyne-Stokes respiration,
with difficult inspiration or exhalation, hyperthermia, especially in case of
ventricular hemorrhage;
2) focal symptoms, which depends on the hemorrhage location.
Hemorrhage in hemisphere (lobar hemorrhage, hemorrhage in internal
capsule). Sometimes there is mydriasis at the side of hemorrhage without
photoreactions. The eyes and head are turned to the side of the lesion,
«the patient looks at the focus» (cortical paresis of gaze). The following
symptoms appear contrlaterally to the focus: nasolabial fold is smoothed,
the angle of the mouth is lowered, when breathing the cheek «sails»
(a symptom of «Sail»), passively raised limbs are falling «as a whips,»
limb muscle tone is lower than the tone of the opposite limbs, foot is
turned out. Babinski’s reflex (Fig. 6) is present, but very often it is two-
sided; deep and cutaneous reflexes disappear. In this condition, there
is an incontinence urine and feces, the retention of urine may happen.
The meningeal syndrome appear after few hours or on the second day
after hemorrhage because of swelling of the brain and its membranes.
The meningeal symptoms are following: neck muscles stiffness, Kernig’s
symptom; Brudzinski’s symptom are more markedly expressed in not
paralyzed leg. There may be «floating» or pendular movements of the
eyeballs, divergent strabismus.
Fig. 6. Babinsky’s vs normal plantar reflexes
Hemorrhage in cerebellum is characterized by pain in the occipital region,

repeated vomiting, diffuse muscle hypotonia, dizziness, decreased blood
pressure, bradycardia. With further suppression of consciousness to coma,
symptoms of brainstem damage occur.
f) diagnosis
1. CT scan and MRI
2. Оphthalmic exam (ocular fundus): papilledema
Fig. 7. Focus of high density Fig. 8. Papilledema — elevated optic

(hyperdensity). Hemorrhage stroke disk
(parenchimatous hematoma (H)
and ventricular (V) hemorrhage)
(CT scan)
3. The Glasgow Coma Scale (GCS) is used for assessing a patient's level
of consciousness and acute changes in neurological status (see topic 6,
Fig. 3).
g) differential diagnosis is carried out with:
- ischemic stroke, at which focal symptoms dominate more often;
- Todd’s palsy that is a focal neurological deficit after seizure;
- uremic or diabetic coma,
- traumatic brain injury;
- bleeding into brain tumor.
h) treatment
Rest, BP monitoring, «triple-H therapy»: hypertension, hypervolemia,
hemodilution. Follow measures are specified in the «topic 6».
5. Subarachnoid hemorrhage (SAH) or brain membrane hemorrhage is
an acute cerebral circulation disorder due to blood entering in subarachnoid
space (Fig. 9 (1, 2)).
a) etiology
SAH is caused by rupture of cerebral vessels aneurysms (Fig. 9 (3)).
Physical or emotional stress, blood pressure fluctuations, congenital defect
1 2 3
Fig. 9. Subarachnoid space (1). Types of Hemorrhage (2).
Brain Aneurysm (3)
of vessel wall are contributed to this. However, SAH often occur without any
apparent external cause. Hemorrhage in subarachnoid space in children can
be developed on the background of septic diseases that cause structural
changes of the vessel wall.
b) clinical picture
The disease begins acutely, by often without predictors. The general cere-
bral symptoms appear with sudden and severe headache. It seems like stab-
bing attack in the occipital area, that accompanied by dizziness and vomiting.
There may be loss of consciousness for a short time (a few minutes, less hours),
psychomotor agitation. For some time the patient is disoriented, euphoric,
sometimes rather sluggish and apathetic. Often there are seizures due to hem-
orrhage focus irritation of cortical motor areas of the brain. In a few hours, or on
the second day, the meningeal symptoms appear (neck stiffness, Kernig’s and
Brudzinski’s signs, zygomatic phenomenona, general hyperesthesia). In case of
basal localization of bleeding, the signs of cranial nerves disorders, particularly
the third pair of cranial nerves (ptosis, strabismus, and diplopia due to paresis
of eye muscles) are observed. Focal neurological symptoms usually do not oc-
cur. In severe SAH the decrease of tendon and periosteal reflexes is observed.
In 2-3 days the body temperature increases and is within 37,5-38° С. A mild
leukocytosis and a white blood cell left shift accompany hyperthermia. Approx-
imatele on the 4-12 day of the disease, the focal symptoms may be occurred
due to local ischemia, caused by vasospasm, which is a result of toxic effects of
blood metabolites to sympathetic plexus of the arteries. It may lead to cerebral
infarction (ischemic stroke) and appearance of severe focal symptoms such as
hemiparesis. Vasospasm maintained up to 4 weeks.
c) diagnosis
1. CT scan (Fig. 10)
2. Angiography (Fig. 11)
3. Lumbar puncture: high blood pressure, bloody CSF.
4. The Glasgow Coma Scale (GCS) is used for assessing a patient's level
of consciousness and acute changes in neurological status (see topic 6,
Fig. 3).
The severity of SAH is set by Hunt & Hess SAH classification:
Table 1
The Hunt & Hess Score of the severity of Subarachnoid Hemorrhage
Add 1 grade if there is serious systemic disease or vasospasm on angiogram
(Serious systemic disease: hypertension, diabetes, chronic obstructive
pulmonary disease, severe artherosclerosis)
0 unruptured aneurysm
1 asymtomatic or mild headache and nuchal rigidity
2 cranial nerve palsy, moderate to severe headache, nuchal rigidity
3 mild focal deficit, drowsiness or confusion
4 stupor, moderate to severe hemiparesis, possible early decerebrate rigidity
and autonomic disturbances
5 deep coma, decerebrate rigidity, moribund appearence
Fig. 10. Subarachnoid Fig. 11. Angiography enables to

hemorrhage (CT scan) verify cerebral vessels aneurysms
d) differential diagnosis is carried out with:

- meningitis;
- meningismus;
- acute hypertensive encephalopathy.
e) treatment
The first step in management of patients with SAH is aimed to ensure the vital
functions. The treatment of SAH is mainly surgical (removal or exclusion of the
aneurysm from blood circulation using neurosurgical clipping and endovascular
coiling) as soon as possible. The conservative management of patients is the same as
treatment of hemorrhage stroke. The traditional treatment of vasospasm is «triple-H»
therapy, denoting hypertension, hypervolemia, and hemodilution. Also all patients
should be started on the oral calcium channel blocker (nimodypin 30 mg 2 tab 5 t/d).
6. Complications of hemorrhagic stroke:
- dislocation brain syndrome occurs due to increasing brain compression
by the hemorrhagic focus, and because of edema and swelling of the brain.
- blood penetrates into the ventricular system that is accompanied by an
expressed worsening of the patient’s state, hyperthermia, breathing disorders,
deterioration of the other autonomic dysfunction, abnormal posturing.
Abnormal posturing is an involuntary flexion or extension of the arms and
legs, indicating severe brain injury.
- vasospasm and secondary ischemic complications.
- hydrocephalus. It may be early — due to mechanical compression of
cerebrospinal fluid pathways, and late — due to adhesive process in these
pathways with their occlusion.
7. Medicines for secondary prevention of hemorrhagic stroke
About the prevention of stroke see topic 6. Strong control of blood pressure
and antihypertensives taking are recommended.
8. Binswanger disease or subcortical vascular encephalopathy, or small
vessel dementia refers to slowly progressive, exclusively white-matter, multi-
infarct dementia.
The main courses are hypertension, diabetes mellitus, small artery diseases.
The brain white-matter damage is the result of the thickening and narrowing
(atherosclerosis) of arteries that feed the subcortical areas of the brain. It
begins late in the fourth decade of life and increases in severity with age.
Clinical criteria for diagnosis are as follows:
- marked subcortical microangiopathic lesions at MRI (Fig. 12)
- a negative family history for strokes, early cognitive impairment, or
psychiatric disorders in first- and second-degree relatives
- documented arterial hypertension: blood pressure higher than 160/95 mm Hg
The main symptoms associated with

Binswanger disease are:
- executive cognitive dysfunction: im-
pairment of short-term memory, organi-
zation, mood, the regulation of attention,
the ability to act or make decisions, and
appropriate behavior. The most charac-
teristic feature of Binswanger disease is
psychomotor slowness - an increase in the
length of time it takes, for example, for the
fingers to turn the thought of a letter into the
shape of a letter on a piece of paper. Other
symptoms include forgetfulness, changes
in speech; changes in personality or mood
(most likely in the form of apathy, irritability,
and depression) Fig. 12. MRI Flair images of
- unsteady gait, clumsiness or brain show multi lacunar state
frequent falls in bilateral periventricular
- urinary incontinence that is not white matter, also known as
caused by urological disease. Binswanger disease
Treatment. The successful manage
ment of hypertension and diabetes can slow the progression of atherosclerosis,
and subsequently slow the progress of Binswanger disease. Because there is
no cure, the best treatment is preventive, early in the adult years, by controlling
risk factors such as hypertension, diabetes, and smoking. Behaviors that slow
the progression of high blood pressure, diabetes, and atherosclerosis.
In another side, treatment is symptomatic. People with depression or
anxiety may require antidepressant medications such as the serotonin-
specific reuptake inhibitors (SSRI). Atypical antipsychotic drugs can be useful
in individuals with agitation and disruptive behavior. Memantine can improve
cognition and stabilization of global functioning and behavior.
TESTS
1. A 58-yaer-old patient is delivered to the emergency department. Her daugh-

ter tells that an hour ago she fell down in the kitchen, lost consciousness, re-
gained consciousness in a few minutes, but face became skew. Weakness
in the right extremities appeared, speech deteriorated. Patient suffers from
arterial hypertension, diabetes mellitus. At examination: BP 200/110 mm Hg,

HR 78-100. Speech is unclear, answers to the questions are either yes or no,
carries out the instructions, but gets tired quickly, falls asleep. In the neurolog-
ical status: central paresis of facial muscles, tongue is deflected to the right,
right-sided central hemiparesis. What is the preliminary diagnosis?
1) ischemic stroke
2) hemorrhagic stroke
3) subarachnoid hemorrhage
4) diabetic encephalopathy
5) hypertensive crisis
2. Indicate changes of cerebrospinal fluid in case of subarachnoid hemorrhage:
1) transparent color
2) erythrocytes in CSF
3) normal pressure of CSF
4) lymphocytic pleocytosis
5) expresses neutrophilic pleocytosis
3. Name the instrumental method for diagnosis of brain aneurysm:
1) cerebrospinal fluid exam
2) CT scan
3) ultrasound research of vessels
4) angiography
5) dopplerography
4. Choose, which of the following signs excludes a hemorrhagic stroke:
1) acute onset
2) slightly expressed focal symptoms
3) aneurysm on angiography
4) brain hyperdensity focus on CT scan
5) brain hypodensity focus on CT scan
5. A 57-year-old patient M. with high blood pressure (220/120 mm Hg), facial
flushing, palpitations, severe sweating was admitted to the neurological
department. Objectively: strained frequent pulse, excessive urination; stiff neck,
Kernig’s symptom. Focal neurologic symptoms weren’t observed. There were
no signs of brain damage on CT scan. What is the preliminary diagnosis?
1) hemorrhagic stroke
2) transient ischemic attack
3) acute hypertension encephalopathy
4) ischemic stroke
5) hypertensive crisis
Headaches 77
Topic 8
HEADACHES
Topic questions:
1. Headache classification
2. Migraine
1) Migraine without aura
2) Migraine with aura
3) Etiology and pathogenesis
4) Phases of migraine attack
5) Factors, which contribute to the onset of migraine attack (migraine
triggers)
6) Migraine complications
- Status Migrainosus
- Persistent aura without infarction
- Migrainous infarction
- Migraine aura-triggered seizure
7) Treatment
- Attack cupping
- Attacks prevention (used for a long time)
3. Tension-type headache (TTH)
1) Infrequent episodic tension-type headache
2) Frequent episodic tension-type headache
3) Chronic tension-type headache
4) Treatment of TTH
4. The trigeminal autonomic cephallgias (TACs)
1) Cluster headache (CH)
- Episodic cluster headache
- Chronic cluster headache
- Diagnostic criteria
- Treatment of CH
2) Paroxysmal hemicranias
- Episodic paroxysmal hemicranias
- Chronic paroxysmal hemicranias
- Diagnostic criteria
- Treatment
5. Secondary headaches
1. Headache classification (based on the International Classification

of Headache Disorders, 3rd edition, 2013)
1. Primary headaches
1.1. Migraine
1.1.1. Migraine without aura
1.1.2. Migraine with aura
1.1.3. Chronic migraine
1.1.4. Complications of migraine (status Migrainosus, persistent aura with-
out infarction, migrainous infarction, migraine aura-triggered seizure)
1.1.5. Probable migraine
1.1.6. Episodic syndromes that may be associated with migraine (re-
current gastrointestinal disturbance, benign paroxysmal verti-
go, benign paroxysmal torticollis)
1.2. Tension-type headache (TTH)
1.2.1. Infrequent episodic tension-type headache
1.2.2. Frequent episodic tension-type headache
1.2.3. Chronic tension-type headache
1.2.4. Probable tension-type headache
1.3. Trigeminal autonomic cephalalgias (TACs)
1.3.1. Cluster headache
1.3.2. Paroxysmal hemicrania
1.3.3. Short-lasting unilateral neuralgiform headache attacks
1.3.4. Hemicrania continua
1.3.5. Probable trigeminal autonomic cephalalgia
1.4. Other primary headache disorders
2.1. Headache attributed to trauma or injury to the head and/or neck
2.2. Headache attributed to cranial or cervical vascular disorder
2.3. Headache attributed to non-vascular intracranial disorder
2.4. Headache attributed to a substance or its withdrawal
2.5. Headache attributed to infection
2.6. Headache attributed to disorder of homoeostasis
2.7. Headache or facial pain attributed to disorder of the cranium, neck,
eyes, ears, nose, sinuses, teeth, mouth or other facial or cervical structure
2.8. Headache attributed to psychiatric disorder
3. Painful cranial neuropathies and other facial pains
4. Other headache disorders
2. Migraine — the primary form of episodic headache, manifested with
intense, often unilateral paroxysmal headaches, as well as various combi-
Headaches 79
nations of neurologic, gastrointestinal and autonomic features. Migraine is

the second in frequency after the tension headache, and its prevalence in
women ranges between 11% and 25 %, in males — 4-10%. It is a disease of
the young people.
1) Migraine without aura is recurrent headaches that are manifested in
attacks lasting 4-72 hours.
Diagnostic criteria:
A. At least five attacks
B. Headache attacks last 4-72 hours (untreated or unsuccessfully treated)
C. Headache has at least two of the following four characteristics:
1. unilateral location
2. pulsating quality
3. moderate or severe pain intensity
4. aggravation by or causing avoidance of routine physical activity (e.g.
walking or climbing stairs)
D. During headache at least one of the following:
1. nausea and/or vomiting
2. photophobia and phonophobia
2) Migraine with aura — recurrent attacks of unilateral fully reversible vi-
sual, sensory or other central nervous system symptoms that usually develop
gradually, are usually followed by headache, and associated migraine symp-
toms. The aura is the complex of neurological symptoms that occurs usually
before the headache, lasting up to 60 minutes, but it may begin after the pain
phase has commenced, or continue into the headache phase.
Before or simultaneously with the onset of aura symptoms, regional cerebral
blood flow is decreased in the cortex corresponding to the clinically affected
area and often over a wider area. Blood flow reduction usually starts posteriorly
and spreads anteriorly, and is usually above the ischaemic threshold. After one
to several hours, gradual transition into hyperaemia occurs in the same region.
A. At least two attacks
B. Aura consists of visual, sensory and/or speech/language symptoms, each
fully reversible
C. At least two of the following four characteristics:
1. at least one aura symptom spreads gradually over ≥5 minutes, and/or
two or more symptoms occur in succession
2. each individual aura symptom lasts 5-60 minutes
3. at least one aura symptom is unilateral
4. the aura is accompanied, or followed within 60 minutes by headache.
3) Etiology and pathogenesis

The development of migraine attack is not fully understood. Predisposing
factor for the development of the disease is genetically determined dysfunc-
tion of vasomotor centre regulation. According to modern theories, the central
mechanism of the migraine attack development is activation of trigeminovas-
cular system (the complex of the trigeminal nerve and brain vessels innervat-
ed by it) and serotoninergic neurons, which form the reaction of head ves-
sels. In case of migraine with aura, the aura symptoms (such as hemianopia,
paraesthesia, visual disturbances and speech difficulties) develop because
of the excitation wave of the brain cortex neurons, which activates afferent
fibres of the trigeminal nerve. These fibres conduct the impulses from men-
ingeal blood vessels and tissues, and brain blood vessels. In migraine with
or without aura, the activation of the trigeminal fibres leads to release of the
vasoactive peptides (neurokinin A, substance P, etc.) which cause neurogenic
inflammation in the vascular wall, protein extravasation, mast cell degranula-
tion and platelets activation.
4) Phases of migraine attack
In the migraine attack development, there are following stages of vascular
reaction — a spasm of the arteries; then their dilatation; then the development
of artery walls swelling; reverse process of certain clinical symptoms develop-
ment, corresponding to these stages (phases):
Phase 1: spasm of extra- and intracranial arteries, caused by increasing
serotonin blood level, accompanied by aura. Aura occurs in case 7 migraine
with aura. Before or simultaneously with the onset of aura symptoms, the
decreasing of regional cerebral blood flow in brain cortex is marked, which
coincides with the region responsible for the aura symptoms or sometimes
this area may be larger.
Phase 2: dilation of arteries, arterioles, venules, veins and arteriovenous
anastomoses (most significant in meningeal, temporal, occipital branches of
the external carotid artery). Vasodilation causes the throbbing headaches as-
sociated with a significant serotonin level decrease, vascular hypotonia, es-
pecialy of extracranial and superficial temporal artery occurs. The expressive
vasodilation occurs. Blood flow slows down in these vessels, including a zone
of meninges. These vessels are overflowed with blood. Simultaneously, the
activation of specific brain systems initiating the unilateral pain occurs. Other
vasoactive substances, such as substance P, calcitonin induce vasodilata-
tion, too. Besides expressed vasodilation, they cause the impaired vascular
permeability, leading to release of prostaglandins, bradykinin, histamine, se-
rotonin, etc into tissue surrounding vessels. A so-called aseptic (non-infec-
Headaches 81
tious) inflammation of tissues, which surround the vessel, occurs. It leads to

the third phase of migraine attack;
Phase 3: swelling in the vascular walls and periarterial tissues and as a con-
sequence — the rigidity of the vascular walls occurs, causing dull headache;
Phase 4: regression of the symptoms.
5) Factors that trigger the migraine attack (migraine triggers):
- diet: hunger, irregular diet, some foods containing tryptophan — sero-
tonin precursor (chocolate, cheese, nuts, alcohol (red wine), creams, yogurt,
chicken liver, avocados, citrus, bananas, soups from concentrates, roasted
pork, sausages, pizza, coffee, cola, tea, etc);
- hormonal factors: menstruation, ovulation, hormonal replacement thera-
py, oral contraceptives;
- psychological: emotional stress, anxiety, depression, fatigue;
- weather changes;
- physical or emotional overstrain;
- lack or sleep excess at night;
- stuffiness, odours (perfume smell);
- visual stimuli (flickering or bright light);
- cold;
- noise;
- staying on height.
6) Migraine complications
- Status Migrainosus is a gruelling migraine attack lasting for more than
72 hours.
Occurs in a patient with migraine without aura and/or migraine with aura
and typical of previous attacks, except its duration and severity:
1. unremitting for >72 hours
2. pain and/or associated symptoms are debilitating
- Migrainous infarction. One or more migraine aura symptoms are associ-
ated with an ischaemic brain lesion in the appropriate area, demonstrated by
neuroimaging.
Occur in a patient with migraine with aura and the previous aura descrip-
tion is typical, except the fact that one or more aura symptoms persists for
more than >60 minutes
Neuroimaging demonstrates ischaemic infarction in a relevant area
- Migraine aura-triggered seizure — a seizure is triggered with an attack of
migraine with aura. The seizure occurs within 1 hour after the migraine attack.
7) Treatment. Therapy of migraine consists of two approaches: 1) abor-
tion of already developed attack and 2) prevention the attacks treatment.
- Abortive therapy:
1. use of simple or combined analgesics (orally or by suppositoria), parac-
etamol (500-1000 mg), naproxen (500-1000 mg), ibuprofen (200-400 mg),
medicines containing codeine (Solpadein, Pandein, Sedalgin-neo, Pentalgin)
during the attack but preferably at its onset.
2. ergotamin-containing drugs — dihydroergotamine mesylate (Digidergot
nasal spray, 500-1000 g).
3. specific therapy — «triptans» — serotonin receptor type 5-hydroxytrypt-
amin 1 agonists: sumatriptan (50-100 mg Sumamigren), eletriptan, zolmitrip-
tan (Rapimig 2.5 mg), frovatriptan, naratriptan.
In the presence of nausea and vomiting — antiemetics: metoclopramide (2-3 tee-
spoon solution (10-20 mg) orally, 10 mg im or iv), domperidone (10-20 mg orally).
- Preventing of attacks (used for a long time)
1) beta-blockers (Metoprolol 50-100 mg 2-3 times/day, Propranolol 20-
40 mg 3 times/day);
2) calcium channel blockers (Flunarizine 5-10 mg p/night, nimodipine
(Nimotop) 30 mg 3 times/day);
3) antidepressants (paroxetine (Rexetin, Paxil 20-40 mg/day), fluoxetine
(Prozac, Fluval 20-40 mg/day), citalopram (Cipramil 20-40 mg/day), sertraline
(Zoloft 50-100 mg/d );
4) NSAIDs — acetylsalicylic acid (125-300 mg daily in 2 divided doses),
naproxen (250-500 mg 2 times/day).
5) anticonvulsants — topiromate (Topamax 100 mg per day: the initial
dose — 25 mg per day, with its increasing on 25 mg per week, the reception
mode — 2 times a day for the treatment duration — 2-6 months).
If attack lasts longer than 72 hours that means status migrainosus a pa-
tient should be addressed in an urgent care or emergency department and
may need to be treated with valproate or dihydroergotamine for a few days.
3. Tension-type headache (TTH) is a very common headache type with
prevalence between 30-78%.
TTH is a special kind of reaction to emotional stress and develops as a
result of involuntary pericranial muscle tension due to mental stress or pro-
longed fixed posture. The TTH clinic is not limited only by pain. Usually TTH
pain syndrome is combined with pain on other sites, such as pain in the heart,
stomach, neck, back and joints. Frequent comorbid syndromes of TTH are
permanent or paroxysmal psychoautonomic disorders. They are blood pres-
sure fluctuations, tachycardia, hyperventilation syndrome, panic attacks, lipo-
timic state, fainting, and premenstrual syndrome (in women).
1) Infrequent episodic tension-type headache
Headaches 83
A. At least 10 episodes of headache occurring on <1 day per month on aver-
age (<12 days per year)
B. Lasting from 30 minutes to 7 days
C. At least two of the following four characteristics:
1. bilateral location
2. pressing or tightening (non-pulsating) quality
3. mild or moderate intensity
4. not aggravated by routine physical activity such as walking or climbing
stairs
D. Both of the following:
1. no nausea or vomiting
2. no more than one of photophobia or phonophobia
2) Frequent episodic tension-type headache
A. At least 10 episodes of headache occurring on 1-14 days per month on
average for >3 months (≥12 and <180 days per year)
B. Lasting from 30 minutes to 7 days
Next items (C and D) — as previous.
3) Chronic tension-type headache
A. Headache occurring on ≥15 days per month on average for >3 months
(≥180 days per year)
B. Lasting hours or is a permanent
Next items (C and D) — as previous.
4) Treatment of TTH. The most effective medicines are antidepressants,
muscle relaxants and NSAIDs (the last should be used with caution because
of the risk of drug abuse). To treat severe cases of chronic TTH lately along
with amitriptyline and selective serotonin reuptake inhibitors (SSRIs) are used
SSRI and noradrenaline — SNRIs (Ixelles, Cymbalta) antidepressants.
The effectiveness of botulinum toxin at TTH, coupled with pericranial ten-
derness is indicated.
In the presence of severe depression, psychological conflict and per-
sistent muscle tension the non-drug treatment has a good effect. It includes
psychotherapy, psychological relaxation, biofeedback, postisometric muscle
relaxation, neck massage, fitness, water treatment, etc.
4. The trigeminal autonomic cephalalgias:
1) Cluster headache (CH). Attacks occur in series lasting for weeks
or months (so-called cluster periods) separated by remission periods usu-
ally lasting months or years. About 10-15% of patients have chronic cluster

headache, without such remission periods. The pain of cluster headache is
maximal in orbital, supraorbital, temporal regions or in any combination of
these sites, but may spread to other regions. During the worst attacks, the
intensity of pain is excruciating. Patients are usually unable to lie down, and
characteristically pace the floor. Pain usually recurs on the same side of the
head during an individual cluster period. During a cluster period in episodic
cluster headache, and at any time in chronic cluster headache, attacks occur
regularly and may be provoked by alcohol, histamine or nitroglycerin.
- Episodic cluster headache is a cluster headache attacks occurring in
periods lasting from 7 days to 1 year, separated by pain-free periods lasting
at least 1 month.
- Chronic cluster headache — cluster headache attacks occurring for
more than 1 year without remission, or with remission periods lasting less
than 1 month. Chronic cluster headache may arise de novo, or evolve from
episodic cluster headache.
- Diagnostic criteria:
A. At least five attacks
B. Severe or very severe unilateral orbital, supraorbital and/or temporal pain
lasting 15-180 minutes (when untreated)
C. Either or both of the following:
1. at least one of the following symptoms or signs, ipsilateral to the headache:
a. conjunctival injection and/or lacrimation
b. nasal congestion and/or rhinorrhea
c. eyelid oedema
d. forehead and facial sweating
e. sensation of fullness in the ear
f. myosis and/or ptosis
2. a sense of restlessness or agitation
D. Attacks have a frequency between one every other day and eight per day.
- Treatment of CH. During pain cluster patients should avoid the possible
instigators of attacks: do not take alcohol and vasodilators, to observe the
regime of sleep-wake. Fast-acting treatments include oxygen, triptans
(used for treating migraines too), local anesthetics, such as lidocaine,
dihydroergotamine.
Basic approaches to preventive treatment of CH — lithium carbonate and
/ or verapamil. More severe cases (more than 5 episodes per day, longer
duration of pain beam — more than 2 months) demonstrates the efficacy of
anticonvulsants and gabapentin use.
Headaches 85
With the ineffectiveness of these approaches, the corticosteroids can be

applied. Along with surgical methods for the treatment of refractory to other
therapies chronic form of CH, the neurostimulation techniques are used (deep
back stimulation of the hypothalamic area, and the great occipital and vagus
nerves stimulation).
2) Paroxysmal hemicranias — attacks of pain characteristics and сon-
comitant symptoms of which are similar to those in cluster headache, but
more momentary, occurring with greater frequency, affecting mostly women
and respond to indomethacin therapy.
- Episodic paroxysmal hemicranias — attacks of paroxysmal hemicra-
nia occurring in periods lasting from 7 days to 1 year, separated by pain-free
periods lasting at least 1 month.
- Chronic paroxysmal hemicranias — attacks of paroxysmal hemicrania
occurring for more than 1 year without remission, or with remission periods
lasting less than 1 month.
- Diagnostic criteria:
A. At least 20 attacks
B. Severe unilateral orbital, supraorbital and/or temporal pain lasting
2-30 minutes
C. At least one of the following symptoms or signs, ipsilateral to the pain:
1. conjunctival injection and/or lacrimation
2. nasal congestion and/or rhinorrhoea
3. eyelid oedema
4. forehead and facial sweating
5. sensation of fullness in the ear
6. myosis and/or ptosis
D. Attacks have a frequency above five per day for more than half of the time
E. Attacks are prevented absolutely by therapeutic doses of indomethacin
- Treatment. In an adult, oral indomethacin should be used initially in a
dose of at least 150 mg daily and increased if necessary up to 225 mg daily.
The dose by injection is 100-200 mg. Smaller maintenance doses are often
employed.
When a headache occurs for the first time in close temporal relation to
another body disorder that is known to cause headache, this one is coded as
a secondary headache attributed to the causative disorder.
General diagnostic criteria for secondary headaches:
A. Another disorder scientifically documented to be able to cause headache
has been diagnosed
B. Evidence of causation is demonstrated by at least two of the following:

1. headache has developed in temporal relation to the onset of the pre-
sumed causative disorder
2. one or both of the following:
a. headache has significantly worsened in parallel with worsening of
the presumed causative disorder
b. headache has significantly improved in parallel with improvement of
the presumed causative disorder
3. headache has characteristics typical for the causative disorder
4. other evidence exists of causation
Headache attributed to trauma or injury to the head and/or neck (whiplash,
craniotomy)
Headache attributed to cranial or cervical vascular disorder
- ischaemic stroke or transient ischaemic attack, non-traumatic intra-
cranial haemorrhage, intracerebral haemorrhage, subarachnoid haemor-
rhage, subdural haemorrhage, cerebral venous thrombosis
- unruptured saccular aneurysm, arteriovenous malformation, dural arte-
riovenous fistula, cavernous angioma, encephalotrigeminal or leptomeninge-
al angiomatosis
- giant cell arteritis, angiitis of the central nervous system
- cervical carotid or vertebral artery dissection, post-endarterectomy headache;
angioplasty, intracranial endovascular procedures or angiography headache
- reversible cerebral vasoconstriction syndrome, intracranial arterial dis-
section, Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts
and Leukoencephalopathy (CADASIL), Mitochondrial Encephalopathy, Lactic
Acidosis and Stroke-like episodes (MELAS)
- pituitary apoplexy
Headache attributed to non-vascular intracranial disorder
- increased cerebrospinal fluid pressure (intracranial hypertension), low
cerebrospinal fluid pressure (post-dural puncture headache)
- non-infectious inflammatory disease (neurosarcoidosis, aseptic (non-in-
fectious) meningitis, lymphocytic hypophysitis, Syndrome of transient Head-
ache and Neurological Deficits with cerebrospinal fluid Lymphocytosis (HaNDL)
- intracranial neoplasia, intrathecal injection, epileptic seizure, Chiari mal-
formation type I
Headache attributed to a substance use or its withdrawal
- Nitric oxide (NO) donor-induced headache, Phosphodiesterase (PDE)
inhibitor-induced headache, Carbon monoxide (CO)-induced headache, Al-
cohol-induced headache
Headaches 87
- Monosodium glutamate-induced headache, Cocaine-induced headache,

Histamine-induced headache, Calcitonin gene-related peptide (CGRP)-in-
duced headache
Medication-overuse headache — Ergotamine, Triptan, simple analgesic,
Opioid, Combination-analgesic
- Caffeine-, Opioid-, Oestrogen-withdrawal headache
Headache attributed to infection
- bacterial meningitis or meningoencephalitis, meningitis or encephalitis, in-
tracranial fungal or other parasitic infection, brain abscess, subdural empyema
- systemic infection
Headache attributed to disorder of homoeostasis (hypoxia and/or hyper-
capnia, dialysis headache, arterial hypertension, phaeochromocytoma, hypo-
thyroidism, cardiac cephalalgia)
Headache or facial pain attributed to disorder of the cranium, neck, eyes,
ears, nose, sinuses, teeth, mouth or other facial or cervical structures (retropha-
ryngeal tendonitis, craniocervical dystonia, acute glaucoma, refractive error,
heterophoria or heterotropia (latent or persistent squint)), ocular inflammatory
disorder, trochleitis, rhinosinusitis, inflammation of the stylohyoid ligament)
Headache attributed to psychiatric disorder (somatization disorder, psy-
chotic disorder)
Treatment — depending on the main disease
Fig. 1. Characteristic of some types of headaches
TESTS
1. Migraine with aura is:

1) recurrent attacks of unilateral fully reversible visual, sensory or other
central nervous system symptoms followed by headache lasting
2) recurrent headaches manifested in attacks lasting 4-72 hours

3) symptoms associated with an ischaemic brain lesion in the appropri-
ate area
4) seizure triggered with an attack of migraine
5) attacks of momentary pain, occurring with great frequency and re-
sponding to indomethacin therapy
2. Status Migrainosus is:
1) recurrent headaches manifested in attacks lasting 4-72 hours
2) symptoms associated with an ischaemic brain lesion in the appropri-
ate area
3) gruelling migraine attack lasting for more than 72 hours
4) seizure triggered with an attack of migraine
5) attacks of momentary pain, occurring with great frequency and re-
sponding to indomethacin therapy
3. Treatment of tension-type headache:
1) beta-blockers
2) calcium channel blockers
3) triptans
4) antidepressants
5) anticonvulsants
4. Type of trigeminal autonomic cephalalgia:
1) cluster headache
2) sinusitis
3) migraine
4) trigeminal neuralgia
5) tension-type headache
5. Secondary headache:
1) occurs for the first time in close temporal relation to another body dis-
order that is known to cause headache
2) is a gruelling migraine attack lasting for more than 72 hours
3) is a recurrent headache manifested in attacks lasting 4-72 hours
4) is a seizure triggered with an attack of migraine
5) is an attack of momentary pain, occurring with great frequency and
responding to indomethacin therapy
Sleep and its disorders 89
Topic 9
SLEEP AND ITS DISORDERS
Topic questions:
1. What is sleep?
2. Physiology of sleep. Dreaming.
3. Sleep phases, their characteristics and diagnosis.
1) slow sleep phase (non-rapid eye movement (NREM) phase)
2) fast sleep phase (REM phase)
4. Sleep disorders (including sleep apnoe):
1) Insomnia
- insomnia risk factors and causes
- insomnia clinical signs (pre -, intra- and postsomnia period disorders)
- insomnia types (transient, acute, subacute, chronic)
- primary insomnia
- secondary insomnia
2) Parasomnias
- somnambulism
- as a result of alcohol and drugs use
- enuresis
- nocturnal myoclonus
3) Hypersomnia
4) Transient sleep disorders
5) Persistent sleep disorders
5. Sleep disorders treatment.
1. What is sleep
Sleep is a natural part of the 24-hour daily cycle, in which it alternates with
non-sleep state. Consciousness is changed during the dream, but the output
a person from this state, that is awakening is an easy. Sleep is very important.
Person, deprived sleep feels tired, becomes irritable and experiences hallu-
cinations. To function well, we spend sleeping approximately one-third of life.
Sleep gives the body a chance to relax, and for the brain — to process the
received during the day information.
Experiments showed that the need in dream and its physiology are deter-
mined, above all, by the highest parts of the nervous system — the cortex.
The nerve cells of the cortex have a special ability: to respond to the slightest
irritation, coming into the brain from the external and internal environment.
But the high reactivity has a downside: cortical cells are extremely sensitive
to depletion and are quickly tired. As a means of self-defense that protects
these delicate cells from depletion and destruction, another nervous process-
es serves — inhibition.
Sleep occurs in an environment, that promotes inhidition to prevail over
excitement. Drowsy action have: long and rhythmically repetitive quiet and
moderate irritations — the ticking of a clock, train clattering, quiet wind noise,
quiet song (lullaby) and others. Anything that reduces the efficiency of nerve
cells in the brain — fatigue, exhaustion, suffering a severe disease — in-
creases the need for sleep and drowsiness. As a result of stimuli received
by the brain during the day, fatigue develops until the evening, following the
need to sleep — a signal of the body need to rest. During sleep, which seems
passive (from outside only, because at this time there are active metabolism
processes inside a cell), brain cells restore normal structure, gaining strength
for further active work. In the dream, when the overwhelming majority of brain
is inhibited, the most favorable conditions are set not only for the brain nerve
cells recovery that are most in need of a rest, but also to relax the whole body.
2. Sleep physiology. Dreaming.

Reticular formation of the brainstem manages sleep. Its neurons form a
network connections with the entire central nervous system. This part of the
brain is dominated by three neurons types that secrete neurotransmitters —
norepinephrine, dopamine and serotonin. Serotonin is able to produce chang-
es in the brain that cause sleep.
Two systems interact in the brain: a system that induces sleep and waking
system.
Circadian rhythm is the cyclical fluctuations of the various biological pro-
cesses intensity, associated with the change of day and night. This is «internal
clock» of the body. It`s period is around 24 hours. This rhythm is regulated by
suprachiasmal nucleus and pineal gland. More precisely, the lights affect the
retinal ganglion cells, then impulse passes through retinohypothalamic tract
and stimulates the suprachiasmal nucleus of the hypothalamus. Multisynaptic
pathways from these nuclei are projected onto the pineal gland, which pro-
duces melatonin. The synthesis of melatonin is inhibited by light and stimu-
lated in the dark. Increased melatonin level was observed between 8-10 pm
with a peak between 2-4 am hours and a gradual decrease in the morning.
Areas of the brain which are involved in the regulation of non-sleep state in-
clude tuberomammillary nucleus of posterior hypothalamus, that contain hista-
mine neurons from which stimulating signals go to the brain stem areas. These
areas are associated with the non-sleep state. They are locus cerulean (norad-
renergic neurons), the dorsal raphe nucleus (serotoninergic neurons), ventral
nucleus of tectum mesencephali (dopaminergic neurons) and basal forebrain
structures (acetylcholinergic neurons). Then impulses are diffusely projected
on the brain cortex and ensure the maintance of the non-sleep state.
The main inhibitory neurotransmitter in the CNS is GABA, which is con-
tained in ventrolateral preoptical nucleus of the anterior hypothalamus. From
there, inhibitory irputs go to tuberomammillary nucleus of posterior hypotha-
lamic and brain stem areas associated with non-sleep (wake) state.
Inhibition of zones, which provide non-sleep state contributes to process-
es that ensure readiness to sleep.
Human behavior during sleep is assessed using electroencephalogra-
phy by difference of brain bioelectric potentials fluctuations or so-called brain
waves. At different physiological state — a state of active mental activity,
slumber or deep sleep — the nature of brain waves is different.
Dreams are images that occur in brain during sleep. Perhaps they are a
side effect of the brain, activity which comprehends the past day impressions
and records them in memory.
Falling asleep, a person passes through four phases of sleep — from
drowsiness to deep (slow) sleep (Fig. 1).
Slow sleep — orthodox sleep or non-REM-sleep

Fast sleep — paradoxical or REM-sleep
Fig. 1. Hypnogramm
3. Sleep phases, their characteristics and diagnosis

Phenomena that occur during sleep, take place in a particular order and
are repeated several times.
During the night a person should «sleep on» up to five sleep cycles. And
every cycle has several phases:
I phase — begins with a nap (5 min), which transforms in 20 min into
II phase — which is characterized by some impulsive bursts of brain activ-
ity (twitching, tremors). It transforms smoothly into:
III phase — the average depth sleep, and then -
IV phase — deep sleep (ortodoxal sleep phase). In the phase of slow
sleep (non-rapid eye movement) the pulse and breathing are slow, tempera-
ture is reduced. During deep sleep the eyes begin to make slow movements
from one side to another. In about an hour the brain comes back to the second
phase of sleep, as if trying to wake up, but instead waking the brain goes to
V phase — REM (rapid eye movement) sleep — (the most interesting).
Eyes begin to make rapid movements. At this time the muscles are completely
relaxed, with the exception of the diaphragm and the eyes muscles. There is
a blockage of the spinal cord (for dream realizing), as a defense reaction, but
there is a powerful work of the brain, it is the most difficult to wake, up being
in this phase despite the fact that thit state is the most similar to wakefulness
(that is why this phase is also called paradoxical sleep phase). EEG param-
eters are identical to the period of non-sleep state. There is a rapid pulse and
breathing, there is a slight increase in pressure and temperature. The cycle is
ended with vivid dream. When we see dreams, our brain is as active as during
wakefullness. REM-sleep duration is only 10 minutes
Then everything is repeated. But slow sleep phase is shortened, and
REM-sleep is prolonged.
Sleep begins with the I phase — falling asleep, after which the II, III,
IV and V (REM-sleep) phases consecutively change each other. Then the
countdown comes: IV, III and II phases. The I phase replaces by the V phase
(REM). Thus, phases change each other from the II to the V phase and back.
At last hours the IV phase is absent.
REM-sleep occurs on average every 70-90 minutes, 4-6 times per night
(depending on the duration of sleep). In the first 75-100 minutes REM sleep
is absent (at that time III and IV phases dominate), then it appears, and with
every sleep cycle its length increases. So, the first period of REM sleep lasts
about 10 minutes, the last one — 20-35 minutes. The closer to morning, the
less time is occupied by III and IV phases, and more by II and V (REM sleep)
phases.
Each of these phases has its physiological significance. During the III and
the IV phases energy is accumulated, the body produces hormones — mel-
atonin, serotonin, growth hormone. No wonder that they say that baby grows
while sleeping.
1) Slow sleep phase (NREM sleep — not rapid eye movement sleep)
When falling asleep, alpha rhythms that is brain waves, typical for a healthy
adult in a non-sleep state with closed eyes, are slowly changed by slow waves.
While sleep is deepening, the frequency of brain waves gradually slows down
and waves amplitude increases. Duration of sleep takes 30-40 minutes, then
process turns back, taking the same amount of time to return to the stage of
light sleep. During this phase the postural muscles keep tone, but heart and
respiratory rate slows down slightly.
Each phase of NREM sleep is char-
acterized by changes at EEG (Fig. 2).
I phase: low-amplitude regular ac-
tivity with a frequency of 3-7 vibrations
per second.
II phase: low-amplitude regular ac-
tivity with a frequency of 12-14 vibra-
tions per second, K-complex and spin-
dle waves.
III phase: the appearance of Del-
ta-waves with a frequency of 0.5-
2.5 vibrations per second.
IV phase: Delta-waves with a fre-
quency of 0.5-2.5 vibrations per sec-
ond — 50% of EEG
2) REM-sleep phase
Unlike slow wave sleep, REM sleep
has a distinct active nature. It starts
from a well-defined center, located
at the back of the brain in pons and Fig. 2. EEG of various sleep phases
medulla oblongata. During this sleep
phase the brain cells are extremely active, but the information transmission
from the senses organs to the brain centers, and from them to the muscular
system is blocked.
EEG: rapid vibrations of electrical activity, similar in meaning to the beta waves.
Quick sleep plays a role of «safety valve» that allows to discharge an
excess energy until the body is completely immovable. It helps to record in-
formation in memory which was obtained during wake state. Some studies
indicate even the close relationship between high levels of intellectual devel-
opment and a long total duration of REM sleep in many people.
Jouvet`s hypothesis looks very attractive, according to which during the
fast sleep the hereditary, genetic information which is relevant to the organi-
zation of coherent behavior, is transferred to memory.
In general it can be concluded that the main function of slow wave sleep
is to restore homeostasis of brain tissue and optimize the internal organs
management. Also it’s well known that sleep is necessary to restore optimal
physical strength and mental state. As for REM sleep, it is believed that it
facilitates long-term storage of information and its reading.
4. Sleep disorders
1) In the current international classification of sleep disorders, INSOMNIA
is a violation of falling asleep, maintaining sleep, early awakening, which does
not bring the expected recovery of the organism, despite the presence of suf-
ficient time and conditions for sleep. It is disorder which leads to a decline of
life quality and daily activities.
- The main insomnia risk factors:
• older age
• female sex
• sleep duration less than 5 hours
• low level of education
• lack of work
• family problems
• somatic illness
- The main reasons of insomnia:
• stress
• neuroses, mental disease
• neurological and somatic disease
• psychotropic drugs, alcohol, toxic substances use
• endocrine-metabolic disease
• syndromes that occur during sleep («sleep apnea»)
• adverse external conditions (noise, light), jet lag, sleep hygiene violations.
In assessing sleep disorders one should count that a healthy person dream
takes 6,5-8,5 hours, and falling asleep takes 3-10 minutes.
- Insomnia clinical signs
It consists of three groups of disorders that can occur separately or in
combination.
1. Presomnia disorder — falling asleep difficulties. Forming abnormal

