Epilepsy

Once sacred disease

Milan Brzdil
1st Department of Neurology
Medical Faculty and St. Anne Hospital

Definition

A chronic neurologic disorder manifesting by

repeated epileptic seizures (attacks or fits) which
result from paroxysmal uncontrolled discharges
of neurons within the central nervous system (grey
matter disease).

The clinical manifestations range from a major

motor convulsion to a brief period of lack of
awareness. The stereotyped and uncontrollable
nature of the attacks is characteristic of epilepsy.

Pathogenesis

The 19th century neurologist Hughlings Jackson

suggested a sudden excessive disorderly
discharge of cerebral neurons as the causation
of epileptic seizures.

Recent studies in animal models of focal epilepsy

suggest a central role for the excitatory
neurotransmiter glutamate (increased in epi) and
inhibitory gamma amino butyric acid (GABA)
(decreased)

Epidemiology and course

Epilepsy usually presents in childhood or

adolescence but may occur for the first time at any
age.

Newborns
Early school age
Adolescents
Seniors

Epidemiology and course

5% of the population suffer a single sz at some

time
0.5-1% of the population have recurrent sz =
EPILEPSY
70% = well controlled with drugs (prolonged
remissions)
30% epilepsy at least partially resistant to drug
treatments = INTRACTABLE
(FARMACORESISTANT) EPILEPSY.

Epilepsy versus epileptic

syndromes
Epilepsy is not a nosological entity not one disease! Not unique aetiology...
Might be a symptom of numerous disorders symptomatic epilepsy (TBI,
tumours, inflammation, stroke, neurodegeneration, ...)
Sometimes the cause remains unclear despite careful history
taking,examination and investigation!

Epilepsy - Classification

The modern classification of the epilepsies is

based upon the nature of the seizures rather
than the presence or absence of an underlying
cause.

Seizures which begin focally from a single

location within one hemisphere are thus
distinguished from those of a generalised
nature which probably commence in a deeper
structures (brainstem? thalami) and project to
both hemispheres simultaneously.

 Causes
Heriditory
Idiopathic
Infection
Head

injury
Neoplasm
Degenerative diseases

pathophysiology
Electrical changes: electrodes placed in
epileptic foci show excitattory synaptic
potentials and spike discharges
Imbalance between excitatory and inhibitory
impulses at cellular or synaptic level
Extracellular concentration of ca+ drops
significantly
Extracellular K+ rises after a brief delay when
compared to the drop in Ca+

 Extracellular

Na+ falls significantly with a

small rise in extracellular Cl-

Synaptic

level:- for the excitatory

neurotransmiter glutamate (increased in

epi) and inhibitory gamma amino butyric
acid (GABA) (decreased)

 Spread
Synchronous

discharge of many neurones

locally which spreads with the changes such
as high K+ and low Mg+.
Factors that decrease GABA mediated
inhibition also facilitate spread

Epilepsy - Classification

Focal seizures account for

80% of adult epilepsies
Simple partial seizures
Complex partial seizures
Partial seizures secondarilly
generalised

Generalised seizures

Unclassified seizures

What are seizures?

Definition

of seizure: paroxysmal episodes of brain

dysfunction manifested by stereotyped alteration in
behavior
Clinical manifestation depends on region of brain seizing
Causes: primary CNS dysfunction, metabolic disorder
Epilepsy: recurrent and unprovoked seizures
Cellular definition: excessive or oversynchronized
discharges of cortical neurons

GABA receptor mediates inhibition responsible for normal termination of a seizure

NMDA (Glutamate) receptor activation required for propagation of seizure activity

NMDA Rcptr
Activation

Seizure

Reduced GABA
Rcptr function

Epidemiology
Approximately

1% population (3 million
epilepsy cases in US).
Second most common neurological disease
Comparable prevalence in men vs. women

Begley CE et al. Epilepsia 2000;41:342-351

MMWR Weekly. November 11, 1994/43(44);810-811,817-818
Sander JW. Cur Opin neurol 2003;16:165-170

Seizure terms

Ictal= seizure
Post-ictal= confusion
following seizure
Aura= abnormal sensation
preceding loc
Automatisms= nonsensical
involuntary movements
Tonic= tonic contraction
producing extension and
arching
Clonic= alternating muscle
contraction-relaxation

Complex= consciousness
impaired
Simple= consciousness
unimpaired
Partial= focal region involved
Generalized= whole brain
Convulsions= shaking
Grand mal and petite mal=street
terms for convulsive and
non-convulsive seizure
respectively

Etiology

CNS

Head trauma

Seizure in 1 week of injury

not predictive of epilepsy

Stroke
Vascular malformations
Mass (tumor/abscess)
Meningitis/encephalitis
Congenital
malformations/ cortical
dysplasias
Idiopathic

Systemic

Hypo/hyperglycemia
Hypo/hypernatremia
Hypocalcemia
Uremia
Hepatic encephalopathy
Hypoxia
Hyperthermia
Drug overdose or
withdrawal

EtOH withdrawal sz occurs

within 48h

Classification of seizure types

Partial (focal)

Simple partial

Complex partial

Motor
Somatosensory
Autonomic
Psychological
Simple partial with impaired
consciousness

Partial seizures with

secondary generalization

Generalized

Absence
Tonic
Clonic
Tonic-clonic
Atonic
Myoclonic

Classification

Partial seizures (focal onset)

Simple partial (without impaired consciousness)

Motor symptoms (focal motor seizure)

Somatosensory symptoms

Involves sensory strip, temporal(hearing and smell) or occipital(visual)

lobe

Autonomic symptoms

Involves motor strip

Manifested by abnormal movement of an extremity
Jacksonian march- spread to involve contiguous regions
Todds paralysis- post ictal transient hemibody weakness

Involves temporal lobe (tachycardia, pallor, flushing, sweating)

Psychic symptoms

Involve frontal or temporal lobe (limbic system): dj vu, jamais vu,

affective disturbances, cognitive deficits, hallucinations

Homunculus

Neurology and Neurosurgery Illustrated. Lindsay, Kenneth, Bone Ian, 3rd edition. Churchill Livingstone, 1999.London

Classification

Partial seizures

Complex partial (impaired consciousness)

Typically frontal or temporal lobe onset

Often stereotyped for the individual patient
Average duration 1-3 minutes
Simple partial onset can be followed by impaired consciousness
Many times will progress to a generalized seizure
Frequently seen in adult onset epilepsy
Automatisms: coordinated involuntary movements, typically
orobuccolingual or nonpurposeful hand movements

Classification of Seizures

Generalized (diffuse onset)

Absence

5-10s LOC w/o loss of postural tone

Mild head turn, blinking common
Immediate return of awareness
Typically resolves by 20y

Tonic arrest of ventilation can cause cyanosis

Clonic without tonic phase
Tonic clonic
Myoclonic brief, shock-like contractions, may be localized or
generalized
Atonic - drop attacks

Classification

Pseudoseizures

Non-epileptic seizures
May be manifestation of conversion disorder, factitious
disorder or malingering
Features that may distinguish from epileptic seizures

Pre-attack preparation, absence of post-ictal confusion

Disorganized movements, pelvic thrusting, thrashing
Bilateral convulsions without loss of consciousness
Violent or goal-directed behavior, obscene language,

Video EEG may help to diagnose

Seizure Phenotypes
think of anatomy!!

Cortex
Central Sulcus

Frontal Eye
Field

Visual Assoc.
Cortex

Brocass
Speech Area

Primary Visual
Cortex
Primary Auditory
Cortex
Sylvian Fissure

Wernickes
Speech

Frontal Lobe

Frontal eye field (Brodmans 8)

Prefrontal cortex (Brodmans 9-12,46,47)

Lesion: deficits in concentration, judgment and behavior

Sz: agitation, odd behavior

Brocas speech area (Brodmans 44,45)

Lesion: deviation of eyes to ipsilateral side

Sz: overstimulation->eyes to contralateral side

Lesion/sz: expressive nonfluent aphasia

Primary motor cortex (Brodmans 4)

Lesion: contralateral hemiparesis, late manifestation spasticity

Sz: contralateral twitching, posturing or convulsions

Temporal Lobe

Hippocampal cortex

Wernickes speech area (Brodmans 22)

Bilateral lesions: Kluver-Bucy syndrome- visual agnosia, hyperorality,

hyperphagia, hypersexuality, docility
Sz: staring/freezing, oral automatisms

Primary auditory cortex (Brodmans 41, 42)

Lesion/sz: loss of receptive speech, fluent aphasia

Anterior temporal lobe

Bilateral lesions: memory dysfunction

Sz: chronic seizures lead to deficits in short term memory

Bilateral lesion: cortical deafness

Sz: auditory hallucinations

Olfactory bulb (Brodmans 34)