«bedtime rituals,» fear «not to fall asleep.» The desire to sleep disappears as
soon as the patient lies in bed, unpleasant thoughts and memories appear,
physical activity is increased, the patient is unable to find suitable position for
sleeping. Nap is interrupted even by soft sounds. Falling asleep can last up to
120 minutes. Insomnia is diagnosed already in the case when the patient can-
not fall asleep for 30 minutes. Reasons of presomnia disorders may include:
- lack of fatigue;
- impact of stimulating factors (anxiety, fear);
- receiving the drugs that excite the nervous system;
- somatic pain syndromes.
2. Intrasomnia disorders is frequent awakes during the night, after which
the patient cannot fall asleep, the feeling of superficial sleep. Awakening
caused by both external (noise) and internal (fear, horror, tachycardia, pain,
urge to urinate) factors. Everything, which is described above may contribute
to the awakening of healthy people too, but for sick patients a process of fall-
ing asleep is more difficult after awakening.
Sleep apnea is characterized by pauses in breathing or periods of shallow
breathing during sleep. Each pause can last for a few seconds to several min-
utes and they happen many times a night. This follows loud snoring. There
may be a choking or snorting sound as breathing resumes. As it disrupts
normal sleep, those affected may experience sleepiness or feel tired during
the day. There are three forms of sleep apnea: obstructive (OSA), central
(CSA), and a combination of the two called mixed. OSA is the most common
form. Risk factors for OSA include being overweight, a family history of the
condition, allergies, and enlarged tonsils. In OSA, breathing is interrupted by
a blockage of airflow. People with sleep apnea may not be aware they have it.
3. Postsomnia disorders occur during morning awakening, characterized
by a loss of working capacity, a sense of «being broken», sleep dissatisfaction.
- By duration there are three types of insomnia: 1) transient and 2) sub-
acute — could be in each person, and 3) chronic insomnia — requires the
favorable factors.
- Transient (acute) insomnia lasts for 1 week (a few nights) and generally
is regarded as adaptive sleep disturbance, because in most cases is a result
of acute situational stress, adverse environmental factors (heat, noise).
- Subacute insomnia includes psychophysiological insomnia, and insom-
nia as a result of sleep hygiene violation. Duration is 1 to 6 months. Is pro-
voked by persistent stressful situations: prolonged illness of close person,
death of relatives, loss of job, etc.
- Chronic insomnia lasts from 6 months and is often associated with men-
tal disorders (depression, schizophrenia, manic phase of manic-depression,
anxiety disorders), intoxication and drug effects, somatic problems, cancer
pathology, accompanied by pain.
- Primary sleep disorders that are accompanied by insomnia.
1. Restless Legs Syndrome: unpleasant feeling in the legs (itching, tingling)
and an irresistible desire to move legs, which occurs at rest in the evening, just
before falling asleep and forces the patient to move limbs, get out of bed to
walk. This feeling is localized deep in the shin. Usually, till morning symptoms
are decreased and the patient falls asleep. In severe cases insomnia develops.
2. «Sleep apnea» syndrome is a potentially life-threatening for a patient. It
is a respiratory disorder that is defined as a period of asphyxia more than 10
seconds during sleep, which leads to the development of excessive daytime
sleepiness, and unstable hemodynamic disorders of cardiac activity. Patients
complain of frequent awakenings during sleep and intrasomnia disorders.
3. There are two types of circadian rhythm violation: 1) when the patient goes to
bed early and wakes up early and 2) when he goes to bed late and wakes up late.
These conditions can be problematic if the patient wants to sleep earlier or sleep
longer in the morning. Failure to do so is regarded by him as sleeping problems.
If all the above reasons for sleep disturbances are absent, and there are
problems with sleep, then primary insomnia is diagnosed.
- Types of Primary insomnia:
I. Psychophysiological insomnia is the result of psychological associa-
tions that violate sleep after prolonged stress, before which sleep was not
disturbed. Patients complain of inability to sleep, doubt about the presence
of normal sleep, agitation, insomnia and fear of the sleep process and fear of
the falling asleep possibility, without necessity to sleep. In such patients, the
following features are present: fear of terrible dreams, normal sleep is not at
home, severe general stress and anxiety.
II. The idiopathic form of insomnia characterized by the absence of a rea-
son. This form is developed in childhood and continues throughout life. It is
manifested by fragmented short sleep, complains of fatigue during the day,
irritability, and depression. This insomnia runs with exacerbations and remis-
sions, sometimes family history is present.
- There are the following types of secondary insomnia.
1. Adaptive insomnia is acute and lasts for a few nights. The main manifes-
tations relate to the presence of stress factors (jet lag, employment change,
admission, examination). After removing the cause or adaptation to it, insom-
nia disappears.
2. Paradoxical insomnia (occurs in persons with mental disease) is

characterized by the distorted sleep phenomenon («sleep agnosia», pseu-
do-insomnia). Patients complain of the complete lack of sleep, insomnia
during a lot of nights, but during polisomnographic investigation sleep
lasts more than 5 hours with a slight deformation of its structure. Patients
complain of implausible short duration of sleep. But in fact so short sleep
duration may be incompatible with life. Pseudoinsomnia prevalence is 5%
of all sleep disorders that should be considered when prescribing hypnot-
ics drugs.
3. Insomnia caused by mental disorders can occur until the development
of mental disorders and be a marker of distress. This type is associated with
the following factors:
- morning depression, caused by early awakening, and inability to sleep;
- unjustified feeling of melancholy, avoiding contact with close people, fa-
tigue;
- high level of anxiety.
4. Insomnia associated with inadequate sleep hygiene and lasts over
a month, is characterized by:
- irregular sleep time;
- day dream, spending the day time in bed;
- alcohol, caffeine, nicotine are taken before bedtime;
- habits to read in bed, study, watch TV before going to bed.
5. Behavioral insomnia of childhood occurs in children who have formed
the wrong association with sleep: sleep only when light is switched on, on
someone’s arms, reluctance to sleep in his crib. While trying to correct this
situation, child resists, that leads to a reduction of sleep duration and wors-
ening it.
VI. Insomnia on a background of organic pathology (neurological and so-
matic), especially for those states where the leading symptom is pain phe-
nomenon, breath shortness, coughing, itching, nocturia. Among neurological
disorders which can cause insomnia are Parkinson disease, cluster and other
headaches that occur during sleep.
VII. Insomnia caused by taking drugs and other substances. Substances
which causes insomnia which are taken extensively. They are alcohol, caf-
feine substances, alpha- and beta-blockers, methyldopa, diphenin, lamotrigin
and other antiepileptic drugs, MAO inhibitors and other antidepressants with
stimulating effects, stimulants (amphetamines), bronchodilators, diuretics,
thiazide derivatives xanthine, corticosteroids, thyroid hormones, nasal vaso-
constrictors etc.
2) Parasomnias.
During sleep, many unpleasant behavioral and physiological effects may
occur. They are considered as separate clinical units. So parasomnias are
functional disorders associated with sleep, sleep phases and incomplete
awakening. They are:
- sleepwalking;
- insomnia due to use of drugs and alcohol;
- enuresis;
- nocturnal myoclonus;
- other functional sleep disorders.
- sleepwalking (somnambulism). People suffering from this disease
suddenly while sleeping sit in a bed, walk or perform automatic complex
movements. Patients are in unconscious state and resistant to awakening.
Sometimes they commit acts that endanger their health, such as trying to
climb out the window. The attack usually lasts less than 15 minutes and ends
with the patient return to bed or awakening. Sleep walking occurs during the
III-d and IV-th stages of slow wave sleep. Before and during the attack we do
not see the signs of seizure readiness, although the clinical manifestations of
this state should be distinguished from nocturnal epileptic seizure that occurs
in case of the temporal lobe lesions.
Somnambulism takes place among children and adolescents: 15% of
them had one or more similar episodes. In a small number of children (1-6%)
attacks at night can be repeated frequently. The presence of attacks and their
constancy in puberty can be a sign of psychopathology.
- due to use of drugs and alcohol.
Usage of substances which have an influence on the central nervous sys-
tem (hypnotics and sedatives, tranquilizers, or alcohol at bedtime) can lead to
sleep disorders and insomnia. As chronic administration of hypnotics leads to
loss of effect, a patient and a doctor try to increase the dose. Despite the fact
that the patient continues to take the drug, sleep disorders may be deepen,
and therefore the person continues to increase the dose. In patients who con-
tinue to take sleeping pills regularly, sleep is interrupted by frequent awaken-
ings (5 minutes or more), especially in the second half of the night. The III-d
and IV-th stages of slow wave sleep are shorter, difference between the sleep
stages becomes less distinct. These phenomena indicate a significant degree
of sleep disorganization.
In addition, some symptoms occur throughout the day. They are an anxi-
ety, nervousness, myalgia, and, in severe cases, symptoms of drug withdraw-
al, including mental confusion, hallucinations and convulsive seizures. These
complications most often occur after barbiturates and benzodiazepines with-

drawal. In case when a patient takes several different sleeping pills in high
doses for a long time, the drugs should be abolished gradually and under
medical control. After that, many patients noted significant improvement in
both objective and subjective characteristics of sleep, although normal sleep
can recover not so fast.
- enuresis is involuntary urination during sleep. At the age of 2 to 4.5 years
20% of children urinates during sleep, 6-7 years — 10%, 15-17 years — 1 %. The
main conditions that contribute to this phenomenon is the physical and emotional
exhaustion, excessive fluid intake before bedtime, alcohol, abnormalities of the
genitourinary system. After the exclusion of the nervous system organic pathol-
ogy throughout the formation of a complex reflex arc urination and genitourinary
system diseases, one should think about the functional forms of enuresis.
- nocturnal myoclonus. In some cases, patients suffering from prima-
ry insomnia, and often in patients with other kinds of insomnia in a dream
there is a periodic motor activity, especially during the phase of slow wave
sleep. These phenomena are the stereotypical repeating flexion of the
lower limbs, sometimes in the knee and hip joints and flexion of the feet
and big toes. These hyperkinesia last about 2 seconds and are repeated
every 20-30 sec. They should be distinguished from the so-called benign
nocturnal tremors, which arise during sleep. Although the pathophysiolog-
ical mechanisms of periodic hyperkinesia in sleep are unknown. Good ef-
fects from taking clonazepam before bedtime in dose of 1 mg was recently
observed.
4) Hypersomnia
The main symptom of hypersomnia is excessive daytime sleepiness or
prolonged nighttime sleep, which has occurred for at least 3 months prior to
diagnosis.
Hypersomnia can be primary (of central/brain origin) — narcolepsy or sec-
ondary.
Secondary hypersomnias are extremely numerous. It can be secondary to
disorders such as:
- a symptom of other sleep disorders, like sleep apnea
- sleep movement disorders, such as restless legs syndrome
- an adverse effect of taking certain medications, of withdrawal from some
medications, or of drug or alcohol abuse
- mood disorders, like depression, anxiety disorder and bipolar disorder
- chronic fatigue syndrome and fibromyalgia
- chronic kidney disease
- autoimmune diseases, especially lupus and rheumatoid arthritis, celiac

disease
- hypothyroidism and iron deficiency
- multiple sclerosis, encephalitis, epilepsy, or obesity etc.
Paraneoplastic syndromes can cause insomnia, hypersomnia, and para-
somnias.
4) Transient sleep disorders
Passing sleep disorders in case of fast changing of time zones are well
known, as well as similar states that occur when a sharp change in work
schedule takes place. These sleep disorders are caused by a change in the
scheme of circadian rhythms. For such state the shortness of sleep with fre-
quent awakenings and daytime sleepiness are typical. Clock recovery takes
from several days up to 2 weeks.
5) Persistent sleep disorders
- syndrome of sleep period deceleration;
- syndrome of sleep early onset;
- syndrome of non-24-hour sleep cycle.
Syndrome of sleep period deceleration can be separated from other forms
of sleep disorders. Patients can`t sleep in the hours, needed to comply with
the relevant regime scheme of work or study; eventually they fall asleep be-
tween the 2:00 and 6:00 am. However, if there is no necessity to adhere to a
strict regime (e.g., weekends, holidays and vacation), the patient sleeps fine if
he has a chance to go to bed and awake at a convenient time. These people
have the normal sleep duration, but a sleep timing violation during the day
takes place. In such cases, a treatment with increasing delay of sleep time
(chronotherapy) has a good effect. Delay of bedtime for 3 hours daily (27-hour
sleep-wake cycle) gives good effect.
Syndrome of sleep early onset is characterized by normal duration and
normal sleep structure, but inadequately early going to bed and early waking
in the morning. In such cases, people rarely seek treatment. With age typical
changes of bedtime choice appear. Older people usually spontaneously wake
up in the morning and go to bed early.
Syndrome of non- 24 -hour sleep cycle is characterized by the patient
inability to adjust to the conventional 24-hour day. These people, despite the
exercise of certain social functions, have the 25-27-hour duration biological
day. Blindness or some personality changes could lead to this condition.
5. Sleep disorders treatment.
In case of insomnia or parasomnia:
A combination of behavioural, cognitive (muscle relaxation and guided vi-
sual imagery techniques), and pharmacologic treatment is likely to produce

the best results.
1) Benzodiazepines: clonazepam (1 mg, 2.5 mg), nitrazepam (5 mg,
10 mg).
2) Barbiturates: phenobarbital, Luminal (5, 50, 100 mg)
3) Other drugs: zolpidem (7.5, 10 mg), Ivadal 10mg, Donormil 15mg.
In case of sleep apnoe treatment may include lifestyle changes, mouth-
pieces, breathing devices, and surgery. Lifestyle changes may include avoid-
ing alcohol, losing weight, stopping smoking, and sleeping on their side.
Breathing devices include the use of a CPAP machine. Without treatment
sleep apnea may increase the risk of heart attack, stroke, diabetes, heart
failure, irregular heartbeat, obesity, and motor vehicle collisions.
In case of insomnia or hypersomnia:
stimulants, such as amphetamine, methylphenidate, and modafinil, may
be prescribed. Other drugs used to treat hypersomnia include clonidine,
levodopa, bromocriptine, antidepressants, and monoamine oxidase inhibi-
tors. Changes in behavior (for example avoiding night work and social activi-
ties that delay bed time) and diet may offer some relief. Patients should avoid
alcohol and caffeine.
Untreated insomnia can lead to a more severe and refractory condition
than can chronic, appropriate use of hypnotic medication.
TESTS
1. Why one of the phases of sleep is called «REM sleep phase»?

1) due to increased the EEG rhythm frequency in this phase
2) due to decreased the EEG rhythm frequency in this phase
3) due to fast movements of the eyeballs in this phase
4) due to an appearance of restless legs syndrome in this phase
5) due to fast muscle bundles twitching of limbs in this phase
2. Name the factors that determine the daily periodic sleep:
1) endogenous factors associated with fatigue and hipnogenic substanc-
es (serotonin, norepinephrine, gamma-hydroxybutyrate, delta peptide, etc.)
2) «internal clock»
3) unconditional (darkness, peace, posture, sensory monotony, the ef-
fect of temperature, atmospheric pressure)
4) conditioned reflex (habituation to a specific time of sleep, its duration, etc.)
5) all of the answers are correct.
3. What are the main factors of insomnia?

1) response to stress, mental phenomena
2) alcohol, drugs
3) pain phenomena
4) hunger, noise, light
5) all answers are correct
4. Intrasomnia is:
1) frequent night awakenings
2) difficulties falling asleep
3) sleep disorders with fast changing of time zones (jet lag)
4) somnambulism
5) syndrome of sleep period deceleration
5. Narcolepsy is:
1) lack of sleep
2) decreased duration of sleep
3) sleep phase distortion
4) excessive sleepiness during the day
5) a large number of dreams
Meningitis. Tuberculosis of the nervous system 103
Topic 10
MENINGITIS. TUBERCULOSIS OF THE NERVOUS SYSTEM
Topic questions:
1. Meningitis: definition, classification.
2. Etiology and pathogenesis of meningitis.
3. The clinical signs of meningitis.
4. Meningismus — definition.
5. Purulent meningitis.
a) primary meningococcal meningitis, symptoms, diagnosis, prevention
b) secondary meningitis. Symptoms, diagnosis, cerebrospinal fluide (CSF) data.
6. Complications of purulent meningitis:
a) early
b) late.
7. Serous meningitis. Primary virus: lymphocytic choriomeningitis,
herpetic, enterovirus (ECHO virus, Coxsackievirus); parotitis meningitis.
8. The special additional tests, differential diagnosis.
9. Treatment of meningitis.
10. Tuberculosis of the nervous system.
a) tuberculous meningitis (clinical features, course, CSF data), treatment
b) tuberculous spondylitis, tuberculoma of the brain. Diagnosis and treatment.
1. Meningitis: definition, classification.

Meningitis is an acute infectious disease with primarily involving of pia and
arachnoid maters of brain and spinal cord.
Classification of meningitis:
Meningitis is classified according to several criteria.
1. Due to etiology:
• bacterial (pneumococcal, tuberculosis, meningococcal etc.)
• viral (enteroviruses: Coxsackievirus and ECHO viruses; herpes virus,
acute lymphocytic choriomeningitis etc.)
• fungal (cryptococcal, candidal etc.)
• protozoan (malaria, toxoplasmosis etc.)
2. Due to the nature of the inflammatory process:
• purulent (CSF: neutrophils predominance) — is caused mainly by bacteria
• serous (CSF: lymphocytes predominance) — is caused by viruses (mainly),
Mycobacterium tuberculosis, spirochetes of Treponema pallidum, etc
3. Due to pathogenesis:
• primary (no general history of infection or infectious disease of any organ)
• secondary (as a complication of an infectious disease or trauma).
4. Due to the process prevalence:
• generalized
• limited
5. Due to the disease rate:
• fulminant
• acute
• subacute
• chronic
6. Due to the degree of severity:
• mild form
• moderate severity
• severe form
• extremely severe form
2. Etiology and pathogenesis of meningitis.
Bacteria and viruses penetrate in the body by different ways:
• lymphogenous, hematogenous, transplacental, perineural pathways.
• by contact: sіnusogenic — sinusitis, otogenic — mastoiditis, otitis
media and odontogenic origin — the infections of teeth and jaw.
• in case of liquorrhea after open brain or vertebral-spinal injuries,
crackes or fractures of the skull base.
As a result of inflammatory changes there are:
- Dyscirculation in brain vessels and the membranes;
- CSF hypersecretion and resorption slowness;
- Intracranial hypertension, hydrocephalus;
- Irritation of membranes and roots of the cranial and spinal nerves.
3. The clinical signs of meningitis.
The diagnosis of meningitis is based on presence of three syndromes:
1) General infectious
2) Meningeal
3) The syndrome of inflammatory changes in the cerebrospinal fluid
General infectious syndrome: fever, hot flashes, temperature rise,
leukocytosis in blood with a left shift, increasing the ESR.
Meningeal syndrome — a syndrome of meninges irritation, which consists of:
- cerebral symptoms: headache, vomiting, seizures, impaired conscious
ness (psychomotor agitation or stupor (sopor) and even coma).
- sheaths symptoms:
1. General hyperesthesia, including phono- and photophobia.

2. Reactive painful phenomena:
- while percussion zygomatic arch;
- while pressing eyeballs, trigeminal points, exit points of occipital nerves.
3. Muscular tonic symptoms:
- neck muscle stiffness;
- Kernig’s symptom, Brudzinski’ signs (upper, middle and lower) (Fig. 1).
Syndrome of inflammatory changes in the cerebrospinal fluid:
In purulent meningitis: neutrophilic (n) pleocytosis (thousands cells/mm3,
neutrophils prevalence: n > l), the identification of the pathogen.
In serous meningitis: lymphocytic (l) pleocytosis (tens or hundreds cells/
mm3, lymphocytes prevalence: l > n), the identification of the pathogen.
Encephalitic syndrome set is possible in case of brain tissue involvement in
the pathological process. It is accompanied by the following neurological sta-
tus: central paresis, paralysis, disturbance of higher brain functions, seizures.
Fig. 1. Meningeal signs
4. Meningismus is a condition when at the presence of meningeal

syndrome there no inflammatory changes in the cerebrospinal fluid (it is
present in various poisoning or infectious disease due to the meninges
irritation. It is not a true inflammation of the membranes. Pneumonia, influenza,
salmonella, dysentery, renal and hepatic failure are the most frequent reasons
of meningismus.
5. Purulent meningitis
Pathogens: meningococcus, pneumococcus, streptococcus, staphylococcus,
Escherichia coli, Pseudomonas aeruginosa, Pfeiffer’s Haemophilus influenza etc.
Clinical features of some forms of meningitis.
a) Meningococcal meningitis (epidemic, cerebrospinal) is the primary
purulent meningitis, can get sick children under 5 years.
Pathogen — Neisseria meningitis (gram-negative diplococcus). The main
pathogenicity factor — bacteria capsule. Endotoxin is released with the death
of the microbe capsules that leads to clinical manifestations.
The originator has tropism to nasopharynx mucosa. There is airborne
contamination
• entrance gate — nasopharynx
• hematogenous bacterial spreading
• entered into the organs, where it is multiplied
• pathogen in blood is destroyed by phagocytes with the release of endotoxin
• іncubation period is 1-6 days
• typical clinical features, which are described above
Meningococci penetration in blood is characterized by the appearance of
hemorrhagic necrotic rash on the trunk and lower limbs of different sizes —
from petechiae to large hemorrhages with skin necrosis (Fig. 2).
Diagnosis (specific) of meningococcal meningitis:
Express diagnostics includes thick blood film bacterioscopy. Smears from
throat and liquor testing can detect meningococcus at 80 %.
Prevention. Isolation of patients and disinfection of rooms, where they
were present.
b) secondary purulent meningitis:
Most often — pneumococcal
meningitis (may be primary, but
often — secondary) may develops
in presence of pneumonia, lung
abscess, bacterial endocarditis.
Mostly children of the second
half of life and people over 40 get
sick. Course and prognosis are
determined by the severity of
clinical presentation, epileptic
syndrome presence, focal brain
lesions (meningoencephalitis
signs). Fig. 2. Meningococcemia petechial rash
6. Complications of purilent meningitis

a) early complications:
- toxic shock
- disseminated intravascular coagulation syndrome
- cerebral oedema;
- cerebral hypertension;
- acute suprarenal insufficiency (Waterhouse–Friderichsen syndrome);
- acute renal insufficiency;
- seizures.
Waterhouse–Friderichsen syndrome or hemorrhagic adrenalitis or Fulminant
meningococcemia, is defined as adrenal gland failure due to bleeding into the
adrenal glands, commonly caused by severe bacterial infection. Typically the
pathogen is the meningococcus Neisseria meningitidis. is characterized by
overwhelming bacterial infection meningococcemia, low blood pressure and
shock, «filiform» pulse, tachycardia, respiratory depression, cyanosis, oliguria
or anuria, disseminated intravascular coagulation (DIC) with widespread
purpura and rapidly developing adrenocortical insufficiency, coma and death.
b) late complications:
- cognitive impairment
- hearing loss
- problems with gait
- epilepsy
- hydrocephalus.
7. Serous meningitis
Serous meningitis is characterized by typical signs of meningitis, which
are described above. For serous viral meningitis the negative bacteriological
data and benign course with spontaneous recovery are typical.
Clinical features of some forms of serous meningitis.
Acute lymphocytic choriomeningitis (acute serous Armstrong’s
meningitis) is caused by a virus which is filtered. The disease is transmitted
from the gray house mice, which are the main reservoir of the virus. Human
contamination is a result of product use, which is contaminated by nasal
mucus, urine and feces of mice. The virus spreads by blood throughout the
body. The clinical features are typical. Perhaps there is the III-d and VII-th
cranial nerves defeat.
Serous meningitis caused by Coxsackievirus and ECHO (the group of
enteroviruses). It develops more frequently in children as epidemic outbreaks.
The meningitis onset is acute with fever, muscle pain, gastrointestinal disorders
and herpetic rash on the lips, sometimes — herpetic sore throat. Meningeal
symptoms occur after 2-3 days of illness onset. Severe manifestations of

intracranial hypertension is marked. Disease course prognosis is favorable.
Serous meningitis, caused by the parotitis virus. It is typical for children
of school age. Clinical manifestations of parotitis may be at the beginning
of meningitis, during its course and after it. Meningeal syndrome is
moderately expressed. Protracted course of disease with clinical signs of
meningoencephalitis can be observed (damage of pons, medulla oblongata
and spinal cord), in pathogenesis of which the autoimmune process play an
important role.
8. Additional examination methods
- CSF research
Table 1
Differential diagnosis of meningitis by CSF analysis
Parameter Purulent Serous Tuberculous
Normal
meningitis meningitis meningitis
Color colorless yellow-green colorless colorless
Transparency Tr. u/Tr. Tr. Tr.
Pressure
mm water 100-200 >> > >
column
Cytosis thousands, the 200-800
50-1500
(l : n) 0-5 tens of thousands (65-80% l
(90-95% l )
(70-90% n) 20-30% n)
Protein (g/l) 0,12-0,45 1-3 and >> 0,33-1 1-4 and >>
Glucose 2,5-4,4 (no <<<<
(mM/l) less than 50% << N or << < 50% of blood
blood level) glucose level
Chlorides
120-130 < N or << <<<
(mM/l)
- Bacteriological and serological testing of the cerebrospinal fluid reveals
pathogen of purulent meningitis. It is importance to determine its sensitivity to
antibiotics.
- Detection of DNA of pathogens in cerebrospinal fluid by polymerase
chain reaction (PCR) method: herpes simplex virus (type 1, 2), Epstein–Barr
virus (type IV) and cytomegalovirus (V type), Mycobacterium tuberculosis.
- EEG in patients with seizures to detect epileptic activity
- CT scan or MRI. The value of these techniques is limited in the acute period
of meningitis. They are important for the diagnosis of meningoencephalitis,
brain abscess.
- While finding brain abscess a neurosurgeon consultation is indicated.

- Ophthalmological research.
- Otolaryngology research for identifying the primary focus of purulent
meningitis.
Differential diagnosis is made with diseases which occur with similar
clinical symptoms: subarachnoid hemorrhage, hemorrhagic stroke, acute
hypertensive encephalopathy, brain abscess, sinus thrombosis, brain
tumor (extracerebral), membranes carcinomatosis of brain and spinal cord,
membranes sarcoidosis, hypertensive syndrome in case of brain trauma;
infections, which are accompanied with meningismus.
9. Treatment of meningitis.
1. Early admission to a specialized infectious diseases hospital (if
necessary — to the intensive care unit) is compulsory.
2. Timely start the intensive causal therapy.
In purulent meningitis
- a third-generation cephalosporins (Cefotaxime, Ceftazidime, Ceftria
xone) — 1-2 g 2 t/d i/v) or a forth-generation cephalosporins (Cefepime) —
1-2 g 2 t/d i/v
- Early therapy initiation with antibiotics, without waiting for bacteriological
research data. Taking into consideration the analysis results (in 3-4 days),
if necessary, therapy that is based on sensitivity of pathogen to specific
antibiotics must be changed:
- Ampicillin i/m or i/v 500 mg 4 t/d
- or Meropenem 2 g iv 3 t/d
Reserve medications in the absence of positive dynamics of initial therapy
for 48-72 hours are meropenem 120 mg/kg/d or cefepime 100 mg/kg/d, or
vancomycin 60 mg/kg/d. This option should be implemented according to the
difinition of sensitivite to antibiotics during bacteriological examinator.
High doses of antibiotics must be entered during at least 10 days and are
required yet further entering at least 7 days after normalization of temperature.
In serous meningitis (viral origin):
- Antiviral agents (Acyclovir, Zovirax — 1 g i/v 3 t/d) for 7-10 days.
- Immunomodulatory agents: Human Imunoglobulin 0,4 g/kg i/v № 3-5.
Criteria for causal treatment withdrawal is liquor restoration. The control
lumbar puncture is carried out after resistant temperature normalization,
meningeal syndrome disappearance, the blood data normalization.
Therapy is finished if the number of cells in 1 ml of CSF does not exceed 50.
3. Symptomatic therapy is conducted taking into account the nature and
severity of clinical manifestations: monitoring of vital signs, if necessary —
mechanical ventilation, hemodynamic monitoring, correction of fluid and

electrolyte balance (Ringer’s solution 400 ml, Trisol 100-250-500 ml/m),
control of intracranial hypertension (osmotic diuretics — Mannitol 200-400 ml
i/v, saluretics — furosemide 2 ml i/m, glucocorticoids (prednisone 60-90 mg
i/v, dexamethasone 4-12 mg i/v), correction of hypovolemia, seizures.
In the recovery period — nootropics, in case of seizures — anticonvulsants.
10. Tuberculosis of nervous system
a) Tuberculous meningitis. Specific secondary serous meningitis occurs
on a background of tuberculosis of lungs, bronchus, internal reproductive
organs, bones, kidneys and other organs. Mycobacterium tuberculosis
penetrates into the subarachnoid space from the primary focus and affects
base of the brain, the III-d and IV-th ventricular ependyma, choroidal plexus.
Most often, tuberculous meningitis is a manifestation of hematogenous
disseminated tuberculosis.
The clinical features. The disease develops gradually: headache,
dizziness, nausea, fever (subfebrile, seldom — high temperature). Two
phases of the disease are typical:
1 phase — typical harbingers are general exhaustion, pallor, anorexia,
drowsiness, weakness, irritability, tearfulness. It lasts 2 weeks.
2 phase — the appearance of typical meningitis symptoms: nausea,
headache, constipation, neck muscle stiffness, Kernig’s and Brudzinski’s
signs. The manifestations of meningitis get more intensive gradually.
As a result of the serous-fibrous exudate accumulation at the brain base, the
irritation of cranial nerves may develop. There are following symptoms: vision
disturbances, facial muscles paresis, strabismus, anisocoria, mydriasis,
ptosis, deafness. Further, the impaired consciousness, clonic seizures, pelvic
and autonomic disorders, signs of bulbar palsy, which are prognostically
unfavorable symptoms for the patient, may develop too.
Diagnostic criteria for tuberculous meningitis: presence of primary focus
of tuberculosis in the body or indication on contact with tuberculous patients,
subfebrile temperature, moderate meningeal syndrome, cranial nerve lesions.
Data of additional methods of examination.
CSF date:
- Transparent, slightly opalescent at the light, it may be xanthochromic or
feculent with high pressure,
- Mild lymphocytic pleocytosis (200-400 cells per 1 mm3). In early period,
neutrophils can dominate (70-80 %).
- Glucose level decreases more than 50 % of that in blood (so just
before the lumbar puncture serum glucose analysis has to be done)!
- The level of protein increases up to 1-4 g/l.

- After upholding the tube of liquor for 12 hours, the fibrin plica appears.
An important diagnostic criterion is the finding Mycobacterium tuberculosis
in the cerebrospinal fluid. Blood features in case of tuberculous meningitis
are the same as in case of active tuberculosis at other sites: slight
leukocytosis, easily marked left shift, slight ESR increase; lymphopenia
is tipical.
Treatment is based on specific therapy start (within 10 days from the
first signs of the disease) timely. It includes etiotropic treatment (use of
4-5 antibiotics anti-TB therapy depending on the state), which is assigned
and treated in a specialized department, and symptomatic treatment of
meningitis (see above). Phased treatment includes early admission to a
specialized hospital, followed by treatment in a sanatorium and outpatient
conditions a total of at least 12-20 months.
b) Tuberculous spondylitis (Pott’s disease)
Etiopathogenesis. TB-spine occurs as a result of the transfer by
mycobacterium from the primary lesion, located in the lungs or lymph nodes
by hematogenous metastatic pathway. It is often affected thoracic spine in
children and thoracic-lumbar spine in adults.
The desease course is divided into three phases: prespondylitis, spondylitis
and postspondylitis.
1-st phase — «mute» (unpainful) tuberculous granulomas are formed in the
vertebral bodies, the tuberculous intoxication manifestations arise. The spread
of the focus outside of the spine causes pain without certain localization, that
often is interpreted as radiculitis, plexites, intercostal neuralgia etc.
2-d phase — there is a reflex contraction of back muscles, pain increases,
irradiates to the periphery. Alluvial abscesses can be formed (intrathoracic,
psoas- abscess). It can migrate down, for example, in pelvis, thigh. Spreading
on soft tissue the abscesses are broken out or organs forming a fistula that
heals long.
3-d phase — the remission process, but there is deformation of the spine
due to vertebral destruction, paresis develop.
General manifestations of osteoarticular tuberculosis are:
1) intermittent pain in the joints or back;
2) periodic restriction of movements;
3 ) slight swelling;
4) local temperature increase;
5) night pain;
6) lameness due to pain, paresis;
7) atrophy of the paretic limb;

8) in future — change the form of spine and restriction of movement in spine.
Complications: paralysis or paresis of the extremities and disorders of
pelvic organs that develop as a result of bone fragments compression or
abscess of spinal cord.
Diagnosis: spine X-ray in two projections (narrowing of the intervertebral
gap and destruction of adjacent vertebral bodies, MRI (paravertebral abscess),
PCR fot detection of mycobacterium DNA.
Treatment duration is very long. In early stage — the creation of long-term
immobilization (gipsum bed, board), the use of anti-TB drugs.
In spondylitis phase, especially which is complicated with abscesses or
spinal disorders, surgical treatment is indicated — radical removal of lesions,
resection of the affected vertebrae.
Fig. 3. MRI of the thoracic spine: paravertebral

abscess (large arrow) just above the fractured and
operated third thoracic vertebra (small arrow)
Tuberculoma of the brain occurs with hematogenous dissemination of

infectious agents from primary tuberculous focus. Macro- and microscopic
picture of brain tuberculoma is similar to pulmonar tuberculoma — a round
encapsulated focus of caseous necrosis with a diameter of 1-4 cm. Necrotic
masses in tuberculoma may be firmed up and calcinated. Tuberculoma of
brain may be symptomatic initially. Progression of tubercular process leads
to tuberculoma increase, causing the increased intracranial pressure and
the appearance of following symptoms: migraine, vomiting, stagnation in the

fundus, then there may be focal symptoms of brain damage, seizures.
Diagnosis of tuberculoma: anamnesis, clinical signs and results of
neurological reseach, X-ray examination, tuberculin skin test, CT scan or
MRI of brain have to be taken into account. Differential diagnosis has to be
done with brain tumors, syphilitic gumma, neuroinfection of nontuberculous
etiology.
Surgical treatment, antituberculosis agents and symptomatic therapy are
indicated.
TESTS
1. During the examination of a patient with influenza the meningeal syndrome

was marked, but no inflammatory changes in the cerebrospinal fluid were
detected. Which diagnosis is most likely?
1) meningismus
2) purulent meningitis
3) serous meningitis
4) tubercolous meningitis
5) Armstrong’s meningitis
2. A patient, who was diagnosed purulent meningitis, has low blood pressure,
«filiform» pulse, tachycardia, respiratory depression, cyanosis, oliguria,
disseminated intravascular coagulation with widespread purpura. Which
complication has developed?
1) Waterhouse–Fridrichsen syndrome
2) intracranial hypertension with herniation
3) subdural effusion
4) arterial thrombosis
5) hydrocephalus
3. A patient has fever, muscle pain, gastrointestinal disorders and herpetic
rash on the lips, herpetic sore throat. Meningeal symptoms are positive. CSF:
pleocytosis (92% of limfocytes). Which diagnosis is the most likely?
1) meningismus
3) serous meningitis caused by Coxsackievirus and ECHO
4) tuberculous meningitis
4. A patient has had general exhaustion, pallor, anorexia, drowsiness,

weakness, irritability, tearfulness that lasted for 2 weeks. Later nausea,
headache, constipation, neck muscle stiffness, Kernig’s and Brudzinski’s signs
strabismus and mydriasis appeared. CSF: pleocytosis (80% limphocytes,
20% neutrophils). Which diagnosis is most likely?
2) tubercolous meningitis
3) serous meningitis
4) meningismus
5. A patient has intermittent backpain, which increases at night, periodic
restriction of movements, paresis and atrophy of the left leg. MRI reveals
paravertebral abscess. What is one of the suspected diagnosis?
1) serous meningitis caused by Coxsackievirus and ECHO
2) meningismus
3) tuberculous spondylitis
Encephalitis 115
Topic 11
ENCEPHALITIS
Topic questions:
I. Encephalitis. Etiology and pathogenesis. Classification. Syndromes of
encephalitis.
1. Primary encephalitis: clinical features, form of the disease, diagnostics
and treatment. Prevention.
1) tick-borne encephalitis
2) lethargic encephalitis
3) herpetic encephalitis.
2. Secondary encephalitis: clinical features, forms of the disease,
diagnostics and treatment.
1) postvaccinal encephalitis
2) parainfectious in case of chickenpox (varicella-zoster), measles
(rubeola), rubella.
3) rheumatic encephalitis (chorea minor [Sydenham’s])
II. Nervous system disturbances in case of influenza (influenza hemorrhagic
encephalitis, encephalopathy).
I. Encephalitis. Etiology and pathogenesis. Classification. Syndromes

of encephalitis.
Encephalitis — is an inflammatory lesion of brain tissue of contagious or
infectious-allergic etiology.
Etiology. Pathogens: mainly viruses (arboviruses, enteroviruses, herpes
virus, lymphocytic choriomeningitis, rabies, etc.), bacteria, rickettsia, fungi.
Pathogenesis. The basis of primary
encephalitis is brain damage caused by direct
penetration of the pathogen through the
blood-brain barrier. Rapid Hyperergic rapid
response to pathogenic effects arises and is
characterized by the development of brain
edema with its dislocation and brain stem
herniation in the foramen magnum, which
lead to fatal end. So-called postinfectious
or acute parainfectious encephalitis are
characterized by periphleboid (perivenous) Fig.1. Ixodes ticks
infiltration and diffuse demyelination, resulting from autoimmune reactions

that cause protracted disease.
Classification.
Due to the agent:
- viral
- bacterial
Due to localization:
brain stem, cortical, mesencephalic, diencephalic
Depending on the prevalence of the brain lesions:
- leukoencephalitis (predominantly the white matter of brain affects)
- polioencephalitis (the gray matter of brain affects (lethargic encephalitis)
- panencephalitis (the damage of gray and white matter of brain)
Due to the course:
acute, subacute , chronic, progressive-remittent
Due to neurological disorders:
typical, asymptomatic, abortive, rarely — fulminant
In addition there are:
Primary encephalitis:
• Viral: tick-borne, mosquito, epidemic Economo, enterovirus, herpetic,
influenza, encephalitis caused by HIV.
Secondary encephalitis is characterized by perivenous infiltration and
diffuse demyelination as a result of immune responses:
• postinfectious or parainfectious: on the background or after measles,
rubella, chickenpox, scarlet fever, poliomyelitis.
• postvaccinal: after ADPT (Adsorbed diphtheria-pertussis-tetanus
vaccine), Rabies vaccinations, poliomyelitis, antidiphtheritic vaccinations.
• caused by microbial, rickettsia: syphilitic, rheumatic, malaria encephalitis
and others.
• conditioned by slow infections (demyelinating encephalitis)
Syndromes of encephalitis:
1. General infectious syndrome: high temperature, blood disorders,
catarrhal phenomena of the upper respiratory tract, gastrointestinal tract
disorders.
2. Cerebral syndrome (headache, vomiting, seizures, impaired con-
sciousness, psychomotor disorders).
3. Typical focal symptoms (hemi-or tetraparesis, cranial nerves
disturbances, ataxia, aphasia, sensitivity disturbances).
1. Primary encephalitis: clinical features, forms of the disease,
Encephalitis 117
1) Tick-borne encephalitis is determined with specific arbovirus with

neurotropic influence. Tick-borne encephalitis is a natural focal zoonosis
that is found in the Far East, Siberia, the Ural Mountains, Eastern Europe,
Transcarpathian region, the Volga region (Russia), Belarus and the Baltic
countries. Ixodid ticks are transmitters of viruses.
Infection occurs by the following ways:
- transmissible (via a tick bite in park, forest)
- alimentary (while consumption raw of milk of goat or cow, which are
infected with virus that enters the body of the animal after the tick bite).
In nature the virus reservoir are rodents (field mice, hedgehogs, rabbits,
etc.), birds. Ticks, biting them, sucks the blood of animals with the virus and
then biting a person or a goat transfer the parasite.
The disease is seasonal. Person can get sick tick-borne encephalitis in
last spring and early summer months, due to the period of ticks’ activity.
Clinical features. The disease begins suddenly with general infectious
symptoms (raising the temperature up to 39-40 °C, myalgia, fever) and
cerebral (headache, vomiting, impaired consciousness) symptoms.
Due to predominant of nervous system structure disturbances there are
the following forms of encephalitis:
Poliomyelitic form is characterized by flaccid paralysis of the muscles of
neck, shoulder girdle and proximal upper extremities. Patients cannot raise
their hands up, in sides, flex, and extend the arm in elbows (Fig. 2). A typical
sign is «hanging head symptom» because of neck muscles weakness. Bulbar
syndrome with dysarthria, dysphagia, atrophy of tongue muscles are marked.
Meningeal form: there are meningeal syndrome (stiff neck, Kernig’s and
Brudzinsky’s symptoms) and cerebral symptoms.
Meningoencephalitic form: focal cerebral syndromes are joined to
meningeal form signs: central paresis, hyperkinesis.
Fig. 2. Symptoms of tick-borne encephalitis

(meningeal pose, «hanging head symptom», mimic
muscles paresis due to facial nerve defeat)
Repairing of motor functions can be complete. Nevertheless, weakness

and atrophy in the muscles of neck, shoulder girdle may be persisted.
In the residual phase, epilepsy partial continua can develop (its constant
myoclonic twitching in certain muscle groups depending on the location of
focus on the background of which generalized seizures may develop (Fig. 3).
Fig. 3. Symptoms and residual effects of tick-borne

encephalitis
Treatment.
1. Early admission to a specialized neurological or infection hospital is
compulsory, compliance a strict bed regime for a period of fever and 7 days
after normalization of body temperature.
2. In the acute period:
- in the first 3 days serotherapy with Unencephalitic human donor
immunoglobulin in amount of 3-6 ml 2-3 times a day, convalescents
serum (people who had tick-borne encephalitis), specific hyperimmune
gamma-globulin, placental gamma-globulin are applied;
- prednisolone 1 mg per 1 kg of the patient depending on the severity
of desease;
- antibiotics — according to indications;
- antiedemic drugs (mannitol, Lasix), Ringer’s solution, antihistamines,
pain relievers;
- complex B vitamins, vitamin C;
- in severe respiratory failure and bulbar disorders — intensive care,
according to indications — the false lung ventilation.
3. In recovery period: anabolic hormones, biogenic stimulants, nootropics,
Cerebrolysin et al. If it is necessary, anticholinergic, massage, treatment with
body position are applied. In epileptic syndrome — anticonvulsants.
Encephalitis 119
Prevention. Vaccination is used as a specific prevention. To form immunity

in early epidemical season, the first dose is administered in autumn, the
second — in winter. Urgent scheme (two injections of interval in 14 days) is
used for unvaccinated persons who come in endemic foci in spring-summer
period. Immunity develops within 2-3 weeks.
2) Economo’s epidemic encephalitis (lethargic encephalitis) is the
primary encephalitis with unknown pathogen.
Between 1915 and 1926 an epidemic of lethargic encephalitis spread
around the world. Nearly five million people were affected, a third of whom
died in the acute stages. Many of those who survived never returned to their
pre-existing «aliveness». No recurrence of the epidemic has since been
reported, though isolated cases continue to occur.
In the course of the disease, there are two stages: acute and chronic.
The acute stage is characterized by inflammatory changes localized mainly
in the gray matter of the 3-d ventricle walls, reticular formation, hypothalamic
area and the area of oculomotor nerve nuclei.
In chronic stage, the morphological changes are degenerative in nature
and often localized in nucleus striatum, nuclei of the hypothalamus, brain
stem and substantia nigra.
Acute phase. Its duration is weeks - month or 1 year. The typical Economo’s
triad includes the following:
1. feverish state
2. oculomotor disorders: diplopia, ptosis, strabismus divergent,
convergence and accommodation paralysis, paralysis of vertical gaze, Argyle
— Robertson reverse symptom (maintaining the pupils reaction to light in
absence of pupils reaction to convergence and accommodation)
3. hypersomnia (lethargy or sleep formula violation: the patient sleeps
during the day and at night he has insomnia).
There are some clinical forms of acute stage:
- classic (oculolethargic)
- vestibulo-ataxic (vertigo, nystagmus)
- hyperkinetic
- abortive.
There are following autonomic disorders: hypersalivation, hyperhydrosis
and facial greasiness. Hyperkinesia, consciousness impairment, delirium,
hallucinations, depression may occur.
Chronic phase.
1. parkinsonian syndrome: bradykinesia, general stiffness, tremors of
hands and lower jaw, flexed posture, slowed speech
2. hyperkinetic syndrome: myoclonus, athetosis, muscle dystonia phenomenon

3. neuroendocrine disorders.
Treatment: there is no specific treatment. Detoxication, desensitizion
therapy, nootropic agents are applied. In case of parkinsonian syndrome —
antiparkinsonian drugs.
3) Herpetic encephalitis caused by herpes simplex virus 1 type.
Pathogenesis. Virus infection of the CNS occurs through the olfactory bulb
and trigeminal ganglia alongside with blood-brain barrier violation. The virus
spread hematogenous or by perineural spaces of the I pair of cranial nerves
from the nasal cavity to the lower areas of frontal lobes and/or temporal lobes.
Provocateur of virus manifestation is intercurrent diseases, the cytotoxic
drugs applying, HIV-infection and others.
Pathomorphology is characterized by hemorrhagic and necrotic changes
in the nervous tissue with forming of destruction foci followed by the cysts
formation, mainly in the gray matter (frontal, temporal, parietal lobe).
Clinical feature is acute onset. There are cerebral symptoms with
consciousness disorders, seizures and focal symptoms: central hemiparesis,
hemianopsia, cranial nerve lesions, violations of higher cortical functions:
aphasia, amnesia, behavioral changes. The disease progresses rapidly.
Diagnosis: lumbar puncture with detection of herpes virus DNA in
cerebrospinal fluid by PCR (Polymerase chain reaction) method. MRI of
brain detects the foci of hyperdensity with brain tissue edema (Fig. 4).
Fig. 4. MRI in healthy and in case of herpetic encephalitis,

caused herpes virus 1 type Herpetic encephalitis can be caused
by herpes virus 2, 3, 4, 5, 6, 7, 8 type as well
Encephalitis 121
Treatment includes the use of acyclovir 10 mg/kg i/v every 8 hours.
2. Secondary encephalitis: clinical features, forms of the disease,
1) Postvaccinal encephalitis occurs in case of rabies vaccination,
ADPT, immunization against smallpox. The white matter of the brain and
spinal cord are affected in the form of leukoencephalitis or encephalomyelitis;
demyelination foci are marked.
Clinical features: acute onset in 7-12 days after vaccination, high
temperature — 40 °C. Cerebral involvement and meningeal symptoms,
generalized seizures, central paresis, coordination disorders are typical.
The test data of cerebrospinal fluid: hypertension, lymphocytic pleocytosis
(100 cells/1ml) with a slight protein increase.
2) Parainfectious encephalitis occur alongside with childhood infections:
measles, rubella, chickenpox, as infectious, allergic process.
It occurs in 3-5th days after eruptions.
Clinical manifestations are hyperthermia, consciousness impairment,
meningeal signs, seizures. Cerebellar and vestibular disorders, paresis and
dysfunction of the cranial nerves may occur.
Changes in cerebrospinal fluid are non-specific. They are lymphocytic
pleocytosis, a slight protein increase. The disease course is severe.
Measles encephalitis mortality is 25 %. Chickenpox encephalitis course
is benigner.
Treatment. Corticosteroids, desensitizing and detoxification therapy.
3) Rheumatic encephalitis. The main forms of rheumatic brain lesions are:
- acute rheumatic meningoencephalitis
- chronic rheumatic meningoencephalitis
- rheumatic encephalopathy
- rheumatic vasculitis
- Sydenham’s chorea (chorea minor).
There is a diffuse lesion of cerebral cortex, subcortical nodes, brain stem,
and meninges. In brain, there are vascular changes in forms of endarteritis,
vasculitis, periarteritis.
The clinical features of acute rheumatic meningoencephalitis are
polymorphic, different focal symptoms (hemi- or tetraparesis, cranial nerve
dysfunction, ataxia, aphasia, sensitivity disturbances, hyperkinesis) are
characteristic.
Sydenham’s chorea occurs in case of subcortical nuclei lesion. School-
age children, mostly girls may get sick. There are psyche disorders (protervity,
irritability), choreic hyperkinesis: involuntary movements in forms of
grimaces, excessive swinging while walking. These children cannot maintain

a given position for a long time (protruded tongue, closed eyes), speech is
fragmentary, frequent eyelids blinking is marked. Proof of rheumatic carditis
nature is arthritis, rheumatoid nodules.
II. Lesions of the nervous system in case of flu (influenza hemorrhagic

encephalitis, encephalopathy).
Influenzal encephalitis is a toxic-infectious lesion of the nervous system
that usually develops alongside with influenza.
Clinical features. Cerebral involvement and meningeal syndrome, pain
while pressing the eyeballs, trigeminal points and points of the occipital nerves
outcome. Mental disorders, the lesions of the III, VI, VII pairs of cranial nerves,
pyramidal tract, speech centers may be observed. The disease course is
severe. CSF is bloody, flows with high pressure, there is high protein content.
Influenza encephalopathy. Brain circulatory changes without cerebral focal
lesions are observed. Clinical manifestations in forms of asthenia, cerebral
hypertension and other syndromes of brain disorders are predominated.
Treatment is symptomatic: antihistamines, vitamins, analgesics,
detoxification therapy (Ringer’s solution, drinking liquids), in case of brain
edema mannitol is used. Human Imunoglobulin 50-100 ml i/v № 3-5.
TESTS
1. Sydenham’s chorea (chorea minor) occurs in case of subcortical nuclei lesion

1) aphasia
2) cranial nerve dysfunction
3) subcortical nuclei lesion
4) hemi- or tetraparesis
5) brain circulatory changes
2. A patient came back from Siberia a few days ago and could not raise his
hands up, in sides, flex, and extend the arm in elbows, his head hangs down,
neck muscles were weak, dysarthria and dysphagia were marked. Detect the
most appropriate diagnosis.
1) tick-borne encephalitis, poliomyelitic form
2) tick-borne encephalitis, meningeal form
3) tick-borne encephalitis, meningoencephalitic form
4) ponto-cerebellar angle arachnoiditis
5) posterior fossa arachnoiditis
Encephalitis 123
3. A patient had fever for 3 days, after which diplopia, ptosis, strabismus
divergent, accommodation paralysis appeared, cannot sleep at night and
feels sleepy during the day. Which diagnosis is the most appropriate?
1. Economo’s epidemic encephalitis, vestibulo-ataxic form
2. Economo’s epidemic encephalitis, hyperkinetic form
3. Economo’s epidemic encephalitis, oculolethargic form
4. tick-borne encephalitis, meningeal form
5. tick-borne encephalitis, meningoencephalitic form
4. A patient has fever, impaired consciousness, seizures, left-sided spastic
hemiparesis, hemianopsia, aphasia. Anamnesis: had fever and vesicular rash
on the right side of his face a few weeks ago. MRI: foci of hyperdensity in
the right hemisphere with brain tissue edema. Which diagnosis is the most
appropriate?
1. herpetic encephalitis
2. postvaccinal encephalitis
3. parainfectious encephalitis
4. rheumatic encephalitis
5. Economo’s epidemic encephalitis
5. A patient has meningeal syndrome, pain while pressing the eyeballs,
trigeminal points and points of the occipital nerves outcome, symptoms of
III, VI, VII pairs of cranial nerves disorders, pathological reflexes and speech
disorders. Anamnesis: had influenza a few weeks ago. CSF: bloody, high
pressure, high protein content. Which diagnosis is the most appropriate?
1. postvaccinal encephalitis
2. parainfectious encephalitis
3. influenza encephalopathy
4. rheumatic encephalitis
5. Economo’s epidemic encephalitis
Topic 12
POLIOMYELITIS. ACUTE MYELITIS. AMYOTROPHIC LATERAL

SCLEROSIS
Topic questions:
I. Poliomyelitis.
1. Etiology and epidemiology.
2. Pathogenesis.
3. Clinical features of
• Paralytic poliomyelitis:
1) preparalytic period;
2) paralytic period. The forms:
- spinal form;
- pontine form;
- bulbar form;
- encephalitic form.
3) recovery period;
4) residual phenomena.
• Atypical poliomyelitis. The forms:
- insidious form;
- abortive form;
- meningeal form.
4. Laboratory diagnosis.
5. Treatment and prevention.
II. Myelitis.
1. Etiology, pathogenesis and pathomorphology
2. The clinical features of various polio forms (according to its location):
• Upper cervical myelitis;
• Myelitis of the cervical enlargement;
• Thoracic myelitis;
• Lumbar myelitis;
• Myelitis of the half spinal cord;
• Subacute necrotizing myelitis.
3. Diagnostics and deferential diagnostics.
4. Treatment.
III. Amyotrophic lateral sclerosis.
1. Etiology and pathophysiology.
Poliomyelitis. Acute myelitis. Amyotrophic lateral sclerosis 125
2. Clinic features of separate forms:

• bulbo-spinal form;
• lumbar-sacral form;
• cerebral (high) form;
• bulbar form.
3. Diagnostics and differential diagnostics.
4. Treatment:
• Slowing down the disease progression
• Symptomatic treatment
I. Poliomyelitis is an acute infectious disease characterized by general tox-

ic symptoms and damage to the nervous system in type of peripheral paralysis.
1. Etiology: virus Poliovirus hominis. According to antigenic properties, it is divided
into 3 types. They share a complement-fixing antigen. It is stable in the environment,
tolerant to cold, dies out by boiling and under the influence of ultraviolet irradiation.
Epidemiology: it is found everywhere. The sources are the sick and the
virus carriers. From the sick, the virus is excreted with feces and nasal secret
during 1-2 weeks. The infection spreads by fecal-oral and airdrop ways. Chil-
dren under the age of 7 fall ill in most cases. After the disease the sustained
humoral immunity is produced.
2. Pathogenesis. The virus penetrates through the oral mucosa. There,
as well as in pharyngeal and small intestine mucosa the primary virus re-
production occurs. The virus enters the central nervous system through the
lymphatic system, spreading along the peripheral nerves axons. Cells of the
anterior horns of the spinal cord are the most sensitive and paralysis develops
at their destruction. After the death of the one third of motor neurons muscles
are paralyzed. In the case of heart defeat interstitial myocarditis develops, in
the respiratory system the catarrhal tracheitis, bronchitis occur.
3. Clinical features. The incubation period is 5-35 days.
Polio is divided into 2 large forms:
1) without damage of the nervous system (inapparent, abortive, meningeal forms);
2) with damage of the nervous system (paralytic form).
Poliomyelitis with damage of the nervous system is called typical, without
such damage it is atypical one.
Paralytic poliomyelitis (typical). Depending on the pathological process loca-
tion — spinal, bulbar, pontine, mixed (bulbospinal). Spinal form is the most common.
Polio is distinguished by the periods:
1) Preparalytic period: acute onset, temperature is 39 °C, catarrhal phe-
nomena, abdominal pain, pain while pressuring the spine, while flexing head
and back. Forced position with head thrown back, positive meningeal symp-
toms are typical for patient. Lumbar puncture data: high pressure, other pa-
rameters are within normal data. The duration is 2-5 days.
2) Paralytic period. Duration is 5-7 days. Its forms are:
- Spinal form: a peripheral paralysis of hands and feet alongside with
normal temperature. Areflexia, muscular atonia are common. Affected ex-
tremities are cold, pale, and cyanotic. Lumbar puncture data: a slight lympho-
cytic pleocytosis, elevated level of protein and sugar.
- Pontine form: the disturbance of the facial nerve nucleus with the pare-
sis of facial muscles.
- Bulbar form: dysphagia, dysphonia, respiratory failure, paralysis of the
diaphragm and respiratory muscles.
- Encephalitic form: loss of consciousness, seizures, speech disorders,
meningeal symptoms, vestibular disorders.
3) The recovery period: the disappearance of intoxication symptoms and pain.
Recovery of functions is slow (long-term atonia, areflexia). The duration is 1-3 years.
4) Residual phenomena: flaccid paralysis,
muscular atrophy, deformation and contractures,
a shortening of the limbs (Fig 1).
Atypical poliomyelitis:
- Insidious form — due to virus carrier state
within the pharyngeal ring and bowel it occurs with-
out clinical manifestations. Diagnostics of this form
is possible only based on virological test;
- Abortive form is characterized by malaise,
appetite decrease, mild catarrhal symptoms, in-
testinal disorders. Neurological disorders are ab-
sent. The course is favourable.
- Meningeal form — intoxication, severe
headache, vomiting, twitching of muscles, horizon-
tal nystagmus, meningeal symptoms are observed
on the 2nd-3th days. CSF data: lymphocytic pleo- Fig. 1. Polio residual
cytosis, a slight increase of protein and glucose. phenomena
There are no paralysis. The course is favourable.
4. Laboratory diagnostics.
Diagnostics is based on the poliovirus allocation from faeces, cerebrospi-
nal fluid, nasopharyngeal swabs and blood on the 3rd -7th day of illness.
A week after the poliovirus infection the IgM and IgG appear in the serum
of infected persons. The level of IgM is 2-8 times as high as the titers of IgG.
After 2 weeks, the level of IgM reaches its peak, after 2 months they disap-
pear. IgG titers gradually increase, antibodies may persist throughout human
life. In some cases, serum IgA may appear in blood serum.
Secretory intestine IgA-antibodies have a crucial role in protection
against polio. Children may be resistant to poliovirus reinfection, even if
they have no serum antibodies but have secretory antibodies in high titres.
5. Treatment: hospitalization to infectious diseases department. Therapy
is supportive. Bed rest, fever and pain control (heat therapy is helpful), and
careful attention to progression of weakness (particularly of respiratory mus-
cles) are important. No intramuscular injections should be given during the
acute phase. Intubation or tracheostomy for secretion control and catheter
drainage of the bladder may be needed. Assisted ventilation and enteral feed-
ing may also be needed
Prevention: Vaccination with alive vaccine starting from 3 months of age
4 drops under the tongue (6 times up to 15 years) schedule according to the
immunization. Contact persons are subjected to one-time immunization.
II. Myelitis is an inflammation of the spinal cord, in which both white and
gray matter are affected.
1. Etiology, pathogenesis.
- Traumatic myelitis occur in the case of open and closed injuries of spine
and spinal cord with joined of secondary infection;
- Secondary infectious myelitis. In their pathogenesis the autoimmune re-
actions and skidding of hematogenous infection from the infection focus to
spinal cord play the main role.
- Post-vaccination myelitis.
- Due to severe exogenous poisoning or endogenous intoxication.
Pathomorphology. Macroscopically the brain matter is porous, swollen,
bulging, the contours of spinal cord gray matter are blurred. Microscopically
in the infectious focus there are hyperemia, edema, small haemorrhages, in-
filtration with hemacytes, cell death, decay of myelin.
2. The clinical manifestations of myelitis occur acute or subacute on the
background of temperature increasing up to 38-39 °C, chills, malaise. Neuro-
logic manifestations of myelitis begin with moderate pain and paresthesia in
the lower limbs, back and chest, with radicular nature. Then motor, sensory and
pelvic disorders appear, grow and reach their maximum within 1-3 days. The
neurological symptoms character depends on the pathological process level.
Myelitis of uppercervical level of the spinal cord is characterized by spastic
tetraplegia, phrenic nerve disturbance with respiratory disorder, sometimes
bulbar disorders. Sensitivity disorders are in form of conductive hypesthesia
or anesthesia with the upper limit, which corresponds to the level of the af-
fected segment. Pelvic disorders occur firstly (retention of urine and feces)
passing into the central type of incontinence.
In case of the spinal cord injuries on the cervical enlargement level the
lower spastic paraplegia with conductive anesthesia develops. Pelvic disor-
ders by central type.
Myelitis on the thoracic spinal cord level is characterized by spastic para-
paresis with conductive sensitivity lesion, pelvic disorders (retention of urine
and feces passing into the central type of incontinence).
Myelitis on the lumbar spinal cord level is characterized by peripheral lower
paraparesis, anesthesia, the level of which begins from the groin. Pelvic disorders
occur (retention of urine and feces passing into the central type of incontinence).
In more rare cases, the inflammatory process covers only the half of the
spinal cord, which clinically is manifested as Brown-Sequard syndrome.
In case of sudden transverse myelitis developing the muscle tone may be
low for some time according to the foci location due to diaschisis phenomenon.
Bed sores develop quickly on the sacrum, trochanter and feet areas.
Subacute necrotizing myelitis is described. It is characterized by the lum-
bosacral spinal cord lesion, followed by the pathological process spreading
up with bulbar syndrome development and lethal outcome.
The course of myelitis is acute. The process reaches its greatest severity
in a few days, and then for a few weeks it is remained stable. The recovery
period lasts from several months to 1-2 years. Often the paralysis or paresis
of the extremities remain. Cervical myelitis is the most severe form because
of tetraplegia, vital centers proximity, respiratory disorders.
3. Diagnostics. MRI of the spinal cord. In cerebrospinal fluid high protein
content and pleocytosis are detected. Among the cells there may be neutro-
phils, and lymphocytes. While carring out liquorodynamic tests the block is
absent. In blood there is leukocytosis and erythrocyte sedimentation rate is
increased (leukocyte formula offsets to the left).
Defferential diagnostics.
- Clinical features of epiduritis in most cases is indistinguishable from the
symptoms of myelitis. It requires urgent surgical intervention. Diagnostic op-
tion is MRI.
- Acute Guillain — Barre polyradiculitis differs from myelitis by absence of
conductive sensitivity violations, central paresis and pelvic disorders.
- Spinal tumors are characterized by slow course, the presence of pro-
tein-cell dissociation in the cerebrospinal fluid, a block while carring out the
liquorodynamic tests.
- Haemomyelitis (bleeding into the spinal cord) occurs suddenly, is not

accompanied by temperature rise, gray matter is mainly affected. In case of
haemorrachis (bleeding under the membrane of the spinal cord matter) the
meningeal symptoms occur. In anamnesis trauma is possible.
- Acute transverse lesion of the spinal cord must be differentiated from
acute spinal circulation disorders.
- Multiple sclerosis is characterized by selective white matter lesions, of-
ten quick and significant regression of symptoms after a few days or weeks,
multiple signs of spinal and brain lesions on MRI data.
- Chronic meningomyelitis has a slower development, normal temperature and
is often caused by syphilitic lesion that is diagnosed by serological reactions.
4. Treatment. Antiviral treatment needs to be tailored to the specific causative
virus, when known. If Epstein-Barr virus, varicella-zoster virus, or HSV-1 or HSV-2
is suspected, acyclovir (10 mg/kg intravenously every 8 hours) should be admin-
istered. If cytomegalovirus is suspected, ganciclovir (5 mg/kg intravenously every
12 hours) or foscarnet (90-120 mg/kg/day), or both, should be administered. There
is no evidence supporting the use of glucocorticoids for viral myelitis; however,
their use is indicated when the pathogenesis is unknown and immune-mediated
processes are considered in the differential. Spasticity that typically ensues in the
chronic phase can be alleviated with baclofen, benzodiazepines, and tizanidine.
III. Amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s
disease) is a progressive neurodegenerative disorder, the hallmark of which
is the destruction of central and peripheral motor neurons. There are sporadic
and hereditary ALS. Basically, the disease affects people of 50-70 years old.
1. Etiology of sporadic ALS cases is unknown. Version that one of the
causes of the disease may be the environmental impact has been proposed
with an increasing number of disease cases in the Western Pacific Region.
Pathophysiology. The defining feature of ALS is the degeneration of upper
and lower motor neurons in brain motor area, brain stem and spinal cord. Im-
munohistochemical study of neurons in these structures exhibit accumulation
of ubiquitin (a sign of degeneration). Mutations in gene that codes the synthesis
of Cu/Zn superoxide dismutase (SOD1) cause familial ALS. This enzyme is a
powerful antioxidant that protects the body from damage caused by the action
of superoxide free radical, which is toxic in high concentrations. It is produced
in mitochondria. Compared with healthy humans, patients with ALS have higher
glutamate level (exitation mediator) in plasma and cerebrospinal fluid.
2. Clinical features. There are four major forms of ALS, depending on
the nature of the identified symptoms: cerebral (high), bulbar, bulbar-spinal,
lumbar — sacral.
A typical symptom of ALS: a combination of peripheral and central paresis

of limbs with brain stem and supranuclear structures.
In case of classical bulbo-spinal form of the disease the first pathological
signs are associated with anterior horns motor neuron lesions at cervical en-
largement, which causes the appearance of arm fibrillar muscle twitching with
gradual atrophy. In typical cases,
atrophy is observed firstly in hands
in form of intercostales muscles loss
between I-II fingers, thenar and hy-
pothenar flattening (Fig. 2). Hand
looks becomes like monkey paw
(Fig. 3).
Atrophy gradually covers the
shoulder muscles, the shoulder gir-
dle and chest (Fig. 4).
Whereas pyramidal pathway Fig. 2. Hand muscles atrophy
is defeated alongside with periph-
eral motor neurons at this level,
hands paresis are mixed: firstly,
deep reflexes and muscle tone are
increased. Then elements of spas-
tic paresis increasingly overlap by
symptoms of flaccid paresis. Ten-
don reflexes and muscle tone are
reduced, muscle atrophy is ampli-
fied. In lower limbs, hyperreflexia is
observed firstly, and subsequently Fig. 3. «Monkey paw» hand
lower spastic paraparesis
developed. Constant fea-
ture of the disease is flex-
ion pathological pyramidal
reflexes more over than
extension. Sensitivity vio-
lation and sphincter disor-
ders are not typical.
In case of bulbar form,
there is a lesion of motor
nuclei in medulla oblonga-
ta. Paresis of muscles in- Fig. 4. Shoulder girdle and chest muscles atrophy
nervated by bulbar nerves (IX, X, XII pairs) joining to paresis of extremities.

It leads to appearance of the bulbar syndrome, which is clinically manifested
with dysarthria, dysphonia, dysphagia. Fibrillations are observed in tongue;
later atrophy of tongue muscles occurs. It is impossible to make one’s lips
into a tube and push tongue from the mouth. As a result of the pharynx and
larynx muscles paresis, the patient’s speech becomes nasal, slurred, unin-
telligible, dysphonic. Significantly swallowing is impaired, liquid food enters
to nose. Sometimes neck extensor muscles weakness occurs.
In case of lumbar-sacral form of ALS the lumbar and sacral segments of
the spinal cord (lumbar enlargement) are affected. Mixed paresis of the legs
occurs: muscle atrophy, fasciculations, hyperreflexia, pathological feet signs.
The process is ascending in nature.
In case of cerebral (high) form of the disease the pathways from the ce-
rebral cortex to the brainstem structures (corticonuclear pathways, on both
sides) are affected. It is characterized by pseudobulbar syndrom, spastic tet-
raparesis. Mandibular and pharyngeal reflexes increase, reflexes of oral au-
tomatism appear, violent laughing or crying may occur. Often pseudobulbar
syndrome is combined with bulbar syndrome. In such clinical situation, the
mandibular and pharyngeal reflexes are reduced or disappeared.
Prognosis. There is unfavorable prognosis regarding recovery and life. The dis-
ease lasts in average 3-5 years, at least — 6-8 years in the case of lumbar-sacral
forms due to later appearence of bulbar disorders. Often aspiration pneumonia occurs.
Patient dies because of respiratory failure due to muscles paralysis involved in breath.
3. Diagnosis of the disease is put with account of main neurological
symptoms: a combination of signs of spastic and flaccid paresis. Diagnosis is
confirmed by electromyography, which reveals generalized lesion of anterior
horns. In limb muscles there are signs of denervation, potentials of fibrilla-
tions, reducing of motor units number with the appearance of giant potentials.
Differential diagnosis.
ALS is differs from syringomyelia because of absence of dissociated sen-
sory disorders and pain.
In case of spinal tumor the radicular pain, sensory disorders, protein-cell
dissociation in the cerebrospinal fluid are observed.
Spondylogenic cervical myelopathy differs from ALS because of sensitivity
disorders presence, supraspinal violations absence.
4. Treatment.
The slowdown of disease progression
Due to data damaging effects of glutamate on spinal cord motor neurons
in ALS the leading trend of therapy is the antiglutamate drugs. The main one
is riluzole (Rilutek), which is prescribed for a long time — 50 mg twice a day.
In case of lumbar-sacral form, it may be more effective.
Symptomatic treatment
- Dysarthria, dysphagia and drooling
M-anticholinergics (platyphylline) inhibit salivation, and acetylcholinester-
ase inhibitors (Neostigmine, Ipidacrine) contribute to temporary overcoming
muscle weakness. The patient is needed to find the appropriate consistency
of food, drink small sips. In dysphagia gastronazal tube or gastrostomy is set.
- Involuntary limbs jerking
Phenytoin, Carbamazepine, Clonazepam and Baclofen.
- Muscle spasms and pain in hands and feet
Phenytoin or Carbamazepine, but severe pain usually does not occur.
- Motor limitations, the difficulty of posture maintaining
Rooms and other facilities should be equipped with assistant devices (railings,
racks, lifts), as much as possible remove the stairs and steps. Tools to facilitate
feeding, shaving, dressing, movements are very important. Special collar helps
to maintain head and corset and box spring tires help to maintain torso and limbs.
- Feet swelling
When oedema is expressed, the patient should keep one′s feet elevated,
wear elastic stockings. Better is not to prescribe diuretics.
- Respiratory insufficiency
In the initial stage of respiratory failure non-invasive mechanical ventilation
helps, such as mechanical ventilation with biphasic positive airway pressure.
Later the question of forced ventilation and tracheostomy usually arises.
TESTS
1. A child has severe headache, vomiting, twitching of muscles, horizontal nys-

tagmus, meningeal symptoms, but there is no paralysis. Anamnesis: a week
ago he visited his friends with fever. CSF data: lymphocytic pleocytosis, slight
increase of protein. Which diagnosis is the most appropriate?
1. Poliomyelitis, meningeal form
2. Poliomyelitis, insidious form
3. Poliomyelitis, abortive form
4. Poliomyelitis, paralytic form
5. Poliomyelitis, encephalitic form
2. A patient had fever, catarrhal phenomena, abdominal pain; pain while pres-
suring the spine and flexing head and back, positive meningeal symptoms for
3 days, after which peripheral paralysis of left hand and foot appeared. CSF:
data slight lymphocytic pleocytosis, elevated level of protein and sugar. Which
diagnosis is the most appropriate?
1. Paralytic poliomyelitis, paralytic period, spinal form
2. Paralytic poliomyelitis, paralytic period, pontine form
3. Paralytic poliomyelitis, paralytic period, bulbar form
4. Paralytic poliomyelitis, paralytic period, encephalitic form
5. Paralytic poliomyelitis, preparalytic period
3. A patient had fever, chills, malaise for 2 days, then moderate pain and
paresthesia in the lower limbs, back and chest, motor, sensory and pelvic
disorders appeared. St. neurological: spastic tetraparesis, respiratory disor-
ders, conductive hypesthesia from the C3 level. Which diagnosis is the most
appropriate?
1. Myelitis of upper cervical level of the spinal cord
2. Myelitis of cervical enlargement level of the spinal cord
3. Myelitis of thoracic level of the spinal cord
4. Myelitis of lumbar level of the spinal cord
5. Myelitis of half of the spinal cord
4. A patient had fever, chills, malaise for 3 days, then flaccid paresis of low-
er limbs appeared, which changed on the spastic tetraparesis with bulbar
syndrome, disorders of breathing in a few days. Which diagnosis is the most
appropriate?
1. Subacute necrotizing myelitis
2. Myelitis of uppercervical level of the spinal cord
3. Myelitis of cervical enlargement level of the spinal cord
4. Myelitis of thoracic level of the spinal cord
5. Myelitis of lumbar level of the spinal cord
5. A patient has fibrillar of muscles twitching on his right arm with gradual
atrophy, specialy of intercostales muscles between I-II fingers, thenar and
hypothenar flattening, deep reflexes and muscle tone are increased in this
limb. There is lower spastic paraparesis with flexion pathological pyramidal
reflexes. Sensitivity and sphincters function are preserved. Which diagnosis
is the most appropriate?
1. ALS, bulbo-spinal form
2. ALS, bulbar form
3. ALS, lumbar-sacral form
4. ALS, cerebral (high) form
5. Subacute necrotizing myelitis
Topic 13
NEUROLOGICAL ASPECTS OF TRAUMATIC BRAIN INJURY.

SPINAL CORD INJURY
Topic questions:
I. Traumatic brain injury (TBI)
1. Classification of TBI
2. Clinical signs of some forms of closed-head injury:
A. Primary TBI
- Cerebral concussion
- Cerebral contusion
- Cerebral hematoma
- Diffuse axonal injury
B. Secondary TBI
3. Measures of severity.
4. Diagnosis
5. Management
6. TBI complications
II. Traumatic spinal cord injury
1. Definitions and classification
2. Clinical patterns
3. Diagnosis
4. Treatment
I. Traumatic brain injury (TBI), also known as acquired brain injury, head
injury, or brain injury, causes substantial disability and mortality. It occurs
when a sudden trauma damages the brain and disrupts normal brain func-
tion. TBI may have profound physical, psychological, cognitive, emotional,
and social effects.
1. Classification of TBI.
1. Primary injury occurs at the moment of initial trauma, including:
• skull fracture (breaking of the bony skull),
• concussions (mild brain injury resulting in functional deficits without
pathological injury),
• contusions (bruise/bleed on the brain),
• hematomas (blood clots in the meningeal layers or in the cortical/subcor-
tical structures as a result of the trauma),
Neurological aspects of traumatic brain injury. Spinal cord injury 135
• lacerations (tears in brain tissue or blood vessels of the brain),

• diffuse axonal injury (traumatic shearing forces leading to tearing of
nerve fibers in the white matter tracts).
2. Secondary injury occurs as an indirect result of the insult. It results from pro-
cesses initiated by the initial trauma and typically evolves over time. These include:
• ischemia (insufficient blood flow);
• hypoxia (insufficient oxygen in the brain);
• hypo/hypertension (low/high blood pressure);
• cerebral edema (swelling of the brain);
• raised intracranial pressure (increased pressure within the skull), which
can lead to herniation (parts of the brain are displaced);
• hypercapnia (excessive carbon dioxide levels in the blood);
• meningitis (infection of the meningeal layers) and brain abscess;
• biochemical changes (changes in levels of neurotransmitters, sodium,
potassium, etc.);
• epilepsy.
Primary injuries can be caused by either a penetrating (open-head) injury
or a nonpenetrating (closed-head) injury.
A penetrating (open-head) injury involves an open wound to the head from
a foreign object (e.g., bullet). It is typically marked by focal damage that occurs
along the route the object has traveled in the brain that includes fractured/per-
forated skull, torn meninges, and damage to the brain tissue (Hegde, 2006).
A nonpenetrating (closed-head) injury is marked by brain damage due to
indirect impact without the entry of any foreign object into the brain. The skull
may or may not be damaged, but there is no penetration of the meninges.
Nonpenetrating injuries can be of two types.
Acceleration injuries- caused by movement of the brain within the unre-
strained head (e.g. whiplash injury). If the force impacting the head is strong
enough, it can cause a contusion at the site of impact and the opposite side of
the skull, causing an additional contusion (coup-contrecoup injury).
Non-acceleration injuries-caused by injury to a restrained head and, there-
fore, no acceleration or deceleration of the brain occurs within the skull (e.g.,
blow to the head). These usually result in deformation (fracture) of the skull,
causing focal localized damage to the meninges and brain.
Skull fractures also can be divided into linear, depressed, or comminuted
types. If the scalp is lacerated over the fracture, it is considered an open or
compound fracture.
In depressed fracture of the skull, one or more fragments of bone are
displaced inward, compressing the underlying brain. In comminuted fracture
there are multiple shattered bone fragments, which may or may not be dis-
placed. Even when closed, most depressed or comminuted fractures require
surgical exploration for debridement, elevation of bone fragments, and repair
of dural lacerations. The underlying brain is injured in many cases. In some
patients, depressed skull fractures are associated with tearing, compression,
or thrombosis of underlying venous dural sinuses.
2. Clinical signs of some forms of closed-head injury
A. Primary TBI. The two main mechanisms that cause primary injury are
contact (eg, an object striking the head or the brain striking the inside of the
skull) and acceleration-deceleration. Primary injury due to contact may result
in injury to the scalp, fracture to the skull, and surface contusions. Primary
injury due to acceleration-deceleration results from unrestricted movement of
the head and leads to shear, tensile, and compressive strains. These forces
can cause intracranial hematoma, diffuse vascular injury, and injury to cranial
nerves and the pituitary stalk.
- Cerebral concussion. Loss of consciousness at the moment of impact
is caused by acceleration-deceleration movements of the head, which result
in the stretching and shearing of axons. When the alteration of consciousness
is brief (less than 6 hours), the term concussion is used. These patients may
be completely unconscious or remain awake but «dazed»; most recover with-
in seconds to minutes (rather than hours) and have retrograde and antero-
grade amnesia surrounding the event. The mechanism by which concussion
leads to loss of consciousness is believed to be transient functional disruption
of the reticular activating system caused by rotational forces on the upper
brainstem. Most patients with concussion have normal CT or magnetic res-
onance (MR) findings, because concussion results from physiologic, rather
than structural, injury to the brain.
- Cerebral contusions are focal parenchymal hemorrhages that result
from «scraping» and «bruising» of the brain as it moves across the inner sur-
face of the skull. The inferior frontal and temporal lobes, where brain tissue
comes in contact with irregular protuberances at the base of the skull, are the
most common sites of traumatic contusion. Tearing of the meninges or cere-
bral tissue, usually a result of cuts from the sharp edges of depressed skull
fragments, is called a laceration. Contusions may occur at the site of a skull
fracture but more often occur without a fracture and with the overlying pia and
arachnoid left intact. Contusions frequently enlarge over 12 to 24 hours; in
some cases, contusions develop 1 or more days after injury.
- Cerebral hematoma. When rotational forces lead to tearing of a small-
or medium-sized vessel within the parenchyma, a intracerebral hematoma
may occur. Intracranial hematoma is

the most common cause of death and
clinical deterioration after TBI. Hemato-
mas are categorized as follows:
Subdural hematomas usually arise
from a venous source, with blood fill-
ing the potential space between the
dural and arachnoid membranes. In
most cases, the bleeding is caused by
movements of the brain within the skull,
which can lead to stretching and tear-
ing of veins that drain from the surface
of the brain to the dural sinuses. Less
often, the source of the hematoma is a
small pial artery.
Acute subdural hematoma, by defi- Fig. 1. Post-traumatic hematomas
nition, is symptomatic within 72 hours
of injury, but most patients have neurologic symptoms from the moment of
impact. Half of patients with an acute subdural hematoma lose conscious-
ness at the time of injury; 25% are in coma when they arrive at the hospital,
and half of those who awaken lose consciousness for a second time after a
«lucid interval» of minutes to hours, as the subdural hematoma grows in size.
Hemiparesis and pupillary abnormalities are
the most common focal neurologic signs; the
usual picture is ipsilateral pupillary dilation and
contralateral hemiparesis.
Chronic subdural hematoma becomes symp-
tomatic after 21 days or later. It is more likely to
occur after age 50. Symptoms may be restricted
to altered mental status, a syndrome sometimes
mistaken for dementia. CT typically shows an
isodense or hypodense crescent-shaped mass
that deforms the surface of the brain, and the
membranes may enhance with intravenous con-
trast. Long-standing chronic subdural hemato-
mas eventually liquify and form a hygroma, and,
in some cases, the membranes may calcify. Fig. 2. Subdural hematoma
Epidural hematoma is a rare complication in right frontal, parietal,
of head injury. Bleeding into the epidural space occipital regions. CT scan
is generally caused by a tear in the wall of one

of the meningeal arteries, usually the middle
meningeal artery, but in 15% of patients the
bleeding is from one of the dural sinuses.
Seventy-five percent are associated with a
skull fracture. Epidural hematoma is primarily
a problem of young adults; it is rarely seen
in the elderly because the dura becomes in-
creasingly adherent to the skull with age. The
clinical course in one-third of patients pro-
ceeds from an immediate loss of conscious-
ness due to concussion, to a lucid interval,
and then a relapse into coma with hemiplegia
as the epidural hematoma expands. The ip- Fig. 3. Epidural hematoma in
silateral pupil becomes fixed and dilated be- left occipital region. CT scan
cause the third cranial nerve is compressed
by the hippocampal gyrus as it herniates over the free edge of the tentorium;
the pupillary change signals impending brainstem compression. As with acute
subdural hematoma, false localizing signs may occur. Epidural blood takes
on a «bulging» convex pattern on CT because the collection is limited by firm
attachments of the dura to the cranial sutures. Progression to herniation and
death can occur rapidly because the bleeding is arterial.
In most cases, subarachnoid blood is detected only by CSF examination
and is of little clinical importance. With more serious injuries, when larger ves-
sels traversing the subarachnoid space are torn, focal or diffuse subarachnoid
hemorrhage can be detected by CT.
- Diffuse axonal injury. The term diffuse axonal injury (DAI) is applied
to traumatic coma lasting more than 6 hours. In these cases, when no other
cause of coma is identified by CT imaging (MRI), it is presumed that wide-
spread microscopic and macroscopic axonal shearing injury has occurred.
Coma of 6 to 24 hours in duration is deemed mild DAI; coma lasting more than
24 hours is referred to as moderate or severe DAI, depending on the absence
or presence of brainstem signs such as decorticate or decerebrate posturing.
Autonomic dysfunction (e.g., hypertension, hyperhidrosis, hyperpyrexia, fe-
ver) is common in patients with acute severe DAI and may reflect brainstem
or hypothalamic injury. Patients may remain unconscious for days, months,
or years, and those who recover may be left with severe cognitive and motor
impairment, including spasticity and ataxia. DAI is considered the single most
important cause of persistent disability after traumatic brain damage.
B. Secondary injury may occur hours or even days after the inciting trau-

matic event. Injury may result from impairment or local declines in cerebral
blood flow (CBF) after a TBI. Decreases in CBF are the result of local edema,
hemorrhage, or increased intracranial pressure (ICP). As a result of inade-
quate perfusion, cellular ion pumps may fail, causing a cascade involving in-
tracellular calcium and sodium. Resultant calcium and sodium overload may
contribute to cellular destruction. Excessive release of excitatory amino acids,
such as glutamate and aspartate, exacerbates failure of the ion pumps. As the
cascade continues, cells die, causing free radical formation, proteolysis, and
lipid peroxidation. These factors can ultimately cause neuronal death.
The exact role of the inflammatory response in secondary injury is not
known. However, it is believed to contribute to cell damage.
Clinical conditions associated with the risk of a decreased CBF are arterial
hypotension, hypoxemia, intracranial hemorrhage and malignant brain ede-
ma, and hyperthermia.
Brain swelling after head injury is a poorly understood phenomenon that
can result from several different mechanisms. Posttraumatic brain swelling
may result from cerebral edema (defined as an increase in the content of
extravascular brain water), an increase in cerebral blood volume due to ab-
normal vasodilatation, or both. Cerebral edema can be further classified as
cytotoxic, vasogenic, or interstitial. The swelling may be diffuse or focal, ad-
jacent to a parenchymal or extradural hemorrhage. Brain swelling can follow
any type of head injury. Curiously, the magnitude of swelling does not always
correlate well with the severity of injury.
3. Measures of severity. Glasgow Coma Scale (GCS) (see topic 6, Fig. 3): A
3- to 15-point scale used to assess a patient’s level of consciousness and neuro-
logic functioning; scoring is based on best motor response, best verbal response,
and eye opening (eg, eyes open to pain, open to command). It consists of 3 sec-
tions, each of which is scored: best motor response, best verbal response, and
eye opening. A total score of 3-8 for the 3 sections indicates severe TBI, a score
of 9-12 indicates moderate TBI, and a score of 13-15 indicates mild TBI.
Duration of loss of consciousnes (LOC): Classified as mild (mental status
change or LOC < 30 min), moderate (mental status change or LOC 30 min to
6 hr), or severe (mental status change or LOC > 6 hr)
Posttraumatic amnesia (PTA): The time elapsed from injury to the moment
when patients can demonstrate continuous memory of what is happening
around them.
4. Diagnosis. A baseline neurologic evaluation should be performed im-
mediately, while airway, breathing, and circulation are assessed. A bloody
discharge from the nose or ear may indicate leakage of cerebro-spinal fluid
(CSF); bloody CSF can be differentiated from blood by a positive halo test (a
«halo» of CSF forms around the blood when dropped on a white cloth sheet).
After determining the patient’s level of consciousness (alert, lethargic, stupor-
ous, or comatose), a focused mental status examination should be performed
if the patient is conversant. Particular attention should be paid to attention,
concentration (counting backward from 20 to 1 or reciting the months in re-
verse), orientation, and memory, including assessment for retrograde and an-
terograde amnesia.
Eye movements and pupillary size, shape, and reactivity to light should be
noted. A sluggishly reactive or dilated pupil suggests transtentorial herniation
with compression of the third nerve. A midposition, poorly reactive, irregular
pupil may result from injury to the oculomotor nucleus in the midbrain teg-
mentum. Nystagmus often follows a concussion. In comatose patients, the
oculocephalic and oculovestibular reflexes should be tested.
Motor examination should focus on identifying asymmetric weakness or
posturing. Spontaneous movements should be assessed for preferential use
of the limbs on one side. If the patient is not fully cooperative, lateralized
weakness can be detected by an asymmetry in tone or tendon reflexes, or
by the presence of an arm drift, preferential localizing response to sternal
rub, or extensor plantar reflex. Noxious stimuli, such as pinching the medial
arm or applying nailbed pressure, may reveal subtle motor posturing in a
limb that otherwise moves normally. Decorticate posturing (flexion of arms,
extension of legs) results from injury to the corticospinal pathways at the
level of the diencephalon or upper midbrain. Decerebrate posturing (ex-
tension of legs and arms) implies injury to the motor pathways at the lev-
el of the lower midbrain, pons, or medulla. Balance and equilibrium, tested
by tandem heel-to-toe walking, are frequently impaired after a concussion.
CT is the imaging method of choice for head injury. MRI is better for de-
tecting subtle injury to the brain, particularly focal lesions related to DAI, but
is generally not suitable for emergency evaluations because of the time and
expense. In general, all patients with head injury should have CT, except for
those who are low risk — without concussion, with no neurologic abnormal-
ities on examination, and with no evidence or suspicion of a skull fracture,
alcohol or drug intoxication.
5. Management. Low-risk patients can generally be discharged from the
emergency room without CT, as long as a responsible person is available to
observe the patient for the next 24 hours. In general, these are patients who did
not sustain a concussion and have normal findings on neurologic examination.
Among patients who have experienced a concussion, a normal Glasgow

Coma Scale score of 15 (alert, fully oriented, and following commands) (see
topic 6, Fig. 3) and normal CT eliminate the need for hospital admission. Pa-
tients with mild-to-moderate neurologic deficits (generally corresponding to
Glasgow Coma Scale scores of 9 to 14) and CT findings that do not require
neurosurgical intervention should be admitted to an intermediate or intensive
care unit (ICU) for observation. A follow-up CT at 24 hours is often helpful to
check for progression of bleeding.
All patients with a serious head injury are admitted to the hospital. An ear-
ly neurosurgical consultation is crucial, because once the patient has been
stabilized, assessed, and imaged, the immediate consideration is whether an
indication exists for emergent surgical intervention.
The goal of intracranial pressure (ICP) management after head inju-
ry is to maintain ICP less than 20 mm Hg and cerebral perfusion pres-
sure (CPP) greater than 70 mm Hg. Mannitol and hyperventilation are
used only after sedation. The initial dose of mannitol 20% solution is 1 to
1.5 g/kg, followed by doses of 0.25 to 1.0 g/kg as needed. Serum osmo-
lality should be monitored closely, with a secondary goal of attaining levels
of 300-320 mOsm/kg. Urinary losses should be replaced with normal saline to
avoid secondary hypovolemia. High-dose barbiturate therapy with pentobarbi-
tal, given in doses equivalent to those used for general anesthesia, effectively
lowers ICP.
Only isotonic fluids, such as 0.9% (normal) saline or lactated Ringer solu-
tion, should be administered to head-injured patients, because the extra free
water in half-normal saline can exacerbate cerebral edema. Central venous
pressure monitoring may be helpful to guide fluid management in hypotensive
or hyporolemic patients.
Severe head injury leads to a generalized hypermetabolic and catabolic
response, with caloric requirements that are 50% to 100% higher than nor-
mal. Enteral feedings via a nasogastric or nasoduodenal tube should be insti-
tuted as soon as possible (usually after 24 to 48 hours). Parenteral nutrition
carries significant risks (primarily infection and electrolyte derangements) and
should be used only if enteral feeding cannot be tolerated.
Fever exacerbates traumatic and ischemic brain injury and should be ag-
gressively treated with acetaminophen or cooling blankets.
If the patient has not experienced a seizure, prophylactic anticonvulsants
should be discontinued after 7 days (see topic 2 «Epilepsy»). Anticonvulsant
levels should be monitored closely, because subtherapeutic levels frequently
result from drug hypermetabolism.
Patients with head injury who are immobilized are at high risk for low-
er extremity deep vein thrombosis and pulmonary thromboembolism. Pneu-
matic compression boots should be routinely used to protect against this
risk, and subcutaneous heparin 5.000 U every 12 hours can be safely add-
ed 72 hours after injury, even in the presence of intracranial hemorrhage.
6. Complications
• Posttraumatic seizures: frequently occur after moderate or severe TBI
• Hydrocephalus
• Deep vein thrombosis
• Heterotopic ossification
• Spasticity
• Gastrointestinal and genitourinary complications
• Gait abnormalities
• Agitation
• Chronic traumatic encephalopathy (CTE)
Long-term physical, cognitive, and behavioral impairments are the factors
that most commonly limit a patient’s reintegration into the community and his/
her return to employment. They include the following:
• Insomnia
• Cognitive decline
• Posttraumatic headache: tension-type headaches are the most common
form, but exacerbations of migraine-like headaches are also frequent
Posttraumatic depression: depression after TBI is further associated with
cognitive decline, anxiety disorders, substance abuse, dysregulation of emo-
tional expression, and aggressive outbursts
II. Traumatic spinal cord injury
1. Definitions and classification
The American Spinal Injury Association (ASIA) and the International Med-
ical Society of Paraplegia (IMSOP) jointly published the «International Stan-
dards for Neurological and Functional Classification of Spinal Cord Injury»
(Maynard et al., 1997).
The following definitions are noted:
Incomplete spinal cord injury: if partial preservation of sensory and/or mo-
tor functions is found below the neurologic level and includes the lowest sacral
segment, the injury is defined as incomplete. Sacral sensation also includes
deep anal sensation. Voluntary contraction of the anal sphincter muscle is
used to demonstrate preserved muscle function.
Complete spinal cord injury: this term is used when there is no sensory
or motor function in the lowest sacral segment. The neurologic level is given
as the lowest level where there is still some evidence of muscle function or
sensation but no preservation in the sacral area.
The American Spinal Injury / International Medical Society of Para-
plegia (ASIA/IMSOP) impairment scale consists of the following categories:
Complete: no motor or sensory function is preserved in the sacral seg-
ments S4 and S5.
Incomplete 1: sensory but not motor function is preserved below the neu-
rologic level and extends through to the sacral segments S4 and S5.
Incomplete 2: motor function is preserved below the neurologic level, and
the majority of key muscles below the neurologic level have a muscle grade
less than 3.
Incomplete 3: motor function is preserved below the neurologic lev-
el, and the majority of key muscles have a muscle grade of 3 or greater.
2. The clinical patterns seen in spinal injury are the following:
• Cauda equina lesions
• Conus medullaris lesions
• Mixed cauda-conus lesions
• Spinal cord injuries
• Spinal cord concussion
• Spinal shock
• Complete cord transection
• Incomplete cord transection
• Brown-Sequard syndrome (is caused by damage to one half of the spi-
nal cord, resulting in paralysis and loss of proprioception ipsilateral, and loss
of pain and temperature sensation contralateral as the lesion).
• Central cervical cord syndrome
• Anterior cord syndrome
• Posterior cord syndrome
Spinal cord concussion is the term for transient neurologic symptoms with
recovery in minutes or hours. Symptoms develop below the level of the blow.
Spinal shock occurs after an abrupt, complete, or incomplete lesion of
the spinal cord. There is immediate complete paralysis and anesthesia be-
low the lesion with hypotonia and areflexia. The plantar responses may be
absent, extensor, or equivocal. The areflexic hypotonic state is gradually
replaced by pyramidal signs, usually within 3 or 4 weeks. The evolution from
an areflexic to hyperreflexic state may be delayed by urinary tract infection,
infected bed sores, anemia, or malnutrition. Chronic and complete transec-
tion of the cord after the period of spinal shock results in permanent motor,
sensory, and autonomic paralysis below the level of the lesion. Chronic and
incomplete transverse section results in different clinical pictures, depending

on the pathways involved.
Clear demarcation between incomplete and complete spinal cord syn-
dromes may be clinically difficult at the time of injury. An accurate neurologic
examination may be feasible only 24 to 48 hours after the injury. This period
permits any interference from alcohol, drugs, or multiple trauma to be dealt
with, resulting in a more alert and cooperative patient.
3. Diagnosis. After clinical neurologic assessment and stabilization, diag-
nosis of the injury is enhanced by diagnostic imaging and neurophysiologic
studies. It is essential to obtain accurate and complete plain radiographs of
the spinal column at the time of injury. This is done to rule out unsuspected
other spinal column pathology.
Computed tomography (CT) is the best procedure for evaluating uncer-
tain findings on plain x-rays, as well as detecting bone pathology. In general,
magnetic resonance imaging (MRI) is the best technique for soft tissue im-
aging and CT is best for detecting bone pathology. Standard myelography
is seldom done under acute circumstances. Neurophysiologic assessment
of spinal cord function is feasible with the use of sensory and motor evoked
responses. Mixed nerve evoked potentials may be useful in determining the
integrity of certain spinal cord pathways (e.g., dorsal columns).
4. Treatment of the spinal-cord-injured patient encompasses five phases:
(1) emergency treatment with attention to circulation, breathing, patent air-
way, appropriate immobilization of the spine, and transfer to a specialized
center; (2) treatment of general medical problems (e.g., hypotension, hypox-
ia, poikilothermy, ileus a disruption of the gastrointestinal tract); (3) spinal
alignment; (4) surgical decompression of the spinal cord, if indicated; and
(5) a well structured rehabilitation program.
Prehospital management is critical in preventing further complications. Cer-
vical traction must be delayed until adequate radiologic studies can be done.
Meticulous attention must be paid to cardiac output and mean blood pressure
to prevent the cardiopulmonary complications that frequently accompany cord
injuries. Because cord injury may result in loss of sympathetic tone with periph-
eral vasodilation, bradycardia, and hypotension, secondary ischemic damage
may aggravate the spinal cord injury resulting from mechanical causes. Treat-
ment of this potential hazard includes judicious administration of intravenous
fluids to prevent fluid overload, alpha-agonists, and, occasionally, intravenous
atropine sulfate to counter unopposed parasympathetic activity. Vasomotor pa-
ralysis may also cause loss of thermal control and lead to poikilothermy, which
can usually be treated by the appropriate use of blankets.
Extrication of the patient from an automobile must be attempted only after the
patient’s head and back have been strapped in a neutral position on a firm base.
In the acute phase, intermittent bladder catheterization must be instituted
to prevent permanent bladder atony that may result from urinary retention.
The insertion of a nasogastric tube will control abdominal distention, reducing
the risk of secondary respiratory impairment.
In the acute phase and before imaging, methylprednisolone therapy is indi-
cated. Methylprednisolone is thought to improve spinal cord function by inhibiting
lipid peroxidase. Other pharmacologic agents being studied include a 21-amino-
steroid, a synthetic nonglucocorticoid steroid that acts as an antioxidant.
Gangliosides (acidic glycosphingolipids) are also being evaluated. These
agents are thought to become part of the lipid bilayer of the plasma membrane and
simulate formation of endogenous gangliosides. Gangliosides are started within
72 hours of injury and continued for 18 to 32 doses over 3 to 4 weeks. Methylpred-
nisolone is administered by bolus injection of 30 mg/kg followed by 5.4 mg/kg per 1
hour for 23 hours. This treatment must be started within 8 hours of the injury.
Formerly, it was customary to operate on most patients with acute spinal
cord injury to decompress the damaged cord. It has become apparent that
surgery has little effect on the neurologic outcome. When cord compression is
certain or the neurologic disorder progresses, benefit may be seen following
immediate decompression (1 to 2 hours).
Administration of low-dose heparin reduces the risk of pulmonary embolus.
Intermittent catheterization of the bladder has replaced use of an indwelling
catheter and suprapubic cystostomy. Rehabilitation therapy should be started
as soon as possible.
TESTS
1. A 43-year-old patient fell dawn at home, lost consciousness for some min-

utes. After regaining of consciousness he noticed a slight wound above his left
ear, nausea and headache. After taking painkillers, patient felt satisfactory.
Next day patient’s condition worsened rapidly, headache intensified, vomiting
was observed followed by a secondary depression of consciousness to stu-
por. Neurological status at hospitalization: coma, right side hemiparesis. What
is the most likely diagnosis?
1) diffuse axonal injury
2) cerebral contusion
3) epidural hematoma
4) subdural hematoma
5) traumatic subarachnoid hemorrhage
2. Patient B. was hospitalized after road accidents. Neurological status: coma,
disorders of vital signs. What of the following is the most likely sign to suspect
a cerebral compression?
1) generalized seizure
2) anisocoria
3) Babinski symptom
4) loss of consciousness
5) a few hours consciousness loss
3. Patient R. was hospitalized in emergency care department after traumatic
brain injury. Examination: wounds of skin with aponeurosis injury on the head,
stupor, weakening reaction of pupils to light, anisoreflexia. Classify the TBI
according to injury nature.
1) closed-head injury
2) open-head injury
3) penetrating injury
5) chronic compression of the brain
4. Patient S. with traumatic brain injury admitted to hospital. Neurological sta-
tus: coma, bradycardia, left side Babinski symptom, anisocoria S>D. What
are the diagnostic procedures?
1) X-ray examination, hospitalization in the neurological department
2) angiography, surgical treatment in subacute period
3) CT scan, surgical treatment in subacute period
4) CT scan, immediate surgical treatment
5) X-ray examination, immediate neuroprotective treatment
5. A 61-year-old patient stumbled and fell dawn at street; lost consciousness
for some minutes. After restoration of consciousness: severe headache, nau-
sea, patient does not remember events before falling. At neurological exam-
ination: sweating, horizontal nystagmus. No motor and sensory disorders.
What is the most likely diagnosis?
2) cerebral concussion
3) cerebral contusion
4) cerebral compression
5) traumatic subarachnoid hemorrhage
Neurosyphilis 147
Topic 14
NEUROSYPHILIS
Topic questions:
1. Definition. Etiology.
2. General information.
3. Forms of neurosyphilis:
1) early (mesodermal) neurosyphilis:
a) asymptomatic meningitis;
b) syphilitic meningitis (meningovascular syphilis).
2) late (parenchimatous) neurosyphilis:
a) tabes dorsalis;
b) progressive paralysis.
3) unspecified — Gumma (syphilitic) of central nervous system
4. Diagnostics of neurosyphilis.
5. Differential diagnosis.
6. Treatment of neurosyphilis.
1. Definition. Etiology
Neurosyphilis is a damage of a nervous system with Treponema pallidum.
It can occur at any stage of syphilis, and depends on the penetration of the
exciter into the brain tissue.
2. General information.
Neurosyphilis is the infectious disease of the nervous system, which is found
in 10 % of patients with syphilis. Syphilis of the nervous system has become a
rare disease, because it is successfully treated with antibiotics. But the number
of neurosyphilis cases increases. Despite abortive and atypical course of the
disease and the patients’ negative Wassermann reaction because of the sero-
resistant forms presence. Well-timed diagnostics of the disease, knowledge of
the etiological factors, diagnostic methods prevent complications of syphilis.
There are two clinical and pathomorphological forms of neurosyphilis:
1) early neurosyphilis (meningovascular or mesodermal form) develops
in the first 3-5 years after infection. Affects mainly vessels and meninges
alongside with the secondary period of syphilis
2) late neurosyphilis (parenchymal or ectodermal form) develops
within 7-25 years after infection. Characterized by inflammatory and
dystrophic lesions of the brain parenchyma; i.e. nerve cells and fibers, glia.
3. Forms of neurosyphilis:
1) early (mesodermal) neurosyphilis:
a) asymptomatic meningitis. Mild headache, dizziness, nausea,
general hyperesthesia, pain while moving the eyeball, passing dysfunction
of the cranial nerves. Malaise, insomnia, irritability, depression are
observed sometimes. The inflammatory changes in the cerebrospinal fluid
are present (slightly expressed lymphocytic pleocytosis) on which the
diagnosis is set.
In blood and cerebrospinal fluid the positive serological tests for syphilis
(Wassermann test, the TPIT — the Treponema pallidum immobilization test)
are marked.
b) syphilitic meningitis (meningovascular or mesenchymal syphilis)
involves inflammation of the sheaths and small blood vessels in the brain. It
is also called the basilar form, because the process mainly covers base of
the brain and blood vessels. In these cases the process is gradual, continues
during weeks and even months, and in the clinical picture the meningeal
syndrome is slight and does not come to the fore.
The damage of cranial nerves is quite typical. The damage of
- oculomotor or abducens nerves lead to diplopia
- facial nerve — to paresis of mimic muscles
- cochlear nerve — to hearing loss, dizziness
- optic nerve — to reduce of visual acuity, optic atrophy.
It can result in a stroke because of the defeat of small blood vessels.
A direct Argyle-Robertson symptom occurs: loss of reaction of pupils to
light with preservation of their reaction to accommodation. The symptom is
not specific enough (can be observed in multiple sclerosis, chronic alcoholism
and diabetes), as a consequence of optic atrophy and uveitis, but the small
size of the pupils and the deformation of contours alongside with other clinical
and paraclinical data may be evidence in favor of syphilis.
2) late (parenchimatous) neurosyphilis:
a) tabes dorsalis. The disease develops within 5-10 years after the initial
infection. At the pathogenesis, probably the autoimmune processes play a
certain role. However, the predominant mechanism remains the neurotoxic
effect of spirochetes that persist chronically (continue to live in membranes
for years, affecting the nervous elements by its metabolic products). This effect
is a unique characteristic for neurosyphilis, unlike other infections (except,
perhaps prions). The increased degeneration of posterior roots of the spinal
cord, sensory and autonomic ganglia, and later the ascending sensory fibers,
mainly the Gaulle and Burdach pathways are found on autopsy.
Neurosyphilis 149
The first stage is the neuralgic. It is characterized by sudden attacks of

pain in the appropriate dermatomes (from several seconds to minutes, hours
or even several days) and splanchnotomes: heart, liver, stomach, bladder or
rectum, etc, though pain may have a shingle character (as in case of intercostal
neuralgia). The pain is strong, unbearable; «stabbing» and can simulate an
attack of angina pectoris or myocardial infarction, perforated gastric ulcer,
biliary colic and other diseases. Although there are not appropriate changes
of blood or ECG, such patients find themselves on the operating table. At
the same time, the complaints on paresthesias in certain parts of the body
or in the lower extremities may be revealed. Disorders of urination (retention,
incontinence), and sexual function, constipation, are joined.
The pathology of cranial innervation in form of primary optic atrophy, direct
Argyle-Robertson symptom, pupils’ deformation (sometimes a quick change
of their diameter, «jumping pupils»), oculomotor dysfunction, face asymmetry
and hearing impairment are detected. Loss of achilles and knee reflexes
are joined. The areas of hypoesthesia by segmental type on the trunk or
extremities are revealed sometimes.
The second stage is ataxia: the process extends to the dorsum column
of the spinal cord. Sensitive ataxia joins the above-mentioned complaints.
This ataxia means instability and loss of coordination during walking, which
significantly increase in the dark with closed eyes. The patients notice the
loss of sense of surface (feel like walking on the «rubber carpet»), they walk
placing the feet widely and leaning mostly on the heel. Muscular hypotonia,
especially in the legs, results in genu recurvatum.
Trophic disorders develop. They are painless arthropathy with deformation
of the joints (ankle, elbow and other joints) with their swelling and increase in
size. Fractures occur as a result of local osteoporosis. Trophic disorders may
be manifested in the form of a painless ulcer on the foot (malum perforans
pedis), tooth loss, disturbance of nail growth and skin trophic.
The third stage of the disease is paralytic stage. Paresis and paralysis are
absent, but owing to ataxia, patients lose the ability to walk, stand and sit.
b) progressive paralysis or general paralysis of insane is manifested by
progressive mental disorder until deep dementia, accompanied by somatic
and neurological disorders. In the initial stage symptoms of neurasthenia
dominate. They are fatigue, irritability, reduction of working capacity. Later
personality changes are joined. Memory disorders, the elements of intellectual
disabilities, the former skills and knowledge are lost. On the base of progressive
dementia absurd delusions of grandeur, good or bad mood, hypochondria,
changing states of depression and manic excitement may occur. Disorders
of speech, movement, writing, epileptic seizures can develop. Characteristic

neurological symptoms are: deformation of pupils, direct Argyle-Robertson
symptom, paresis of eye muscles, hyperreflexia, hand tremor.
3) unspecified neurosyphilis — Gumma (syphilitic) of central nervous
system (granulomas). Gumma (from gummi-glue) may be quite small,
looking like grayish nodules resembling miliary tubercles, but more common
are solitary gumma with size up to 30 mm in diameter. The clinical course
is the same as a tumor of the brain (general cerebral syndrome and focal
signs depending on the location). As they are formed mainly in pia mater
of the brain base, focal manifestations include cranial nerve roots lesions.
The clinical picture of gumma in spinal cord is the same as extramedullary
tumors (lesions of the spine root, Brown-Sequard syndrome) with probable
compression of the spinal cord.
Ocular fundus: optic nerve swelling.
CSF data: protein-cell dissociation, positive serological tests.
4. Diagnosis of neurosyphilis is set on the base of 3 main criteria:
- clinical picture
- changes in the CSF and positive test results for syphilis
- the evaluation of neurosyphilis clinical features is possible only after a
neurologist’s and an ophthalmologist’s examination (an overview of the pupils,
ocular fundus).
Laboratory tests for syphilis are applied comprehensively and repeatedly
if it is necessary: RPR-test (Rapid Plasma Reagin — detects IgG and IgM
antibodies to lipid and lipoprotein materials released from damaged cells of
patients with syphilis), IFR (im-
munofluorescence reaction),
TPIT (Treponema pallidum im-
mobilization test). Examination of
cerebrospinal fluid reveals Trepo-
nema pallidum, elevated protein,
lymphocytic pleocytosis. The re-
sult of the IFR is positive.
MRI and CT scan of the brain
or spinal cord in case of neu-
rosyphilis find mostly non-specif-
ic pathological changes in form of A B
thickening of the meninges, hy- Fig. 1. Syphilitic gummy using
drocephalus, atrophy of the brain T1-weighted images (A) and
matter and the localization of T2-weighted images (B), MRI
Neurosyphilis 151
syphilitic gumma that allows setting a differentiated diagnosis of neurosyphilis

and other similar in clinic diseases.
6. Differential diagnosis is carried out with multiple sclerosis, tumors of
brain and spinal cord, stroke, infectious polyneuritis, funicular myeloses
7. Treatment of neurosyphilis.
Basic treatment of all forms of neurosyphilis includes penicillin G prescribed
by a dermatovenerologist. The result is assessed on the base of normal level
of cells in the cerebrospinal fluid (increased protein can remain longer, for
several months). Serological reactions in cerebrospinal fluid may remain
positive for years or during all lives, despite the positive clinical effect.
Symptomatic treatment: complex B vitamins, ascorbic acid, physiotherapy
treatments (massage, balneotherapy).
TESTS
1. What changes in the cerebrospinal fluid in syphilitic meningitis are not

marked?
1) albuminocytologic dissociation
2) neutrophilic pleocytosis
3) lymphocytic pleocytosis
4) direct Argyll Robertson symptom
5) increased pressure
2. Name the symptom, which is characterize the absence of direct and
consensual reaction of pupils to light while preserving their reaction to
convergence and accommodation.
1) Claude-Bernard-Horner syndrome
2) reverse Argyll-Robertson symptom
3) direct Argyll-Robertson symptom
4) Brudzinski sign
5) Foster-Kennedy syndrome
3. Patient suffering from neurosyphilis has ataxia due to the damaged of
following nervous system structure
1) pyramidal pathway
2) anterior horns of spinal cord
3) lateral columns of spinal cord
4) dorsal columns of spinal cord
5) Flechsig’s and Gowers’ pathways
4. Progressive paralysis is characterized by:

1) depression
2) dementia
3) antisocial behavior
4) changes in personality
5) all answers are correct
5. What is the main clinical feature of syphilitic meningitis?
1) sensitive ataxia
2) damage of IIIth, IVth, VIIth pairs of cranial nerves
3) alternating hemiplegia
4) reverse Argyll-Robertson symptom
5) tabetic crises
Nervous system lesions in HIV-positive patients 153
Topic 15
NERVOUS SYSTEM LESIONS IN HIV-POSITIVE PATIENTS
Topic questions:
1. Neuro-AIDS etiology.
2. Neuro-AIDS classification.
3. Neuro-AIDS pathogenesis.
4. The main nosological forms of early neuro-AIDS:
1) AIDS-dementia (HIV encephalopathy)
2) HIV-associated meningitis
3) Vascular neuro-AIDS
4) HIV-associated vacuolar myelopathy
5) Inflammatory polyneuropathy
5. Late neuro-AIDS:
1) Progressive multifocal encephalopathy
2) Toxoplasma encephalitis
3) Cryptococcus meningitis
4) Herpetic encephalitis
5) Vasculitis and cerebral circulation disorders
6) CNS Tumors
6. Clinical features of HIV-infection in children.
7. Neuro-AIDS treatment.
1. Neuro-AIDS etiology.
Nervous system lesions occur in 90% of AIDS patients, although clinical
neurological complications are detected only in 50-70% of cases.
The causative agent of the disease is human immunodeficiency virus
(HIV), which belongs to the retroviruses family. Certain body fluids can
transmit the virus (blood, scmen, pre-seminal fluid, rectal fluid, vaginal fluid,
breast milk).
2. Neuro-AIDS classification.
A. Early neuro-AIDS.
B. Late neuro-AIDS.
3. Neuro-AIDS pathogenesis.
HIV-related neurological disorders disorolers may develop directly from
infection with HIV (early neuro-AIPS) or result of opportunistic illnesses or
treatment complication (late neuro-AIPS).
In the HIV life cycle a few key points are distinguished:

- attachment of viral particles to human lymphocytes;
- virus genetic material is formed due to the action of HIV reverse
transcriptase enzyme;
- the provirus DNA is integrated into the human DNA by the HIV integrase enzyme;
- forming virus proteins under HIV protease action.
The central nervous system is affected at an early stage of the disease. HIV
infection penetrates the hematoencephalical barrier with macrophages and
monocytes. Virus doesn`t infect directly neurons but numerous neurological
complications are associated with neurotoxic action of substances that
produce HIV or factors that are released by infected macrophages or microglial
cells (for example, cytokines, amino acids, etc). It is suggested that some
viral proteins, for example, GP 120, connecting with neurons can empire
functioning of calcium or other ion channels or affect neurotransmission.
These processes ultimately lead to the death of neurons.
4. The main nosological forms of early neuro-AIDS.
1) AIDS dementia (HIV encephalopathy). Morphological substrate of
HIV encephalopathy is a primary cerebral hemispheres white matter lesion of
the inflammatory and demyelinating nature, mainly in subcortical structures,
which is caused by multifocal giant cells encephalitis and progressive diffuse
leukoencephalopathy. Characteristic features:
a. cognitive-mnestic disorders,
b. behavior changes
c. movement disorders.
Cognitive-mnestic disorders: reduced memory, impaired concentration,
slowing and reduction of intellectual activity occur at an early stage of the
disease. In the neurological status hyperreflexia, oral automatism symptoms,
tremor and mild ataxia, hypomimiya are observed.
Changes in behavior: gradually arise cognitive function violations,
drowsiness, untidiness and apathy.
Movement disorders: stiffness, central paresis, ataxia, hyperkinesis,
seizures, pelvic organ dysfunctions.
Akinetic mutism (loss of contact with reality, loss of interest in reality, the
lack of desire to communicate with others, poor emotional expressions),
abulia, lower spastic paraplegia, incontinence of urine and feces, generalized
seizures, psychotic disorders occur at the last stage of the disease.
Diagnostic criteria according to CT scan or MRI:
• cortex atrophy with subarachnoid space and brain ventricles extension.
• subcortical foci in the frontal and parietal lobes.
2) HIV-associated meningitis.
The meningitis diagnosis is based on the presence of three common
syndromes: general infectious, meningeal syndrom inflammatory changes
in the cerebrospinal fluid. However, atypical variants of HIV-associated
meningitis are observed in most cases.
Seizures, mental disorders, consciousness disorders are possible in the
case of severe meningoencephalitis.
Diagnostic criteria for HIV-associated meningitis are slight, but persistent
lymphocytic pleocytosis, HIV infection and antibodies to it in CSF, while their
absence in blood is possible.
3) Vascular neuro-AIDS.
In case of neuro-AIDS virus-induced brain and spinal cord vas culitis
development is possible. Therefore, 20% of patients may experience a
stroke. HIV-infected patients have vascular wall infiltration with leukocytes,
edema and proliferative changes of the internal layer. This leads to vascular
obstructions, thrombosis with subsequent development of cerebral infarction,
blood vessels rupture with hemorrhage occurrence.
4) HIV-associated vacuolar myelopathy.
It may be isolated or combined with AIDS dementia. Spinal cord demyelization
and spongy degeneration are morphologically determined mainly in the lateral
and posterior columns in the middle and lower thoracic segments level. Vacuolar
myelopathy is characterized by slowly progressive spastic paraparesis with
high tendon reflexes, pathological plantar signs, sensitive ataxia, conductive
type sensitivity disorders with the upper limit of the body skin corresponding
to the affected segment. Central type pelvic organs disorders are also
characteristic. MRI detects atrophy and stretch enhanced signal in T2-weighted
mode at the thoracic level of the spinal cord involving the cervical level or not.
5) Inflammatory polyneuropathy.
It may occur at any stage of HIV infection. In case of the distal symmetric
polyneuropathy patients are concerned with numbness, burning, paresthesia
in the lower limbs that strengthen by the slightest touch. Pain increase at
night and its reduction when putting the lower limbs in cold water is typical. In
neurological status «gloves» and «socks» hypoesthesia types are detected,
vibration sensitivity is decreased and reduction of Achill es reflexes occurs.
5. Late neuro-AIDS.
1) Progressive multifocal encephalopathy with subcortical
hyperkinesis and progressive dementia is a demyelinating disease
of the nervous system, which is caused mainly by papovavirus JC (John
Cunningham virus — the patient`s name). Its replication occurs as a result
of immunosuppression. Clinical manifestations are headache, dementia,

aphasia, hyperkinesis, progressive paresis, sensitivity disturbances and
epileptic seizures. The clinical course is rapidly progressive, death occurs
within 6-9 months.
2) Toxoplasmosis encephalitis is the most common cause of tumor
processes in case of AIDS. Disease onset may be acute or subacute in the
form of focal or generalized seizures. Attention is drawn to focal neurological
symptoms: aphasia, cranial neuropathy, hemiparesis, sensory and coordinate
disorders on cerebral symptoms background — headaches, disorientation
and confusion. Optical lesions (uveitis, focal necrotic chorioretinitis, papillitis)
are prior or simultaneous to the central nervous system disorders that occur
without obvious inflammatory reactions.
Diagnosis of toxoplasmosis encephalitis is based on CT scan or MRI
data and detection of Toxoplasma DNA in blood and cerebrospinal fluid by
polymerase chain reaction (PCR).
3) Cryptococcus meningitis usually occurs on the base of severe
immunodeficiency due to the fungus Cryptococcus neoformans, which is
acquired via the respiratory tract. The disease begins acutely or subacutely with
headache, fever, nausea, photophobia, confusion, weight loss, temperature
up to 37.5-38.0 oC. Local granulomas development is possible in brain tissue
in the form of accumulated Cryptococcus that clinically resembles a tumor.
The CSF examination shows a slight pressure, increase mild lymphocytic
pleocytosis, a moderate increase in protein content, decreased glucose levels.
4) Herpetic encephalitis (Fig. 1). In clinical course course the following
stages are distinguished:
- early stage,
- clinical manifestations,
- stabilization stage,
- symptoms regression stage.
The disease may begin with meningeal type
at the early stages: general infection symptoms,
expressed general cerebral symptoms with
consciousness disorders are observed. Sometimes
the disease begins with cortical (delirious) type:
inappropriate behavior, disorientation in time and
place, amnesia. A stroke-like start is possible:
sudden generalized seizures, loss of consciousness Fig. 1. Herpetic
with the rapid coma development. Patients encephalitis MRI
with seizures and such changes of behavior as scanning in HIV
disorientation in place and time, hallucinations, infected patient
agitation will be admitted to a psychiatric department (30% of cases). Rarely

brain stem type lesions occur, characterized by diplopia, dysarthria, ataxia,
alternating syndromes.
At late stages of the disease, there may be general cerebral syndrome
and liquorice-induced symptoms, pyramidal and extrapyramidal system
syndromes, seizures, severe cognitive violations. Diagnosis is based on a
CSF study, in which moderate lymphocytic pleocytosis, high IgG levels and
positive PCR to herpes simplex viruses are detected.
5) Vasculitis and cerebral circulation lesion. Most frequently necrotic
vasculitis is localized in the medial parts of the temporal lobe. Aggression,
negativism and seizures are characteristic.
The development of parenchymatous and subarachnoid hemorrhage is
possible due to mycotic aneurysm rupture (sustainable local expansion of
blood vessels), bleeding is possible in the brain tumor, Kaposi’ sarcoma. Along
with of signs vascular pathology vascular changes in the skin, myocarditis
and optic lesions are observed.
6) Neoplasms of the CNS : primary
lymphoma is the most common (Fig. 2). It
is found in 2% of cases, usually as a result
of profound immunosuppression. The initial
manifestations reflect single or multiple lesions
of the brain parenchyma and intracranial
hypertension. The variety of clinical symptoms is
determined by the process location. Confusion,
stupor, decreased memory, behavior disorders,
cranial nerve lesions, hemiparesis, aphasia and
seizures are typical.
6. Clinical HIV infection in children
HIV in early childhood contributes to the Fig. 2. Primary EBV-CNS
physical and psychomotor development reten- lymphoma in the case of
tion of physical and psychomotor development. AIDS
Recurrent bacterial infections are marked more
often in children than in adults, lymphoid pneumonitis, pulmonary lymph
nodes increase, encephalopathy and anemia are also common.
A common cause of infant mortality in case of HIV infection is hemorrhagic
syndrome as a result of severe thrombocytopenia.
The disease in children who have get HIV from their mothers during
pregnancy or in the perinatal period proceeds considerably more difficult and
rapidly progressive than in children infected after one year of life.
7. Neuro-AIDS treatment should be comprehensive and pathogenic.

In case of primary neuro-AIDS specific highly active antiretroviral therapy
(HAAT) prescribed which slows down the disease progression and temporarily
stabilizes the patient’s condition. Today, about 20 drugs of HAAT are used.
There are two groups of drugs:
• HIV reverse-transcriptase inhibitors (Zidovudine, Abacavir, Stavudine,
etc.);
• different viral enzyme protease inhibitors (Indinavir, Ritonavir).
The positive clinical effect is observed in patients with neuro-AIDS when
the recombinant Interleukin-2 is added to the treatment. It significantly
improves the cellular immunity indices.
The treatment of the patients with secondary neuro-AIDS is based on
the application of specific treatment of nervous system lesions caused by
opportunistic infections.
If cytomegalovirus is the cause of the nervous system lesion, a combination
of ganciclovir and foscarnet is used; if toxoplasmosis is the cause, induction
treatment of pyrimethamine, sulfadiazine, leucovorin are prescribed. For
patients with cryptococcal meningitis, induction treatment with amphotericin
B and flucytosine are given followed by fluconazole.
Drugs used to treat neuro-AIDS: Videx, Dovir, Retrovir, Zydovir, Lamivir,
Epivir, Stavir, Nevimune, Efavir, Viracept, Kaletra etc.
TESTS
1. The patient with weakness in the legs was observed by neurologist. After
examination the doctor suspected that neurological symptoms may be caused
by immunodeficiency virus. What is the difference between HIV and AIDS?
1) HIV is a virus and AIDS is a autoimmune disease
2) AIDS is a reason of HIV
3) HIV is a virus and AIDS is a bacterial disease
4) HIV is the virus that causes AIDS
5) there is no difference between HIV and AIDS
2. A 29-year-old patient was diagnosed with brain tumor on MRI examination. In
anamnesis: frequent infections resistant to treatment, generalized candidosis.
Blood analysis: lymphopenia. What form of neuro-AIDS can be diagnosed?
1) AIDS-dementia
2) primary neuro-AIDS
3) secondary neuro-AIDS

5) HIV-associated meningitis
3. A 25-year-old patient was hospitalized with mnestic disorders. General
status: reduced memory, apathy, loss of interest to communicate with others,
poor emotional expressions. No motor and sensory disorders. Doctor suspects
neuro-AIDS because of positive test detecting antibodies to the HIV antigens.
What form can it be suspected first of all?
1) AIDS-dementia
2) vascular neuro-AIDS
3) progressive multifocal encephalopathy
5) CNS Tumors
4. Patient R. was hospitalized with HIV-associated vacuolar myelopathy. What
is a pathogenesis of neurological disorder in primary neuro-AIDS?
1) HIV destroys neurons
2) HIV destroys glial cells
3) substances produced by HIV destroy neurons
4) different infectious agents alter nervous system at immunosuppression
5) oxidative stress
5. A 25-year-old patient was hospitalized with HIV-associated meningitis.
What treatment will you apply in primary neuro-AIDS?
1) corticosteroids
2) immunosuppressive drugs
3) antiretroviral therapy
4) treatment of opportunistic infections
5) neuroprotection
Topic 16
DEMYELINATING DISEASES OF THE NERVOUS SYSTEM. ACUTE

DISSEMINATED ENCEPHALOMYELITIS, MULTIPLE SCLEROSIS,
SCHILDER’S ENCEPHALITIS AND VAN BOGAERT’S DESEASE
Topic questions:
I. Multiple sclerosis.
1. Definition.
2. Etiology, pathogenesis, pathomorphology.
3. Classification of disease (according to clinical forms, course, periods of
disease, degree of severity).
4. Clinical syndromes and symptoms of multiple sclerosis.
5. Diagnosis.
7. Treatment:
- in exacerbation period (period of relapse);
- preventive.
8. Prognosis.
II. Acute disseminated encephalomyelitis (ADEM).
1. Definition, etiology and pathogenesis.
2. Clinical picture.
3. Diagnosis.
5. Treatment.
6. Prognosis.
III. Diffuse myelinoclastic sclerosis (Schilder’s encephalitis).
1. Definition, etiology.
2. Symptoms, diagnosis, treatment and prognosis.
IV. Van Bogart’s disease.
1. Definition, etiology and pathogenesis.
2. Symptoms, diagnosis, treatment and prognosis.
I. Multiple Sclerosis
1. Definition. Multiple sclerosis (MS, disseminated sclerosis, sclerosis
disseminate — SD) is a chronic, unpredictable disease of the central nervous
system (CNS), which is made up of the brain, spinal cord and optic nerves. It
is thought to be an immune-mediated disorder, in which the immune system
Demyelinating diseases of the nervous system. Acute disseminated encephalomyelitis, Multiple sclerosis,
Schilder’s encephalitis and Van Bogaert’s desease 161
incorrectly attacks healthy tissue in the CNS.) The role of inflammation,

acute and chronic axonal loss, and neuro-degeneration is in the core of
pathophysiology of MS. It often leads to disability. In most cases there is an
undulating course with alternating exacerbations and remissions on the early
stages of the disease, rare steadily progressive course is possible. Mostly
people aged 15 to 45 years can get sick, rarely after 55 years. Women get
sick 2-3 times more often than men do. As nosological form, MS first was
discovered and described by Charcot in the late nineteenth century.
The terms:
Debut of the disease: the first manifestation, the beginning.
Relapse is the appearance of a new symptom or a group of symptoms.
Relapse is accompanied by the appearance of objective neurological
symptoms lasting at least 24 hours. Duration of the relapse is 24 hours, for
2 months. The interval between exacerbations is at least 1 month.
Remission is clear reduction or disappearance of symptom/symptoms
according to neurological examination of at least 1 month.
2. Etiology has not been fully cleared up. MS is considered a multifactorial
disease occurs due to a combination of viral infection, genetic predisposition
and geographical factors. The disease causes are considered virus infection
persistent that occurs in childhood or adolescence. The most likely candidates
for the role of viruses’ pathogen are called herpes group: Epstein-Barr virus and
herpes virus type VI.
Genetic predisposition and determination is linked to the presence of
certain genes in the human genotype.
Geographical factors are associated with features of the climate, the nature
of water and soil, the content of trace elements, including zinc, cobalt, and
copper. The morbidity rate of MS is dissimilar in different regions of the globe.
Most commonly, MS is found in the temperate climate countries and northern
regions. The highest incidence is in Northern Ireland (130 per 100 thousand
population), the U.S.A (80 per 100 thousand), the Baltic States, Belarus and
Ukraine (60 persons per 100 thousand). Mostly people do not suffer from MS
in tropical countries — China, Japan. It rarely occurs in Africa and India.
Smoking has been shown to be an independent risk factor for MS. Several
other possible risk factors, such as diet, vitamin D deficiency, obesity in child-
hood and hormone intake, have been looked at.
Pathogenesis, pathomorphology (Fig. 1). The major pathological manifes-
tation of MS is the destruction of the myelin membrane of the pathways within
the central nervous system (Fig. 2). In the early stage, the activation of T-lym-
phocytes in peripheral blood occurs due to an unknown trigger factor, leading to
Fig. 1. Inflammatory cascade in multiple sclerosis

the proinflammatory cytokines secretion, up-regulation of adhesion molecules,
which penetrate the activated cells (T- and B-cell, macrophages, and monocytes)
through the hematoencephalic barrier. This leads to the production of proinflam-
matory cytokines in brain
and the development of
a limited inflammatory re-
sponse. Later it leads to
the formation of antibodies
to myelin, causing to focal
demyelination, axonopathy
with degeneration and oligo-
dendrocytes damage. Orig-
inally, pathological process
may end with remyelination, Fig. 2. Healthy nerve and nerve in case of
but it is not complete. In ar- demyelination
eas of repeated damage, the proliferation of astrocytes and the formation of scle-
rotic plaques occur.
Due to generally accepted ideas, the pathological process in MS can be
divided into 3 stages:
- the development of immune responses in the periphery and in the CNS;
- demyelination;
- axonal degeneration.
These foci scattered in the CNS, in which disappearance of myelin,
formation of gliosis and fibrous plaques (scars) are observed. Predominantly
foci or plaques are localized in sections of the optic nerves, periventricular
area, brain stem, the lateral and posterior columns of the spinal cord,
cerebellum.
3. Classification of disease.
• Due to the course (Fig. 3):
- Clinically isolated syndrome (CIS),
which may be the first episode of neurological
dysfunction;
- Remitting-relapsing (RR);
- Primary-progressing (PP);
- Secondary-progressing (SP),
which occurs after the PR form after
10-15 years of the debut,
- Progressing-relapsing (PR) MS.
CIS is an acute or subacute isolated solitary
in time episode of neurologic disorders connected Fig. 3. Variants of multiple
with one (focal CIS) or more (multifocal CIS) foci. sclerosis course:
Clinical variants of CIS are: optic neuritis, brain A — primary progressing,
stem syndrome (including ataxia, dizziness, al- B — relapsing-remitting,
ternate syndrome), spinal syndrome, sensory dis- C — secondary-progressing,
orders. Pelvic disorders, paroxysmal syndromes D — progressing-relapsing
(paroxysmal dysarthria or ataxia, tonic seizures,
etc.) are rare. Not everyone who experiences CIS goes on to develop MS.
RR form is observed in 90% of MS patients in the early stages of the
disease and is characterized by the relapses (exacerbations) and followed by
complete or partial functional recovery in remission.
PP form is characterized by a gradual steady progression from onset.
SP form is characterized by transition of the RR form to the progression
of gradual neurological symptoms with infrequent exacerbations (progressive-
relapsing form) or without them.
• Due to the periods of disease:

I — relapse;
II — remission (first remission longer than the next).
3. Clinical symptoms and syndromes of MS.
Clinical manifestations are associated with focal lesions of brain and
spinal cord. Functional System Score is used most commonly to assess the
neurological manifestations. This score evaluates the severity of symptoms of
various major CNS systems.
Functional system lesions:
1) Pyramidal tract lesion symptoms are a major cause of disability because
of hemi-, para-, three- or tetraparesis. Monoparesis are observed rarely.
Lower limbs suffer more likely than upper. Spasticity may prevail over the
severity of paresis and is characterized by the restriction of active movements,
involuntary reflex muscle spasms.
2) Cerebellar lesion symptoms are characterized by static and dynamic
ataxia, the main manifestations of which are body balance and gait disorders,
dysmetria. Other manifestations are asynergia and muscular hypotonia.
Ataxia is one of the main causes of disability, too.
3) Brain stem and cranial nerve lesion symptoms in MS:
• eyes movement disorders;
• peripheral paresis of the facial muscles;
• nystagmus;
• trigeminal neuralgia;
• bulbar disorders (dysarthria, dysphagia, dysphonia).
4) Visual disorders are characterized by:
• single or bilateral decrease in visual acuity;
• color perception violation, especially of red color;
• pallor of the temporal halves of optic disks, atrophy of optic disks;
• occurrence of scotomas.
5) Sensory disorders: paresthesia and dysesthesia, deep sensitivity
disorders, including vibrative. At later stages of the disease, conductive
anesthesia, rarely segmental disorders appear.
6) Dysfunction of pelvic organs are represented by the disorders of
urination (incontinence, imperative urgency incontinence, bladder emptying
disorder, urine retention); the disorders of defecation (constipation, rarely fecal
incontinence), sexual dysfunction (erectile problem, ejaculatory dysfunction,
libido decrease, anorgasmia).
7) Mental activity changes: the disorders of attention, deterioration,
memory, mood (depression, asthenia and hysteric reactions, euphoria), high
level of anxiety in social contacts, emotional tension, dissatisfaction with the

living situation.
8) Chronic Fatigue Syndrome means a general fatigue, decrease of
working capacity without connection with depression and muscle weakness.
This condition manifests itself in frequent need in rest, motivation reduce,
difficulty while performing the repeated actions, drowsiness.
9) Paroxysmal states of epileptic and nonepileptic origin are manifested by
seizures, autonomic visceral paroxysms, syncopes, migraine.
A scale of MS severity is EDSS (Expanded Disability Status Scale, 2005;
by J. Kurtzke) that assesses the disability by 10 points (Fig. 4):
1-5.5 points: patient is considered to be ambulant without severe limitations
in daily activities.
6 points: intermittent or unilateral constant assistance (cane, crutch, and
brace) required to walk about 100 meters with or without resting;
7 points: unable to walk beyond approximately 5 meters even with aid,
essentially restricted to wheelchair; wheels self in standard wheelchair and
transfers alone; up and about in wheelchair some 12 hours a day;
8 points: essentially restricted to bed or chair or perambulated in wheelchair,
but may be out of bed itself much of the day; retains many self-care functions;
generally has effective use of arms;
9 points: helpless bed patient; can communicate and eat;
10 points: patient is helpless, confined to bed; disease is the cause of death.
The specific features in MS:
Clinical dissociation is the discrepancy of dysfunction degree to objective
neurological status date. For instance: 1. In case of externally satisfactory
Fig. 4. EDSS (Expanded Disability Status Scale, 2005) by J. Kurtzke

state of the patient and the absence of movement disorders, the hyperreflexia,
clonuses and pathological reflexes are observed; 2. The optic disks may be
changed without the clinical signs of visual analyzer disturbances.
Fluctuation of symptoms are caused by changes of nerve impulses
conduction by demyelinated fibers (for example, pelvic and/or pathological
reflexes may occur periodically).
5. Diagnosis of Multiple sclerosis:
1) disease onset at a relatively young age;
2) polymorphism of clinical symptoms at all stages of the disease;
3) variability, «flashing» symptoms even during one day;
4) there is the typical course of the disease. It can be either:
- periodic exacerbations and remissions or
- slow progression.
5) MRI of brain and spinal cord with the compulsory contrast (Gadovist)
injection. This method allows to visualize the foci of demyelination in the
CNS (Fig. 5, 6). If the focus accumulates a contrast, it indicates the process
activity.
MRI criteria which support MS diagnosis are reflected in MAGNIMS
Consensus Guidelines (2015). Multiple Sclerosis setting means the
dissemination of lesions in spaceat least 2 of 5 areas of the CNS as follows:
≥3 periventricular lesions, ≥1 infratentorial lesions, ≥1 spinal cord lesion,
≥1 optic nerve lesion, ≥1 cortical/juxtacortical lesion.
Fig. 5. The demyelinating foci in the

corpus collosum and their orientation Fig. 6. Multiple demyelination
along the fibers of the white hyperdensity foci are localized in the
matter (MRI, T2 -weighted images white matter periventricularly
parasagital cut) (MRI-T2WI)
6) detection of DNA of pathogens in blood using polymerase chain reaction

(PCR) method: herpes virus type 4 (Epstein-Barr virus) and herpes virus
type 6.
7) cerebrospinal fluid investigation for the presence of oligoclonal IgG
bands.
8) Ophthalmic research:
- /optic fundus/ central scotoma, sectoral loss of visual fields, pallor of the
temporal halves of optic discs or atrophy of optic discs.
- /Optical Coherence Tomography/ OCT is an ultrasound of the eye, but
uses light instead and gives reproducible cross-sectional images of the retinal
layers.
- evoked potential test is used in identifying clinically silent lesions in
patients with suspected multiple sclerosis.
Currently, the criteria recommended by the expert group (2001) are known
as the McDonalds criteria, revised in 2005 and in 2010. They are the most
widely used criteria for evidence of «dissemination of lesions on place and in
time». These criteria take into account both the clinical manifestations and
MRI of brain and spinal cord, and presence of oligoclonal immunoglobulin in
cerebrospinal fluid.
At the various stages of MS, the differential diagnosis should be made among
autonomic vascular dysfunction, labyrinthitis, retrobulbar neuritis, tumors of
brain, spinal cord and cerebellum, acute disseminated encephalomyelitis,
degenerative diseases of the nervous system.
7. Treatment of MS.
The main attention is paid to the pathogenetic treatment, which depends
on the process activity.
In case of MS relapse, the following have to be prescribed:
• methylprednisolone pulse therapy (Metypred, Solumedrol) 1000 mg/dai-
ly in 200 ml of saline solution iv № 5 (plus Omeprazol and potassium medica-
tions);
• plasmapheresis. Antibodies, myelin degradation products, proinflamma-
tory cytokines, circulating immune complexes are removed from blood. It can
be used in case of severe flares in remitting-relapsing MS;
• Human Immunoglobulin simple (Oktagam 0,4 mg/kg iv № 5).
Disease-modifying therapy includes:
- the first-line treatment (interferon beta, glatiramer acetate, teriflunomide,
dimethyl fumarate),
- the second-line treatment (natalizumab, fingolimod, alemtuzumab),
- Mitoxantrone (antineoplastic, immunomodulatory agent) is approved for

certain aggressive or severe types of MS.
Several new compounds are in development. Additionally vitamins,
antioxidants, nootropic agents are prescriped, although there is no evidence
of the effectiveness of this therapy.
For reducing muscular hypertonia, myorelaxants (Baclofen, tizanidine) are
used. For correction of pelvic disorders the anticholinergic drugs (Spazmolex,
Dryptan) are administered.
Patients should avoid infections, intoxications, defatigation, climate
change, hyperinsolation and any overheating, physiotherapeutic procedures.
8. Prognosis. At least 25% of patients are capable for self-service after
15 years of MS setting. About 10% of patients cannot walk already after
5 years. On average, MS shortens the life span on 10 years.
II. Acute disseminated encephalomyelitis (ADEM).

1. Definition, etiology and pathogenesis. ADEM is an acute infectious and
allergic disease, in which the inflammatory foci of demyelization in brain and
spinal cord are observed, both white and gray matter are affected. Sheath, roots
and peripheral nerves can also be damaged. The formation of sclerotic plaques
in ADEM is possible. ADEM is divided into primary, which develops because of
primary impact of filtering virus to the nervous system, and secondary, which
occurs on a background of influenza, malaria and other acute infections.
The main feature of ADEM is the development of disseminated
inflammation, perivascular infiltration by lymphocytes or macrophages, or
monocytes, especially around small and medium-sized veins; perivascular
demyelination is characteristic.
2. Clinical features. There are:
- presence of recent acute viral infection or vaccination;
- acute onset with fever and symptoms of intoxication, characteristic
changes in peripheral blood;
- meningeal syndrome;
- neurological disorders indicated the disseminated disorders of nervous
system.
3. Diagnosis is based on following:
• clinical picture;
• MRI data can reveal the multifocal changes in the white matter of the
cerebral hemispheres, cerebellum, and brain stem;
• CSF data: a slight increase of protein content and lymphocytic pleocytosis
(up to 100 cells in 1 ml).
The course of disease is acute and often with severe state of the patient.
After 3-4 weeks, symptoms regress. Sometimes the moderate consequences
in form of ataxia and paresis may be remained. Exacerbations unlike MS are
not observed.
4. Differential diagnosis is carried out with MS. The main features of
ADEM are the prevalence of cerebral and general infectious syndromes,
the acute onset of diffuse damage of central nervous system and possibly
involving peripheral nervous system, with subsequent regression of clinical
symptoms. The conclusion in favor of a particular disease can be made based
on the dynamic monitoring of patients.
5. Treatment of ADEM is the same as in case of acute inflammatory
diseases of the nervous system. In acute phase antibiotics, antivirals,
antihistamines, corticosteroids are administered. During recovery period
anticholinergic, vitamins, neurotrophic agents, physiotherapy, massage,
physical therapeutic techniques are used.
6. Prognosis is favorable. Usually there is complete recovery, but
sometimes paresis, disturbances of sensitivity, reduced vision are remained.
The severe course of ADEM with rapid violation of consciousness, severe
bulbar disorder and death is possible.
III. Schilder’s disease (Diffuse myelinoclastic sclerosis).
1. Definition.
Schilder’s disease is a progressive demyelinating disease, which primarily
affects the white matter of the cerebral hemispheres, cerebellum, pons with
the following glia excrescence and the development of sclerosis.
The etiology and pathogenesis have not been defined.
Autopsy features: there are diffuse sclerosis and inflammatory foci in brain
white matter; axons demyelization.
Disease occurs predominantly in
children under the age of 5-15, but can
be in adults too.
2. The clinical features. There is
a subacute onset of the disease. The
earliest symptoms are mental disorders
and visual disturbances. The child’s
behavior is changed; interest in games,
learning is decreased; emotional
disorders, aphasia are occurred. Fig. 7. Severe spasticity —
Dementia is rapidly progressed. Opisthotonus
Seizures, myoclonus and other (C. Bell «The contracted», 1809)
hyperkinesis may be appeared. Central paresis and paralysis are observed

early and in time become more severe. The II pair of cranial nerves is affected
with progressive decrease of visual acuity, atrophy of the optic disks. Ataxia,
coordination disorders are observed in case of cerebellum involvement.
Sometimes the moderate intracranial hypertension signs occur. Disease is
lasted from several months up to 1-3 years.
3. Diagnosis is difficult. Schilder’s disease should be differentiated with
multiple sclerosis, idiocy, brain tumor.
Treatment. Corticosteroids, symptomatic agents are recommended.
Prognosis is unfavorable.
IV. Van Bogaert encephalitis.
1. Definition. Subacute Sclerosing encephalitis is a progressive disease
of the nervous system, which occur as panencephalitis.
Etiology. Measles virus is possile pathogen. Children can get sick under
the age of 5-15.
2. Clinical features: there are the combination of intellectual and mnestic
degradation symptoms (dementia) with hyperkinesis, seizures and muscle
tone changes, trophic and autonomic disorders.
The desease course is divided into 4 stages:
I stage. Children are irritable, fearful, stubborn, often go out from home;
memory is disturbed, there are periods of lethargy, mutism, apraxia, agnosia,
loss of vision; there are pigmentary changes in the retina.
II stage (the first 2-3 months of disease). Myoclonic jerking of the head,
then of torso and limbs. Sometimes myoclonus are very severe: children
suddenly fall or rise sharply, trunk is flexed while walking («bows» symptom).
There is a wide variety of dyskinesias: choreoathetosis, head tremor, as
well as ataxia. On the 6-th month of the disease, the generalized seizures,
central paresis with oral automatism reflexes may appear.
III stage. Spasticity increases to opisthotonus. Irregular, noisy breathing
appears and reaction to pain stimuli disappears. Vasomotor disorders
(pallor, flushing, sweating, cyanosis), temperature variations from normal
to severe hyperthermia (41 °C) occur occasionally. Swallowing is disturbed.
Terminal (IV) stage lasts from 2 to 6 months. Disorderly movements,
violent laughing and weeping are appeared. Head is turned to one side,
decerebrate rigidity position (hypertonicity flexing of arms and extension
of legs) is characteristic. CSF data: unsteady protein increase, moderate
pleocytosis. Disease is terminated by death inexitable in a period of 3 to
22 months.
Diagnosis is based on clinical signs, data of CSF, CT scan and MRI.
Treatment. Anti-inflammatory drugs, high doses of corticosteroids, antie-

pileptic, drugs for dehydration, nootropics, multivitamins, immunocorrectors,
higher doses of vitamin B12 and E are adminestered. It is advisable to use
antiviral drugs; various forms of interferon (alpha-, beta-, viferon) can slow the
progression of the disease.
TESTS
1. Patient was discharged from the neurological department after the treatment
of MS exacerbation. Currently patient is in remission. Assign a preventive
treatment.
1) methylprednisolone
2) plasmapheresis
3) β-interferon
4) α-interferon
5) nootropics
2. A 23-year-old woman has been having slowly progressive left side vision
decrease, weakness in the legs, imperative feeling to urinate a few months
after childbirth. Neurological status: horizontal nystagmus, lower central
paraparesis, dysfunction of the pelvic organs. The ophthalmic fundus: temporal
pallor of the optic discs. What is the most likely pathogenetic mechanism of
the disease?
1) metabolic lipoprotein disorders
2) autoimmune demyelination
3) violation of blood rheology
4) disorders of hemodynamics
5) axonal degradation
3. A 31-year-old patient has unsteadiness at walking, weakness of limbs, urinary
retention. She has multiple sclerosis for 8 years with periodic exacerbations
in autumn annually and remissions with recovery to the previous neurological
symptoms after exacerbations. Neurological status: mild central tetraparesis,
cerebellar ataxia, urinary retention. What clinical type of MS does the patient
have?
1) stable
2) primary-progressive
3) secondary-progressive
4) remitting-relapsing
5) relapsing-progressive
4. A 26-year-old patient has numbness in the right leg and instability at standing
and walking. Symptoms slowly progress for 3 months. A year ago there was
an episode of vision reduce in left eye, that quickly passed. Neurological
status: nystagmus, unsteadiness at Romberg test and walking, hyperreflexia
of knee and Achilles reflexes, absence of abdominal reflexes. What diagnosis
can you suspect and what method of examination is most likely to confirm the
diagnosis?
1) multiple sclerosis, MRI
2) multiple sclerosis, cerebrospinal fluid examination
3) tumor of the brain, MRI
4) tumor of the brain, cerebrospinal fluid examination
5) acute disseminated encephalomyelitis, MRI
5. Corticosteroid therapy in patients with multiple sclerosis primarily reduces:
1) duration of exacerbation
2) limb spasticity
3) loss of vision
4) permanent weakness
5) sexual dysfunction
Peripheral nervous system diseases (№1). Classification. Infectious immune-mediated polyneuropathy (Guillain-Barre
syndrome). Polyneuropathies in case of alcoholism, diabetes mellitus, botulism, connective tissue diseases etc. Treatment 173
Topic 17
PERIPHERAL NERVOUS SYSTEM DISEASES (№1).

CLASSIFICATION. INFECTIOUS IMMUNE-
MEDIATED POLYNEUROPATHY (GUILLAIN-BARRE SYNDROME).
POLYNEUROPATHIES IN CASE OF ALCOHOLISM, DIABETES
MELLITUS, BOTULISM, CONNECTIVE TISSUE DISEASES ETC.
TREATMENT
Topic questions:
I. Features of terminology.
II. Classification of the peripheral nervous system diseases.
III. Polyneuropathy (PNP): definition, classification, etiology.
IV. Primary PNP. Guillain-Barre syndrome.
V. Secondary PNP:
1. Alcoholic PNP.
2. Diphtheritic PNP.
3. PNP in botulism.
4. Diabetic PNP.
5. PNP in case of connective tissue diseases and vasculitis.
6. Dysmetabolic PNP.
I. Features of terminology
Depending on the localization of lesions, among the disorders of the
peripheral nervous system there are following:
neuropathy (neuritis) — lesion of one nerve,
neuralgia — nerve damage, the main manifestation of which is pain,
polyneuropathy (polyneuritis) — damage of the distal parts of nerves of
limbs,
radiculopathy (radiculitis) — lesion of spinal roots,
plexopathy (plexitis) — lesion of the nerve plexus,
ganglionopathy (ganglionitis) — ganglia lesion.
The terms with end -it («neuritis», «radiculitis», «plexitis») literally means
inflammation (bacterial or viral) of the particular structure of peripheral
nervous system. However, inflammatory process is not the only basis of the
peripheral nervous system damage, but also ischemic, toxic and metabolic
nerve injuries. That is why the injury of the peripheral nerve fibers with motor,
sensor and autonomic disorders is called neuropathy.
II. Classification of the peripheral nervous system diseases (based

on the anatomical principle)
1. Vertebrogenic injury of the peripheral nervous system.
2. Injury of spinal roots (radiculopathy), ganglions (ganglionitis), plexuses
(plexopathy).
3. Multiple injury of peripheral nerve, roots (acute infectious immune-
mediated Guillian-Barre polyneuropathy, polyneuropathy due to diphtheria,
botulism; allergic, paraneoplastic, congenital, metabolic (diabetic or alcoholic)
polyneuropathies).
4. Injury of peripheral nerves (of traumatic, compressive, ischemic and
inflammatory origin).
5. Injury of cranial nerves (neuralgia, neuropathy).
III. Polyneuropathy (PNP)
Definition. Polyneuropathy (poly- + neuro- + -pathy) is damage or disease
of peripheral nerves with peripheral paresis, sensory, vasomotor or autonomic
and trophic disorders. It usually begins in hands and feet (distal parts of limbs)
and may involve arms and legs.
Classification. Polyneuropathies may be classified according to some
features. There are following types:
1) axonal and demyelinating PNP that depends on primary lesion of the
various structures of peripheral nerve;
2) motor, sensory, autonomic and mixed PNP that depends on primary
lesion of the functional nerve portion (lesion of motor or sensitive, or autonomic
portions of the peripheral nerve);
3) primary (primary lesion of peripheral nerves), secondary (peripheral
nerve is injured due to the influence of known disease or intoxication).
Etiology. The causes of secondary polyneuropathies:
- alcohol, arsenic compounds, lead, mercury, thallium intoxication etc;
- iatrogenic factors arising from the treatment with bismuth, salts of gold,
sulfonamides, isoniazid, antibiotics, chemotherapy and others;
- viral and bacterial infections;
- connective tissue disease, vasculitis, cryoglobulinemia and others;
- after the introduction of serums and vaccines;
- vitamin deficiency;
- paraneoplastic processes: small cell lung cancer; stomach, breast, ovari-
an, esophageal, kidney cancer; lymphoma; Hodgkin’s lymphoma (lymphogran-
ulomatosis); myelogenous leukemia. The development of the syndrome is as-
sociated with immunological processes that are provoked by the presence of
cross-reacting antigen in tumor cells and in the nervous system;
- in case of the diseases of internal organs (liver, kidney, pancreas),

endocrine glands (diabetes mellitus, hyper-
and hypothyroidism, hypercorticoidism), the genetic defects of enzymes
(porphyria).
IV. Primary PNP. Guillain-Barre syndrome (Landry’s ascending
paralysis) — acute inflammatory demyelinating polyradiculoneuropathy with
flaccid paresis, sensory and autonomic disorders.
Etiology of Guillain-Barre syndrome is unknown. However, two thirds of
people with Guillain-Barre syndrome have experienced an infection (respira-
tory, gastrointestinal or HIV), vaccinations, surgery, malignancies, including
Hodgkin’s disease before the onset of the condition. Approximately 30% of
cases are provoked by Campylobacter jejuni that usually results in enteritis.
Further 10% cases are attributable to cytomegalovirus (CMV, HHV-5).
Immunopathogenesis. This syndrome causes the destruction, removal, or
loss of the myelin sheath of a nerve. Guillain-Barre syndrome is considered as
acquired immune neuropathy that develops because of pathological immune
response to vaccination, viral infection, etc. Autoimmune reaction against my-
elin antigens of peripheral nerves leads to edema, infiltration and lymphocytic
segmental demyelination of spinal and cranial nerves. Autoimmune reaction
against axons of peripheral nerves leads to axonal variant of syndrome (less
often).
Clinical picture. The classic clinical picture of GBS is muscle weakness.
The lower limbs are usually involved before the upper limbs. Lower extremities
weakness usually ascends symmetrically and progressively over the first
several days. Trunk, facial, and oropharyngeal weakness is observed to a
variable extent. Weakness develops acutely and progresses over days
to weeks. Severity may range from mild weakness to complete tetraplegia.
Respiratory muscle weakness with shortness of breath may be present.
Reflexes are absent or reduced early in the disease course. Hypotonia can
be observed with significant weakness.
Most patients complain of paresthesias, numbness. Sensory symptoms
often precede the weakness. Paresthesias generally begin in the toes and
fingertips, progressing upward but generally not extending beyond the wrists
or ankles. Despite frequent complaints of paresthesias, objective sensory
changes are minimal.
Cranial nerve involvement (III-VII and IX-XII) can be observed: facial
drop, diplopia, dysarthria, dysphagia, oropharyngeal weakness. The Miller-
Fisher type of GBS is unique as it limits with oculomotor nerves deficits and
hyporeflexia.
Pain in patients with GBS can result from the direct nerve injury or from the
paralysis and prolonged immobilization. Pain is the most severe in the shoul-
der girdle, back, buttocks, and thighs and may occur with even the slightest
movements. The pain is often described as aching or throbbing in nature.
Autonomic nervous system involvement with dysfunction in the sympathetic
and parasympathetic systems can be observed: paroxysmal hypertension,
orthostatic hypotension, tachycardia and bradycardia. Urinary retention and
constipation are not typical.
Course. The duration of the augmentation of symptoms is 2-4 weeks. A
plateau phase of persistent, unchanging symptoms lasts up to 2-4 weeks
followed by gradual symptom improvement (3-12 month).
Diagnosis. GBS is generally diagnosed on clinical grounds, electromyo
graphy and nerve conduction studies (signs of demyelination) and albumi
nocytologic dissociation in cerebrospinal fluid (which is an elevation in CSF
protein without an elevation in white blood cells).
Treatment. Approximately one third of patients with GBS require admission
to an intensive care unit (ICU), primarily because of respiratory failure (oxygen
or intubation can be required). After medical stabilization, patients can be
treated on a general medical/neurologic floor department.
1. Immunomodulatory therapy, such as plasmapheresis (plasma exchange)
or the administration of iv immunoglobulins (IVIGs — Octagam 0,4 mg/kg/d,
5 days) is frequently used. The efficacy of plasmapheresis and IVIGs appears
to be about equal in shortening the average duration of disease.
Plasma exchange carried out over a 10-day period may aid in removing
autoantibodies, immune complexes and cytotoxic constituents from serum
and has been shown to decrease recovery time.
Corticosteroids (oral and intravenous) have not been found to have a
clinical benefit in GBS.
2. Anticonvulsants may be beneficial for patient with pain (gabapentin,
pregabalin). Nonpharmacologic pain relief therapies include frequent passive
limb movements, gentle massage, and frequent position changes.
3. In the recovery period: vitamins, anticholinergic drugs, massage,
exercise therapy, electrical stimulation of muscles, acupuncture.
V. Secondary PNP
1. Alcoholic PNP
Etiology. The disease occurs in patients with chronic alcoholism, which
affects the liver and stomach.
Pathogenesis. Nutritional deficiency, the direct toxic effect of alcohol or
both have been implicated. Vitamin deficiencies (especially thiamine) leads
to carbohydrate metabolism disorder, resulting accumulation of lactic and

pyruvic acids in tissues that causes the destruction of myelin and axonal
degeneration.
Clinical manifestations of alcoholic neuropathy can be summarized as
slowly progressive (over months) abnormalities in sensory, motor, autonomic
functions and gait disorder.
Sensory symptoms include early numbness of the soles, followed by
dysesthesia of feet and legs, especially at night. «Pins and needles» sensation,
which is reported commonly, progresses to severe pain that is described as
burning or lancinating. Symptoms typically start distally and progress slowly
to proximal involvement. When symptoms extend above the ankle level, the
fingertips often get similarly affected, giving rise to the well-known stocking
and glove pattern. Paresthesia might become unpleasant, even painful.
Motor manifestations include flaccid distal feet paresis with muscle
weakness, hypotonia and hypotrophy; deep tendon reflexes usually are
decreased or absent. There are sings of peroneal nerve pathology (paresis of
foot and fingers extensors) with foot drop and changed gait — steppage (gait
is characterized by high lifting of leg to put fingers first, and then the whole
foot).
When proprioception is involved, sensory ataxia will occur giving rise to gait
difficulty, independent of alcoholic cerebellar degeneration. Ataxia combined
with loss of knee and Achilles reflexes resemble the tabes dorsalis (found in
neurosyphilis), called pseudotabes peripherica.
There are vasomotor and trophic disorders: excessive sweating, swelling
of distal limbs, stasis dermatitis, thinness of skin, and changes in skin
temperature. Occurrence of trophic ulcers is rare.
Charcot arthropathy, also known as neuroarthropathy, is most commonly
associated with diabetes mellitus, despite a variety of other etiologies (Fig. 1).
It has also been associated with chronic alcoholism in no diabetic individuals.
The diagnosis is based on accurate history of prolonged and excessive
alcohol intake, clinical signs and symptoms, and electrophysiological testing.
Minimum of 100 ml of ethyl alcohol (3 L of beer or 300 ml of spirits) per day for
3 years will precipitate the neuropathy.
Treatment is directed toward stopping further damage to the peripheral
nerves and returning to normal functioning. These can be achieved by alcohol
abstinence, medications (vitamin B complex, preparations of α-lipoic acid,
ascorbic and nicotinic acid, anticholinergic drugs), physiotherapy treatment
(magnetic, ultraviolet radiation, reflexology), a nutritionally balanced diet
supplemented by all vitamins.
2. Diphtheritic PNP
Etiology. Diphtheritic neuropathy is an acute demyelinating polyneuropathy,
which has long been recognized as the most common severe complication
of Corynebacterium diphtheriae infection.
Pathogenesis. Diphtheria intoxication leads to inhibition of the synthesis
of core protein and lipoprotein myelin that is to demyelination. The process
applies to nodes and spinal roots.
Clinical manifestations. Diphtheritic neuropathy classically follows primary
diphtheria infection, which usually involves tonsils, pharynx and larynx with
a characteristic membranous exudates or skin. The latency in development
of diphtheritic polyneuropathy varies from 18 to 46 (mean 30) days after the
initial infection and is manifested syndrome by bulbar syndrome.
Neurologic manifestations of diphtheria are biphasic, characteristically
producing early cranial nerves disturbance and late motor weakness in the
truck and extremities. The disturbance of cranial nerves III, IV, VI, VII, IX, X,
XI, XII, and V were most frequently observed during weeks 3 through 5 of
initial diphtheria: numbness in gingivae, tongue, and face, nasal speech, nasal
regurgitation, dysphonia, dysphagia, palate paralysis, laryngeal paralysis.
Physical examination reveals accommodation, convergence or papillary light
reflex disturbance in case of injury of oculomotor nerve parasympathetic
fibres, diplopia, ptosis, and weakness of sternocleidomastoid muscles and
tongue.
Generalized peripheral neuropathy usually appears in 5 to 8 weeks.
Weakness in limbs is followed by atrophy in severe cases. Hypotonia and
gait abnormality are also found. Tendon reflexes are depressed or absent.
Paralysis of the diaphragm and respiratory muscles were observed,
requiring mechanical ventilation from 17 to 62 days. Patients have sensory
disturbances in all modalities with numbness, paresthesia of distal extremities
and sensory ataxia.
Autonomic disturbances are sinus tachycardia, arterial hypotension,
urinary retention, hyperkeratosis and xerodermia, or hyperhidrosis of face,
neck, and chest.
Treatment: antidiphtheritic serum 5000-10000 ME iv, prednisolone 1-2 mg/
kg/day (80-100 mg/day), antihistamines drugs, vitamin C. In the acute phase
plasmapheresis (plasma exchange) can be used. Patients with bulbar
syndrome requires immediate hospitalization in the intensive care unit.
3. PNP in botulism
Etiology. Botulism is an uncommon, life-threatening poisoning caused by
toxins produced by the bacteria Clostridium botulinum.
Causes:
- food-borne botulism occurs when food contaminated with the toxins is eat-
en. The most common sources of food-borne botulism are home-canned foods,
particularly foods with a low acid content, absent oxygen (as in sealed jars).
- wound botulism occurs when Clostridium botulinum contaminates a wound.
- infant botulism develops in infants who eat food containing spores of the
bacteria rather than toxins.
Pathogenesis. Botulism toxins paralyze muscles by preventing nerves
from releasing a neurotransmitter acetylcholine in synapse.
Clinical picture. Symptoms of botulism develop suddenly, usually 18 to
36 hours after toxins enter the body, although symptoms can start as soon as
4 hours or as late as 8 days after ingesting the toxins.
In food-borne botulism the first symptoms are often nausea, vomiting,
stomach cramps and diarrhea. People who have wound botulism do not have
any digestive symptoms. The first neurological symptoms result from loss of
strength in the muscles of the face and head: oculomotor disorder (double
vision, drooping eyelids, difficulty focusing on nearby objects, the pupils of
the eyes do not constrict normally when exposed to light), bulbar syndrome
(dysarthria, dysphagia). Because swallowing is difficult, food or saliva may be
inhaled (aspirated) into the lungs, causing choking or gagging and increasing
the risk of pneumonia.
Nerve damage by the toxins affects muscle strength but not sensation.
Typically, after strength is lost in the muscles of the face and head, strength
is then gradually lost in the muscles of the neck, arms and legs and the
breathing muscles.
Diagnosis: symptoms, anamnesis, electromyography, tests to detect
toxins in food, blood or stool (when possible).
Treatment. Polyvalent antitoxic serum types A, B, C and E is appointed
from the early days when the pathogen is unknown, after determination of the
pathogen type monovalent serum is appointed. Native antitoxin — 0,5 ml of
each type (2 ml) during the first infusion, 1 ml of each type (4 ml) during the
second and third infusion, which is prescribed in 5-7 days. Non-specific drugs:
gastric lavage, 5% glucose i/v, vitamins, ascorbic acid.
If bulbar disorders (breathing problems) begin, people are transferred to
an intensive care unit and may be temporarily placed on a ventilator.
4. Diabetic PNP
Etiology. Diabetic neuropathy is the most common complication of diabetes
mellitus, affecting as many as 50% of patients with type 1 and type 2 of diabetes
mellitus. Sometimes PNP symptoms precede manifestations of diabetes.
Pathogenesis: metabolic, vascular, dysimmune and genetic factors in

patients with diabetes mellitus.
Classification.
1. Progressive forms of diabetic PPN:
a) distal sensorimotor polyneuropathy,
b) autonomic polyneuropathy.
2. Reversible forms of diabetic PPN:
a) transient hyperglycemic polyneuropathy,
b) acute sensory polyneuropathy,
c) proximal motor neuropathy,
d) radiculoplexopathy,
e) multiple mononeuropathy,
f) cranial neuropathy.
Clinical picture. The most common form of PNP — distal sensorimotor PNP.
Sensory symptoms usually is insidious in onset and shows a stocking-
and-glove distribution in the distal extremities.
Damage of thin fibers in distal sensorimotor PNP: tingling sensation,
heartburn, pain in the legs (worsening at night), numbness and loss of
sensation, cold in the extremities; swelling of feet, change of skin — dryness,
cracks, redness of the plantar surface of the foot, the formation of blisters,
sores on the feet.
Damage of large fibers in distal sensorimotor PNP: violation of feeling of
movement in the fingers or feet, loss of balance, paresis of small foot muscles,
pathological changes in the small joints of the foot and ankle joint, resulting in
the dropping of the arch and the formation of «flat» or «hollow» foot (Fig. 1).
Diabetic neuropathy gives rise to an imbalance in the intrinsic and extrinsic
muscles of the foot with the result that most patients with diabetes will develop
fixed claw- or hammer-toe deformities (Fig. 2). Typically there is plantar flexion
deformity of the proximal metaphalangeal joint (hammer toe). Such patients
has a risk for development of recurrent dorsal or plantar ulcerations.
Fig. 1. «Hollow» foot in diabetes mellitus Fig. 2. Hammer toe
Multiple mononeuropathy — lesions of single peripheral nerves (femoral,

sciatic, ulnar, median nerve), accompanied by paresis of muscles, pain,
sensory disorders (see theme 33).
Cranial neuropathy — lesions of oculomotor, abducens, trigeminal nerves.
Treatment: correction of glycemia, dyslipidemia, vitamin B complex,
preparations of α-lipoici acidi; in pain syndrome — gabapentin, pregabalin,
physiotherapy.
5. PNP in connective tissue diseases and vasculitis
Systemic lupus erythematosus is characterized by lesion of skin, joints,
kidneys and polyneuropathy. There are proximal muscles paresis or paralysis,
areflexia, hypoesthesia. Sometimes PNP symptoms precede manifestations
of connective tissue diseases.
Vasculitis. Neuropathy often occurs in polyarteritis nodosa, Wegener’s gra
nulomatosis, microscopic polyarteritis. In other systemic vasculitis neuropathy
is less common. They are Henoch-Schonlein purpura, Takayasu’s arteritis, Hor-
ton arteritis (temporal or giant cell arteritis), and Kawasaki disease. Causes of
peripheral nerve lesions: deposition of immune complexes in the vessel wall,
inflammatory reactions with occlusion of blood vessels — vasa nervorum.
Clinical picture of vasculitis neuropathy: multiple mononeuropathy (dam-
age of two or more nerves in various parts of the body) or polyneuropathy.
Treatment. Treatment of the main disease.
6. Dysmetabolic PNP
Dysmetabolic neuropathy can occur in somatic diseases: disease of liver,
kidneys, digestive tract, etc (see topic 22).
TESTS
1. In a 41-year-old male patient, a week after acute tonsillitis, weakness in the

legs was revealed, two days after — weakness in the arms and intercostal
muscles, a day after — swallowing difficulties. Neurological status: frequent
and superficial respiration; pharyngeal reflex is absent, the hyolaryngeal ex-
cursion decrease, flaccid tetraparesis, reduced of all kinds of sensitivity like
stocking & glove distribution. What is the most likely diagnosis?
1) multiple sclerosis
2) asthenic syndrome
3) acute inflammatory demyelinating polyradiculoneuropathy
4) cervical myelopathy
5) diphtheritic neuropathy
2. The main clinical signs of polyneuropathy:

1) symmetric and diffuse lesions of the peripheral nervous system
2) multiple lesions of peripheral nerves
3) headache and fatigue
4) diffuse lesions of the peripheral nervous system
5) damage of cranial nerves
3. A 56-year-old patient M. suffers from diabetes mellitus; medications are not
taken regularly. Gradually during 3 years, he complained of numbness, pain,
weakness of distal extremities (especially of feet). Examinations: muscle
hypotrophy and hypotonia of distal lower extremities, lack of carpi radial and
Achilles reflexes, decreased muscle strength in the feet, reduced all kinds of
sensitivity as a «high-gloves» and «stocking» type. What is the most likely
diagnosis?
1) toxic polyneuropathy
2) toxic radiculopathy
3) diabetic neuropathy
4) diabetic myelopathy
5) inflammatory polyneuropathy
4. A 54-year-old male patient with chronic alcoholism complains of pain in
feet and calves, burning feelings in feet and hands, gait imbalance, especially
in the darkness. Neurological status: lack of tendon reflexes, hypoesthesia
«socks» and «gloves» type, deep sensitivity disorders, sensitive ataxia. What
is the course of ataxia?
1) cerebellum degeneration
2) poliomyelitis
3) damage of proprioceptive fibers
4) multiple sclerosis
5) damage of spinal cord posterior columns
5. «Hollow» foot is typical for patients with
1) diabetes mellitus and alcoholism
2) vasculitis and alcoholism
3) diabetes mellitus and botulism
4) diphtheria
5) alcoholism
Peripheral nervous system diseases (№2). Plexopathies. Neuropathies of upper and lower extremities 183
Topic 18
PERIPHERAL NERVOUS SYSTEM DISEASES (№2). PLEXOPATHIES.

NEUROPATHIES OF UPPER AND LOWER EXTREMITIES
Topic questions:
I. Cranial neuropathy:
1) facial neuropathy
2) trigeminal neuralgia
II. Herpetic ganglionitis and postherpetic neuralgia.
III. Plexopathy:
1) brachial plexopathy:
- upper brachial plexopathy (Erb–Duchenne palsy)
- lower brachial plexopathy (Dejerine–Klumpke palsy)
2) lumbo-sacral plexopathy
IV. Mononeuropathies of the upper extremities:
1) radial nerve lesion
2) ulnar nerve lesion
3) median nerve lesion
V. Mononeuropathies of the lower extremities:
1) femoral nerve lesion
2) peroneal nerve lesion
3) tibial nerve lesion
VI. Tunnel syndromes
1) carpal tunnel syndrome
2) cubital canal syndrome
3) tarsal tunnel syndrome
4) entrapment of the lateral femoral cutaneous nerve
VII. General principles of treatment of the peripheral nervous system
pathology.
I. Cranial neuropathy
1) Facial neuropathy
The most often primary facial nerve neuropathy is its idiopathic form Bell’s
palsy. It has two main factors of development: 1) the narrow bone canal in
the pyramid of the temporal bone through which the facial nerve passes
and 2) endogenous or exogenous factors that together provoke facial nerve
compression (tunnel syndrome).
Etiology (endogenous or exogenous factors):

- local hypothermia (blowing by cold air, air conditioner)
- in case of decreased immunity — activation of viruses which persist in
facial nerve ganglion — HSV-1, mumps virus,
- infection (tick-borne encephalitis, Lyme’s disease, poliomyelitis),
- Melkersson-Rosenthal syndrome (a rare hereditary disease with recur-
rent orofacial swellings, relapsing facial paralysis
and fissured tongue (Fig. 1).
- inflammation of the ear,
- face and skull traumatic injuries.
Additional causes of neuropathy: stroke, diabetes,
arterial hypertension, damage of stylomastoid artery,
supplying facial nerve, demyelination in multiple scle-
rosis, pontocerebellar angle tumor, leukemic infiltration
of the brain membranes and surgery on parotid gland.
Pathogenesis. In case of primary neuropathy
(Bell’s palsy) as a result of above-mentioned factors
there may be edema with nerve compression and Fig. 1. Fissured tongue
its ischemia, aseptic inflammation, that lead to the
development of compression-ischemic lesion with facial nerve dysfunction.
Clinical picture. Typically neuropathy of the facial nerve is unilateral,
bilateral Bell’s palsy occurs only in 2 % of cases. Sometimes the relapsing of
the facial neuropathy may occur.
Facial neuropathy symptoms depend on the level of injury:
In most cases, lesions of the facial nerve occurs in place of its exit from the
temporal bone at stylomastoid foramen.
Symptoms:
1) prosoparesis (Fig. 2) — mimic
muscles paresis of (usually) one half of
the face with facial asymmetry at rest
that increases with mimic movements:
- disappearance of the nasolabial fol
der, patient can’t arise the corner of mouth
for smile, whistle or blow out cheek;
- difficulty in chewing a food on the
affected side; food may get trapped
between gum and cheek. Drinks and
saliva may escape from the side of
mouth; Fig. 2. Prosoparesis
- patient can’t close an eye (lagoftalm), arise eyebrow, wrinkle forehead;

- Bell’s phenomenon is a sign that allows observers to notice an upward
and outward movement of the eye, when an attempt is made to close the eyes;
- eyewatering (due to weakness of m. orbicularis oсuli (paretic lower
eyelid) tear misses the nasolacrimal duct and flow out from eye).
2) short (up to 2 days) slight pain behind the ear before prosoparesis
appearance occurs due to the presence of close links between the fibers of
the facial nerve and sensory branches of the trigeminal nerve in the area of
mastoid processus.
Impairment of facial nerve in the pyramid canal of temporal bone:
- above chorda tympani: prosoparesis + absence of taste feeling on 2/3
front of tongue — ageusia,
- above n. stapedius: prosoparesis + ageusia + hyperakusis (unpleasant
auditory feeling),
- above n. petrosus superficialis major: prosoparesis + ageusia +
hyperakusis + dryness of eye (xerophthalmia).
Hunt’s syndrome — herpetic impairment of geniculate ganglion:
prosoparesis + ageusia + disorders of hearing and balance because the
damage of n. vestibulo-cohlearis + strong pain in ear with irradiation to face,
neck + herpetic eruption in the external auditory canal.
Impairment of facial nerve root in pontocerebellar angle (in case of acoustic
neuroma) (Fig. 3):
- prosoparesis + ageusia +
dryness of eye,
- hearing loss, balance disor-
der due to the damage of n. ves-
tibulocohlear),
- double-vision, strabismus con-
vergent (damage of n. abducens),
- ipsilateral facial hemihypes-
thesia and masticatory muscles
paresis (damage of n. trigeminal),
- cerebellum ataxia.
Impairment of facial nerve Fig. 3. Compression the facial nerve by
nucleus in pons Varolii in case of acoustic neuroma
stroke:
- simultaneous impairments of facial nerve nucleus and pyramidal ways
is called alternating Millard-Gubler’s syndrome (Fig. 4) lead to ipsilateral
peripheral facial neuropathy and contralateral central hemiparesis,
- simultaneous impairments of facial nerve nucleus, abducens nerve

nucleus and pyramidal ways is called alternating Foville’s syndrome (Fig. 5)
(ipsilateral peripheral facial neuropathy, ipsilateral strabismus convergence
with diplopia, and contralateral central hemiparesis).
Fig. 4. Millard–Gubler’s syndrome Fig. 5. Foville’s syndrome
Facial neuropathy diagnosis:

- clinical symptoms,
- electroneuromyography (EMG),
- CT scan or MRI to detect focal lesions of the brain, which could cause
lesions of the facial nerve.
Treatment of facial neuropathy:
1. Do not apply heat at place of facial nerve exiting through the stylomastoid
foramen.
2. Corticosteroids — at the first 72 hours of illness — to reduce the

inflammatory edema and nerve compression in the bone canal: dexamethasone
topically (mastoid process region) or i/v (5 days).
3. Diuretics — to reduce the inflammatory nerve edema (3-5 days).
4. Preparations for the improvement of microcirculation — pentoxifylline,
nicotinic acid.
5. Vitamin B group.
6. Аcetylcholinesterase inhibitors are used just after 7-10 days from the
onset of the disease to improve the conduction of excitation along the nerve.
Early application may trigger the development of facial muscles contractures.
7. From the first days of the disease — a gentle massage, facial muscles
exercises, acupuncture.
8. In case of viral Hunt’s syndrome — antiviral drugs (Aciclovir).
9. Eye care to protect the affected eye from damage caused by an eye
unable to close — artificial tears, wet tape at night.
Prognosis. Full recovery occurs in 75% of cases of facial neuropathy.
With long-term course of the disease (over 3 months), the probability of full
recovery is greatly reduced. Approximately 3 from 10 people with Bell’s palsy
will continue to experience weakness in their facial muscles, and 2 from 10
will be left with a more serious long-term problems — complications:
- a contracture — permanently tense of facial muscles with facial disfigure-
ments, which is often caused by early application of anticholinergics drugs;
- loss or reduced sense of taste, speech problems (as a result of facial
muscles damage), eye drying and corneal ulceration, tears when eating,
known as ‘crocodile tears’;
- eye-mouth synkinesis (it can cause patient eye to wink when eating,
laughing or smiling).
2) Trigeminal neuralgia is defined as a syndrome characterized by
sudden, short-time, intense, recurring pain in the area of innervation of one
or more branches of the trigeminal nerve, usually on one side of the face.
Etiology. The most common cause of trigeminal neuralgia is its compression
for additional influence of extra- and intracranial factors.
Extracranial factors:
- tunnel syndrome (trigeminal nerve root compression in bone canal due to
its congenital or acquired (dental caries, sinusitis) narrowness).
Intracranial factors:
- superior cerebellar artery loop in the pontocerebellar angle (Fig. 6),
- aneurysm of basilar artery,
- tumors in the pontocerebellar angle,
Fig. 6. Trigeminal nerve compression: 1 — superior

cerebellar artery loop in the pontocerebellar angle
- tumors in the posterior cranial fossa,
- local rhinogenic or odontogenic inflammatory processes.
Infection processes, vascular, endocrine-metabolic and allergic disorders, demy-
elination of the trigeminal nerve root in multiple sclerosis may also cause neuralgia.
Pathogenesis. It is considered that trigeminal neuralgia is caused by
the appearance of paroxysmal discharges that resemble the mechanisms
of epilepsy. Paroxysmal pain is generally thought to be due to aberrant
transmission of nerve impulses from somatosensory to nociceptive fibers
within the trigeminal nerve in a site of local damage to myelin sheaths. The
myelin lesion is attributed to above mentioned factors or due to aging.
Clinic of typical attack:
- recurrent paroxysms of sharp, lancinating or stabbing pain (electric
shock type pain) that may last a few seconds or minutes;
- pain distribution: maxillar (II) or mandibular (III) branches of the trigeminal
nerve are the most commonly affected;
- each attack is unilateral (may alternate sides in up to 3-5% of cases);
- attacks may occur as often as multiple times daily or as infrequently
as monthly, attacks become more frequent and severe over time, attacks are
very rare during sleep;
- some patients are sensitive in certain areas of the face, called trigger
zones, light touch or other minimal stimulation in these zones triggers an attack.
These zones are usually near the nose, lips, eyes, ear, or inside the mouth;
- everyday activities can trigger an episode. Triggers of pain: talking,
eating, kissing, drinking, shaving, teeth brushing, face washing, cold exposure;
- appearance of facial muscles twitching at the height of the paroxysm —

pain teak;
- trismus — spasm of the masticatory muscles and reduced opening of
the jaws caused by trigeminal motor fibres irritation;
In periods between attacks, complaints and neurological symptoms are absent.
At examination, there is pain at the exit point of the affected branch, but no
violations of sensitivity in the area of innervation.
Treatment.
Medications:
1. Antiepileptic drugs: carbamazepine (Tegretol) 600-1600 mg, gabapen-
tin 300-2400 mg, pregabalin (Lyrica) 75-600 mg in 2-3 times daily.
2. Tricyclic antidepressant amitriptyline 25 mg 3 times daily.
In case of ineffective medication treatment during 6 months, surgery is to
be used:
- microvascular decompres-
sion (Fig. 7) — reroute the blood
vessel from compressing the
trigeminal nerve by padding the
vessel with a sponge,
- stereotactic surgery: gam-
ma knife, cyber knife (nerve de-
stroying by ionizing radiation),
nerve electrocautery.
II. Herpetic ganglionitis and
postherpetic neuralgia
Shingles (also termed herpes Fig. 7. Microsurgical trigeminal nerve
zoster) is a disease caused decompression (vessel compressed nerve
by reactivation of a previous isolation by inert material)
infection with the herpes zoster
virus (also named varicella-zoster virus, VZV, HHV-3 or chickenpox virus).
VZV may remain to persist in the body after an individual had chickenpox,
usually in the roots of nerves that control sensation (very often — in trigeminal
Gasser’s ganglion). The virus «wakes up» or reactivates in people who have
a decreased ability to fight off infection due to stress or immune deficiency.
Clinical picture of herpetic ganglionitis. Stages of the disease:
- general infectious syndrome onset with headache and fever. Duration is
2-3 days;
- intense pain like itching, tingling, burning, shooting in the area of innerva-
tion of the trigeminal nerve branch (mostly it’s the Ist). Duration is 2-3 days;
- a rash with
blisters (fluid-filled
sacs) on top of red-
dish skin in the same
distribution as the
pain appears. There
is the threat of her-
petic eruptions on the
cornea). Duration is
1-2 weeks (Fig. 8),
- the rash disap-
pears as the scabs fall Fig. 8. Herpetic eruptions
off in the next two to
three weeks, and scarring may result
Neurological examination: hyperesthesia or hypoesthesia relevant parts
of the face, hyperpathia, pain at the exit point of the affected branch of the
trigeminal nerve.
Herpetic ganglionitis lasts 3-6 weeks and in most cases ends by recovery.
Some patients has postherpetic neuralgia in which the localized pain
of shingles remains even after the rash has gone. Postherpetic neuralgia
develops in 16-25 % of cases, often in people over 50 years of age, and can
last for a long period of time (years).
Postherpetic neuralgia is similar to the classic neuralgia but has some
differences:
- pain occurs spontaneously, lasts for hours,
occasionally enhanced, especially at night;
- no trigger zones and factors;
- pain is localized mainly in the area of inner
vation of the Ist branch of the trigeminal nerve.
Besides injury of the trigeminal nerve
herpetic lesion of spinal sensitive ganglions
can be observed. Signs and treatment does not
differ from that described above, vesicular rash
on the extremities have the form of longitudinal
stripes, on the body — a broad band on one
side of the body (Fig. 9).
In cases of recurrent herpetic ganglionitis
(more than 1 time in 3 months) HIV and Fig. 9. Herpetic lesion of Th1-4
oncology should be excluded. spinal sensitive ganglions
Herpetic ganglionitis treatment

1. Antiviral medications (acyclovir (Zovirax), 5-10 mg/kg iv or 800 mg orally
5 times daily for 5-7 days, valacyclovir (Valtrex) 1000 mg 3 times daily for 7 days).
2. Human Immunoglobulin (Octagam — 0.4g/kg iv), desensitizing agents.
3. Acyclovir ointment on the affected skin.
4. Topical creams (Lidocaine cream) can relieve the itching. Do not scratch
the skin where the rash is located. This may increase the risk of secondary
bacterial infection and scarring.
5. Vitamin B group.
Postherpetic neuralgia treatment.
1. Antiepileptic drugs: gabapeptin 300-2400 mg daily in divided doses
(3 times), pregabalin (Lyrica) 75-300 mg, daily in divided doses (2 times).
2. Tricyclic antidepressant amitriptyline 25 mg 3 times daily.
3. Laser therapy.
4. In case of ineffective conservative treatment, hormone or radiotherapy
is to be applied.
III. Plexopathy
1) Brachial plexopathy (see Fig. 10).
Etiology: an abnormal or difficult childbirth or labour, collarbone fracture, dislo-
cated shoulder, wounds, plexus compression between the clavicle and the Ist rib
or shoulder head in case of fixed arms during prolonged anesthesia, compres-
sion by cervical ribs, callus after clavicle fracture, scalene muscle contracture.
Fig. 10. Formation of the brachial plexus
Clinical picture.
Upper brachial plexopathy (Erb–Duchenne palsy) (damage to the upper
primary trunk of the brachial plexus formed of the C5-C6 roots, Fig. 9) —
dysfunction of the proximal limb muscles (biceps, triceps, brachioradialis
muscles) causes their flaccid paresis.
Patients unable to lift the arm; all power of flexion of the elbow is lost, as
is also supination of the forearm. There are biceps reflex lack, hypoesthesia
in the area of dermatomes C5-C6 (neck, shoulder girdle, shoulder area, the
deltoid muscle, radial side of the forearm and hand), neck pain and pain in
external surface of proximal arm.
Lower brachial plexopathy (De-
jerine–Klumpke palsy) (damage to
the lower primary trunk of the brachi-
al plexus formed of the C8-Th1 roots,
Fig. 11) — dysfunction of the distal
limb muscles that is flaccid paresis of
hand muscles, except those, which
are innervated by the radial nerve.
There are hypoesthesia in the area
of dermatomes C8-Th1 mainly on the
ulnar side of the forearm and hand,
vasomotor disturbances in the area
of the corresponding dermatomes;
Bernard-Horner syndrome (ptosis, mi-
osis, enophthalmos) (Fig. 12) due to
lesion or compression of sympathetic
fibres.
2) Lumbo-sacral plexopathy (plex- Fig. 11. Segmental innervation of the
us is formed of the L5, S1-S2 roots). upper extremities
Etiology: infections, tumors of the
pelvis and abdomen.
Clinic: flaccid paralysis of the
foot, shin, thigh adductors, loss of
Achilles reflex, sensor and autonomic
disorders in the foot and shin.
IV. Mononeuropathies of the
upper extremities
1) Radial nerve neuropathy Fig. 12. Left side Bernard-Horner syndrome
Etiology: humerus fractures, (ptosis, miosis, enophthalmos)
compression of the nerve during the operation, in case of crutch using, while
sleeping on arm (Saturday Night Palsy), especially after drinking alcohol.
Clinical picture:
- wrist drop that is the inability to extend the wrist upward when the hand
is palm down (Fig. 13);
Fig. 13. Wrist drop in radial nerve neuropathy
- inability to voluntarily straighten the fingers or extend the thumb;

- loss of wrist extension due to paralysis of the posterior compartment of
forearm muscles;
- hypoesthesia of interval between I and II metacarpal bone of hand
dorsum.
2) Ulnar nerve neuropathy
Etiology: trauma.
Clinical picture:
- «claw hand» — hyperextension of the IVth and Vth fingers (the fingers
bend up) at the metacarpophalangeal (proximal) joints, and flexion (the
fingers bend down) at the interphalangeal joints (middle joints) (Fig. 14),
Fig. 14. «Claw hand» in ulnar nerve neuropathy
- atrophy of hand interossei muscles,

especially in Ist–IId fingers space and
hypothenar,
- weakness of forearm and hand elbow
flexion, IVth and Vth fingers flexion (Fig. 15),
- impossibility of adduction and
abduction of IId, IIId, IVth and Vth fingers,
- weakness of the Ist finger adduction,
- Froment’s sign in ulnar nerve
neuropathy — a patient is asked to hold Fig. 15. The restricted IV -V
th th
an object, usually a flat object such as a fingers flexion in ulnar nerve

piece of paper, between their thumb and neuropathy
index finger — in right hand, the patient will
experience difficulty maintaining a hold and
will compensate by flexing the flexor pollicis
longus (innervated by median nerve) of the
thumb to maintain grip pressure causing a
pinching effect (Fig. 16),
Right hand Left hand
- sensitivity disorders in dorsal and
palmar surfaces of the Vth and medial Fig. 16. Froment’s sign
aspect of IVth fingers, ulnar part of hand
palmar and dorsal surfaces (Fig. 17).
3) Median nerve neuropathy
Etiology: trauma.
Clinical picture:
- lack of ability to abduct and oppose
the thumb due to paralysis of the thenar
muscles with their atrophy, «ape-hand Fig. 17. Anesthesia of hand ulnar
deformity» forming (Fig. 18); surface in ulnar nerve neuropathy
- weakness in forearm pronation and
wrist, and in finger flexion;
- weakness of radial hand flexion and
I, II, III fingers flexion — impossibility of
bending of the I, II and III (partially) fingers,
«prophet hand» forming (Fig. 19);
- Froment’s sign in case of median
nerve neuropathy — a patient is asked to
hold an object, usually a flat object such as Fig. 18. «Ape-hand deformity»
a piece of paper, between their thumb and in median nerve neuropathy
Fig. 19. Hand of benediction Fig. 20. Anesthesia of lateral surface of

in median nerve neuropathy hand in median nerve neuropathy
index finger — in left hand patient can hold a piece of paper only by m.
adductor pollicis (innervated by ulnar nerve) (Fig. 16),
- sensory loss in the thumb, index finger, long finger, and the radial aspect
of the ring finger (Fig. 20);
- vasomotor and trophic disorders, causalgia — intensive pain in hand
due to the lesion of the autonomic sympathetic fibers.
V. Mononeuropathies of the lower extremities
1) Femoral nerve neuropathy
Etiology: hip fracture, inflammation of the pelvis, diabetes mellitus.
Clinical picture:
- knee extension is impossible;
- loss of knee reflex;
- sensitivity disorder that is hypo- or anesthesia on the inner surface of the
shin and front of the thigh.
2) Peroneal nerve neuropathy
Clinical picture:
- paresis of the extensor muscles of foot and fingers;
- foot drop (Fig. 21) and changed gait — steppage (gait is characterized
by high lifting of leg to put fingers first and then the whole foot) (Fig. 22);
- heeling is impossible;
- Achilles reflex is saved;
- sensitivity disorder that is hypo- or anaesthesia on the external surface
of shin and dorsal surface of foot.
3) Tibial nerve neuropathy
Clinical picture:
- paresis of foot and fingers flexors, impossibility of foot bending;
- unability to tiptoe;
- absence of Achilles reflex;
Fig. 21. Foot drop Fig. 22. Steppage Fig. 23. «Claw foot»

in peroneal nerve in peroneal nerve in tibial nerve
neuropathy neuropathy neuropathy
- atrophy of the small muscles of the foot — «сlaw foot» (Fig. 23);
- sensitivity disorders: anaesthesia on posterior surface of shin and sole;
- foot trophic disorders.
VI. Tunnel syndromes
Etiology: peripheral nerves compression in anatomical constrictions
(tunnels): rigid fibrous or muscular channels, aponeurotic holes. There are
more than 30 types of tunnel syndromes. The most common types of tunnel
syndromes are:
1) Carpal tunnel syndrome
Etiology: transverse ligament thickening
in endocrine diseases, heavy manual
work or exposure to vibration, in case of
bursitis and tendonitis as a result of repeated
manual motions provoke medial nerve
compression (Fig. 24).
Clinical picture:
- pain, numbness of I-III fingers, en-
hanced while raising arm;
- Tinel’s sign — lightly tapping (percus
sing) over the nerve to elicit a sensation of Fig. 24. Medial nerve
tingling or «pins and needles» in the distribu- compression area in carpal
tion of the median nerve, tunnel syndrome
- I-III fingers hypoesthesia.
2) Cubital canal syndrome — compression of the ulnar nerve at the elbow
level (there is a bump of bone on the inner portion of the (medial epicondyle)
under which the ulnar nerve passes).
Fig. 25. Pain and paresthesia area in the ulnar nerve irritation in cubital canal
Clinical picture:
- numbness, tingling, and pain on the
ulnar portion of the hand, V and IV fingers,
forearm; interossei muscles and hypothenar
hypotrophy (Fig. 25).
3) Tarsal tunnel syndrome (compression
of the tibial nerve in the tarsal tunnel. This
tunnel is found along the inner leg behind the
medial malleolus) (Fig. 26).
Clinical picture: Fig. 26. Tibial nerve
- numbness in the foot, radiating to compression area
the big toe and the first 3 toes, pathological area int tarsal
- pain, burning, electrical sensations and tunnel syndrome
tingling over the base of the foot and the
heel, especially at walking.
4) Entrapment of the lateral femoral
cutaneous nerve (Bernhardt — Roth
syndrome, meralgia paresthetica, derived
from the Greek word meros, meaning thigh,
and algo, meaning pain) — nerve entrapment
or compression where it passes between the
upper front hipbone (ilium) and the inguinal
ligament (Fig. 27):
Clinical picture:
- paresthesia or burning pain, numbness
in the lateral and anterolateral thigh, Fig. 27. Entrapment of the
- symptoms worsen during walking and lateral femoral cutaneous
standing. nerve under inguinal ligament
VII. General principles of

the peripheral nervous system
pathology treatment: vitamin
B group, drugs improving micro-
circulation, acetylcholinesterase
inhibitors, analgetics, massage,
exercises, local anesthetic block-
ade, physiotherapy.
Tunnel syndromes treatment: Fig. 28. Corticosteroid application
local corticosteroid application in in the carpal tunnel
place of compression — Dexa-
methasone, betamethasone
dipropionate (Fig. 28, 29, 30),
electrophoresis with novocaine,
surgery decompression.
TESTS
1. A 35-year-old patient has a

strong burning pain on the skin
of the chest after herpetic erup- Fig. 29. Corticosteroid application
tions that took place month ago. in the tarsal tunnel
Neurological status: pain while
pressing the paravertebral points
in the thoracic region, sensitivity
disorders in the form of annular
strips on the body surface. What
is the most likely diagnosis?
1) postherpetic neuralgia
2) herpetic ganglionitis
3) thoracalgia
4) spinal cord tumor
5) thoracic radiculopathy
2. A 23-year-old female patient Fig. 30. Corticosteroid application
was sitting in the train at the open in the cubital tunnel
window. In the morning patient
could not close the right eye; her right mouth angle dropped down, the food
was stuck between the right cheek and gum. Neurological status: asymmetry
of the face, right nasolabial fold is smoothed, the right eye is wider than the
left, eyewatering on the right side, the right eyebrow does not rise. Taste is
saved. What is the most likely diagnosis?
1) Bell’s palsy
2) pontocerebellar angle tumor
3) brainstem stroke
4) facial myositis
5) brainstem tumor
3. A 33-year-old male patient after falling on the left shoulder complained of pain
in the left subclavian area, weakness and movement limitation in the distal left
arm. Neurological status: atrophy of the left hand muscles, violations of sensi-
tivity on inner surface of hand and forearm. What is the most likely diagnosis?
1) traumatic brachial plexopathy C7-Th1
2) thoracic radiculopathy
3) defeat of the cervical spinal cord C7-Th1
4) traumatic brachial plexopathy C5-C6
5) hematomyelia
4. A 33-year-old male patient had fallen asleep after drinking, placing the left hand
under the body. In the morning he felt numbness in left hand, could not extend his
hand and fingers. Neurological status: left-sided wrist drop, paralysis of extensor
muscles of the wrist and fingers, reduced left carpo-radial reflex, hypoesthesia of
the dorsal aspect of the first intermetacarpal area. What is the most likely diagnosis?
1) compression-ischemic neuropathy of the left radial nerve
2) traumatic left-sided lower brachial plexopathy (Dejerine–Klumpke palsy)
3) traumatic left-sided brachial upper brachial plexopathy (Erb–
Duchenne palsy)
4) compression-ischemic neuropathy of the left ulnar nerve
5) compression-ischemic neuropathy of the left median nerve
5. A 24-year-old male patient has traumatic injury of the right clavicle and
shoulder joint. His complaints are a sharp pain in supraclavicular area and
right upper limb while examining it was found the decrease of muscle tone
and strength, reflexes loss, decrease of all kinds of sensitivity on the right
arm. What is the most likely diagnosis?
1) traumatic neuropathy of right median nerve
2) hematomyelia
3) right-sided traumatic brachial plexopathy
4) traumatic neuropathy of right radial nerve
5) traumatic neuropathy of right ulnar nerve
Topic 19
VERTEBROGENIC DISORDERS OF THE PERIPHERAL NERVOUS

SYSTEM
Topic questions:
I. Vertebrogenic disorders of the peripheral nervous system. Etiology,
pathogenesis.
II. Classification of vertebrogenic disorders of the peripherl nervous system
depending on the lesion level.
III. Nerve stretch tests.
IV. Cervical lesion level
1. Reflex syndromes
2. Radicular syndromes (radiculopathy C6, C7, C8).
V. Thoracic lesion level
1. Reflex syndromes
2. Radicular syndromes.
VI. Lumbosacral lesion level
1. Reflex syndromes
2. Radicular syndromes (radiculopathy L4, L5, S1).
VII. Spinal stenosis.
VIII. The diagnosis of radicular syndromes and disk herniation.
IX. Conservative treatment of vertebrogenic disorders of the peripheral
nervous system.
X. Neurosurgical treatment of vertebrogenic disorders of the peripheral
nervous system.
I. Vertebrogenic disorders. Etiology, pathogenesis

1. Injury of vertebral body (tumor, trauma).
2. Anomalies of the spine (vertebral arch cleft — spina bifida,
sacralisation — fusion of the fifth lumbar vertebra to the first sacral vertebra,
lumbalisation — separating the first sacral vertebra from the sacrum).
3. Bone inflammation (spondilitis, coxitis, saсroiliitis).
4. Degenerative changes in spine.
Each intervertebral disc consists of a fibrous ring (annulus fibrosus) and
soft cartilage in the center of the disk, which is surrounded by annulus —
nucleus pulposus.
In the pathology of intervertebral discs it must be stressed the impotance
Vertebrogenic disorders of the peripheral nervous system 201
of congenital abnormalities, age-related changes; endocrine, metabolic

disturbances. The effects of micro-traumas that occurs throughout life lead
to the gradual drying, structural changes, reducing of elasticity, osteoporosis,
and microfractures. In response to these changes the Degenerative Spine
Disease develops in the disk locking plates in adjacent vertebral bodies above
and below. Weakened fibers of the annulus fibrosus may rupture, allowing
disk material to escape in the annulus fibrosus, forming disk protrusion or
even beyond, forming disk herniation (Fig. 1). Reactive spondylosis and
spondylarthrosis can develop in this case (Fig. 2).
Fig.1. Disk protrusion and disk herniation
Fig. 2. Types of vertebrogenic disorder
Degenerative Spine Disease includes a lesion of the vertebral disc,

adjacent joint surfaces, vertebral bodies, vertebral ligaments.
According the morphological and clinical changes there are 4 periods of
osteochondrosis:
I — nucleus pulposus moves toward the back longitudinal ligament and
irritates its synuvertebral nerve endings;
II — instability-abnormal mobility of segment;
III — complete rupture of the fibrous ring that causes various neurological
disorders;
IV — spreading of the pathological process in other elements of the spine.
Spondylosis is a degeneration of the annulus fibrosus with forming of
osseous connections, which may lead to coossification between the adjacent
vertebrae.
Spondylarthrosis is a degeneration of intervertebral joints of the spine.
Depending on which structures the pathologically changed elements
of the spine influence, the reflex and compression syndromes are
distinguished.
For the initial stages of spine pathology, the development of reflex
syndromes is more typical. In the receptors of degenerative changed fibrous
ring, ligaments, capsules of intervertebral joints the pathological pulsation
arises. It enters through dorsal roots of the spinal cord into the posterior
(sensitive) horns, causing pain syndrome, and into the front (motor) horns,
causing reflex muscle tension (muscular tonic syndrome) and into the lateral
(autonomic) horns of the spinal cord, causing vasomotor or autonomic and
trophic syndrome.
The source of reflex syndromes is an irritation of fibres of the sinuvertebral
nerve, or recurrent nerve of Luschka (a branch of spinal nerve), which
innervates intervertebral discs, back longitudinal ligament, periosteum, joints,
vessels and dura mater. Only outer layers of the fibrous ring contain nerve
fibres and receptors, but in the case of disc degeneration, the nervous fibres
spread into the deeper layers until its central areas. Moreover, such increase
of innervation density intensifies pain.
The causes of vertebrogenic compression syndrome are the
compression of the root and its vessels, the arising of aseptic inflammation
and vascular abnormalities in the spinal nerve root (Fig. 3). Herniation into the
intervertebral (neural) foramen can compress the nerve root, causing pain,
motor, sensory, and reflex disturbances in a proper dermatome. If the hernia
of intervertebral disc bulges into the spinal canal, it may compress the dural
sac and its contents.
A B
Fig. 3. Compression of spinal nerve root (A) and spinal cord (B) by
intervertebral disc herniation
II. Classification of vertebrogenic disorders of the peripheral nervous
system depending on the level of lesion
1. Cervical level:
• reflex syndromes (cervicalgia, cervicocephalgia, cervicobrahialgia) with
muscular tonic, vasomotor and trophic disorders;
• compressive radicular syndromes (radiculopathy);
• compressive radicular and vascular syndromes (nerve root ischemia).
2. Thoracic level:
• reflex syndromes (thoracalgia);
• compressive radicular syndromes.
3. Lumbosacral level:
• reflex syndromes (lumbago, lumbalgia, lumbalishalgia) with muscular ton-
ic, vasomotor and trophic disorders;
• compressive radicular syndromes (radiculopathy);
• compressive radicular and vascular
syndromes (nerve root ischemia).
III. Nerve stretch tests.
Vertebrogenic disorders are often charac-
terized by pain while palpating the paraverte-
bral regions and by positive stretch tests:
- Lasegue’s sign (straight Leg rise).
Patient is lying down on his back; bend-
ing of leg in the coxal joint causes pain in
the lumbar area and on course of sciatic Fig. 4. Straight Leg rise
nerve (this is result of nervous root and sometimes used to help
sciatic nerve stretch) (Fig. 4, 5(1)). diagnose a lumbar herniated disc
- Wassermann's sign (femoral nerve stretch test). Patient is lying down

on his stomach; unbending of leg in the coxal joint causes pain in the lumbar
area and on the front surface of thigh (this is result of nerve root and femoral
nerve stretch), (Fig. 5(2)),
- Neri’s sign. Bending of head causes pain in the lumbar area and knee
flexing (this is a result of nerve root stretch), (Fig. 5(3)).
Fig. 5. Nerve stretch tests:

1 — Lasegue’s sign, 2 — Wassermann's sign, 3 — Neri’s sign
IV. Cervical lesion level.

1. Reflex syndromes:
A feature: absence of sensory, motor and reflex (changed reflexes)
disorders.
- cervicalgia (vertebral artery syndrome or Barre-Lieou syndrome) is
characterized by neck pain, headache, dizziness caused by irritation of the
sympathetic plexus of vertebral artery;
- cervicocephalgia is characterized by neck pain, painful spasms and
neck muscles tension, enforced head and neck position;
- cervicobrachialgia is characterized by pain in muscles of neck, shoulder
and arm, elbow and shoulder joints, tension and limited mobility in these joints
with possible arising of:
- scapulohumeral periarthrosis (muscular tonic and trophic violations of
the tissues around the shoulder joint)
- Steinbrocker (shoulder-hand) syndrome (scapulohumeral periarthrosis
signs and trophic disorders in the hand with skin atrophy, hyperhidrosis).
2. Compressive radicular syndromes (radiculopathy):
The features:
• signs of reflex syndromes,
• sensory deficits — hypalgesia in the area of innervation,
• motor and reflex deficits — muscular weakness and atrophy, reflexes
are usually markedly diminished or absent
• autonomic disorders — skin atrophy, hyperhidrosis
• electromyography reveals a decrease of conduction velocity of those

nerves, which are formed by certain roots.
Nerve root C6 (intervertebral C5-C6 foramen): pain is projected from neck
into the thumb; hypoesthesia of radial forearm and thumb; biceps weakness,
decreased or absent of biceps reflex.
Nerve root C7 (intervertebral C6-C7 foramen): pain is projected into the
back surface of shoulder and forearm to the middle finger; weakness of triceps
and extensor fingers muscle; decreased or absent triceps reflex.
Nerve root C5 (intervertebral C4-C5 foramen): pain in the shoulder;
weakness of the deltoid, supra- and infraspinatus muscles.
V. Thoracic lesion level.
1. Reflex syndromes: thoracalgia, dorsalgia — pain in the chest, back.
The features: contractions of the thoracic muscles and muscles of the
back, limited movement due to pain, absence of sensory, motor or reflex
abnormalities.
A disk herniation can compress a thoracic
nerve root with sensory and motor deficits. These
syndromes are rare.
VI. Lumbosacral lesion level.
The signs similar to those of reflex and
compressive syndromes:
• limitation of movements at the lumbosacral lev-
el (while inclining ahead, backwards, sideways) and
increased pain when coughing, laughing, sneezing);
• contralateral (to pain) defensive tension of
long back muscles;
• flatness of lumbar lordosis; or intensification of
the kyphosis at the lumbosacral level;
• antalgic scoliosis (spine curvature) (Fig. 6);
• sings of nerve stretch (Lasegue’s, Vaserman’s,
Neri’s).
1. Reflex syndromes (Low back pain): Fig. 6. Antalgic
A feature: an absence of sensory, motor or reflex scoliosis, flatness of
abnormalities. lumbar lordosis in the
• lumbago is an acute pain at the lumbar level after vertebrogenic disorders
physical activities or awkward movements, accompanied of the peripheral
by a significant constriction of back muscles and limited nervous system at the
mobility. It lasts from several hours to several days; lumbosacral level
• lumbalgia is a chronic pain at the lumbar level;

• lumbalishalgia — subacute or chronic pain at the lumbar level, which is
projected to the leg.
A feature: see the compressive syndromes at the cervical level.
Compressive syndromes at the lumbar level are most common. Sciatica is the
clinical description of pain in the leg that occurs due to lumbrosacral nerve root
compression usually secondary to lumbar disc prolapse or extrusion. L5-S1 disc
level is the most common site of disc herniation. The following are the characte
ristic «lower back syndromes» associated with nerve root compression.
Nerve root L4 (intervertebral L4-L5 foramen): pain and hypoesthesia on
the front of the thigh and the inner tibia surfacee, weakness and atrophy of the
quadriceps muscle, decrease or loss of knee reflex.
Nerve root L5 (intervertebral L5-S1 foramen): pain and hypoesthesia in the
buttocks, outer thigh surface, anterior outer surface of the calf, thumb; the weak-
ness of the extensor muscles of foot and big toe, hypotonia and muscle hypotro-
phy on the front side of shin. A patient has difficulty to stand on the heels.
Nerve root S1 (intervertebral S1-S2 foramen): pain and hypoesthesia in
buttock, on the outer surface of thigh, calf, foot, little toe; weakness of flexors
of the foot and big toe; reduced or absence of Achilles reflex. A patient cannot
stand on toes.
VII. Spinal stenosis is a disorder that is caused by a narrowing of the spinal
canal (Fig. 7). This narrowing happens as a result of the degeneration of both
the facet joints and the intervertebral discs. In this condition, bone spurs (also
called osteophytes) grow
into the spinal canal. The
facet joints also enlarge
as they become arthritic,
which contributes to a de-
crease in the space avail-
able for the nerve roots.
There are complaints
on pain in the buttocks,
thigh or leg that develops
with standing or walking,
and improves with rest.
In some cases, a person
will complain of leg pain
and weakness without Fig. 7. Spinal stenosis
having any back pain. More severe symptoms include numbness, tingling,
and weakness in the lower extremities. Certain positions can alleviate the
symptoms of spinal stenosis by increasing the amount of space available for
the nerves.
VIІI. The diagnosis of Radicular Syndromes and Disk Herniation.
• X-ray of the spine at different levels to diagnose injuries, osteoporosis,
anomalies of the spine, bone changes, indirect signs of intervertebral disc
herniation (Fig. 8, 9),
Fig. 8. X-ray of the cervical spine Fig. 9. Osteochondrosis С5-7

(lateral projection): (1, 3) — osteo intervertebral discs, abnormal
phytes, (2) — reduced height of the mobility of C6 vertebrae
intervertebral disc
• MRI of the spine and spinal cord (degenerative changes of the spine,
joints, intervertebral disc herniation, spinal cord pathology) (Fig. 10).
VIII. Conservative Treatment of Vertebrogenic Disorders.
Acute period (its duration in case of reflex syndromy is up to 3-5 days,
and in radicular syndrome it is 2 weeks).
1. Immobilisation, bed rest on hard surface, such as a firm mattress or
the floor.
2. Spine extension (on sloping surface) (Fig. 11).
3. Reduction of edema (dehydration), using diuretics during 2-3 days.
4. Anaesthetic blockades (lidocaine, corticosteroids).
5. Nonsteroid antiinflammatory preparations: diclofenac, ketophrofen,
dexketophrofen, ketorolac, meloxicam, nimesulide, ibuprofen, lornoxicam.
6. Myorelaxants: Baclofen, Sirdalud.
Fig. 10. Lumbar MRI scan. L5-S1 disc herniation 11mm

(red color points area of lesion)
7. Vitamin B Complex
8. Physiotherapy (electropho-
resis, phonophoresis, laserothera-
phy), local anesthetic procedures.
9. Massage, gymnastics.
After acute period, a maximal
effect has physiotherapy, mas-
sage, and gymnastics.
Chiropractic manipulation in
Vertebrogenic Disorders is contra-
indicated in patients with disk her-
niation, as soon as it may lead to Fig. 11. Spine extension (on sloping surface)
damage of the spinal cord.
IX. Neurosurgical treatment
of Vertebrogenic Disorders.
Neurosurgical treatment is indicated in following circumstances:
• massive herniation with bilateral weakness of legs or/and sphincter
disturbances;
• frequent recurrences or persistence of symptoms for 2-4 weeks despite
the conservative treatment;
• intensive pain despite correct conservative treatment.
TESTS
1. A 42-year-old patient has the pain and hypoesthesia on the front of

the left thigh and the inner tibia surface, weakness and atrophy of the
quadriceps muscle, decrease of knee reflex. Which nerve root compression
is characterizes by these symptoms?
1) L2
2) L4
3) L5
4) S1
5) Th12
2. What signs of the X-ray radiography allow suspecting a disc herniation?
1) osteoporosis
2) spondylarthrosis
3) reduced height of the intervertebral disc
4) spina bifida
5) spondylosis
3. Specify the objective symptom, which is not refer to stretch tests
1) Lasegue’s sign
2) Wassermann's sign
3) Babinski’s sign
4) Neri’s sign
4. Reflex syndromes at the cervical level are not characterized by the next
features:
1) Barre–Lieou syndrome
2) forced head and neck position
3) neck pain, painful spasms and neck muscles tension
4) sensory, motor and reflex (changed reflexes) disorders
5) absence of sensory, motor and reflex (changed reflexes) disorders
5. A 28-year-old patient has being periodically treated because of the intensive pain
for 2 years. At last 3 weeks, the intensive back pain has not disturbed him, but the
weakness of the extensor muscle of left foot has been observed. MRI: L5-S1 disc
herniation 9 mm. Which of the following is a direct indication to surgical treatment?
1) age of patient
2) weakness of feet
3) previous intensive pain
4) size of disc herniation
5) level of disc herniation
Topic 20
CONGENITAL DEFECTS OF SPINE AND SPINAL CORD.