Lesion: anosmia
Sz: olfactory and gustatory hallucinations

Parietal and Occipital Lobes

Primary

sensory cortex (Brodmans 3,1,2)

Lesion: contralateral hemihypestheisa and

astereognosis
Sz: contralateral sensory symptoms ie tingling,
heat

Occipital

lobe (Brodmans 17)

Lesion: contralateral hemianopsia with macular

sparing
Sz: flashing or colored lights in contralateral visual
field

Focal (partial) seizures

Simple partial seizures

Motor, sensory, vegetative or psychic symptomatology
Typically consciousness is preserved

Focal (partial) seizures

Simple partial seizures

Motor, sensory, vegetative or psychic
symptomatology
Typically consciousness is preserved

Focal (partial) seizures

Simple partial seizures

Motor, sensory, vegetative or psychic
symptomatology
Typically consciousness is preserved

Focal (partial) seizures

Complex partial seizures (= psychomotor seizures)

Initial subjective feeling (aura), loss of
consciousness, abnormal behavior (perioral and
hand automatisms)

Usually originates in TL

Focal (partial) seizures

Partial seizures evolving to tonic/clonic convulsions

secondary generalised tonic/clonic seizures
(sGTCS)

Generalized seizures
(convulsive or non-convulsive)

Absences
Myoclonic seizures
Clonic seizures
Tonic seizures
Atonic seizures

Generalized seizures

Absences
Myoclonic seizures
Clonic seizures
Tonic seizures
Atonic seizures

Seizure Management

Diagnosis
Clinical history
Physical examination: focal deficits, Todds paralysis
Diagnostic work-up: pulse ox, glucose, electrolytes,
calcium, CBC, renal function, hepatic function, tox
screen/EtOH level
Head imaging: CT/MRI
LP if fever or meningeal signs present
EEG confirmation if possible: ictal event or inter-ictal
spikes, polyspike discharges, spike-wave complexes

Epilepsy Investigation

The concern of the clinician is that epilepsy may be symptomatic of

a treatable cerebral lesion.
Routine investigation: Haematology, biochemistry (electrolytes,
urea and calcium), chest X-ray, electroencephalogram (EEG).
Neuroimaging (CT/MRI) should be performed in all persons aged 25
or more presenting with first seizure and in those pts. with focal
epilepsy irrespective of age.
Specialised neurophysiological investigations: Sleep deprived
EEG, video-EEG monitoring.
Advanced investigations (in pts. with intractable focal epilepsy
where surgery is considered): Neuropsychology, Semiinvasive or
invasive EEG recordings, MR Spectroscopy, Positron emission
tomography (PET) and ictal Single photon emission computed
tomography (SPECT)

Epilepsy
Differential Diagnosis
The following should be considered in the diff. dg. of epilepsy:
Syncope attacks (when pt. is standing; results from global reduction
of cerebral blood flow; prodromal pallor, nausea, sweating; jerks!)
Cardiac arrythmias (e.g. Adams-Stokes attacks). Prolonged arrest of
cardiac rate will progressively lead to loss of consciousness jerks!
Migraine (the slow evolution of focal hemisensory or hemimotor
symptomas in complicated migraine contrasts with more rapid
spread of such manifestation in SPS. Basilar migraine may lead to
loss of consciousness!
Hypoglycemia seizures or intermittent behavioral disturbances may
occur.
Narcolepsy inappropriate sudden sleep episodes
Panic attacks
PSEUDOSEIZURES psychosomatic and personality disorders

Seizure treatment
Acute

90% of seizures stop without treatment in under 5 minutes

Can give lorazepam or diazepam for seizures >5min
Monitor ABCDs, avoid injury and aspiration
Treat underlying medical conditions

Long

Term Management

Decide if therapy needed

Management

Sz due to secondary causes (metabolic d/o, EtOH withdrawal, immediately following head
trauma/stroke) may not need longterm tx
Single generalized tonic-clonic seizure recurs in about 50%

Anti-epileptic medications

Try single therapy

Add second medication if: sz not controlled with single drug and maximal levels/side effects
are achieved
Treat the seizures, not drug levels

Anti-epileptic medications

Older Agents

Phenytoin
Carbamazepine
Phenobarbital
Primidone
Valproic acid
Ethosuxamide

Newer Agents

Lamotrigine
Levetiracetam
Topiramate
Oxcarbazepine
Lacosamide
Zonisamide

Other treatment options

Ketogenic

diet in children

Surgery

Removal of epileptic focus

Mostly for patients with temporal lobe seizures

Possibility of a 70% chance of cure!!