SYRINGOMYELIA
Topic questions:
- A definition of the terms:
• Atlas assimilation
• Basilar impression
• Hydromyelia
• Meningocele
• Status dysraphicus
• Synostosis
I. Craniovertebral anomalies
1. Dandy–Walker syndrome
2. Chiari syndrome
1) Type I malformation
2) Type II malformation
II. Anomalies and secondary spinal deformity (Klippel–Feil syndrome)
III. Dysraphia of spine and spinal cord, spinal hernias
1. Spina bifida occulta
2. Complete rahischisis
3. Spina bifida anterior
4. Spina bifida complicata
5. Spinal hernias
IV. Syringomyelia
1. Pathomorphology
2. Pathogenesis (idiopathic (genuine) and secondary syringomyelia)
3. Classification
4. Clinical picture
5. Diagnosis
6. Treatment
7. Prognosis
A definition of the terms:

Atlas assimilation — a partial or complete fusion of the I-st cervical verte-
bra and occipital bone of the skull, which may not be accompanied by clinical-
ly significant impairment, while in other cases it leads to compression of the
Congenital defects of spine and spinal cord. Syringomyelia 211
Fig. 1. Atlas assimilation Fig. 2. Basilar impression:

craniovertebral structures the herniation of lower part
(upper cervical spinal of clivus, anterior parts of
cord and medulla oblon- the I-st and the odontoid
gata), limiting the upper Fig. 3. Cavernous
bone of II-nd cervical
cervical spine mobility, hemangioma
vertebra into the cranial of the
development of lower thoracic spinal
cavity, (MRI, T1-weighted cord,
cervical spine instability image) hydromyelia
(Fig. 1).
Basilar impression: funnel impression in the clivus of the occipital bone,
occipital-vertebral joints and the foramen magnum (Fig. 2). There is slight dis-
location of the spine towards the cranial cavity with the decrease of the pos-
terior fossa size. The II-nd cervical vertebra odontoid bone is localized higher
than normal, that is at foramen magnum level or even it gets into the cranium.
Hydromyelia: distention of the
central canal of the spinal cord, the
cause of which can be either the
canal congenital anomaly, usually
observed simultaneously with spina
bifida and hydrocephalus internus, or
it is developed secondary in vivo, as
a result of various pathological condi-
tions (compression of the spinal cord,
cerebellar tumor) when an excessive
amount of fluid can stretch central
chanel (Fig. 3).
a b
Meningocele: spinal meningo-
cele or craniocele (Fig. 4), in case of Fig. 4. Mielomeningocele (a),
meningocele (b)
which hernia consisting of skinned modified arachnoid and pia mater, filled
with cerebrospinal fluid, protrudes through the bone defect.
Platybasia: ratio changes between the skull base bones and the upper
cervical vertebrae, which are characterized by an increase of the basilar skull
angle, ie the angle between the planum sphenoideum and clivus, which nor-
mally ranges between 135° and 143°.
Normal clival angle (a) measured by the NTB angle of Welcker joining the
nasion (N), tuberculum (T) and basion (B). The angle should be less than
130°. Platybasia (b) is marked by an increased NTB angle. This raises the
basion and forces the foramen magnum plane (dotted line) to tilt upwards.
The same upward tilt of this plane also occurs with a short clivus (c) (Fig. 5).
a b c
Fig. 5. Clival angle: normal (a), inplatybasia (b), in short clivus (c)
Status dysraphicus includes those anomalies of the anatomical structure

of the human body that can be detected at birth or in early childhood, which
may increase with age or disappear: chonechondrosternon or funnel chest
(Fig. 6), kyphoscoliosis (Fig. 7), lengthening or shortening of the upper limbs,
peculiar bending of the fingers («monkey paw»), various size and location
of the breasts, sensitivity disorders, often by segmental type, acrocyanosis,
Fig. 6. Fig. 7. Kyphoscoliosis

Chonechondrosternon
incontinence of urine at night, mainly in combination

with spina bifida, and a number of degenerative signs
(high palate, abnormal hair-covering, odontatrophy).
Synostosis is fusion of bones, that is union of
separate bones into a single bone. Pathological syn-
ostosis are formed in unusual place and can lead to
severe illness: craniostenosis, congenital radioulnar Fig. 8. Multiple
synostosis, vertebrae blocking, etc. synostosis of the
I. Craniovertebral anomalies are characterized by cranial sutures with the
defects of the occipital bone and structures localized in development of tower
the posterior fossa, upper spine and spinal cord. skull (oxycephaly)
1. Dandy–Walker syndrome (Fig. 9)
is a congenital malformation of the trunk
and caudal part of brain stem, cerebellar
vermis, leading to incomplete opening of
the median (Magendie) and lateral (Lus-
chka’s) apertures of the IV-th ventricle. It
is manifested by hydrocephalus and often
hydromyelia signs. The last one can cause
the development of syringomyelia, syrin-
gobulbia in accordance with the hydrody-
namic Gardner theory. Gardner theory: due
to Magendie hole incomplete opening the Fig. 9. MRI of a patient with
CSF pressure becomes higher in the ven- Dandy–Walker syndrome.
tricular system of the brain, that contributes Cystoid formation in the posterior
to drainage and expansion of the central fossa, cerebellar hypoplasia, high-
canal of spinal cord and hydromyelia de- riding of cerebellum tentorium
velopment, that accompanied by degener-
ative changes in adjoining to the enlarged central canal gray matter, and then
to other spinal structures. Dandy–Walker syndrome is characterized by func-
tional insufficiency of the cerebellum and the medulla oblongata, the symp-
toms of hydrocephalus, intracranial hypertension.
Diagnostics: CT scan and MRI. Signs of hydrocephalus are revealed, in
particularly with expressed dilatation of the IV-th ventricle. MRI can detect
deformation of these brain structures.
2. Arnold–Chiari anomaly is a congenital abnormality of hindbrain which
is manifested by size inconsistency between the posterior fossa and brain
structures, localized in this region. It leads to the ptosis of brain stem and cer-
ebellar tonsils into the foramen magnum and their compression at this level.
There are 4 types of Chiari malformation.

Type I Chiari malformation (adult type)
(Fig. 10) is the most common form of cerebel-
lar abnormalities. Such complex of symptoms
is following: mono- or bilateral cerebellar ton-
sillar ptosis through the foramen magnum into
the spinal canal (the tonsils, that is the lower
part of the cerebellum, normally are localized
above the foramen magnum). The most im-
portant factor is the fact that the clinical man-
ifestations appear only on the 3-4th life de-
cade, being a random finding on MRI.
Clinical picture: headache, neck pain,
Fig. 10. Type 1 Chiari anom-
weakness, numbness of the hands, loss of
aly. Cerebellar tonsillar ptosis
pain and temperature sensitivity in them, stag-
up to the I-st cervical vertebra
gering, dizziness, «beating down nystagmus».
level: MRI T2-weighted image
Type II Chiari malformation (children type)
(Fig. 11) consists of not only the cerebellum and
brain stem displacement through the foramen
magnum but also the IV-th ventricle. Character-
istic feature is the meningomyelocele presence
in the lumbar region. Neurological defects oc-
cur on the base of the abnormalities of occipital
bone and cervical spine. Hydrocephalus occurs
always, the cerebral aqueduct stenosis is often.
Neurological symptoms are present at birth.
The typical clinical picture: pain in the nape
area aggravated by coughing, sneezing, faint-
ing; dizziness, reduced vision, decreased of
Fig. 11. Type II Chiari anomaly.
pain and temperature sensitivity, as well as
The brain stem and cerebel-
muscle strength in extremities, muscular spas-
lum are displaced caudally.
ticity. Sometimes episodes of apnea are joined
The IV-th ventricle is com-
(cessation of breathing for a short period), the
pressed at craniovertebral
decrease of gag reflex, involuntary rapid eye
junction and almost is not
movements.
differentiated. Cerebrospinal
Type IIІ Chiari malformation is that the cer-
hernia at upper thoracic level
ebellum and brain stem with meninges are
and syringomyelia (below)
shifted into the meningocele, localized in the
are also determined (MRI,
cervical occipital area.
T1-weighted image)
In case of type IV Chiari malformation the cerebellar hypoplasia is marked

and caused by its total hernia; cerebellum can not be distinguished. Type III
and IV Chiari malformation are extremely rare.
To date, the pathogenesis of the disease is not completely confirmed. In all
likelihood, there are three pathogenetic factors:
1) the congenital hereditary osteoneuropathy, 2) traumatic lesions of sphe-
noid — ethmoid and sphenoid — occipital part of the clivus due to birth trauma,
3) hydrodynamic liquor slap into the wall of the central canal of spinal cord.
Diagnosis: MRI of the brain, cervical and thoracic parts of spinal cord (for
syringomyelia exceptions). Ultrasound diagnosis of Arnold–Chiari anomaly in
the fetus is available.
Treatment. In case of «asymptomatic variant», the dynamic monitoring with
annual survey is carried out. If the slight intensity pain is the only symptom, con-
servative therapy is used: nonsteroidal anti-inflammatory drugs and myorelax-
ants. Dehydrating therapy is used periodically. In case of treatment inefficiency
within 2-3 monthes or occurrence of neurological deficit (numbness, paresis,
etc.) surgery is carried out. In some cases the final diagnosis is determined
during the surgical revision. The aim of surgery is to eliminate the compression
of nerve structures and cerebrospinal fluid outflow, due to enlarging of the pos-
terior cranial fossa (laminectomy, foramen magnum dilatation, etc).
II. Anomalies and secondary spinal deformities

Klippel–Feil syndrome (short neck) is a cervical vertebrae congenital
anomalies and fusion. It can be the cervical vertebrae incomplete differentiation
and reducing of their number, sometimes
their number is no more than four. The clin-
ical picture is characterized by a triad: short
neck («the man with no neck», «frog neck»),
low hairline on the neck, a significant limita-
tion of the head mobility. In severe cases, the
chin rests upon the sternum, earlobes touch
the shoulder girdles. Sometimes the folds
of skin hang from the ears to the shoulders
(Fig. 12).
The syndrome may occur in conjunction
with other cervical congenital abnormalities;
for example, the basilar impression and at-
lanto-occipital fusion. In addition, there may
be scoliosis, facial asymmetry, torticollis (a Fig. 12. Klippel–Feil syndrome
neck deformation, characterized by the head inclination to the affected side,

and slight face turn to the healthy side), wrinkling of the neck skin, synkinesias
(mirror movements, mainly in hands, but sometimes in whole arm) and less
frequently the facial muscles paralyzes, ptosis, high cleft palate. Systemic
congenital anomalies are also possible: of the genitourinary system (eg, uni-
lateral absence of kidney), cardiovascular, central nervous systems. In third of
patients, there is deafness due to defects of the inner ear bones.
Due to the X-ray examination there are two forms of Klippel–Feil syndrome:
1) atlas is fused with other cervical vertebrae, the total number of which is
reduced in this regard. Usually there are no more than 4 of them;
2) cervical vertebrae synostosis, the height of their bodies is reduced. It is
often combined with platybasia.
III. Dysraphia of spine and spinal cord. Spinal hernias

Spinal dysraphia is a malformation caused by the incomplete closing of
mesodermal and ectodermal tissues origin along the median suture (Greek:
«Rhaphe»): spine midline. Manifestations of spinal dysraphias are splitting
of the vertebrae arches (spina bifida) and sagittally localizated soft tissue;
as well as different variants of spinal hernias, sometimes dermoid cysts (cyst
containing hair, hair follicles and sebaceous glands), lipoma.
There are following degree dysraphia depending on their underdevelop-
ment (Fig. 13): 1) spina bifida (split spine) occulta; 2) spina bifida complicata;
3) spina bifida anterior; 4) spinal hernias: meningocele, meningoradiculocele,
myelomeningocele, myelocistocele; 5) partial and total rahischisis.
Fig. 13. Spine and spinal cord dysraphia
1. Hidden spina bifida — spina bifida occulta. It is the most common

form of the spine anomalies — the splitting of vertebrae arches (spina bifi-
da occulta). There can be one or two cleft vertebrae, but sometimes great-
er number of them are cleft. The ends of cleft arcs are often pressed into
the lumen of the spinal canal and cause the compression of the dura mater,
subdural space and cauda equina, while the bone defect is covered with un-
changed soft tissue. Such form of anomaly is detected on spondylogram, usu-
ally on lower lumbar and/or upper-sacral levels. Sometimes the wrinkled and
atrophied skin is marked in the area of arc splitting, the occurrance of tissue
swelling, scars, pigmentation, hypertrichosis is also possible.
2. Total rahischisis is the severe dysraphia manifested not only by split-
ting of arcs and vertebral bodies, but also the adjacent soft tissue. Spinal cord
can be seen through a cleft in the soft tissues immediately after birth. Hernial
protrusion is absent. Vertebral bodies can adhere in the ventral part of cleft.
Malformations of other vertebrae, ribs are possible.
3. Spina bifida anterior: incomplete closing of the vertebral bodies. It oc-
curs rarely and is occasionally found on spondylograms, but can be combined
with other defects of development.
4. Spina bifida complicata: incomplete closing of the vertebral arches in
combination with tumor-like growths, represented only by fat or fibrous tissue
beneath the skin and filling vertebrae arches bone defects, growing together
with meninges, roots and the spinal cord. It is often localized on the lumbosa-
cral level of the spinal column.
5. Spinal hernia, arising from incompletely closed vertebrae arches and
the soft tissues splitting, are congenital hernial protrusion of the spinal canal
contents. Their types
are (Fig. 14, 15):
- meningocele —
hernial protrusion of
the meninges, filled
with CSF;
- meningoradiculo-
cele — hernia, consist-
ing of the meninges,
spinal roots and CSF;
- mieloradiculome-
ningocele — hernia, in- a b c
cluding the structures Fig. 14. Types of spinal hernias:
of the spinal cord, spi- meningocele (a), myelocystocele (b, c)
nal roots, meninges and ce-

rebrospinal fluid;
- myelocystocele —
hernial sack containing an
area of the spinal cord with
signs hydromyelia.
b
Diagnostics. It is not dif- a
ficult to diagnose spinal her-
nia. Precise diagnosis can
be achieved by performing
spondylography and MRI
studies.
Only surgical treatment
is possible.
IV. Syringomyelia — a c d
chronic, slowly progressing Fig. 15. Localization of spinal hernias
disease of the young and a — typical localization; b — non typical
middle aged people, which localization (in thoracic part); c — giant spinal
is based on the formation of hernia; d — rahischisis, lower paraplegia
cavities in the spinal cord,
mainly at the cervical enlargement level.
1. Pathomorphology. In case of syringomyelia spinal cord is deformed
in the anteroposterior direction. Cavities of different diameters (1-1.5 cm and
barely noticeable) are visible on cross sections in most cases.
They are located in the
central channel areas, dis-
tributing in the side sec-
tions to the posterior horns
of the spinal cord. In the
case of the large cavities
formation the spinal cord is
compressed to narrow plate
that surrounds syringomyel-
itic cavity, if the cavities are
smaller than the spinal cord
diameter, it is deformed,
asymmetric. Posterior horns a b
and posterior cords are of- Fig. 16. Spinal cord:
ten deformed. (Fig. 16). with syringomyelitic cavity (a), normal (b)
2. Pathogenesis. Dysonthogenetic theory links the gliosis occurrence and

the pathological cavities in the spinal cord tissue formation with embryonic devel-
opment violation in the early stages (3-6 week). It results in incomplete or incor-
rect closure of neural tube with violation of posterior suture formation (dysraphia).
This leads not only to the spinal cord central canal expansion with diverticula
formation, but also to the fetal tissue accumulation behind the central canal.
Hydrodynamic theory. In normal during the first 6-8 weeks of embryonic
development due to increased production of cerebrospinal fluid, its pressure
in the neural tube, which leads to the Magendie and Luschka holes opening
increases. There is a connection with the ventricular system and subarach-
noid space and central channel obliteration occur. In case of stenosis or oc-
clusion of draining holes the cerebrospinal fluid goes into the central canal
under pressure, extends it and forms a cavity.
Arnold–Chiari anomaly is combined with syringomyelia in 40% of cases
because of onthogenesis pathology.
Malformations of the spinal cord can also
be accompanied with impaired development of
other organs and tissues. These are manifest-
ed by signs of dysraphic status (Fig. 17), which
include malformations of the skin, muscles,
bones, internal organs, the nervous system:
spine curvature, funnel sternum, deformation of
the hands and feet, extra nipples, vertical wrin-
kle between the eyebrows, split tip of the tongue
and upper lip, high palate, dental anomalies,
excessive hair growth, facial asymmetry, eyelid Fig. 17. Deformation of the upper
hypertrophy, akromegaloid features, short neck, limbs when dysraphic status
enuresis, short stature, long or short arms, etc.
However, unlike genuine syringomyelia, various necrotic, and ischemic
adhesions can lead to gliomatosis with the formation of the cavities that is
called secondary syringomyelia. It is possible after hematomyelia (hemor-
rhage into the spinal cord), spinal cord injury, necrotizing myelitis, a spinal
cord benign tumor, etc.
3. Classification:
1. According to the etiologic and pathogenetic mechanisms:
• idiopathic (genuine);
• secondary.
2. Syringomyelitic process localization:
• spinal (cervical-thoracic, cervical, thoracic, lumbar, sacral, total) level;
• brain stem level;

• brain stem and spinal cord level.
3. According to the clinical manifestations:
• posterior horn form;
• anterior horn form;
• autonomic-trophic form;
• mixed form;
• bulbar form.
4. Clinical picture. The classic version of syringomyelia is the entire le-
sion of gray matter at the cervical-thoracic spinal cord level. This presupposes
the development of a typical triad of symptoms:
1. Sensitive violations: segmental dissociated posterior horns (sensory
disturbances).
2. Movement disorders: peripheral (flaccid, atrophic) upper paraparesis.
3. Autonomic dysfunctions: trophic and vascular disoders.
Sensory disorders are the main characteristic for the disease. This type of
violation is also called «syringomyelitic». It is characterized by pain and tem-
perature sensitivity loss while maintaining the tactile and muscule and joint
senses on the upper limbs and upper torso («jacket type») (Fig. 18).
Sometimes firstly the patients refer to a surgeon or traumatologist com-
plaining about painless chronic wounds, burns.
Sensory disorders include «deep»
pain of different localization. It has a
nagging character, sometimes ac-
companied by paresthesias, often
with hyperpathic component. Pain
may occur long before any objective
evidence of disease.
Movement disorders in the up-
per extremities are represented by
flaccid, atrophic paresis, which are
localizated mainly in the distal parts.
They are characterized by small
muscles hypotrophy of the hands
with the formation of «clawed hand» Fig. 18. Loss of pain and temperature
or «monkey paw». Fibrillary twitch- sensitivity in form of a «jacket» while
ing are observed in atrophic mus- forming the cavities at the cervical,
cles. Tendon and periosteal reflexes thoracic segments of the spinal cord
are reduced or absent. and brainstem in case of syringomyelia
With the defeat spreading to the lateral spinal cord funiculi the signs of the
violation of motor and sensitive pathways occur. Spastic lower paraparesis,
conductor sensitivity violation are observed.
Lumbosacral form of the disease is rare. It is characterized by the same
sensory and motor violation, but of the lower extremities.
Syringomyelia is often accompanied by syringobulbia, which may be a
separately manifestation of the disease. Thus the cavities are formed in the
medulla oblongata and / or pons. The nuclei of V-th, VII-th, VIII-th, IX-th, X-th,
XII-th cranial nerves are affected. In this case patients have facial pain, tem-
perature and pain hypoesthesia on the face in Zelder areas while maintaining
tactile sense. Peripheral paresis of the facial muscles, hearing loss are de-
tected. There are nystagmus, bulbar syndrome: dysphonia, dysphagia, dys-
arthria, tongue atrophy, fibrillar twitching in its muscles.
Autonomic and trophic disorders are extremely polymorphic. It can be a
violation of sweating: hyperhydrosis is more often on the face, upper limbs,
trunk; anhidrosis is rare. Peripheral circulatory disorders are also possible
which are manifested by hyperemia, acrocyanosis. Over time, autonomic dis-
orders increase. Dry, flaky skin, hyperkeratosis with deep cracks or sores that
do not heal occur, there may be hypo-or hyperpigmentation, eczematous pro-
cesses. Nails are easy to crumble, break. Trophic disorders of osteoarticular
system is manifested by kyphoscoliosis of the thoracic spine, arthrosis, osteo-
arthropathy, pathological sprains of joints, chiromegaly (increasing of hands
and fingers of the upper extremities). The disease is often accompanied by
stomach ulcer, myocardial hypoxia, the pituitary-adrenal system insufficiency,
sexual dysfunction.
5. Diagnosis. MRI is the most infor-
mative method: typically there are the
increase of spinal cord diameter, pres-
ence of cysts filled with cerebrospinal
fluid, which are often localized in the
thoracic and cervical spine (Fig. 19).
In some cases, the increase of cystic
formations leads to the development of
spinal deformities, such as scoliosis.
6. Treatment is surgical. Indi-
cations for neurosurgical treatment
are rapid progression of the disease,
the increase of liquorodynamic viola- Fig. 19. Syringomyelitic cavity in
tions, craniovertebral anomalies. The MRI (color coded)
surgery means withdrawal of cerebrospinal fluid into the other cavities and
craniovertebral junction decompression.
7. Prognosis for life is relatively favorable, for recovery is unfavorable.
TESTS
1. Determine the congenital malformation of the trunk and caudal part of brain stem,
cerebellar vermis, leading to incomplete opening of the median IV-th ventricle apertures.
1) Dandy–Walker syndrome
2) Arnold–Chiari anomaly
3) Klippel–Feil syndrome
4) Syringomyelia
5) spina bifida
2. Hidden spina bifida is:
1) splitting of arcs and vertebral bodies and adjacent soft tissue
2) splitting of vertebrae arches
3) incomplete closing of the vertebral bodies
4) incomplete closing of the vertebral arches in combination with tumor-like growths
5) hernial protrusion of the meninges, filled with CSF
3. Syringomyelia is based on the formation of _______ in the spinal cord:
1) tumors
2) cysts
3) absceses
4) cavities
5) haemorrhages
4. «Syringomyelitic» sensory disorders:
1) «jacket type» of the sensory loss
2) stocking & glove distribution
3) hemianalgesia
4) parestesias
5) tactile hallucinations
5. «Frog neck» is a symptom of:
1) Klippel–Feil syndrome
2) Dandy–Walker syndrome
3) Arnold–Chiari anomaly
4) Syringomyelia
5) spina bifida
Topic 21
PERINATAL LESIONS OF THE CENTRAL NERVOUS SYSTEM
Topic questions:
I. Perinatal lesions of the central nervous system (CNS).
1. Definition.
2. Classification.
3. Etiology.
4. Periods and main syndromes of perinatal CNS lesions.
5. Diagnosis of perinatal lesions of the CNS.
6. Treatment of perinatal lesions of the CNS.
II. Cerebral palsy (CP).
1. Definitions.
2. Classification.
3. Clinical characteristics of the major forms of cerebral palsy.
4. Treatment and rehabilitation of children with cerebral palsy.
I. Perinatal lesions of the central nervous system.

1. Definition.
Perinatal CNS lesions are pathological conditions that occur under the influ-
ence of many factors. Perinatal period includes: 1) time before delivery, starting
from the 22-d full week of pregnancy — antenatal period, 2) the actual childbirth —
intranatal period, and 3) time after childbirth, which lasts until the 7-th day of the life
of the newborn — the early neonatal period. Pathological conditions that occur in
the perinatal period, take the second place in the structure of infant morbidity. The
consequence of such CNS lesions can be the worsening of life quality.
2. Classification was proposed in 1995 at the First Ukrainian-Bavarian
Symposium «Medical and social rehabilitation of children with organic lesions
of the nervous system.»
1. Damages of the nervous system at birth.
2. Hypoxic-ischemic damages of the central nervous system.
3. Lesions of the nervous system in cases of infectious diseases specific
to the perinatal period.
4. Hemolytic disease of the fetus and newborn. Other metabolic enceph-
alopathies.
5. Congenital malformations of the nervous system development, defor-
mations and chromosomal abnormalities (see topic 20).
Damages of the nervous system at birth.

Among the injuries, which the newborns have at birth are the injuries of
the brain and spinal cord. All intracranial hemorrhages due to location are
divided into epidural, subdural, subarachnoid, intraventricular, intracerebral,
including cerebellar hemorrhages. Subarachnoid, intracerebral and intraven-
tricular hemorrhages can be of a traumatic as well as of a hypoxic origin (hy-
poxic-hemorrhagic lesion of CNS).
Hypoxic-hemorrhagic lesions of CNS are more common for the deep pre-
matures (29-31 weeks of gestation, weighing less than 1500 g) and extreme-
ly premature borns (less than 29 weeks of gestation and weighing less than
1000 g). In the pathogenesis of intraventricular hemorrhage, in prematures,
an important link is the germinal matrix represented by the randomly located
immature capillary network, the walls of which are composed of a single endo-
thelial layer without the support of tissue layers, such as smooth muscle fibers,
collagen or elastin. The presence of high level of blood flow, fibrinolitic activity
and lack of cerebral autoregulation are the reason for the vulnerability of hermi-
nal matrix, and which can cause it to rupture and bleed. It is manifested mainly
in the subependymal area of the lateral, third and fourth ventricles of the fetus
and occurs between 24 and 32 weeks, resulting in frequent occurrence of intra-
ventricular hemorrhage of hypoxic genesis in case of preterm birth. Therefore,
hemorrhage in premature newborns is from the germinal matrix often localized
in subependymal and paraventricular areas, above the caput and trunkus of
the caudate nucleus, at the level of the interventricular foramen. Intraventricular
hemorrhage occurs on average in 25% of premature newborns.
Spinal Cord injury is the least-studied birth damage of the nervous system.
Severe hemorrhages lead to respiratory failure at birth and to high mortal-
ity in the neonatal period. Stretching of the spine can lead to the lowering
of the brain stem and its herniation in the foramen magnum. Dislocation or
fracture of the vertebrae immediately point to a severe spinal cord lesion. In
mild lesions unstable transient muscle hypotonia, weakened cry, mildly ex-
pressed respiratory disorders are observed. In cases of more serious dam-
ages, symptoms occur, characteristic of spinal shock. They are respiratory
distress syndrome, adynamia, muscle hypotonia, areflexia, straightened and
abducted legs, immobilized, sometimes with a few spontaneous movements.
Sometimes a bilateral (rarely unilateral) total paralysis of the brachial plexus
or its upper part paralysis — Erb–Duchenne paralysis, occurs as well the
diaphragm paralysis, Bernar-Horner syndrome. In prematures clinical symp-
toms may appear several days after the injury, i.e., there is a latent period of
well-being from the moment of injury to its clinical manifestations.
Perinatal lesions of the central nervous system 225
Hypoxic-ischemic lesion of CNS (hypoxic-ischemic encephalopathy)

Most often occurs in premature newborns due to cerebral hypoperfusion,
caused by hypoxemia. Mechanisms of cerebral ischemia in matures and pre-
matures are relatively different and have their own characteristics. Thus, in
mature neonates undergoing asphyxia metabolic acidemia (lactic acidosis)
occurs, which causes cardiovascular insufficiency, which in its turn leads to
a drop in blood pressure and ultimately — to brain hypoperfusion, ischemia.
Severe brain damage in premature borns is associated with its immaturity,
peculiarities of the vascularization at different term of gestation, increased
capillary permeability, cerebral blood flow dependence on the total hemody-
namic disturbances due to imperfections of autoregulation mechanisms.
There are 3 degrees of hypoxic-ischemic encephalopathy (Aicardi, 1995):
- Grade I (light) is characterized by excitation or inhibition of the central
nervous system function, lasts the first 5-7 days of life;
- Grade II (moderate): inhibition or excitation lasts more than 7 days,
may cause seizures, intracranial hypertension syndrome and autonomic-vis-
ceral disorders;
- Grade III (severe) is characterized by progressive loss of cerebral ac-
tivity lasting more than 10 days, a profound inhibition of physiological func-
tions, a coma is possible.
3. Etiology
Risk factors.
Before pregnancy:
1. Mother’s age (younger than 20 and older than 35 years).
2. Harmful conditions of work.
3. Somatic and endocrine diseases (cardiovascular disease, diabetes).
4. Toxic substance abuse, drug addiction.
During pregnancy:
1. Any disease of the mother during pregnancy (including anemia, tox-
emia, SARS — severe acute respiratory syndrome).
2. Intrauterine infection.
3. Taking drugs causing potential danger to the fetus (Propranolol, Nadolol,
clonidine, Reserpine, Nifedipine, Enalapril, salicylates, etc.) during pregnancy.
4. Premature placental detachment.
5. Placenta Previa.
6. Preeclampsia.
7. Polyhydramnios.
8. Multiple pregnancy.
9. AB0 and Rh factor-incompatibility.
During delivery:
1. Premature and late-term delivery.
2. Having meconium in amniotic fluid, resulting in changing its color,
which is a sign of intrauterine hypoxia (oxygen starvation) and risk factors for
meconium aspiration of a newborn.
3. Long waterless period.
4. Improper management of management of childbearing.
5. The rapid (less than 2 h) or prolonged (more than 12 hours) manage-
ment of childbearing.
6. Forceps overlay.
7. Cesarean section.
8. Vacuum extraction of the fetus.
9. Fetal umbilical cord entanglement.
4. Periods of illness:
Despite the variety of causes that lead to perinatal lesions of the nervous
system, in the course of the disease three periods are distinguished:
- acute — one month;
- reduction — up to one year;
- long-term effects.
The characteristic feature of the acute period is the dominance of cerebral
violations with no severe local symptoms.
The main clinical symptoms and syndromes of the acute period:
- syndrome of increased neuro-reflex excitability
- cerebral (total) inhibition syndrome
- hypertension-hydrocephalic syndrome
- seizures
- neonatal coma (coma syndrome)
- apnoe
- bulbar, pseudobulbar syndrome
- disorders of muscle tone: hypo-/atoniya or hypertonicity
- autonomic dysfunction syndrome
Syndrome of increased neuro-reflex excitability:
- amplification of spontaneous motor activity
- superficial sleep
- frequent unmotivated crying
- small amplitude tremor of limb and chin
- nystagmus.
Cerebral (total) inhibition syndrome:
- weakness, reduced movement of a baby
- general muscular hypotonia, hyporeflexia

- weakening of heart tones, tendency to bradycardia
- focal symptoms in the form of convergent strabismus, nystagmus,
asymmetry of the facial muscles, ptosis, anizocorie.
Hypertension-hydrocephalic syndrome:
- increasing of the head size of a baby of 1-2 cm compared with the nor-
mal size. Opening of the sagittal suture over 0.5 cm
- increasing and bulging of bregma
- piercing (brain) cry
- positive Graefe symptom (With spontaneous movements of the eye-
balls down or during rapid head movement in the space between the eyelid
and the iris white scleral band appears)
- divergent strabismus
- muscular dystonia, usually in the distal extremities in the form of «seal
fins» and «heel feet» symptoms
- general hyperesthesia.
Fig. 1. Children with Graefe symptom
Coma and epileptic syndromes are manifestations of severe brain damage.

Coma syndrome:
- severe weakness, adynamia, weak or absent cry
- muscular hypotonia up to atony
- sharply depressed or absent inborn reflexes (including sucking and
swallowing)
- pupils constricted or dilated, anizocorie is possible
- reaction of pupils to light is weak or absent
- strabismus, nystagmus, «floating» movement of the eyeballs
- no response to painful stimuli

- attenuated or absent tendon reflexes
- breathing is harshly suppressed, arrhythmic, with frequent apnea
- attenuated heart tones, bradycardia, arrhythmical heart rate, blood
pressure lowering.
Seizures:
- tonic-clonic or tonic seizures
- equivalents of seizures. Equivalents include: spontaneous sucking reflex,
chewing motions, nominations and tremor of the tongue, eye paroxysmal phenom-
ena (tonic or vertical deviation of the eyeballs with or without nystagmus, eye open-
ing, paroxysmalically dilated pupils), twitching eyelids, paroxysmal «swimmer’s
movements» in the upper limbs and «bicyclist movements» in the lower extremi-
ties, overall immobilization, change the rhythm of breathing (apnea, tachypnea).
The syndrome of autonomic dysfunction:
- autonomic-vascular spots («marble hue» of the skin), intermittent cya-
nosis, acrocyanosis
- disorders of thermoregulation
- gastrointestinal dysfunction (pilirispasm, increased intestinal peristal-
sis, rumbling, regurgitation, vomiting, constipation)
- lability of the cardiovascular and respiratory systems
- increased thirst, hypotrophy.
The main clinical syndromes of the recovery period.
- syndrome of increased neuro-reflex excitability
- cerebroasthenic syndrome
- delay of static and dynamic development
- delay of psychic and pre-speech development
- the syndrome of motor disorders
- hypertension-hydrocephalic syndrome
- epileptic syndrome
- febrile seizures. Affective-respiratory spasms
- bulbar, pseudobulbar syndrome.
The syndrome of increased neuro-reflex excitability during the recovery
period has two types of the course:
1) favorable type is characterized by disappearance or decrease of symptoms
of increased neuro-reflex excitability during the period from 4-6 months to 1 year
2) unfavorable type, especially in premature babies, is characterized by epilepsy.
Cerebroasthenic syndrome is observed in children with mild CNS dam-
age, against normal mental and physical development. It is characterized by
emotional lability, irritability, movement anxiety, superficial disturbing sleep,

increased tendon reflexes and reflexes of a newborn, spontaneous Moro re-
flex (with a slam on the surface, where a newborn baby lies, it abducts arms
and opens fists — phase I, a few seconds later arms go back — phase II), as
well as periodic small amplitude tremor of chin, arms, and a shudder.
The syndrome of motor disorders (most often occurs as a result of periven-
tricular leukomalation):
- spastic paresis, pyramidal insufficiency
- hyperkinesis
- changes in muscle tonus (hypo -or hypertension, dystonia)
- ataxia.
Epileptic syndrome:
- tonic or clonic seizures
- equivalents of seizures.
The syndrome of static and dynamic development delay
Children fail to keep the head, return from back to belly, sit and start walk-
ing according to their age. Age-related motor function is beginning to be com-
pensated after 6-7 months and usually recovered to 1-1,5 years.
The syndrome of psychic and pre-speech development delay
Begins to emerge from 1-2 months of life. There is not a stable gaze fixa-
tion; there is no reaction to the mother’s voice, failure of auditory concentra-
tion. Up to 3 months of age lack of revival in communication is observed, ab-
sence of babbling occasionally there is a smile, in the age of 6 months babies
are not actively enough interested in toys and other things, do not react to the
presence of the mother, and babble inactively.
Long-term effects:
- minimal brain dysfunction
- cerebroasthenic syndrome
- delayed speech and psychic development
- psychoorganic syndrome
- compensated normotensive or progressive hydrocephalus
- Cerebral Palsy
- sensory or physical impairment (blindness, deafness and dumbness)
- epilepsy.
The syndrome of minimal brain dysfunction:
- disorder of cognitive functions: perception disturbances, absence of
mind, spelling difficulties, logical thinking difficulties
- motor skills (poor orientation, hypomimia, clumsiness).
5. Diagnosis
The duration of pregnancy and childbirth, family anamnesis are very im-
portant. Perinatal functional disorders can manifest themselves in different
terms, and their decompensation may occur only during the growth of ad-
aptation requirements withing the development of the child. Careful study of
neurological status, conducted by a neurologist in collaboration with neonatol-
ogists and / or intensive care specialists in acute stage of illness or a pediatri-
cian (GP — General Physician) in the recovery period of the disease.
Paraclinical methods:
- complete blood count with determination of reticulocytes count (their
number increases with hemolytic disease, massive hemorrhage)
- determination of babies` blood group and Rh-factor
- determination of blood glucose, calcium, magnesium, sodium, urea, bil-
irubin, potassium
- urine and blood serum screening to determine the defect of amino ac-
ids and organic acids metabolism: diagnosis of fenylketonuria, homocystin-
uriya, glutaric acidemia, the maple syrup urine disease — branched-chain
ketoaciduria
- TORCH-infections test: the pathogens of toxoplasma, rubella, cytomeg-
alovirus, herpes simplex virus
- study of cerebrospinal fluid for diagnosis of subarachnoid hemorrhage
and meningitis because of possible fetal infection
- ophthalmologist’s examination
- neurosonohraphic study
- CT-scan, MRI, Dopplerography
- electroencephalography.
Neurosonography is the ultrasonic method (visualization) of the brain ex-
amination that allows to assess the brain tissue condition, cerebrospinal fluid
circulation through the baby’s bregma. Can be used as a screening method
when intracranial lesion is suspected.
6. Therapy
Acute period:
- elimination of brain edema
- elimination of bleeding (in case of birth trauma, hypoxic-hemorrhagic
lesions of the CNS).
It begins with resuscitation in the delivery room and proceeds in the inten-
sive care unit, neonatal ward of the maternity hospital or if necessary — in the
intensive care neonatal unit.
In recovery period, the syndromological principle of treatment is used.
The drug of choice for treatment of hydrocephalic and hypertensive-hy-

drocephalic syndrome is Diacarb, which has a diuretic effect and decreases
the secretion of cerebrospinal fluid. Progression of hydrocephalus and the
absence of drug effect is the indication to ventriculoperitoneal shunting.
In case of convulsive syndrome barbiturates, hydantoin (Diphenine), ben-
zodiazepines, valproic acid derivatives are used in the neonatal period.
In case of movement disorders syndrome the treatment is carried out in
accordance with the nature of the movement disorders. To reduce muscle
tone the drugs such as Mydocalm, Baclofen, tolpiresone are used. In the
treatment of movement disorders physiotherapy plays an important role: mas-
sage, physical exercises, reflexotherapy, hydrotherapy).
In case of mental and pre-speech development delay, the basic drugs are
nootropic agents (cyticolin, piracetam, pantogam, encefabol), vitamin B com-
plex, vasoactive drugs. Educational programs aimed at developing the mental
and linguistic functions are widely used.
II. Cerebral palsy
1. Definitions. Cerebral palsy is a group of non-progressive syndromes
due to the brain damage or underdevelopment in prenatal, intrapartum and
early postnatal periods characterized by motor, mental and speech develop-
ment delay.
As cerebral palsy is a result of perinatal CNS lesions, the etiology and their
pathology is the same as above.
2. Classification of Cerebral Palsy
- spastic diplegia (Little’s disease)
- spastic hemiplegia
- double hemiplegia (spastic tetraparesis)
- hyperkinetic form
- atonic-astatic form
3. Clinical characteristics of the main
forms of cerebral palsy
Spastic diplegia. It occurs most frequently.
According to the prevalence of movement disor-
ders, it is classified as tetraparesis, in which the
upper limbs are affected much less than the low-
er ones. Sometimes the pyramidal insufficiency
is detected only in arms. Spasticity dominates in
the extensor and abductor muscles of the legs.
A baby has usually elongated legs in a supine Fig. 2. Patient with cerebral
position. When forced to stand, the baby`s knee palsy, spastic diplegia
comes in and the baby stands on its toes. Due to constant hip abductor mus-
cle hypertonus the legs are slightly flexed at the hip and rotate inward.
The 30-35% of patients have intellectual retardedness in the form of mod-
erate debility, often speech disorders delayed speech development, dysar-
thria, alalia, peech disorders due to the reduced of intelligence, seizures,
sometimes athetoid hyperkinesis and choreoathetosis. Dynamically, the men-
tal and speech disorders are well compensated, locomotor disorder regress
worse. The contractures of large joints are observed.
Spastic hemiplegia is characterized by unilateral central paresis of the
limbs, more expressed in arm, in its distal part. The stunting of paretic limbs,
their shortening and thinning are its features. Speech disorders are observed
in 30% of cases in the form of dysarthria, less often motor alalia. Quite often
seizures, psychic disorders occur due to delay of their development.
Double hemiplegia. It is the most severe form, i.e., spastic tetraparesis
equally expressed in both the upper and lower extremities; unequal lesion
of the sides is possible. As a rule, joint contractures are developed early.
Children do not acquire the skills of walking. Speech development is delayed,
incomplete. Intelligence is significantly reduced. There are constant seizures,
apathico-abulic disorders.
Hyperkinetic form is developed in case of lesion affecting mainly the bas-
al ganglia. The clinical picture shows different types of hyperkinesis. They
are athetosis, chorea, choreoathetosis, torsion dystonia. The variability of
musclular tonus that leads to the clumsiness of movement is characteristic.
Hyperkinesis are often combined with paresis. There are speech disorders.
Mental development suffers less than in case of other forms of cerebral palsy.
Atonic-astatic form is differed from other forms with low muscle tonus and
the coordination disorders. Intentional tremor, dysmetria, ataxia are typical.
The moderate hyperkinetic signs, pyramidal insufficiency can occur. Infants
start to sit, stand and walk late. The development of voluntary movements is
delayed. Intelligence is disturbed slightly.
4. Treatment and rehabilitation in patients with Cerebral Palsy
- should begin as soon as possible, be individual and complex.
- in case of movement disorders: exercises, punctuate massage, drugs
that reduce muscular tonus (Baclofen, Mydocalm, etc.); measures to prevent
the contractures and deformities of the limbs (mineral tallow, orthopedic sur-
gery, etc.); local injections of botulinum toxin (Dysport)
- actions for correction of the violations of higher brain functions (gnosis,
praxis, speech): training with a logopedist, psychologist, ducator. Medications
that improve CSF circulation and neurometabolism: nootrops, etc
- antiepileptic drugs used according to the origin of attacks

- the System of Intensive Neurophysiological Rehabilitation (the Inter-
national Clinic of Reabilitation in Truskavets in Western Ukraine) is a highly
effective treatment technology for patients with cerebral palsy. The basis of
rehabilitation system is a polymodal approach using varied methods of in-
fluence the patient. The main component of this method is a biomechanical
correction of the spine and large joints, combined with a complex of treatment
measures: reflexotherapy, physiotherapy, massage, rhythmic gymnastics, hy-
drotherapy and apitherapy (use of bee products including bee venom, bee
sting treatment).
To form a correct movement
stereotype of biodynamic move-
ment correction program is applied
with the use of the suit «Spiral».
By means of stimulation the body’s
compensatory abilities and activa-
tion of the brain plasticity, the sys-
tem creates a new functional status
in the patient with cerebral palsy,
which opens the opportunities for
rapid motor and mental develop-
ment of the child.
Principles of rehabilitation:
- adaptation to life with a se- Fig 3. Suit «Spiral»
vere defect
- the sequence of social and health care according to age: specialized
kindergartens, boarding school, vocational school, technical school
- out-patient, in-patient, sanatorium treatments (neurological, orthopedic
hospitals, prosthetic companies)
- the participation of different specialists (rehabilitator, psychologist, neu-
rologist, pediatrician, logopedist, orthopedist, etc.)
- the combination of conservative and surgical treatment
- rational prosthesis
- early development of labor skills, according to the defect origin
- appropriate career-guidance.
TESTS
1. Syndrome of increased neuro-reflex excitability due hypoxic-ischemic

lesions of CNS is characterized by:
1) small amplitude tremor of limb, chin
2) weakness
3) lack of consciousness
4) muscular hypotonia
5) hyporeflexia
2. Set the most frequent location of intracranial hemorrhage in premature
baby
1) subdural
2) epidural
3) haemorrhage in cerebellum
4) intraventricular
5) subcortical haemorrhage
3. What are the main signs for the formulation of diagnosis «Cerebral palsy»?
1) movement disorders
2) mental disorders
3) speech disorders
4) autonomic dysfunction syndrome
5) seizures
4. Which form of speech disorders does not occur in children with Cerebral
Palsy?
1) delayed speech development
2) dysarthria
3) aphasia
4) alalia
5) speech disorders due to the reduced of intelligence
5. What form of movement disorder is a basis for diagnosis «Cerebral Palsy»?
1) paresis — different degrees of prevalence and expression
2) hyperkinesis
3) coordination disorders
4) pathological synkinesis
5) all mentioned
Somatoneurologic Disorders (respiratory, cardiac, hematologic, digestive, hepatic, renal, endocrine,
collagen diseases, paraneoplastic syndrome) 235
Topic 22
SOMATONEUROLOGIC DISORDERS (RESPIRATORY, CARDIAC,

HEMATOLOGIC, DIGESTIVE, HEPATIC, RENAL, ENDOCRINE,
COLLAGEN DISEASES, PARANEOPLASTIC SYNDROME)
Topic questions:
І. Pathogenesis of neurologic disorders at systemic diseases (toxic,
dysmetabolic, hypoxic, reflector mechanisms).
ІІ. Neurologic disorders due to:
1. respiratory diseases (pneumonia, pulmonary thromboembolism, chronic pul
monary diseases: chronic obstructive pulmonary disease, pneumosclerosis etc);
2. cardiac and blood vessels diseases (congenital and acquired defects,
myocardial infarction, cardiac rhythm disorders, atrioventricular block,
thromboangiitis obliterans, bacterial endocarditis; chronic obliteration of the
abdominal aorta, chronic obliteration of the abdominal bifurcation of aorta and
major vessels of the lower extremities);
3. hematologic diseases (Addison–Birmer’s anemia, iron deficiency
anemia, leukemia, multiple myeloma, Hodgkin’s disease, hemorrhagic
diathesis);
4. digestive and hepatic diseases (hepatic cirrhosis, jaundice, pancreatitis,
peptic ulcer, chronic gastritis, cholecystitis);
5. renal diseases (renal failure, dialysis consequences, chronic nephritis);
6. endocrine diseases (hyperthyroidism, hypothyroidism,
hyperparathyroidism, hypoparathyroidism, Cushing’s disease, diabetes);
7. collagen diseases (rheumatism, antiphospholipid syndrome, temporal
arteritis, polyarteritis nodosa, polymyositis, lupus erythematosus).
III. Paraneoplastic syndromes.
Nearly all the systemic diseases may cause important neurologic
symptoms. This is the field of common interest for neurologists and internal
medicine specialists.
І. Pathogenesis of neurologic disorders at systemic diseases (toxic,

dysmetabolic, hypoxic, reflex mechanisms).
Nervous system disorders in systemic diseases are caused by dysmetabolic,
toxic, hypoxic, reflex mechanisms.
Dysmetabolic mechanisms are disorders of water, minerals, protein,
carbohydrate, fat metabolism and vitamin deficiency, accompanying somatic
pathology, with emphasis on one or another pathology-specific metabolism

type.
Toxic mechanisms (eg — renal or hepatic failure): the phenomenon of
intoxication, particularly in case of infection, renal and hepatic lesions.
Hypoxic mechanisms occurs in respiratory diseases (pneumonia,
obstructive pulmonary disease, pneumosclerosis) and anemias of different
genesis, heart failure, blood vessels diseases.
Reflex mechanisms cause reflex spasm of the brain blood vessels in
pulmonary embolism, reflected pain and hyperesthesia at reflex zones
(Ged’s zones), which are the areas on the skin, where certain organs are
«projected» due to a common afferent innervation of internal organs and
specific dermatomes corresponding to a particular segment of the spinal cord
(Fig. 1). Pain in this areas is of great diagnostic significance.
Fig. 1. Reflex zones (Head's zones)
ІІ. Neurologic disorders due to:

1. Respiratory diseases.
Neurological disorders can develop on the background of both acute
pulmonary diseases (pulmonary embolism, severe bilateral pneumonia) and
chronic nonspecific lung diseases (emphysema, chronic bronchitis, bronchial
asthma, pneumosclerosis).
Hypercapnia, hypoxemia, falling blood pressure in the big circulation,
vascular spasm, homeostasis violations arising from disorders of ventilation
and pulmonary gas exchange play the leading role in the pathogenesis of
neurologic disorders. All this leads to hypoxia, which is more prominent, than
in other systemic diseases, resulting in frequent and variable focal brain

lesions.
In the case of uncomplicated pneumonia moderate headache, photophobia,
hypersensitivity are observed. When pneumonia is severe, neuropsychiatric
complications occur involving cerebral, membrane and autonomic synolromes.
Pulmonary thromboembolism can be complicated by the following
neurological syndromes: psychomotor agitation, meningeal, epileptic
syndrome.
Chronic lung injury (chronic obstructive pulmonary disease,
pneumosclerosis etc.) manifestes it self with headache, increased fatigue,
irritability.
The basic disease therapy has the leading value in the treatment of
neurological disorders; it is necessary to ensure sufficient ventilation;
sedatives should be terminated because they suppress ventilation.
2. Diseases of the heart and blood vessels (congenital and acquired
defects, myocardial infarction, heart rhythm disorders, bacterial endocarditis,
etc.). The pathogenesis of these diseases is caused by changes in blood
and CSF flow, vascular occlusion, embolism, and sometimes by spreading
inflammation in the blood vessels of the brain (in vasculitis, septic endocarditis).
Initial period of these diseases most often is characterized by asthenic and
autonomic disorders.
Symptoms of congenital heart disease manifest themselves in childhood:
the lack in physical and mental development, syncope, thrombotic stroke,
brain abscess can be observed.
Myocardial infarction can be complicated with drowsiness, irritability,
headache, cardioembolic stroke.
Changes in heart rhythm (paroxysmal tachycardia, atrial fibrillation,
bradycardia) is a common cause of fainting (non-epileptic paroxysmal states).
Atrial fibrillation is the most common cause of cardioembolic stroke.
In the case of atrioventricular block (Adams–Stokes syndrome) syncope,
seizures occur most often on the background of heart rate slowing to 10-
30 beats/minute.
Cerebral form of thromboangiitis obliterans is characterized by simultaneous
destruction of the brain vessels, manifested by repeated transient ischemic
attacks, and blood vessels of the limbs and internal organs.
In the case of infectious endocarditis ischemic stroke, infectious arteritis,
mycotic aneurysm with the development of hemorrhagic stroke, purulent
meningitis or abscess may develop due to the ingress infected emboli in of
the blood vessels the brain.
Chronic obliteration of the abdominal aorta, the aortic bifurcation and

major vessels of the lower limbs is manifested by a gradual development of
symptoms of myelopathy with autonomic, sensory and motor disorders.
If surgical treatment of heart defect is successful, it usually significantly
improves physical and mental development of children.
The incidence of stroke in atrial fibrillation is reduced when using indirect
(Warfarin) or direct (Dabigatran) anticoagulants or aspirin.
In patients with infectious endocarditis antibiotics are used for a long
time (6-8 weeks) followed by surgery. If you detect mycotic aneurysms or
brain abscess, surgical treatment is needed. Prophylaxis of neurological
complications are based on the treatment of heart diseases.
3. Hematologic diseases (pernicious anemia — Addison–Birmer’s
disease, iron deficiency anemia, leukemia, multiple myeloma, Hodgkin’s
disease, hemorrhagic diathesis).
Addison–Birmer’s disease resulting from vitamin B12 deficiency, may
complicated by myelopathy, mainly affecting the posterior and then the lateral
columns of the spinal cord, which causes subacute combined degeneration
of spinal cord, also known as Lichtheim's disease or Subacute combined
degeneration of spinal cord. It is characterized by pain and paresthesia in
the legs, combined with the loss of deep sensitivity, clinically manifested by
sensitive ataxia. Lower spastic paraparesis, dysfunction of the pelvic organs
occur at disease progression.
Daily use of vitamin B12 leads to regression of symptoms.
Patients with Iron Deficiency show general weakness, fatigue, dizziness,
tinnitus, headache, loss of consciousness.
The defeat of the nervous system in patients with leukemia can be caused
by infiltration of leukemic cells elements of the nervous system as well as
hemorrhages, neurotoxic effect of chemotherapy and radiation, electrolyte
disorders, blood circulation due to leukostasis.
Meningeal leukemia — the most common neurological complication
of blood diseases, which is manifested by nausea, vomiting, headache.
Sometimes these symptoms are combined with meningeal syndrome,
seizures, impaired consciousness. In the cerebrospinal fluid leukemic
(«blast») cells are detected.
In the case of chronic and acute leukemia leukoencephalopaty may develop
accompanied by ataxia, aphasia, dementia, seizures, paresis / paralysis.
Neurological complications of multiple myeloma are characterized by
compression of spinal cord, cauda equina, spinal roots by tumors; and
bycranial neuropathy, intracranial myeloma, peripheral neuropathy.
Hemorrhagic diathesis (hemophilia, thrombocytopenic purpura,

hemorrhagic capilar toxicity (Schonlein-Henoch disease) manifests itself with
the tendency to bleeding. Lesions of the nervous system are the result of
bleeding in the brain, meninges, spinal cord.
Prophylaxis of neurological complications of bleeding diathesis is based
on treating the main disease.
4. Digestive and hepatic diseases (hepatic cirrhosis, hepatic
encephalopathy, jaundice, pancreatitis, peptic ulcer, chronic gastritis,
cholecystitis). One of the main symptoms of the digestive tract disorder is
ache in the Head’s zones.
Hepatic encephalopathy occurs frequently in patients with cirrhosis
and is associated with toxic effects of ammonia on the nervous system. It
is manifested by impairment of memory and attention, cognitive disorders,
inadequate behavior, frequent psychomotor agitation and hyperkinesis
(choreoathetosis), tremor («asterixis»).
Asterixis (Gk.: a, sterixis - disability to fixate a position) is also called
hepatic tremor, flapping tremor, a symptom of «hand-flapping». An abnormal
tremor consisting of involuntary jerking movements, especially in the hands.
The tremor is usually induced by extending the arm and dorsiflexing the wrist.
Disorders of consciousness are typical: clear and confused consciousness
can be observed during the day (the «on-off» phenomenon).
The development of sensory form of polyneuropathy is possible.
Treatment of acute hepatic encephalopathy is ineffective, except liver
transplantation. In the case of cerebral edema corticosteroids (Dexamethasone
16-20 mg a day i/v) or osmotic diuretics (Mannitol 15% 200 ml) can be
temporarily effective.
Jaundice may lead to toxic encephalopathy.
In the pathogenesis of neurological complications due to pancreatitis, the
leading role is played by enzymatic dysfunction of pancreas with production
of proteolytic enzymes in large amount. This leads to water and electrolyte
balance disorder and intoxication. In the case of severe pancreatitis, there
is a change of vascular walls, brain edema with development of acute
encephalopathy, manifested by a sharp psychomotor agitation, meningeal
syndrome.
Neurological complications of peptic ulcer, chronic gastritis are often
manifested by a neurotic syndrome and polyneuropathy. They are caused
by different types of faulty metabolism: disruption of proteins, vitamins, fats,
carbohydrates, minerals absorption. Lack of B vitamins is considered as one
of the causes of peripheral nerves damage.
Cholecystitis may be accompanied by an asthenic syndrome, which has

two types — hypersthenic (irritability, emotional lability) and asthenic (fatigue,
resentment). Treatment presupposes prescription of psychotropic drugs.
5. Kidney diseases. Kidney failure of various genesis can be complicated
with both uremic encephalopathy and neuropathy.
Uremic encephalopathy is caused by metabolic disorders as well as the
toxic effect of nitrogenous slag on the brain as a result of kidney failure.
Brain hypoxia, weakening of the functional activity of neurons are noted. The
disease develops gradually: anxiety appears first, then slow perception of
environment, reduced concentration, apathy occur. With the progress of renal
failure cognitive dysfunction, inappropriate behavior, hallucinations occur.
In the case of acute renal failure epileptic seizures may occur.
Management of uremic encephalopathy requires treatment of renal failure:
dialysis and kidney transplantation. For the treatment of epilepsy higher doses
of anticonvulsants are often needed, due to changes in the pharmacokinetics
of certain drugs (dyphenine, valproate) at uremia.
Polyneuropathy is a frequent complication of kidney failure, its main effects
are weakening of vibration sensitivity, loss of Achilles and knee reflexes; patients
complain of unpleasant tingling, a feeling of fullness and pain in the distal leg,
crumps. Regular dialysis may stabilize and reduce the severity of polyneuropathy.
Treatment of chronic kidney failure by hemodialysis has lead to the emergence
of new form of neurological disorders: dialysis encephalopathy, which is mani
festated mainly by dementia. The cause of this complication remains unclear.
Cerebrovascular disorders are more common in chronic nephritis
complicated with hypertension.
Significant hypo- or hyperpotassemia often leads to syndrome of
paroxysmal myoplegia, which is paroxysmal weakness of muscles in arms,
legs, torso to full immobilization (see topic 25).
6. Endocrine diseases. Affection of nervous system diseases often occurs
in thyroid gland diseases with increased (hyperthyroidism) or decreased
(hypothyroidism) of its hormonal function, as well as diseases of parathyroid
gland (hyperparathyroidism, hypoparathyroidism), Cushing’s disease, diabetes.
Hyperthyroidism is characterized by mental disorders, irritability, emotional
lability, sleep disorders. Thyrotoxicosis can lead to the increase of migraine
attacks frequency, appearance of tension headaches, emergence of Graves’
ophthalmopathy, which is characterized by exophthalmos, eyelid retraction,
wide eye slits, pain in the eyes, diplopia is possible.
Optic nerve damage is caused by its compression by increased ocular
muscles. Reduced vision develops gradually and requires regular monitoring.
Hyperthyroidism may lead to myopathic syndrome mainly in the shoulder and

pelvic girdle muscles, which can lead to significant motor disorders and to significant
muscle atrophy (thyrotoxic myopathy). Development of hypopotassemia form of
paroxysmal myoplegia is possible, which is characterized by episodes of muscle
weakness, which can develop to paralysis and last up to several hours.
Patients with hypothyroidism often have slowdown thinking, reduced
concentration, increased drowsiness. Mono- and polyneuropathies at
hypothyroidism occur more frequently than at hyperthyroidism. Almost 10%
of patients there is one tunnel syndrome — carpal tunnel syndrome, which is
caused by the deposition of mucopolysaccharides in the tissues surrounding
the median nerve, and is accompanied by pain in the first three fingers of hand.
In case of hyperparathyreosis the secretion of parathyroid hormone is
increased. It increases phosphorus excretion with the urine and hypercalcemia
development due to calcium extraction from the bones. Neurological
symptoms are observed most often in the form of myopathic syndrome. It is
characterized by fatigue, muscular hypotonia, pain in the limbs.
Hypoparathyroidism often is caused by a decrease in the secretion of
parathyroid hormone with decreased levels of calcium in the blood serum. Clinically
it is manifested by tetanic seizures that occur more frequently in distal limb muscles.
Upper limb muscle cramps are characterized
by a typical position of wrist («obstetrician
hand» — tonic contraction of wrist muscles with
involuntary abduction of straightened fingers)
(Fig. 2). Muscles that unbend foot are involved
in case of lower limbs affection («horse’s foot»).
Seizures of facial muscles are accompanied by tris- Fig. 2. «Obstetrician hand»
mus (lockjaw), eyelids seizures, sardonic smile that looks in hypoparathyreosis
like «fish mouth». Seizures are very painful. Sometimes
epileptic seizures may occur. On CT scan intracerebral calcifications may be revealed.
Cushing’s disease (pituitary basophilic adenoma with excessive release
of adrenocorticotropic hormone) is characterized by fatigue, lethargy, sleep
disturbances, increased blood pressure, faulty of fat metabolism, sexual
dysfunction, bone and skin lesions, steroid myopathy.
The treatment of thyroid and parathyroid gland dysfunction usually leads to
regression of neurological symptoms. At severe oculomotor disorders in patients
with hyperthyroidism it is advisable to administer corticosteroids 60-80 mg per day.
The disorder of the nervous system in diabetes mellitus (DM) is caused by
metabolic faulty caused by hyperglycemia as well as DM treatment with the use of
blood glucose-lowering drugs, which is sometimes accompanied by hypoglycemia.
The pathogenesis of neurological complications of diabetes is based on

microangiopathy.
Therefore, first of all diabetes is a risk factor for stroke.
Polyneuropathy is accompanied by pain in the legs, especially at rest,
and can lead to progression of the diabetic foot syndrome with lower
limbs amputation. Mononeuropathies are possible, including patholgy of
cranial nerves, mostly oculomotor. Hyperglycemia also leads to autonomic
neuropathy with violation of internal organs autonomic innervation.
Acute hypoglycemia due to blood glucose-lowering drugs overdose
begins with the adrenergic symptoms: irritability, anxiety, hunger, tachycardia,
diaphoresis, tremor. Neurological symptoms occur: confusion, drowsiness,
psychomotor agitation, myoclonus, seizures.
When the blood glucose concentration is about 1 mmol/l, a deep coma
developes, accompanied by mydriasis, shallow breathing, muscle atony.
Subacute hypoglycemia does not lead to adrenergic symptoms; it is characteri
zed by slowed thinking, gradual disturbance of consciousness and hypothermia.
7. Collagen diseases (rheumatism, antiphospholipid syndrome, temporal
arteritis, polyarteritis nodosa, dermatomyositis, lupus erythematosus).
The pathogenesis of neurological diseases caused by these disturbances
is due to the autoimmune degenerative and inflammatory changes in the
membranes of brain, spinal cord and blood vessels.
Rheumatism may be complicated by cerebral disorders in children with
major lesion of subcortical nodes — small chorea, which is characterized by
hyperkinesis (rapid, irregular movements, varying in frequency and intensity
mainly in the limbs and face), incoordination, mental and autonomic disorders.
Particular attention is attracted by antiphospholipid syndrome — chronic
vessel-occlusive process with the development of multiple organ ischemia,
including stroke. It occurs mainly in young people because of recurrent blood
clots in small vessels on the background of lupus anticoagulant circulation
and antiphospholipid antibodies presence in blood.
Giant cell arteritis (Horton's disease) is the most common systemic
vasculitis. It is characterized by a sharp local pain in the temporal region due
to the granulomatous inflammation of external branches of carotid vessels.
Palpation shows thickened and painful temporal artery. Blindness may appear.
Polyarteritis nodosa is a lesion of small arteries, pathomorphologically characterized
by formation of compact nodules along the vessels. When the blood pressure
increases, the vascular changes contribute to the ischemic or hemorrhagic stroke.
Due to vasculitis lesions of the peripheral nervous system multiple
mononeuropathy, distal polyneuropathy may occur. Multiple mononeuropathy
is characterized by lesions of peripheral nerves and/or cranial nerves,

particularly the trigeminal, facial or vestibular-cochlear.
Dermatomyositis is a disease with systemic inflammatory lesions of cross-
striated muscles. The absence of cutaneous syndrome indicates the presence
of polymyositis.
The beginning of the disease can be acute with temperature increasing
to 38-39 °C, then the appearance of pain in the muscles and facial erythema.
The most characteristic symptom is a severe muscle weakness, in which the
patient is unable to sit in bed, comb, hold a spoon, and in severe cases, a person
is immobile with gradual atrophy of muscles. In case of involving the muscles
of pharynx and esophagus, swallowing difficulties may develop. Involvement
of muscles of the diaphragm and intercostal muscles is accompanied by
ventilation disorders, development of congestive pneumonia. Diagnostic criteria
of dermatomyositis are clinical, biochemical, electromyographic parameters.
The treatment of the underlying disease (corticosteroids — prednisone 60-
80 mg per day; immunosuppressive therapy — azathioprine 150-200 mg per
day) causes regression of neurological symptoms.
VII. Paraneoplastic syndrome (PNS) is a clinical and laboratory
manifestation of malignant tumor, which isn’t the result of its local or metastatic
growth, but is caused by a nonspecific reaction of various organs and
systems, including the nervous system; or ectopic production of biologically
active substances by the tumor. PNS is common for patients of middle and
old age; structures of the central and peripheral nervous system are involved.
Most often, it develops in lung, breast, ovary cancer, as well as lymphoma.
Sometimes PNS symptoms occur before diagnosis of a malignant tumor.
The most common syndroms:
- Lambert–Eaton myasthenic syndrome;
- Subacute cerebellar degeneration;
- Opsoclonus-myoclonus syndrome;
- Limbic encephalitis;
- Sensory polyneuropathy with severe pain.
Lambert–Eaton myasthenic syndrome (LEMS) develops in patients with
malignant tumors (mostly small cell lung carcenoma) that trigger the autoimmune
process. Violations occur at the presynaptic level: blocking of acetylcholine release.
The most common is proximal muscles weakness. Patients feel difficulty when
walking, it is difficult to climb the stairs, to get up from a chair, some increase of
muscle strength after exercises is characteristic. In addition, autonomic dysfunction
is common (dry mouth, impotence), and while rhythmic electrical stimulation of motor
nerve strenghs of muscle contraction increases (a phenomenon of «increment»).
If LEMS is associated with a malignancy, symptoms often improve dramatically

with tumor removal. If no malignancy is found at initial presentation, patients should
undergo regular surveillance, because the presentation of LEMS can predate
the detection of neoplasm by years. For those with no underlying neoplasm, or
insufficient symptom control with tumor removal, pharmacotherapy is employed.
3,4-Diaminopyridine (3,4-DAP) improves muscle strength and autonomic
symptoms by blocking voltage-gated potassium channels, the drug prolongs
action potentials at motor nerve terminals. Guanidine hydrochloride inhibits
mitochondrial calcium uptake, facilitating the release of acetylcholine at the
motor nerve terminal, but its use is limited by side effects.
LEMS is not very responsive to anticholinesterase drugs, which, however, do
potentiate the effects of 3,4-DAP and guanidine, allowing the use of lower doses.
Patients with small cell lung carcenoma, breast cancer or genital tumors
may have subacute degeneration of cerebellum neurons, which is clinically
manifested by cerebellar ataxia, dysarthria and nystagmus; dysphagia, ptosis,
deafness are also possible.
Opsoclonus-myoclonus syndrome occurs mainly in childhood in case of
neuroblastoma, and in adults in case of lung cancer, cancer of the uterus,
breast, skin. There are opsoklonus — myoclonic hyperkinesia of eye muscles,
which is characterized by rapid chaotic, mainly horizontal movements of
the eyeballs («dancing eyes»). Also myoclonic twitching of facial muscles,
muscles of the trunk and extremities are observed and the third sign is ataxia.
Paraneoplastic limbic encephalitis is characterized by depression,
convulsions, irritability and loss of short term memory. Neurological symptoms
develop quickly and can cause dementia. This encephalitis often happens in
patients with small cell lung carcenoma.
Sensory neuropathy is typically associated with lung cancer, is caused
by degeneration of ganglia, begins with paresthesias and severe pain,
hyporeflexia with a decrease of superficial and proprioceptive sensitivity and
sensitive ataxia; deafness, changes in taste and smell.
Treatment is symptomatic.
TESTS
1. What change in the heart rhythm is the most common cause of

cardioembolic stroke?
1) paroxysmal tachycardia
2) long Q–T syndrom
3) bradycardia
4) atrial fibrillation
5) Adams–Stokes syndrome
2. A 36-year-old patient complains of the pain and paresthesia in the legs.
Neurological examination detected the loss of deep sensitivity, sensitive atax-
ia, lower spastic paraparesis. Patient suffers from the Addison–Birmer’s dis-
ease. What structures are mainly affected in this case?
1) only lateral columns of the spinal cord
2) peripheral nerves
3) anterior columns of the spinal cord
4) posterior and then lateral columns of the spinal cord
5) brain stem
3. What mechanism does play the leading role in the pathogenesis of neuro-
logic disorders in respiratory diseases?
1) dysmetabolic mechanism
2) toxic mechanism
3) hypoxic mechanism
4) reflex mechanism
5) all mentioned
4. What changes in the cerebrospinal fluid are typical in the meningeal leukemia?
1) albumin-cytological dissociation
2) leukemic («blast») cells
3) spider web clot
4) T-tau (tau-protein)
5) decrease in protein level, glucose increasing
5. A 67-year-old patient has small cell lung carcinoma. He complains of the
proximal muscles weakness, feels difficulty when walking, it is difficult to climb
stairs, some increase of muscle strength after exercises is characteristic. On
the rhythmic electrical stimulation of motor nerve a phenomenon of «incre-
ment» is detected. Name this syndrome.
1) Adams–Stokes syndrome
2) Addison–Birmer syndrome
3) Lambert–Eaton syndrome
4) myopathic syndrome
5) paroxysmal myoplegia
TOPIC 23
SOMATONEUROLOGICAL SYNDROMES (ASTHENIC, AUTONOMIC

DYSFUNCTION, POLYNEUROPATIC, NEURO-MUSCULAR
DISORDERS)
Topic questions:
I. Asthenic syndrome.
II. The syndrome of autonomic dysfunction (AD).
1. AD with predominance of sympathoadrenal nervous system tone.
2. AD with predominance of parasympathetic nervous system tone.
3. The cardiac type AD.
4. Panic attacks.
5. Autonomic visceral dysfunction.
6. Diagnosis.
7. Treatment of autonomic dysfunction.
III. Syndrome of polyneuropathy.
IV. Syndrome of neuromuscular disorders.
1. Myopatyc syndrome.
2. Myasthenic syndrome.
3. Syndrom of paroxysmal myoplegia.
4. Encephalopathy syndrome.
I. Neurasthenic syndrome, or asthenic reaction, or neuro-psychological

weakness, is the morbid condition, which is characterized by:
- fatigue and exhaustion with mood instability;
- the weakening of self-control;
- intolerance;
- sleep disorders;
- loss of the long-term mental and physical stress capacity;
- intolerance to loud noises, bright light, sharp odor;
- irritability and rapidly occurring exhaustion that follows;
- affective lability with prevalence of depressed mood with features of
petulance and discontent.
Asthenia, neurasthenia result from internal organs diseases, infections,
intoxication, emotional, mental and physical overstrain.
The treatment is aimed at eliminating the main cause of asthenia. The
proper use of vitamins, organization of work and leisure, walking, regular and
Somatoneurological syndromes (asthenic, autonomic dysfunction, polyneuropatic, neuro-muscular disorders) 247
adequate nutrition, sleep recovery, physical exercises should be applied. Also

the nootropic agents (piracetam, Ginkgo biloba) are prescribed.
II. The syndrome of autonomic dysfunction. Its clinical manifestations
are associated with the violation of neurohumoral regulation of cardiac activity
and systemic circulation as a result of functional disorders of the autonomic
structures at various levels. The conventional term is «somatoform autonomic
nervous system dysfunction», which belongs to the class of «mental and
conduct disorders».
AD is classified according to the prevalence of the autonomic tone:
1. Autonomic dysfunction with predominance of sympathoadrenal nervous
system function.
2. Autonomic dysfunction with predominance of parasympathetic nervous
system tone.
3. The cardiac type AD.
4. The mixed (vascular-cardiac) type AD.
1. AD with predominance of sympathoadrenal nervous system tone
(hypertensive type) is characterized by sympathicotonia:
- headache;
- increased irritability;
- fatigue;
- pain in the heart area;
- tendency to high blood pressure;
- accelerated heartbeat;
- various neurotic reactions and states;
- constipation.
2. AD with predominance of parasympathetic nervous system tone
(hypotonic type) is manifested by vagotonia:
- general weakness;
- fatigue;
- headache;
- hypotension;
- bradycardia;
- dizziness, syncope;
- cardialgia;
- diarrhea.
3. The cardiac type AD is manifested by ache or discomfort in the heart,
feeling short of breath on exertion, palpitations. ECG data show functional
extrasystoles, PQ interval shortening by slowing of intraventricular conduction,
signs of ventricular repolarization dysfunction.
Mixed type AD is characterized by clinical symptoms, inherent for cardiac

AD type in combination with sympathetico- or vagotonia.
4. Panic attacks (autonomic paroxysms) — spontaneous, sporadic, intense
periods of anxiety. The duration of such an attack lasts for 20-30 minutes.
The symptoms of a panic attack:
- pain or discomfort in the chest;
- arterial blood pressure rising;
- stuffiness;
- dizziness or weakness;
- fear of losing control;
- fear of death;
- fear of «going mad»;
- nausea or stomach discomfort;
- numbness or tingling;
- frequent palpitations;
- shaking.
The attack ends with the excessive urination.
5. Autonomic-visceral dysfunction is a clinical and pathogenetic form of
autonomic dysfunction associated with violations of autonomic regulation of internal
organs. The most common manifestations of autonomic-visceral dysfunction are
such functional secretory-motor disorders of the gastrointestinal tract as irritable
bowel syndrome, biliary dyskinesia, neurogenic bladder, asthma etc.
6. Diagnosis.
The presence of autonomic dysfunction symptoms requires the exclusion
of various diseases, accompanied by dysfunction of autonomic nervous
system. Laboratory and instrumental methods of examination are conducted
to diagnose the somatic function.
7. Treatment of autonomic dysfunction.
Prevention and treatment of autonomic dysfunction should begin in
childhood. It has already been proved, that the autonomic dysfunction that
begins in children or teenagers, can become an unfavorable background of
many diseases in adults.
The treatment of autonomic dysfunction is conducted against a background
of the basic therapy that lead to it. Herewith day regime optimization is
recommended: night sleep — at least 8-10 hours, daily walks — 2-3 hours,
limited television watching and computer work to 1,5 hours, morning exercises.
Nutrition for patients with sympathicotonia should consist of meals with
salt content restriction, exclusion of spices, coffee, tea, chocolate, whereas in
case of a vagotonia these products can be included into the diet.
Physiotherapy place an important role in the treatment of autonomic

dysfunction. In case of sympathicotonia electric sleep, music and
aromatherapy, baths with a decoction of pine and melissa or mint, bubble
baths, showers, massage of neck area by a calming technique, followed by
electrophoresis of sodium bromide are used. In case of vagotonia ultraviolet
irradiation, mineral, salt, carbon dioxide or oxygen bath, power shower and
circular shower, whirlpool are more appropriate.
Also sedative therapy (tincture or extract of valeriana root, melissa,
motherwort, solutions of bromine), nootropic agents (piracetam, Ginkgo
Biloba) are used.
In patients with sympathicotonia, antihypertensive drugs are prescribed:
β-blockers, diuretics (hypothiazide, indapomid).
Patients with vagotonia undergo courses of treatment with ginseng
tincture, Eleutherococcus, Shizandra Chinese, aralia, Levzei, Beresh drops.
III. Syndrome of polyneuropathy is a multiple lesion of the distal regions
of peripheral nerves (see topic 17). It is observed in infections (influenza,
diphtheria), intoxications (alcohol, lead, etc.), metabolic disorders (diabetes
mellitus, ets), avitaminosis.
Depending on the affected trunks of peripheral nerves (autonomic, sensory,
motor), polyneuropathy is characterized by pain, numbness in the limbs,
sensitivity disturbances by the type of «gloves» and «socks», weakness and
hypotonia of muscles in distal parts of arms and legs accordingly.
The therapy is based on treating the main disease, also vitamin B complex,
anticholinergic agents, massage, physical therapy, exercise therapy are used.
IV. The syndrome of neuromuscular disorders:
1. Myopathic syndrome in the majority of cases is the symmetrical,
painless and slowly progressive muscle lesion in proximal parts of extremities.
Clinical signs:
- motor impairments, which are manifested by muscle weakness: the
reduce of force and range of the active movements;
- the absence of sensitivity violations;
- muscle atrophy often occurs.
The patient can not raise their hands above the horizontal line, for example,
comb their hair; difficulties in climbing stairs are also marked (see topic 24).
It is difficult to get up from a low chair; the patient should lean against their
arms or thighs or against what is in front (table, chair). The same difficulties
the patient feels in bending and then trying to straighten up. If they sit on their
haunches, they often can not stand up. In cases where it is necessary to get
up from the floor, the patient is performing a number of additional movements:
first kneels, leaning his hands against the floor, then puts one foot forward,
leans his hands against the thigh and begins to straighten the body; finally
pulls up and puts the second leg in the same position and leaning with both
hands on his hips, slowly moves to a vertical position.
The weakness progresses during months or weeks (polymyositis), or even
a few hours (acute paroxysmal myoglobinuria).
Restoring the muscle function involves treating the main disease.
Physiotherapy plays an important role.
2. Myasthenic syndrome is associated with violations of the allocation
of acetylcholine from presynaptic stores and is characterized by intermittent
weakness in the proximal muscles of the limbs (see topic 11).
Occurs in paraneoplas-
tic processes, particularly
in bronchogenic cancer
(Lambert–Eaton myas-
thenic syndrome), botu-
lism (botulinum toxin pen-
etrates the nerve endings
through presynaptic mem-
brane and cleaves pro-
teins that participate in the
release of acetylcholine in
the synaptic cleft), at treat-
ment with aminoglycoside
antibiotics (Neomycin, Fig. 1. Neuromuscular synapse
Gentamicin, Kanamycin,
Streptomycin, polypeptide antibiotics (Colistin, Polymyxin B). While using pen-
itsyllamin D can cause the block of postsynaptic membrane potential.
The treatment involves medications that promote the release of acetylcholine
from the nerve terminals of neuromuscular connections — guanidine chloride
(20-50 mg/kg/day) and amiridin (1 mg/kg/day). In myasthenic syndrome
occurring due to the use penicillamin D, anticholinergic medications are used
(neostigmine, pyridostigmine).
3. Syndrome of paroxysmal myoplegia is characterized by recurring
paralysis of the limbs (see topic 11). During the attack of myoplegia, the
muscle tone is reduced, tendon reflexes disappear, the muscles do not
respond to mechanical and electrophysiological stimulation. The syndrome
is the result of endocrine disorders: hyperthyroidism, Conn disease (primary
hyperaldosteronism), Addison disease, and others. The pathogenesis of
paroxysmal myoplegia is associated with decreased levels of potassium

and sodium metabolic disorders. Mineral metabolism is regulated by
mineralocorticoids (aldosterone), which is highlighted by the glomerular zone
of the adrenal glands. The excretion of corticoids is regulated by pituitary
hormones, which are regulated by release factors of hypothalamus. Thus, the
disease may develop as excited adrenal function, as well as in violation of
regulatory influences of hypothalamic-pituitary sites.
Using potassium salts (potassium chloride, potassium bromide) 2-25 g per
day, aldosterone antagonist (Aldactone 100-200 mg per day), Veroshpiron,
blood transfusions are necessary.
4. Encephalopathy syndrome is a global brain dysfunction due to a
variety of different organic and inorganic causes. It is divided into hepatic
encephalopathy, hypoxic- ischemic, neonatal, uremic, acute hypertension,
chronic traumatic, toxic encephalopathy, etc.; Lyme disease (borreliosis),
Hashimoto’s Encephalopathy.
A distinctive feature of encephalopathy is an altered mental state. Depending
on the type and severity of encephalopathy, common neurological symptoms
are loss of cognitive function, personality changes, inability to concentrate,
lethargy, and syncope. Other neurological symptoms may include myoclonus
(involuntary twitching of a muscle or group of muscles), nystagmus, tremor,
seizures, agitation, and respiratory disorders, such as breathing with apnea,
Cheyne-Stokes breathing, posthypercapnia apnea.
The therapy of encephalopathy syndrome involves the use of
memantine — the antagonist of glutamate N-methyl-D-aspartate (NMDA)
receptors, inhibiting glutamatergic neurotransmission and progression of
neurodegenerative processes. Cholinesterase inhibitors in brain are used
(donepezil, rivastigmine); they block the disintegration of acetylcholine, which
transmits neural excitation in the CNS. Also nootropic agents are used.
In the presence of one of the above-mentioned syndromes, the main
disease should be diagnosed and treated.
TESTS
1. A 52-year-old patient complains of frequent headache, dizziness, nausea,

weakness, loss of memory, insomnia, emotional disorders. Subcortical
reflexes are positive, tendon reflexes are increased. Disorder of coordination
of the Romberg test. Name the neurological syndrome.
1) myelopathy
2) radicular
3) encephalopathy
4) asthenic
5) acute disorder of cerebral blood circulation
2. Myasthenic syndrome occurs in case of:
1) bronchogenic cancer
2) fibromyoma
3) leukemia
4) Kaposi sarcoma
5) ischemic stroke
3. Name clinical signs of myopathic syndrome.
1) sensitivity violations
2) motor impairments
3) ataxia
4) oculumotor disorders
5) seizures
4. A 43-year-old patient complains of numbness and weakness in the legs
after long walk. Neurological status: feet are cold to the touch, stocking & glove
distribution sensitivity disorders. Achilles reflexes are decreased, pathological
reflexes are absent. Name the neurological syndrome.
1) myasthenic syndrome
2) polyneuropathy
3) myelopathy
4) encephalopathy
5) radicular
5. What are the main clinical symptoms of panic attacks?
1) pain or discomfort in the chest
2) dizziness or weakness
3) fear of death
4) nausea or stomach discomfort
5) everything correct
Hereditary degenerative diseases of the nervous system (primary and secondary myodystrophy) 253
Topic 24
HEREDITARY DEGENERATIVE DISEASES OF THE NERVOUS

SYSTEM (PRIMARY AND SECONDARY MYODYSTROPHY)
Topic questions:
1. Definition and classification of progressive muscular dystrophies.
2. Pathogenesis of progressive muscular dystrophies.
3. Pathomorphology of progressive muscular dystrophies.
4. Primary muscular dystrophy (myopathy); inheritance, clinical picture,
course and diagnosis:
1) pseudohypertrophy malignant Duchenne muscular dystrophy
2) benign Becker muscular dystrophy
3) juvenile scapulohumeral muscular dystrophy (Erb’s type)
4) facioscapulohumeral muscular dystrophy (Landouzy–Dejerine type).
5. Secondary muscular atrophy; inheritance, clinical picture, course and
diagnosis:
1) spinal amyotrophies:
- acute malignant infantile-onset spinal muscular atrophy (Werding–
Hoffmann disease or spinal muscular atrophy type I;
- intermediate spinal muscular atrophy type II;
- late-onset juvenile spinal muscular atrophy (Kugelberg-Welander
disease or spinal muscular atrophy III type).
2) neural muscular atrophy (Charcot–Marie–Tooth desease).
6. Treatment of progressive muscular dystrophies.
1. Definition and classification of progressive muscular dystrophies.

Hereditary diseases of the neuromuscular system are a large heteroge-
neous group of pathological conditions; characterized by muscle atrophy,
muscle weakness, static and locomotor functions disorders. The base of dis-
eases is genetically determined by the destruction of muscle tissue or periph-
eral motor neuron — anterior horns of the spinal cord or peripheral nerves.
The group of hereditary diseases of the neuromuscular system includes pro-
gressive muscular dystrophies (myopathy, amyotrophy), paroxysmal myople-
gia, myotonia.
Depending on neurological status, morphological changes and localiza-
tion of the pathological process, progressive muscular dystrophies are divid-
ed into two groups:
1) primary muscular dystrophies — myopathies — associated with primary

muscle lesion; the function of peripheral motor neuron is saved;
2) secondary (neurogenic) muscular atrophies — muscular atrophy — as-
sociated with primary disorders of muscles innervation due to peripheral nerve
or anterior horn cells of the spinal cord lesion; muscle tissue suffers secondary.
Classification of progressive muscular dystrophies
Primary muscular dystrophies (myopathies)
1. Pseudohypertrophy malignant Duchenne muscular dystrophy;
2. Benign Becker muscular dystrophy;
3. Juvenile scapulohumeral muscular dystrophy (Erb’s type);
4. Facioscapulohumeral muscular dystrophy (Landouzy–Dejerine type).
5. Rare and atypical forms:
- Progressive external ophthalmoplegia (Graefe disease);
- Bulbar-paralytic Hoffmann form;
- Distal Hoffman-Navil form;
- Myosclerotic Sestan-Lezhan form.
Secondary muscular atrophies (muscular atrophies)
1. Spinal muscular atrophies:
- Acute malignant infantile-onset spinal muscular atrophy of Werd-
ing-Hoffmann (spinal muscular atrophy type I);
- Intermediate spinal muscular atrophy type II;
- Late-onset juvenile spinal muscular atrophy (Kugelberg-Welander dis-
ease or spinal muscular atrophy III type).
2. Neural muscular atrophy (Charcot–Marie–Tooth desease).
3. Rare and atypical neural muscular atrophies:
- Dejerine–Sottas syndrome (progressive hypertrophic interstitial poly-
neuropathy of childhood);
- Neural Sestan-Lezhan muscular atrophy;
- Neural Roussy–Levy amyotrophy (Roussy–Levy hereditary areflexic dystasia);
- Refsum’s disease (polyneural ataxic degeneration).
2. Patogeneis of progressive muscular dystrophies is not completely
known. There are several theories of primary muscular dystrophies: muscle
hypoxia, neurogenic theory, defective membranes theory, impaired metabo-
lism of cyclic nucleotides and neurotransmitters theory.
Muscle hypoxia theory: microcirculatory changes play a leading role in the
origin and development of trophy disorders of muscle tissue. However, identi-
fied changes are nonspecific and can not be evaluated as primary.
Neurogenic theory: it has been suggested that nerve damage may be the
cause of primary dystrophies.
Due to the theory of «defective membranes», primary muscular dystrophy

is caused by initial demage of the structure of muscle membranes. Due to
increased diffusion across cell membranes muscle fibers lose a number of
components (enzymes, glycogen, amino acids, etc.). These substances pass
into the blood and decrease the amount of biologically active substances in
the muscle tissue. Degeneration of muscle fibrils is determined by the rate of
loss of enzymes, especially creatine phosphokinase. There is also a theory
that the structural and functional defects in muscle membrane lead to exces-
sive calcium penetration in the muscle fibers that damages muscle cells.
Theory of impaired neurotransmitters metabolism: increased synthesis of
adrenaline and noradrenaline in the muscles at primary progressive muscular
dystrophy is observed; it causes increased level of acetylcholine and toxic
action on the muscle fiber.
Thus, based on above-mentioned theories there is a complex of neurogenic
factors and biologically active substances affecting muscle tissue. These fac-
tors act through mediators — cyclic nucleotides (cyclic adenosine monophos-
phate) directly involved in the regulation of metabolism of muscle fibers.
A problem of neurogenic muscular atrophy pathogenesis also remains un-
solved. It is believed that spinal muscular atrophy develops as a result of incor-
rect development of anterior horn cells in the spinal cord. Neural muscular at-
rophy can be caused by disturbances of myelin synthesis of peripheral nerves.
3. Pathomorphology of progressive muscular dystrophies. During
the histological examination of muscles in patients with myopathy uneven
diameter of muscle fibers and their replacement by connective and adipose
tissue was observed. There is an increase in amount of connective tissue and
formation of dense fibrous ring along the muscle fibers and blood vessels
with disease progression. The proliferation of adventitia, blood vessel lumen
narrowing and sometimes thrombosis occurs in vessel walls intensifying the
myodystrophy process.
4. Primary muscular dystrophies (myopathies) — inheritance, clinical
picture, progression and diagnosis:
1) Pseudohypertrophy malignant Duchenne muscular dystrophy
Inheritance: recessive, sex-linked type (X-chromosome type). Only boys
are ill.
Debut. Symptoms of the disease appear in the first three years of life.
Clinical picture. During the 1st year, a delay in motor development of chil-
dren manifests itself: children start to sit, get up, and walk late. At 2-3 years
muscle weakness, muscle fatigue during exercise occur, as well as atrophy of
pelvis muscles and proximal muscles of the legs.
A characteristic symptom
of the disease is enlarged
calf muscles («dwarf calf»)
(Fig. 1). Pseudohypertrophy
is a state characterized by the
abnormality of the muscle tis-
sue due to the replacement of
the muscle tissue by adipose
tissue («false enlargement»).
Reflexes are reduced (es-
pecially the knee ones). Re-
traction of Achilles tendon is
observed. The children feel
difficulty to climb the stairs, Fig. 1. Pseudohypertrophy of calf muscles
they cannot jump, they get up
from the floor with big effort. After a while there comes a weakness and atro-
phy of muscles of the shoulder girdle.
Duchenne muscular dystrophy is characterized by a combination of mus-
cle atrophy with osteo-articular, cardiovascular and neuroendocrine systems
disorders. Osteo-articular violations are characterized by deformities of verte-
brae, feet and chest. Changes occur in muscles of heart with the development
of cardiomyopathy. In 30-50% there are patients develop neuroendocrine dis-
orders (Cushing’s syndrome, adiposo-genital dystrophy). This form of myop-
athy is characterized by changes in intelligence.
The disease progresses rapidly, malignant. Children of 7-10 develop se-
vere movement disorders and 14-15 year-olds get bedridden. Patients die
early from heart and respiratory failure.
Diagnosis is based on clinical-genealogical analysis, clinical features of
the disease, the data of biochemical studies (increased serum creatine phos-
phokinase levels in 30-50 times), electromyography (signs of primary type of
muscle injury).
2) Benign Becker muscular dystrophy — benign version of myopathy
Inheritance: recessive, sex-linked (X-chromosome type), which is charac-
terized by slower progress than Duchenne muscular dystrophy — a mild form.
Only boys are ill.
Debut. The first signs of the disease manifest themselves in 10-15 year-
olds.
Clinical picture. Initial symptoms: muscle weakness, abnormal muscle fa-
tigue, hypotrophy of muscles that develops symmetrically. These signs ini-
tially appear in the proximal muscle groups of the lower extremities (pelvic
and thigh muscles) and then extend to the proximal muscle groups of the up-
per limbs. Consequently «duck march» or waddling gait is formed. A person
moves alternately to one or the other side while walking, i. e. tilts the body
towards the loaded limb.
Pseudohypertrophy of calf muscles is characteristic. Tendon reflexes are
preserved for a long time, only knee reflexes dicrease later.
Cardiac disorders are absent or mild (cardiomyopathy, bundle branch
block). Endocrine disorders are manifested by gynecomastia, decreased libi-
do, impotence. Colour abnormalities are possible, e. g. daltonism. Intelligence
in case of this form does not suffer.
The disease progresses slowly. Patients keep working for a long time.
3) Juvenile scapulohumeral muscular dystrophy (Erb’s type)
Inheritance: autosomal recessive type. Males and females are ill, but boys
are ill more often.
Debut. The first symptoms occur at the age of 14-16: muscle weakness,
fatigue.
Clinical picture. Due to weakness and atrophy of proximal muscles groups
of the shoulder girdle (including mm. serratus, trapezius) the symptom of
«free shoulders« (at sudden lifting of a child under the armpits, the head gets
disposed between shoulders) and winged scapula (wing-shaped shoulder
blades) occur (Fig. 2).
Fig. 2. Winged scapula, shoulder girdle muscle hypotrophy in patients with

juvenile scapulohumeral muscular dystrophy (Erb’s type)
Sometimes myodys-
trophic process begins
in pelvic muscles or si-
multaneously affects the
muscles of the pelvic and
shoulder girdles, then
the process involves the
muscles of the back and
abdomen with waist thin-
ning (Fig. 3). Trying to get
up from the floor the pa-
tient rises in some stages,
helping himself with his
hands (Fig. 4).
Lumbar lordosis is in-
creased due to the weak- Fig. 3. Increased lumbar lordosis, waist thinning
ness of the long muscles of in patients with juvenile scapulohumeral
the back, buttocks and ab- muscular dystrophy (Erb’s type)
dominal muscles (Fig. 3).
Fig. 4. Boy with muscular dystrophy walks his hands up

his legs to get into standing
Waddling gait is characteristic. Pseudohypertrophy, joint contractures are

absent. Reflexes get reduced or absent early.
Course. Patients keep working for a long time.
4) Facioscapulohumeral muscular dystrophy (Landouzy–Dejerine
type). Name of the disease indicates the predominant localization of injured
muscles.
It’s inherited by an autosomal-dominant type.

Debut. The disease begins at the age of 15-20.
Clinical picture. There is weakness and mus-
cle atrophy of scapulas muscles, which later
spreads to the facial muscles. Patients have poor
facial expression, without wrinkles — «myopathic
face» (Fig. 5). Orbicular oris and orbicular oculi
muscles are affected early, patient can not move
lips to form a tube, cannot whistle; mouth an-
gles do not rise up while smiling and mouth gets
stretched («transverse smile»). Lips are bulged
due to pseudohypertrophy («tapir mouth»). Due
to the weakness of anterior serratus and a trape-
zius muscle the symptom of «free shoulders» and
Fig. 5. «Myopathic face»
winged scapula occur. Muscle tone is reduced
in the facioscapulohumeral
in the proximal muscle groups of arms. Tendon
muscular dystrophy
reflexes of the upper extremities (biceps, triceps)
(Landouzy–Dejerine type)
are reduced. Mental abilities are not affected.
The disease is slowly progressive.
Course. Patients keep working for a long time.
Diagnosis is based on clinical-genealogical analysis of the disease, pecu-
liarities of the clinical course and muscular dystrophy localization.
5. Secondary myodystrophies (muscular atrophies) — type of inheri-
tance, clinical picture, progression and diagnosis.
This group of diseases includes spinal (occurring due to lesion of the an-
terior horns of the spinal cord), and neural muscular atrophy (occurring due to
lesion of the peripheral nerves).
1) Acute malignant infantile-onset spinal muscular atrophy (Werd-
ing-Hoffmann disease or spinal muscular atrophy type I).
It is inherited by an autosomal recessive type.
Debut — age from birth to 6 months. Decreased motor activity of the fetus
can be observed even in utero due to sluggish movement.
Clinical picture. Sick children have general weakness in the proximal mus-
cle groups, hypotension and tendon areflexia. There is a «frog posture» in the
supine position with external rotation of the hips. Strength of mimic muscles is
relatively saved, eye muscles are not involved.
There may be a paradoxical respiration associated with paralysis of the
intercostal muscles, which precedes paresis of the diaphragm. With the de-
velopment of bulbar syndrome pharyngeal reflex disappears, muscle atrophy
and fasciculation of the tongue occur, feeding gets greatly hampered, which
can lead to the death of a child from aspiration pneumonia.
Deformity of the chest occurs. Contractures of large joints, vertebral defor-
mity and delayed psycho- and speech development are not typical.
Course. Some children are able to sit but never walk. If muscle weakness
is detected immediately after birth, death usually occurs approximately at the
age of 6 months. If muscle weakness is detected after 3 months of life, the
term of survival may be about 2 years. The main cause of death — intercur-
rent respiratory diseases.
Diagnosis. The concentration of creatine phosphokinase is normal or
slightly increased. According to electroneuromyography signs of affection of
anterior horns are shown: potentials of fasciculation at rest, the speed of the
impulse by peripheral motor nerves is not changed.
2) Intermediate spinal muscular atrophy type II.
Debut of muscle weakness occurs usually between 6 and 24 months of
life, but may occur at 3 months.
Clinical picture. Initial signs of weakness are usually symmetrical and occur in
the proximal muscle groups of the extremities. The weakness of the muscles of the
hips is the most noticeable symptom. Throughout the early period of life weakness
of distal muscle is minimal or absent. Tendon reflexes of the affected muscles are
depressed or disappear. All patients are able to sit, the majority can stand, some —
can walk. Mimic muscles and external eye muscles at the early stages of the disease
are not affected. Contractures usually form in childhood. Often there is pseudohy-
pertrophy of calf and gluteal muscles, which can be mistaken for Duchenne myo-
dystrophy. Feet gradually
turn to ecvinovarus position.
Children show deformity of
the spine and chest, con-
genital dislocation of the hip
joint (Fig. 6).
Course. Muscle weak-
ness progresses slowly. In
some cases, it remains sta-
ble for many years and then
progression resumes. Pa-
tients survive until adulthood.
When weakness begins be-
tween 3 and 6 months, the Fig. 6. Deformity of the spine and chest
disease is more severe. in spinal muscular atrophy type II
Diagnosis. EMG data indicate anterior horns lesion: potentials of fibrilla-

tion and fasciculation are detected. The concentration of creatine phosphoki-
nase in blood is normal.
3) Late-onset juvenile spinal muscular atrophy (Kugelberg-Velander
disease or spinal amyotrophy type III)
Motor activity during the prenatal period is sufficient; child is healthy after birth.
Debut — between 2 and 15 years of life, mostly under 5 years and always
after 18 months of life.
Clinical picture. Firstly, there is an unstable gait with increasing proximal
muscle weakness in the legs. Sometime there is pseudohypertrophy of calf
muscles, which often leads to a false diagnosis of Duchenne myodystrophy.
Progressive weakness may also occur in the distal leg parts or proximal arm
regions. Hands are affected later. Facial muscles may be weak, but the move-
ments of the eyeballs are always normal. Bulbar disorders are not typical.
Approximately half of patients may develop bone deformities, rare — tendon
retraction and contractions in joints. Tendon reflexes of weakened muscles
are absent or greatly reduced. Postural tremor of hands is often observed.
Course. The disease progresses very slowly, and often its progress stops.
Diagnosis. Creatine phosphokinase concentration may exceed the normal
rate significantly, and the increase of the enzyme is in direct correlation with
duration of illness. Half of the patients on EMG shows spontaneous activity:
fasciculation and fibrillations indicating anterior horns injury. Conduction by
sensitive nerves’ fibers is always normal, whereas the speed of the motor
fibers at long duration of disease can be reduced.
4) Neural muscular atrophy (Charcot–Marie–Tooth desease).
Frequency: one case per 50 000.
Inheritance: autosomal recessive, autosomal dominant or X-linked type.
Pathomorphology: segmental demyelination of peripheral nerves, dener-
vation and fiber atrophy of muscles.
Debut. The first signs of the disease appear during the 1st decade of life or
at the beginning of the 2nd decade, rarely — at a younger age.
Clinical picture. At the onset of the disease: muscle weakness in the calf
muscles during long lasting walking is observed. Patients quickly get tired
when standing at one place, and to reduce fatigue they often march in place.
Atrophy develops initially in the muscles of legs and feet. Peroneal muscle
group is mainly affected, as a result the legs take the form of «inverted bottle»
or «stork legs» (Fig. 7).
The feet are deformed: foot with a high arch — «hollow foot» (so-called
Friedreich’s foot), hammer-like deformity of the fingers (Fig. 8).
Fig. 8. «Hollow foot» in neural muscular

atrophy (Charcot–Marie–Tooth desease)
Paresis of extensor muscles of feet
Fig. 7. Symptom of «inverted changes the walking of patients — steppage
bottle» or «stork legs» in neural (gait is characterized by high lifting of leg
muscular atrophy (Charcot– to put fingers first and then the whole foot);
Marie–Tooth desease) walking on heels is impossible. A few years
after the development of changes in the
legs, there is a weakness with atrophy of hands muscles that take the form
of «clawed» or «monkey» type. Muscle tone is reduced diffusely in the distal
parts of extremities. Tendon reflexes change unevenly: achille reflexes disap-
pear in the early stages of the disease and knee reflexes as well as reflexes
of the triceps and the biceps remain preserved for a long time.
Less commonly, the disease begins with sensory disorders: pain, pares-
thesia, tingling in the distal parts of lower extremities. In the late stages of the
disease sensory disorders are present in the majority of patients.
Often there are autonomic disordes in the form of distal hyperhidrosis,
hyperemia of hands and feet.
Prognosis is usually favorable.
The diagnosis is based on the data of genealogical analysis, clinical neu-
rological features (muscle atrophy in distal parts of extremities, sensitivity dis-
orders by polyneural type, slow progressive course) of the disease, data of
electromyography (reduced speed of peripheral nerve conduction because of
demyelination).
6. Treatment of progressive muscular dystrophies.
Treatment of progressive neuro-muscular diseases is only symptomatic:
exercises, massage, physiotherapy, orthopedic correction, diet, prevention of
osteoarticular deformities and contractures of the limbs.
Therapeutic exercises include active and passive motion in all joints in

all positions: at standing, sitting and lying down. Active movements are per-
formed in isometric mode (muscle tension without changing their length while
preserving the desired posture) with elements of a limited power tension de-
pending on the stage of the process. Exercises should be conducted regu-
larly — several times daily. Breathing exercises are very important especially
after immobilization of the patient.
Orthopedic correction of a concervative nature (special splints, bandages)
and surgical treatment (Achilles tendon tomia, myotomia) are aimed to prevent
the formation of contractures and pathological posture, as well as saving the
independent mobility of the patients. In each case, it is necessary to consider
the expected benefits and possible damage from the surgical intervention.
Patients with contractures need thermal procedures and careful muscle ex-
tension up to 30-20 times daily followed by the imposition of tires during sleep.
Diet: high amount of proteins, reduced amount of fat (especially animal
products) and carbohydrate, optimal and balanced content of vitamins and
minerals.
TESTS
1. A 26-year-old patient complains of the weakness and fatigue in the muscles

of feet. Neurological status: gait with high lifting of legs (steppage), stand-
ing on heels is impossible. Hypotrophy of affected muscles changes legs in
the form of «inverted bottle» or «stork legs». What nerve innervates affected
muscles in this disease?
1) tibial
2) femoral
3) peroneal
4) sciatic
5) sural
2. Parents of an 11-month-old boy complain of his weakness, «frog posture»
in the supine position with external rotation of the hips, disorders of respiration.
Neurological status: general weakness in the limbs, paresis of the intercostal
muscles, fasciculations in the muscles of extremities, tongue.
What sign from the following allows to exсlude the primary muscular dystro-
phy in patient?
1) general weakness
2) disorders of respiration
3) fasciculations
4) age of patient
5) «frog posture»
3. A 20-year-old patient complains of the weakness and fatigue in the muscles
of the pelvic and shoulder girdle, problems while walking, getting up off the
floor in some stages, helping himself with his hands. Symptoms slowly prog-
ress since 15 years.
Neurological status: atrophy of proximal muscle groups of the pelvic and
shoulder girdle, the symptoms of «free shoulders», «duck march». Reflexes
are reduced. Pseudohypertrophy is absent. What is the most likely diagnosis?
1) Duchenne muscular dystrophy
2) Erb’s muscular dystrophy
3) facioscapulohumeral muscular dystrophy (Landouzy–Dejerine type)
4) neural muscular atrophy (Charcot–Marie–Tooth desease)
5) muscular atrophy type III
4. A 32-year-old patient complains of the weakness of scapulas and facial
muscles. Neurological status: biceps and triceps reflexes are reduced. Pa-
tient has poor facial expression, without wrinkles — «myopathic face», cannot
move lips to form a tube, and cannot whistle. Lips are bulged due to pseudo-
hypertrophy. Where is origin of injury in this disease?
1) anterior horn cells of spinal cord
2) lateral horn cells of spinal cord
3) peripheral nerves
4) muscle tissue
5) nuclei of cranial nerves in brainstem
5. A 29-year-old patient has been suffering from weakness in the calf and feet
muscles while walking for 4 years, as well as pain while standing at the same
place for a long time. Neurological status: paresis of extensors of feet, achille
reflexes are absent, walking on heels is impossible. What is the most likely
diagnosis?
1) Duchenne muscular dystrophy
2) juvenile scapulohumeral muscular dystrophy (Erb’s type)
3) facioscapulohumeral muscular dystrophy (Landouzy–Dejerine type)
4) neural muscular atrophy (Charcot–Marie–Tooth desease)
5) muscular atrophy type III
Hereditary degenerative diseases with lesions of the pyramidal and extrapyramidal nervous systems 265
Topic 25
HEREDITARY DEGENERATIVE DISEASES WITH LESIONS OF THE