VNS

(Vagal nerve stimulator)

Current given to vagus nerve with theory of

decreasing seizures over time

Treatment of the seizing

patient
Ensure

Do not place anything in the mouth except when to suction

airway protection/ position to prevent aspiration

DO NOT try to force suction/airway through clenched teeth

When the patient stops convulsing, place patient in lateral decubitus.

Begin supplemental oxygen

Assess

Ensure lights in room are on

Remove any object within reach of patient that could cause injury
Loosen clothing
Side rails should be up if patient is in bed
Do not try to hold the patient down

Obtain

safety of patient

vitals including pulse ox, obtain stat accucheck

If glucose is < 70 mg/dl (or if accucheck unobtainable) administer amp D50.

Note: Ideally,100mg thiamine IVPB should be given prior to, or soon after, glucose

Order

diagnostic labs: cbc, cmp, mg, phos, tox screens,

etoh level, AED levels
Most seizures cease w/o medical intervention in 1-3 minutes

Status epilepticus
Lorazepam

0.1 mg/kg IV push at rate of 2 mg/min (can be given

IM)
Phenytoin 20 mg/kg IV no faster than 50 mg/min

Fosphenytoin 20 mg/kg IV up to 150 mg/min (can be given IM)

Additional 5-10 mg/kg of either can be given

Consider

phenobarbital 20 mg/kg or VPA 10-15 mg/kg IV

If seizure continues: intubation required
General anesthesia titrate to burst suppression (continuous
EEG monitoring required)

Pentobarbital (5 mg/kg load, 0.5-3 mg/kg/hr maint.)

Propofol (1-2 mg/kg load over 5 min, 2-10 mg/kg/hr maint.)
Midazolam (0.2 mg/kg slow IV bolus, 0.05-0.5 mg/kg/hr maint.)

Epilepsy - Treatment

The majority of pts respond to drug therapy

(anticonvulsants). In intractable cases surgery may be
necessary. The treatment target is seizure-freedom and
improvement in quality of life!

The commonest drugs used in clinical practice are:

Carbamazepine, Sodium valproate, Lamotrigine (first line drugs)

Levetiracetam, Topiramate, Pregabaline (second line drugs)
Zonisamide, Eslicarbazepine, Retigabine (new AEDs)

Basic rules for drug treatment: Drug treatment should be

simple, preferably using one anticonvulsant
(monotherapy). Start low, increase slow.
Add-on therapy is necessary in some patients

Epilepsy Treatment (cont.)

If pt is seizure-free for three years, withdrawal of

pharmacotherapy should be considered. Withdrawal
should be carried out only if pt is satisfied that a further
attack would not ruin employment etc. (e.g. driving
licence). It should be performed very carefully and slowly!
20% of pts will suffer a further sz within 2 yrs.

The risk of teratogenicity is well known (~5%), especially

with valproates, but withdrawing drug therapy in
pregnancy is more risky than continuation. Epileptic
females must be aware of this problem and thorough
family planning should be recommended. Over 90% of
pregnant women with epilepsy will deliver a normal child.

Epilepsy Surgical Treatment

A proportion of the pts with intractable epilepsy will

benefit from surgery.
Epilepsy surgery procedures: Curative (removal of
epileptic focus) and palliative (seizure-related risk
decrease and improvement of the QOL)
Curative (resective) procedures: Anteromesial temporal
resection, selective amygdalohippocampectomy,
extensive lesionectomy, cortical resection,
hemispherectomy.
Palliative procedures: Corpus callosotomy and Vagal
nerve stimulation (VNS).

Status Epilepticus

Status epilepticus
Definition

Continuous seizure lasting greater than 30

minutes
Two or more sequential seizures without recovery
of full consciousness lasting >30 minutes

Types

Generalized convulsive (GCSE)

Nonconvulsive status epilepticus (absence, CPS)
Simple partial status epilepticus

Status Epilepticus

A condition when consciousness does not return

between seizures for more than 30 min. This state may
be life-threatening with the development of pyrexia,
deepening coma and circullatory collapse. Death
occurs in 5-10%.
Status epilepticus may occur with frontal lobe lesions
(incl. strokes), following head injury, on reducing drug
therapy, with alcohol withdrawal, drug intoxication,
metabolic disturbances or pregnancy.
Treatment: AEDs intravenously ASAP, event. general
anesthesia with propofol or thipentone should be
commenced immediately.