PYRAMIDAL AND EXTRAPYRAMIDAL NERVOUS SYSTEMS
Topic questions:
1. Hereditary degenerative disease with lesion of the pyramidal system:
- Hereditary spastic paraplegia (Strümpell–Lorrain disease).
2. Hereditary degenerative diseases with lesion of the extrapyramidal
system:
1) Hepatocerebral degeneration (Wilson disease)
2) Huntington’s chorea
3) Parkinson’s disease (trembling paralysis)
4) Essential tremor
3. Myotonia congenita (Thomsen disease).
4. Myasthenia gravis.
5. Paroxysmal myoplegia:
1) Hyperkalemic;
2) Hyperkalemic;
3) Normokalemic;
4) Secondary (symptomatic) forms of paroxysmal myoplegia.
1. Hereditary degenerative diseases with lesions of the pyramidal

system
Classification
- Strumpell’s spastic paraplegia.
- Family spastic paralysis with amyotrophic, retinal degeneration and
oligophrenia (described by Kellin).
- Family spastic paralysis with ichthyosis and oligophrenia (described by
Sjogren and Larsson).
- Hereditary spastic paraplegia (Strümpell–Lorrain disease) occurs
most commonly, and is caused by the degeneration of the pyramidal tracts,
thin (fasciculus gracilis) and cerebellar roots at the level of spinal cord.
Type of inheritance: autosomal dominant.
Clinical picture. Initial symptoms are found in any age manifested by
slow motion in the lower limbs and fatigue during fast walking. Progressive
spasticity develops slowly in the legs with tendon hypereflexia, pathological
reflexes, clonus of feet and knee cups. Pathological synergy of muscles during
gait causes the varus foot

(Fig. 1), muscle and tendon
contractures. Sometimes,
the typical picture of spastic
paraplegia syndromes are
combined with lesions of
cerebellar tract and posterior
columns of spinal cord
(cerebellar and sensitive
ataxia).
Typical features are:
- Prevalence of spasticity Fig. 1. Varus foot deformation
over paresis;
- Preservation of abdominal reflexes;
- Lack of sensory disorders;
- Preservation of intelligence;
- Absence of the pelvic organs dysfunction.
Differential diagnosis is carried out primarily with multiple sclerosis, a
tumor of the thoracic level of the spinal cord.
Life prognosis is favorable. Disability depends on the degree of motor
function disorders manifestation.
Treatment. Muscle relaxants are prescribed: Mydocalm, Baclofen, Sirdalud,
including injections of botulinum toxin type A (Disport, Botox). Physiotherapy
(electrophoresis with sodium oxybutyrate on the lower limbs), exercises, and
if necessary — orthopedic correction.
2. Hereditary degenerative diseases with lesion of the extrapyramidal
system.
Classification:
- Hepatocerebral degeneration (Wilson’s disease);
- Huntington’s Chorea;
- Parkinson’s disease (tremor paralysis);
- Essential tremor;
- Torsion dystonia;
- Double athetosis;
- Myoclonus epilepsy (described by Unverriht and Lundborg);
- Generalized Tourette’s tic;
- Rülf’s seizures;
- Gunn’s trigemino-oculomotor synkinesis.
1) Hepatocerebral degeneration (HCD) (hepatolenticular degeneration,

Wilson’s disease) — a chronic progressive hereditary degenerative disease,
which is characterized by mainly affecting the basal ganglia of the central
nervous system and liver.
Etiology and pathogenesis. Type of inheritance: autosomal recessive,
it occurs with equal frequency in men and women. HCD gene is mapped
to the long branch of chromosome 13. The pathogenesis of the disease is
based on hereditary copper metabolic disorders. In healthy individuals, the
bulk copper delivered with food, after absorption in the intestine, is excreted
via bile or through the kidneys via ceruloplasmin. Only a small part (direct
copper) comes to organs and tissues in combination with albumin. In case of
HCD, due to reduction of the ceruloplasmin concentration, there is a violation
of withdrawal and excessive copper and it is accumulation in various tissues,
mostly in basal ganglia (firstly, n. Lenticularis), in the liver, iris and in the
cerebral cortex, the cerebellum, spleen, lens. Focal sclerosis and softening
are developed in the affected organs.
Clinical picture. The first symptoms of the disease occur at age of
6-35 years, most often at 10-15 years. The clinical picture is characterized by:
a) gradual increase of muscles rigidity,
b) various hyperkinesia (chorea, torsion dystonia, athetosis)
c) psychical disorders.
Seizures are possible. Along with neurological manifestations, liver
enlargement and its dysfunction are observed.
The specific symptom is the
appearance of Kayser–Fleischer rings
on the iris, of golden-green or greenish-
brown color (Fig. 2), which is seen in
light of the slit lamp.
There are five main forms of HCD:
- abdominal;
- rigid-arrhythmic-kinetic;
- trembling;
- trembling-rigid;
Fig. 2. Kayser–Fleischer ring
- extrapyramidal-cortical.
The abdominal form is characterized by
impaired liver function, jaundice, hepatic- and splenomegaly, ascites, hemorrhagic
syndrome. Neurological symptoms occur in the late stages of the disease.
The rigid-arrhythmic-kinetic form is the most malignant. Neurologic
manifestations develop in the age of 7-15; they are usually preceded by liver
damage. The clinical picture is dominated by muscle rigidity and hyperkinesia

(hemiballismus). There are also amimia, dysphagia and dysarthria.
The trembling form is characterized by the tremor, which is aggravated
when performing voluntary movements and may include facial and masticatory
muscles as well as ones of eyeballs. Speech is trembling and scanning.
In many cases, the tremor is combined with rigidity, the tremor appears in
the upper and rigidity appears in the lower extremities (the trembling-rigid form).
The extrapyramidal-cortical form is characterized by disorders of higher
brain functions, the presence of paralysis, stiffness, seizures, decreased
intelligence with degradation of the personality.
Diagnosis. HCD should be suspected in case of development of
extrapyramidal symptoms in combination with liver disease and mental
disorders.
The main diagnostic criteria:
- presence of Kayser–Fleischer ring;
- decrease of ceruloplasmin level in plasma;
- increase of urinary copper excretion — hypercupruria;
- hypo-copper-aemia.
MRI data: atrophic changes in the area of the
cerebral hemispheres, cerebellum, subcortical
nuclei, as well as reduction of signal intensity
from nucleus lentiformis and increase of signal
along the contour of these lesions (Fig. 3).
Treatment. The drug of choice, which
excretes the copper, is penicillamine (Cuprenyl)
at a dose of 250 mg per day orally with a further
increase the dose to 1-2 grams with urine
copper excretion control. Physicians prescribe
Zinc sulfate at a dose of 200 mg 3 times a day.
Doctors also use hepatoprotectors.
Diet is of great importance, excluding
products containing copper: nuts, chocolate, Fig. 3. MRI of the brain of a
liver, mushrooms, spinach. patient with hepatocerebral
2) Huntington’s disease — one of degeneration (T1 weighted
the most malignant progressive hereditary image)
diseases of the nervous system caused by
systemic degeneration of extrapyramidal motor structures and cerebral
cortex, characterized by a combination of chorea-athetoid movements and
progressive dementia. Men suffer more than women do.
Type of inheritance: autosomal-dominant with high penetrance of the

mutant gene (chromosome 4 that codes huntingtin protein).
The classic description was made by George Huntington, who observed
patient members of one family that lived next door to him in New York.
Pathological changes. Pathognomonic for Huntington’s disease are
considered changes in the subcortical ganglia, atrophy of the caudate nucleus
and, to a lesser extent, other structures of basal nuclei (putamen and globus
pallidus). In addition, there is diffuse atrophy of cortex gyrus.
Pathogenesis. The pathogenesis is not sufficiently studied. Deficiency of
GABA is observed in brain cells, there is the increased ferrum level in the cells
of the black substance, dopamine metabolism violation occurs. The disease
is considered to be caused by the increased toxicity of huntingtin.
Clinical picture. Motor disorders usually occur in young or middle age (35-
50 years), sometimes — up to the age of 20.
The first symptoms can be restlessness; patient and his relatives do not
regard restlessness movement as a disease. Over time, motor impairment
increases and can lead to disability. Frequent, sudden, not rhythmic
movements of the limbs or trunk are typical. There are spasms of facial
muscles, sobs, disorders of articulation. Loss of coordination when walking:
walking is «dancing like» — choreiform gait. The memory is preserved until the
later stages of the disease, but attention, thinking and executive functions are
violated at the very beginning. Often there are depression, apathy, alienation,
periodic disinhibition. In some cases, delusions and obsessive-compulsive
disorders develop, and therefore mental disorders are misdiagnosed.
The course, the prognosis. The duration of the disease is in average
15 years. Death occurs of intercurrent infection or because of suicide.
Diagnosis:
1. Clinical and genealogical analysis
2. CT scan and MRI of the brain (cerebral cortex atrophy)
3. DNA analysis.
Treatment. Currently, there is no treatment that can stop the disease.
There is currently no effective treatment for HD dementia.
If chorea is severe enough to interfere with function, consider treatment
with benzodiazepines, such as clonazepam or diazepam; valproic acid;
dopamine-depleting agents, such as reserpine or tetrabenazine; and finally,
neuroleptics.
The drug tetrabenazine has shown some positive effects in the treatment
of chorea, for patients with HD. It selectively depletes central monoamines by
reversibly binding to the type-2 vesicular monoamine transporter.
3) Parkinson’s disease (tremor paralysis) is a chronic progressive

degenerative disease of the central nervous system, which is clinically
manifested by voluntary movements’ disorder. The cause is unknown and
Parkinson’s disease (PD) is not considered hereditary, although genetics may
play a small role.
The English physician James Parkinson, first described PD in 1817 in his
«An Essay on the Shaking Palsy» who outlined the results of observations by
six patients, described precisely and in full picture of primary disease.
Epidemiology. In Ukraine, the prevalence of PD is approximately 133
cases per 100 000 inhabitants. The average age of debut of PD is 55 years.
Etiological structure of Parkinsonism.
Due to recent agreements of the European Parkinson’s Disease
Association, the Parkinson syndrome is divided into four groups:
- Idiopathic Parkinsonism — PD (approximately 75% of all Parkinson
syndromes). If the onset occurs by the age of 40, then it is called juvenile PD;
- Genetic forms of PD, Parkinsonism family syndrome — a hereditary
form, marked by gene localization (eg, PARK1);
- Symptomatic (secondary) Parkinsonism: vascular, drug-induced (due to
use of reserpine, cinnarizine, antidepressants, neuroleptics, etc.), toxic (due
to poisoning by manganese, mercury, carbon monooxide) postencephalitic,
on the background of brain tumors, hydrocephalus, metabolic disorders (in
hypothyroidism, hepatic failure);
- Parkinsonism within other neurodegenerative diseases (atypical forms
of Parkinson’s disease, sometimes called «syndrome of Parkinsonism plus»
due to additional symptoms).
Pathomorphology. PD is characterized by morphologically abnormal
loss of dopaminergic neurons in the black substance, the presence of
cytoplasmic inclusions (Lewy bodies), degenerative changes mainly in
the basal ganglia and hippocampus and often the atrophy of the cerebral
cortex. The causes of idiopathic PD are not fully studied. Never the less,
three main factors are considered as the most likely causes of PD: aging,
heredity, and toxins.
Pathogenesis. Due to modern concepts, PD is a disease of neurotransmitter
metabolism. Normally, extrapyramidal system sends impulses to the peripheral
motor neurons, providing the myostatic tone by muscles’ willingness to
voluntary movements, their purposefulness and smoothness, via balance of
activity of striatum and pallidum parts, that is, cholinergic and dopaminergic
neurotransmitter components of extrapyramidal system. Striatum has
inhibitory effect on the motor system and pallidum inhibits «the inhibitory
effect» of the striatum. In case of PD, due to the deficiency of dopamine,

which activates pallidum, there is extra inhibitory effect of the striatum on
movements and static.
There are three clinical forms of PD:
- akinetic-rigid;
- rigid-tremor;
- tremor, that is expressed mainly by tremor, rigidity of movement in these
patients is negligible.
Stages of PD by Hoehn and Yahr.
0 — there are no symptoms.
1 — unilateral manifestations of symptoms
2 — bilateral manifestation without imbalance.
3 — from moderate to severe, some postural instability, but does not need
any help; the maintenance of equilibrium is required when performing test for
postural instability.
4 — severe disability, but can walk and stand independently.
5 — bedridden, if there is no help.
Features of the disease debut: the first motor disorders occur in one hand
or leg in the form of tremor and/or stiffness. After that, the process captures
new muscular body segments, develops to hemiparkinson stage, and only
then moves to the other side of the body.
The main symptoms of Parkinson’s disease at the onset are always one-
sided:
I. Bradykinesia and hypokinesia, which manifest themselves with poor and
slow movements that severely limit patient’s activity.
- acheirokinesia (no associated movements such as waving hands when
walking) (Fig. 3);
- short steps when walking (microbasia) (Fig. 4);
- shuffling gait;
- out of the dummy (arms bent at the elbows, legs — at knees, torso tilted
to the front);
- masked face — hypomimia or amimia, seldom blinking;
- micrographia — violation of writing in the form of reduced size of letters;
- speech becomes monotonous and slow (bradylalia).
II. Muscle rigidity is the tension of muscles — their tone is increased.
Raising the tone in Parkinsonism leads to plastic, wax flexibility. During
passive movements of the limbs, the symptom of «cogwheel» is observed.
- rigidity at the time of movement can be accompanied by discomfort and
pain.
Fig. 5. The patient view with

Fig. 4. Slow gait and acheirokinesia at Parkinson’s disease (stature
Parkinson’s disease of the «petitioner»)
- the stature of the
«petitioner» (stiffness in the
muscles of the trunk flexor)
(Fig. 5)
III. Resting tremor
- uni- and then bilateral
tremor, which disappears or is
reduced during movement;
- simultaneous move-
ments of the thumb and fore-
finger resemble the movement Fig. 6. Tremor by type «rolling pills»
of «counting coins» or «rolling
pills» (Fig. 6).
The tremor of head is not
characteristic of PD.
III. Postural disorders —
difficulty in overcoming inertia
of rest as well as inertia
of motion. It is difficult for
a patient to start moving,
and when started — it’s
difficult to stop. There are the
phenomena of propulsion Fig. 7. Postural disturbances at
(propulsio — pushing forward), Parkinsonism — propulsion
lateropulsion and retropulsion.
They lie in the fact that, starting to move forward, to the side or back, the body
is usually ahead of the legs, resulting in disturbed position of the center of
gravity, a person loses stability and falls down (Fig. 7.)
Paradoxical kinesis are possible, when the patient, because of emotional
expression, begins to move freely, then again falls into a state of hypokinesia.
Besides major clinical symptoms of Parkinsonism, there are also:
- autonomic disorders (hypo- or anosmia (violation of smell), constipation,
hyperhidrosis, greasiness of the skin, orthostatic hypotension, salivation,
pollakiuria — frequent urination);
- swallowing difficulties;
- depression (30-90% of cases);
- pain, internal tremor, paresthesia;
- sleep disorders. Sleep may be interrupted by pollakiuria, nocturnal
akinesia, abnormal movements (dystonia, myoclonus), or irresistible need to
move the legs (restless leg syndrome);
- disorders of cognitive and memory functions (weakening of memory,
decrease of mental alertness).
Diagnosis. In clinical practice, it is possible to confirm PD by levodopa
test. The essence of the test — receiving therapeutic daily dose of levodopa
+ carbidopa (Nakom) or levodopa + benserazide (Madopar) within 4-5 days.
The average dose for testing is 200-250 mg/day taken 3 times.
Treatment strategy.
PD is incurable; all existing methods are aimed at reducing the symptoms of
the disease. Drug therapy is lifelong and currently it is the basis of pathogenic
treatment of PD. The principle of pathogenic therapy is the combined use of
different means of influence on the main pathogenic links.
Recently, drugs of the following groups have been widely used:
1. substitution therapy by levodopa drugs (Nakom, Madopar). Dosage for
L-dopa is 100 mg 2-3 times a day, and if needed it can be increased, but
usually it does not exceed 600 mg per day in 3-4 times;
2. dopamine agonists: piribedillum (Pronoran), pramipexole (Mirapex),
ropinirol, rotigotine (Neupro).
3. Monoamine oxidase В inhibitor (MAO-B): selegiline (Eldepryl, Jumex).
4. catechol-O-methyltransferase inhibitors (COMT): entacapone.
5. NMDA-receptor antagonists: amantadine (Neomidantan, PK- Merz).
6. antocholinergics: trihexyphenidyl (Parcopan, Cyclodol).
It should be noticed that taking cholinolytics leads to cognitive disorders.
Surgical treatment includes stereotactic interventions (talamotomy and
pallidotomy), which break the abnormal ring connections that unfortunately
are able to recover themselves. The duration of effect is from several months

to 1-3 years.
Deep brain stimulation through introducing special electrodes is the
modern method of treatment. It inhibits brain regions responsible for the
symptoms of PD.
4) Essential tremor. ET is a progressive neurological disease with
involuntary rhythmic trembling of hands, head, and sometimes voice, legs
and torso. ET doesn’t not affect life expectancy, but interrupts social activity
and lowers self-esteem and sometimes causes invalidity.
Type of inheritance: autosomal-dominant with large variations in
expressiveness. The average age from the onset of the disease is 50 years
(from 10 to 70). Men suffer more often than women do.
Clinical picture. Bilateral postural tremor with/without kinetic tremor involving
arms and forearms, which is visible and constant. Usually there is tremor of hands,
but it may involve the head, tongue, throat and legs. Postural tremor is characteristic,
intentional tremor is less expressed, later may be joined by resting tremor.
To diagnose the disease, the patient should suffer over 5 years.
The main drug in the treatment of the disorder is propranolol (60-800 mg/
day), topiramate (up to 400 mg/day), nadolol (120-240 mg/day). Surgery is
also effective — deep brain stimulation in the area of ventral intermediate
nucleus of the thalamus, thalamotomia.
3. Myotonia congenita (Thomsen disease).
Inherited by an autosomal dominant type.
Violations of myo-neural conductivity play an important role in the
pathogenesis of the disease. There are elevated levels of acetylcholine
found in muscles of such patients, and in the blood and cerebrospinal fluid —
reduced cholinesterase activity.
Clinical picture. The first symptoms appear between the ages of 8-15 years.
Myotonic spasms are present — difficulty to relax muscles after their active
reduction. Spasms are located in different groups of muscles of the trunk,
limbs and circular muscles of the eye. Clenching fist, prolonged static tension
of the lower limbs, jaws closure, eyelids folding cause tonic spasms. Relaxed
phase of tense muscles is delayed, patients cannot move fingers apart,
open mouth, open eyes, reposition the lower extremities. However, repeated
motions reduce manifestations of the spasms.
Mechanical stimulation of muscles is increased: when hit by hammer on
the tenor, the thumb moves apart and is opposed to other fingers from a
few seconds to 1 minute; after being hit by the hammer on the tongue fossa
appears on it, due to the inability to relax muscles instantly.
Patients with myotonia look odd: due to hypertrophy of different muscle

groups, they resemble professional athletes. During palpation, the muscles
are tense, hard, but their strength in them is objectively reduced. Tendon
reflexes are not affected.
The course is slowly progressive. The efficiency remains ongoing.
Treatment. Patients are prescribed phenytoin (Diphenin) — 0.1-0.2 g
3 times a day. Thermal treatments and massage also has positive effect.
4. Myasthenia gravis.
Definitions. Myasthenia gravis is the most common autoimmune disease,
characterized by lesions of neuromuscular synapses due to production
of autoantibodies to acetylcholine receptors (AcHR) (85%) or a specific
enzyme — muscle-specific tyrosine kinase (MuSK). As a result, muscle
fatigue develops, which increases on background of physical activity, and
decreases after rest, or after receiving anticholinesterase agents.
Epidemiology. Prevalence — 1 case per 10,000-20,000 population.
Women are affected twice more often than men are. It can occur in any age,
but most often, the disease manifests itself at 2-3-rd decade.
Pathogenesis. The key neurotransmitter, that transmits nerve impulses
from presynaptic nerve fiber membrane to postsynaptic muscle membrane,
is acetylcholine, which binds with receptors of postsynaptic membrane, leads
to the formation of action potential and muscle contraction. Acetylcholine is
destroyed by the enzyme cholinesterase in the synaptic cleft, which leads to
the cessation of nerve impulses.
Loss (blocking) of 60% of acetylcholine receptors leads to muscle
weakness. In 40-60% of cases, the cause of myasthenia gravis is changing the
thymus gland (hyperplasia, thymoma). This causes autoimmune aggression
with immunological cross-reaction to the cholinergic receptors, leading to
receptor blockage and violation of the nerve impulse conduction.
Classification, offered by Myasthenia Foundation of America (Myasthenia
Gravis Foundation of America).
Class I — eye form; strength of other muscles is preserved
Class II — eye muscles are involved, mild weakness in other muscles.
Class III — eye muscles are involved, moderate weakness in other
muscles.
Class IV — eye muscles are involved, severe weakness in other muscles.
Class V — the need for intubation accompanied or not accompanied by
the artificial ventilation.
Clinical picture. Chronic progress is typical, with periodic exacerbations
as crises.
Characteristic features of clinical picture:

- prevalence of pathological process on different muscle groups can be
quite variable from one-sided ptosis to involvement of almost all muscles;
- dynamic symptoms (in the morning the patient feels better)
- symptoms reduces after rest and after taking anticholinesterase drugs;
- ophthalmoparesis that does not fit into the innervation zone III, IV,
VI pairs of cranial nerves, diplopia,
ptosis;
- weakness of facial muscles
(difficulty when trying to inflate cheeks,
closing eyes);
- chewing muscle weakness;
- weakness of the pharynx muscles,
larynx, tongue (bulbar syndrome);
- respiratory failure due to Fig. 8. Strabismus and ptosis in
weakening of the intercostal muscles, patients with myasthenia that occur
diaphragm; when trying to open eyes
- disruption of the extremities;
- weakness of the neck muscles (hang head) and trunk;
- reflexes are normal;
- sensitive and pelvic disorders are not present.
Diagnosis
1. Tests on muscle fatigue. To provoke:
- ptosis, the patient is asked to look up or aside, or move eyelids, or close
eyes for 30 seconds
- dysarthria — read text;
- weakness of the masticatory muscles — to make about 100 chewing
movements with a closed mouth;
- weakness of the neck muscles — lower head and look at your navel for
1 minute;
- weakness of muscles of the shoulder girdle — extend hands forward or
to the sides and keep for 3 minutes;
- weakness of the legs — squat.
Walker phenomenon: repeated palm compression and extension cause
weakness of the forearm and even strengthening of the ptosis.
2. A positive neostigmine test: neostigmine 0.05% in doses of 1.5-2 ml is
injected subcutaneously. Regression of all symptoms appears after 20-
40 minutes, and after 2-3 hours symptoms are renewed.
3. Electroneuromyography: decrement test, which is to reduce the amplitude
of the M-response: due to the repetitive electrical stimulus of the nerve,

the strength of the muscle innervated by this nerve is a lot less at the 5th
electric stimulus compared to the 1st one.
4. CT scan to exclude mediastinal thymoma.
5. Detection of antibodies to acetylcholine receptors — AcHR or a specific
enzyme — muscle-specific tyrosine kinase — MuSK.
Differential diagnosis.
- Lambert–Eaton syndrome (see topic 22) develops in patients with
malignant tumors (mostly — small cell lung cancer) that trigger the
autoimmune process. Violations occur at the presynaptic level: blocking the
release of acetylcholine. The most common is proximal muscle weakness.
Differences: decreased or absent tendon reflexes, autonomic dysfunction
occurs (dry mouth, impotence), and under repetitive electrical nerve
stimulation, «increment» arises (amplitude of M-response is not decreasing,
but increasing).
- Neurasthenia, when patients complain of weakness and fatigue, but in
reality, it is lethargy, decreased activity, and not the true muscle fatigue.
- Thyrotoxicosis is also accompanied by the fatigue of muscles. Research
of thyroid function has to be carried out in suspected myasthenia.
- Botulism. Enzyme synthesis is disturbed, which activates the formation
of acetylcholine, i.e., the problem occurs in presynaptic membrane. There are
also ptosis, diplopia and bulbar paralysis phenomena. However, in case of
botulism, mydriasis may occur, expressed dry mouth, constipation.
- Intracranial tumor, for example meningioma of small wing of sphenoid
bone. Patients suffer from diplopia. MRI helps to identify these tumors.
The course, life expectancy. With modern methods of diagnosis and
treatment, mortality is less than 1%, mainly from aspiration pneumonia or
respiratory failure. About 80% achieve complete or partial remission during
treatment. The course of myasthenia gravis associated with development of
antibodies to MuSK is more favorable and never leads to a fatal outcome.
Treatment.
Etiotropic treatment is absent. In the presence of thymoma, after
thymectomy remission is achieved in 75%.
The purpose of pathogenic treatment is to «unload synapse» and
«eliminate muscle blockage»:
- Plasmapheresis is conducted for individuals with decompensation of
clinic and high titer of autoantibodies.
- Human immunoglobulin intravenous (0.2-0.4 g/kg/day)
Next, it is necessary to stop the production of antibodies:
Corticosteroids — prednisone 1 mg/kg;

Cytostatics — azathioprine, cyclosporine, cyclophosphamide should be
prescribed.
Symptomatic therapy. Anticholinesterase drugs:
- Pyridostigmin bromide 30-60 mg 3 times/day;
- Or neostigmine methylsulfate by 0.5-1.5 mg subcutaneously 3 times/
day;
In addition, potassium salts agents.
Complications of Myasthenia gravis: myasthenia and cholinergic crisis.
Myasthenic crisis occurs in 10% of cases, usually due to a change in the
functional state of synaptic apparatus, under the influence of various factors:
infection with feverish conditions, menstruation, fatigue and so on, or due to
decrease of anticholinesterase drugs dose, because of different reasons. The
main dangerous are: the bulbar dysfunction, weakness of respiratory muscles
with the increase of respiratory failure. In intensive care unit, patients undergo
pathogenic therapy; mechanical ventilation is applied as indicated.
Cholinergic crisis occurs in 90% of cases. It is associated with an overdose
of anticholinesterase drugs, resulting in symptoms of muscarinic and nicotinic
intoxication: muscle fasciculation, salivary hypersecreting, sweating, pallor,
bradycardia, abdominal pain and diarrhea. Anticholinesterase drugs are
temporarily canceled. Patients are moved to intensive care unit, where they
are slowly intravenously injected 0.5-1.0 ml of 01% solution of atropine,
mechanical ventilation is appointed, plasmapheresis is performed.
5. Paroxysmal myoplegia.
Hereditary paroxysmal myoplegias are a group of diseases, inherited by
autosomal dominant type, as well as clinical syndromes of sudden attacks of
muscle weakness, up to complete immobilization. In the interacted period,
there are no neurological symptoms.
Classification, depending on the level of potassium during the attack:
- Low potassium (hypokalemic);
- High potassium (hyperkalemic);
- Normal potassium range (normokalemic).
Paroxysmal myoplegias are associated with dysfunction of cellular
membrane channels, that regulate the cell electrolyte penetration: penetration
of chlorine, sodium and calcium into the cell is disrupted, leading to membrane
depolarization, followed by reduction of sarcolemma excitability and the
development of paresis or plegia.
- Hypokalemic myoplegia.
Disorder of potassium channels is the basis of pathogenesis. Excessive
intake of potassium in the muscle cell causes the membrane potential

violations.
Clinical manifestations. The first symptoms often appear at the age of 15-
25 years. Paroxysms are manifested by sudden development of myoplegia,
often at night. Immobilization occurs in the muscles of the limbs, neck and
torso. Cranial and respiratory muscles are not usually involved, but sometimes
due to paralysis of respiratory muscles, death can occur. During the attack,
a decrease in muscle tone, tendon reflexes, and autonomic dysfunction: the
labiality of heart rate, blood pressure, and hyperhidrosis occur. There are also
violations of cardiovascular activity: changes in the ECG — flattening of the T
wave, depression of ST segment. Consciousness is always maintained.
Duration of attacks — from several hours to 3 days, the frequency varies.
The concentration of potassium in the blood during the attack is reduced.
The attacks are provoked by excessive carbohydrate foods, cooling,
physical activity, excessive consumption of salt, the use of alcohol.
Treatment. Diet plays an important role: food, poor in carbohydrates and
salt but rich in potassium: prunes, nuts, beans, cocoa, dried apricots, potatoes,
raisins. During the attack potassium chloride is prescribed — intravenous or
per oral.
- Hyperkalemic myoplegia.
Pathogenesis. Molecular-genetic defect, associated with the dysfunction
of the alpha-chain of protein, responsible for the penetration of sodium ions
into the cell. Herewith, hyperpolarization of sarcolemma takes place.
Clinical manifestations. The disease begins in the early years of life. Unlike
hypokalemic paralysis, hyperkalemic myoplegia usually develops during the
day and runs easier. Paroxysms of myoplegia last from 30 minutes to 2 hours.
Attacks are preceded by paresthesia. Clear paralysis are rare.
During the attack, potassium level in the blood is increased. The attacks
are provoked by starvation, physical activity, and food rich in potassium.
Treatment. Paroxysm disappears after eating, sweet tea or i/v injection of
20 ml of 10% calcium chloride solution. Diet, high in carbohydrates, salt, but
poor in potassium is prescribed.
- Normokalemic myoplegia.
Clinical manifestations. The disease starts before the age of 10 years.
Slowly (for several days) moderate weakness in the muscles of the trunk,
limbs and chewing muscles increases, and then, also slowly (for 1-3 weeks),
there is the regression of symptoms. Provoking factors: rest after physical
activity, long stay in a fixed position, hypothermia, alcohol drinking, use of
potassium drugs. The level of potassium in the blood is within normal limits.
Treatment. A diet rich in sodium chloride (up to 10 g). The attack disappears
after glucose is injected. In addition, acetazolamide (Diacarb) is prescribed.
- Secondary (symptomatic) forms of paroxysmal myoplegia are caused
by hyperthyroidism, hyperaldosteronism and excessive loss of potassium with
the urine, when vomiting and having diarrhea, that accompany the diseases
of kidney or digestive tract, the use of saluretics (see topic 22).
TESTS
1. A 23-year-old patient C. complains of slow motion in his lower limbs and

fatigue during fast walking. Neurological status: tendon hyperreflexia, patho-
logical reflexes, ankle and knee clonus. Strumpell’s spastic paraplegia is sus-
pected. What clinical feature is the most important for this diagnosis?
1) prevalence of spasticity over paresis
2) pathological reflexes
3) ankle clonus
4) knee clonus
5) all mentioned
2. A 31-year-old patient N. entered the neurological department be-
cause the tonic-clonic seizures. Patient has jaundice, Kayser–Fleіscher
rings on the iris, liver enlargement. Neurological status: decrease of in-
telligence, muscles rigidity, torsion dystonia and athetosis. These symp-
toms begin to occur 2 years ago with a progressive increase of symp-
toms. What are the main paraclinical criteria for correct diagnosis?
1) ceruloplasmin level decrease in plasma, urinary copper excretion in-
crease
2) urinary copper excretion decrease, ceruloplasmin level in plasma in-
crease
3) serum iron level decrease
4) serum iron level increase
5) red color of urine
3. A 32-year-old patient has frequent, sudden, not rhythmic movements of
the limbs and trunk, spasms of facial muscles, violation of articulation. Her
walking is «dancing like». Sometimes she has depression, apathy, alienation,
periodic disinhibition. These symptoms occurred 1 year ago and had pro-
gressive course. What is the main of the paraclinical criteria of diagnosis?
1) decrease of serum iron level
2) CT scan and MRI of the brain

3) DNA analysis
4) Walker’s phenomenon
5) decrease of serum copper level
4. Patient D. complains of tremor in right hand and leg. Neurological ex-
amination: bradykinesia and hypokinesia, hypomimia, bradylalia, mus-
cle rigidity, unilateral tremor of «rolling pills», which disappears or is re-
duced during movement. What drugs are contraindicated for this patient?
1) substitution therapy by levodopa drugs
2) Haloperidol
3) Monoamine oxidase В inhibitor
4) dopamine agonists
5) NMDA-receptor antagonists
5. A 62 year-old patient complains of one-sided ptosis and diplopia,
weakness of the extremities. In the morning the patient feels better,
symptoms are reduced after rest. Tests on muscle fatigue and Walk-
er’s phenomenon are positive. What is your preliminary diagnosis?
1) Myasthenia gravis
2) Lambert–Eaton syndrome
3) botulism
4) intracranial tumor
5) paroxysmal myoplegia
REFERENCES
1. Неврологія: підручник / І.А. Григорова, Л.І. Соколова, Р.Д. Герасимчук [та

ін.]; за ред. І.А. Григорової, Л.І. Соколової. — К.: Медицина, 2014. — 639 с.
2. A-Z of neurological practice: a guide to clinical neurology / Larner A.J.,
Coles A.J., Scolding, N.J., Barker, R.A. — Springer Science and Business
MEDIA, 2011; 819 p.
3. Adams and Victor's Principles of Neurology 10th Edition 10th Edition / Allan
Ropper, Martin Samuels, Joshua Klein NY, McGraw-Hill Education —
2014. — 1654 p.
4. Aids to the Examination of the Peripheral Nervous System, 5e 5th Edition /
Michael O'Brien, LA, Saunders Ltd. — 2010. — 72 p.
5. Billington M. Adult Status Epilepticus: A Review of the Prehospital and
Emergency Department Management / M. Billington, O.R. Kandalaft O.R.,
I.P. Aisiky // J. Clin. Med. — 2016. — Vol. 5(9). — 74 p.
6. Clinical Neurology / Michael Aminoff, David Greenberg, Roger Simon: Ph.
McGraw-Hill Education / Medical; 9 ed. — 2015. — 448 p.
7. Comprehensive Review in Clinical Neurology: A Multiple Choice Question
Book for the Wards and Boards 1 / by Esteban Cheng-Ching), Lama
Chahine, Eric P. Baron, Alexander Rae-Grant ТН LWW; 2011. — 730 р.
8. DeJong's The Neurologic Examination Seventh Edition / William W.
Campbell NY, LWW; Seventh edition, 2012. — 830 p.
9. Hankey’s clinical neurology / Gorelick P.B., Testai F., Hankey G.,
Wardlaw J.M. — Second ed., 2014; 976 p.
10. Kondziella D. Neurology at the bedside / D. Kondziella, G. Waldemar.
Springer UK.; 2013; 375 p.
11. Lecture notes. Neurology / Lionel Ginsberg. WILEY-BLACKWELL; 9th
revised edition edition, 2010; 208 p.
12. Localization in Clinical Neurology Sixth Edition / Paul W. Brazis,
Joseph C. Masdeu, José Biller NY, LWW, 2011. — 668 p.
13. Merritt's Neurology Thirteenth Edition / Elan D. Loui, Stephan A. Mayer,
Lewis P. Rowland NY, LWW. — 2015. — 1200 p.
14. Neuroanatomy Through Clinical Cases, Second Edition, Text with Interac-
tive eBook / Hal Blumenfeld // NY., Sinauer Associates. — 2011. — 975 p.
15. Neurological Differential Diagnosis / John P. Patten NY, Spronger. —
1998. — 449 p.
16. Neurological Examination Made Easy, 5e 5th Edition / Geraint Fuller Ph.,
Churchill Livingstone. — 2013. — 252 p.
References 283
17. Neurology for the Non-Neurologist (Weiner, Neurology for the Non-
Neurologist) Sixth Edition / ed. William J. Weiner, Christopher G. Goetz,
Robert K. Shin, Steven L. Lewis NY LWW. — 2010. — 624 p.
18. Neurology: textbook for stud. of higher med. institutions / L. Sokolova,
O. Myalovitska, V. Krylova [et al.]; ed. by prof. L. Sokolova. Vinnytsia:
Nova Knyha, 2012; 280 p.
19. Neurology Video Textbook DVD1st Edition / by Jonathan Howard MD / Demos
Medical; 1 edition (March 15, 2013) CD20. Shkrobot S.I. Neurology in
lectures / S.I. Shkrobot, I.I. Hara. — Ukrmedknyha, 2008; 319 p.
ANSWERS:
1 2 3 4 5
Topic 1 4) 3) 3) 3) 3)
Topic 2 1) 4) 1) 3) 1)
Topic 3 3) 1) 4) 2) 3)
Topic 4 2) 2) 2) 3) 5)
Topic 5 2) 1) 2) 4) 1)
Topic 6 4) 2) 1) 4) 1)
Topic 7 2) 2) 4) 5) 3)
Topic 8 1) 3) 4) 1) 1)
Topic 9 3) 5) 5) 1) 4)
Topic 10 1) 1) 3) 2) 3)
Topic 11 3) 1) 3) 1) 3)
Topic 12 1) 1) 1) 1) 3)
Topic 13 3) 2) 2) 4) 2)
Topic 14 1) 3) 4) 5) 2)
Topic 15 4) 3) 1) 3) 3)
Topic 16 3) 2) 4) 1) 1)
Topic 17 3) 1) 3) 3) 1)
Topic 18 1) 1) 1) 1) 3)
Topic 19 2) 3) 3) 4) 2)
Topic 20 1) 2) 4) 1) 1)
Topic 21 1) 4) 1) 3) 5)
Topic 22 4) 4) 3) 2) 3)
Topic 23 3) 1) 2) 2) 5)
Topic 24 3) 3) 2) 4) 4)
Topic 25 1) 1) 3) 2) 1)
Погорєлов О.В., Школьник В.М.,

Бараненко О.М., Юдіна Т.В.,
Кальбус О.І., Петров О.С.
Гострі та невідкладні стани

в неврології
Навчальний посібник
К.: Видавничий дім Медкнига, 2017. — 140 с.
ISBN 978-966-1597-36-4
У сучасних літературних джерелах пи-
тання гострих та невідкладних станів у ціло-
му наведені в достатньому обсязі, але при
цьому пошук та систематизація цих знань
може викликати труднощі саме внаслідок
великого обсягу та кількості видань, тема-
тичне наповнення яких може бути найрізно-
манітнішим. Тому особливістю цього видання є саме влучна і зручна систематиза-
ція викладеного матеріалу.
До того ж, обсяг інформації, знань та побудованих на них рекомендацій, у тому
числі, з позиції доказової медицини, зростає з великою швидкістю, що визна-
чає потребу постійної роботи зі структурування, методичного та дидактичного
оформлення таких знань і рекомендацій для навчальних цілей.
У посібнику описано основні гострі та невідкладні стани в клініці нервових
хвороб, обов’язкові дії лікаря на дошпитальних і шпитальних етапах надання до-
помоги, наведено таблиці шкал і діагностичних ознак при гострих та невідклад-
них станах. Розділи мають аналітичне узагальнення у вигляді таблиць.
Уся наведена інформація базована на сучасних керівництвах і найновіших
протоколах надання допомоги, затверджених МОЗ Украї–ни.
Посібник призначений для лікарів невідкладної допомоги, неврологів, пси-
хіатрів, терапевтів, лікарів загальної практики, слухачів кафедр системи після
дипломної освіти, студентів та викладачів медичних ВУЗів, інтернів.

Required book 285
Катеренчук І.П.
Клінічне тлумачення
й діагностичне значення
лабораторних показників
у загальнолікарській
практиці
Навчальний посібник
К.: Медкнига, 2015. — 224 с.
ISBN 978-966-1597-21-0
Інтерпретація лабораторних даних є од-
нією з найважливіших проблем. Складним
залишається поняття «норма» при оцінці ла-
бораторних показників. Існує необхідність
максимально індивідуалізувати діагностичний,
у тому числі лабораторний, процес. Різноманітні види обміну речовин в організмі
тісно пов’язані з індивідуальними особливостями хворого – статтю, віком, вели-
чиною поверхні тіла, масою тіла, особливостями харчування і способу життя. При
оцінці результатів лабораторних аналізів важливо враховувати момент обстеження
хворого – фізичне напруження, емоційний фон, психологічні особливості особи-
стості, для жінок – фази статевого циклу, вагітність та клімакс.
У навчальному посібнику наведено діагностичні значення й клінічне тлумачен-
ня лабораторних показників у терапевтичній клініці, визначено референтні норми
клінічних і біохімічних показників крові й сечі та інших біологічних рідин залежно
від віку й статі, висвітлено механізми змін цих показників при різних захворюваннях
і патологічних станах, акцентовано увагу на тому, що точний результат можливий
лише за умови чіткого дотримання правил проведення діагностичної процедури.
Посібник-довідник буде корисним не лише для студентів старших курсів і ліка-
рів-інтернів, він також стане в пригоді сімейним лікарям, лікарям-інтерністам, прак-
тикуючим лікарям інших спеціальностей, а також усім тим, хто цікавиться питання-
ми визначення лабораторних показників на практиці.
СONTENTS
Topic 1. Medications used in neurology........................................................ 3
Topic 2. Epilepsy......................................................................................... 15
Topic 3. Paroxysmal non-epileptic states.................................................... 24
Topic 4. Lesions of the nervous system under the influence

of professional and domestic toxins; and physical factors impact............... 34
Topic 5. Cerebral vascular diseases. The blood supply of the brain and
spinal cord. Cerebral autoregulation........................................................... 49
Topic 6. Transient ischemic attack. Ischemic stroke, its diagnostics.

Treatment. Prevention................................................................................. 56
Topic 7. Hemorrhagic stroke, the differential diagnosis. Treatment.

Prevention: Binswanger's disease............................................................... 67
Topic 8. Headaches..................................................................................... 77
Topic 9. Sleep and its disorders.................................................................. 89
Topic 10. Meningitis. Tuberculosis of the nervous system........................ 103
Topic 11. Encephalitis.................................................................................113
Topic 12. Poliomyelitis. Acute myelitis. Amyotrophic lateral sclerosis....... 125
Topic 13. Neurological aspects of traumatic brain injury.

Spinal cord injury....................................................................................... 134
Topic 14. Neurosyphilis............................................................................. 147
Topic 15. Nervous system lesions in HIV-positive patients....................... 153
Contents 287
Topic 16. Demyelinating diseases of the nervous system. Acute

disseminated encephalomyelitis, Multiple sclerosis, Schilder’s
encephalitis and Van Bogaert’s desease................................................... 160
Topic 17. Peripheral nervous system diseases (№1). Classification.

Infectious immune-mediated polyneuropathy (Guillain-Barre syndrome).
Polyneuropathies in case of alcoholism, diabetes mellitus, botulism,
connective tissue diseases etc. Treatment................................................ 173
Topic 18. Peripheral nervous system diseases (№2). Plexopathies.

Neuropathies of upper and lower extremities............................................ 183
Topic 19. Vertebrogenic disorders of the peripheral nervous system........ 200
Topic 20. Congenital defects of spine and spinal cord. Syringomyelia...... 210
Topic 21. Perinatal lesions of the central nervous system......................... 223
Topic 22. Somatoneurologic disorders (respiratory, cardiac, hematologic,

digestive, hepatic, renal, endocrine, collagen diseases, paraneoplastic
syndrome)................................................................................................. 235
Topic 23. Somatoneurological syndromes (asthenic, autonomic

dysfunction, polyneuropatic, neuro-muscular disorders)........................... 246
Topic 24. Hereditary degenerative diseases of the nervous system

(primary and secondary myodystrophy).................................................... 253
Topic 25. Hereditary degenerative diseases with lesions of the pyramidal

and extrapyramidal nervous systems........................................................ 265
References................................................................................................ 282
Сontents.................................................................................................... 286
Серія «Бібліотечка практикуючого лікаря»
Гриб Вікторія Анатоліївна

Дорошенко Олександр Олександрович
Геник Софія Ігорівна
Грицюк Тетяна Дмитрівна
Купновицька-Сабадош Марта Юріївна
Ліскевич Ірина Ігорівна
Максимчук Любов Тарасівна
Михалойко Ольга Ярославівна
Ткачук Наталія Павлівна
КЛІНІЧНА НЕВРОЛОГІЯ
За редакцією д.мед.н., проф. Гриб В.А.
Посібник висвітлює основні напрямки клінічної неврології, які представлені в програмі для
забезпечення навчального процесу з дисципліни «Неврологія», спеціальність 7.12010001.
Призначено для студентів університету, інтернів, лікарів, неврологів.
Видавничий дім Медкнига

Kиїв, 2017
Свідоцтво про внесення суб’єкта видавничої справи в державний реєстр видавців,

виготовлювачів та розповсюджувачів видавничої продукції ДК 5123 від 10.06.2016
Спеціалізоване видання, призначене для лікарів та медичних установ.
За достовірність фактів, цитат, імен, посилань, використання спеціальних термінів, географічних та інших
назв несуть відповідальність автори.
Правову відповідальність за розміщення, зміст, достовірність та графічне відтворення рекламно-
інформаційних матеріалів про лікарські засоби чи пристрої несе виробник, дистриб’ютор або інша
структура, яка надала відповідні матеріали.
Шеф-редактор О.Влас, тел. +38-066-7851156, e-mail: zdovado@ukr.net

Літредактор і коректура О. Заяц, e-mail: medkniga@ukr.net
Відділ маркетингу Т. Овчаренко, тел. +38-066-7538178
Відділ додрукарської підготовки В. Макарович
Підписано до друку 16.08.2017. Друк офсетний.
Відгуки та пропозиції надсилайте на адресу: а/с-18, м. Київ-108, 04108

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IVANO-FRANKIVSK NATIONAL MEDICAL UNIVERSITY

Bibliotechka praktykuyuchoho likarya

Publishing house Medknyha

Recommended by Commission of therapeutic disciplines of Ivano-Frankivsk National Medical

Special acknowledgement to scientists-neurologists for the relevant corrections and

© Gryb V.A., Doroshenko O.O., Genyk S.I., Hrytsiuk T.D.,

MEDICATIONS USED IN NEUROLOGY

1. Neuroprotective and neurotrophic drugs

choline alfos- Gliatilin 400 mg 4 ml 1000 mg;

2. Drugs improved brain microcirculation

3. Drugs used for Parkinson’s disease treatment

ACE Inhibi- Captopril 25 mg - 25-100 mg; 1-4 t/d;

6. Drugs used for treating migraine headaches

9. Drugs that stabilize autonomic activity

10. Drugs that affect coagulation system of blood

unfractionated Heparin - 5 ml/vial 7500-22500 U; s/c

11. Acetylcholinesterase inhibitors (AChEI)

galantamine Galantamine, 5, 10 mg 1 ml - 5-40 mg;

12. Drugs used in Multiple Sclerosis

13. Drugs used in Myasthenia gravis

14. Antiviral drugs

15. Antispastic drugs (muscle relaxants)

baclofen Baclofen 10, - 15-75 mg;

16. Treatment of pain

1. First-line treatment for epilepsy (according to the AAN Epilepsy Guidelines)

Acute symptomatic seizure is a seizure that occur at the time of a systemic

- generalized epilepsy and epileptic syndromes are characterized by dif-

other gestures). The attacks of fear, happiness, and a sense of unreality of

There are following types of generalized seizures:

Benzodiazepine is the initial therapy of choice (Level A):

PAROXYSMAL NON-EPILEPTIC STATES

Non-epileptic seizures disorders are events superficially resembling an ep-

Obvious spasmophilia clinical picture:

Seizures Psychogenic seizures

Fig. 1. Psychogenic nonepileptic seizures in woman

2. The states without seizures:

occurs as a result of short lasting disturbance of cerebral blood flow and,

• E — Abnormal ECG

- Epileptic atonic seizures should be differentiated from a sudden drop,

1. A generalized epileptic seizure occurred in a 6-month child on the back-

LESIONS OF THE NERVOUS SYSTEM UNDER THE INFLUENCE

1.3. Intoxication with manganese (manganism)

A headache is the most common symptom of mild carbon monoxide poi-

thesia of the extremities, paralysis of muscles (extensor muscles are affected

Signs and symptoms of organophosphate poisoning:

2. Food intoxication, botulism

is complete, worsening can be prevented and recovery time can be shorten.

3. Wernicke–Korsakoff syndrome and other neurological manifesta-

3. Ultra short acting — Thiopentone, Methohexitone

• There may be other manifestations from damage to bone and muscles.

6. Ionising radiation damage of the nervous system

in case of convulsions — diazepam i/v; in case of the digestive tract dysfunc-

7. Electrical injury of the nervous system

8. Lesions of the nervous system in the heat and sunstroke

1. Why does a patient with botulism require artificial respiration?

Замовити книги можна за телефоном (044) 485-15-86,

CEREBRAL VASCULAR DISEASES. THE BLOOD SUPPLY OF THE

I. Blood supply of the brain

The internal carotid artery

flow becomes dependent on mean