NEUROLOGY

Stroke definition
Stroke is a neurological deficit of sudden
onset accompanied by focal dysfunction
and symptoms lasting more than 24 hours
that are presumed to be of non-traumatic
vascular origin (WHO definition)
or
An acute clinically relevant brain lesion on imaging in
patients with rapidly vanishing symptoms

NEUROLOGY
 STROKE FACTS

 Leading cause of adult disability

 Third leading cause of death in the US
 #2 killer disease worldwide
 Most important cause of mortality in Asia
 75% of all strokes occur in patients > 65 years of
age

NEUROLOGY
Stroke Burden

1,000,000 population

0.2% will have stroke / year

(2000 people)

1/3 1/3 permanently

Dead over the next 1/3 recover
disabled
year 666 / M per year

3rd most common 2/3 survivor

cause of death 1300 / M

10,000 / 1,000,000 prevalence

5000 / 1,000,000 (Phil.)

NEUROLOGY
Stroke Mortality Over Time

One year mortality: 25%-40%

Three year mortality: 32%-60%

Over 50 percent dead in 5 years

Ten-year survival in the Framingham study: 35%

30-day mortality rates for hemorrhagic stroke are

1.5 - 2.5 times greater than for all strokes
NEUROLOGY
Risk Factors and Predictors of Stroke

Non-modifiable Modifiable
Older age Elevated blood pressure
Male gender Diabetes mellitus
Non-white ethnicity Atrial fibrillation
Family history Carotid artery disease
Hyperlipidemia
Cigarette smoking
Obesity
High alcohol consumption
Cerebrovasc Dis. 2003;6(Suppl 1):14-19, Adv Neurol. 2003;92:165-72
Stroke. 1997;28(7):1507-17, Stroke. 2001;32:2559-2566 NEUROLOGY
RIFASAF Study
Independent Risk Factors for Stroke Among Filipinos

 Hypertension
 Diabetes
 Atrial fibrillation
 Myocardial Infarction
 Rheumatic Heart Disease
 Smoking
 Snoring
 Stress
 Frequent Alcohol Intake
Reference: Roxas A, Phil J. Neurology, 2002

NEUROLOGY
What are the types of
Stroke?

NEUROLOGY
Distinguishing Features:
Hemorrhagic vs Ischemic Stroke
 Hemorrhagic Stroke

› Early and prolonged loss of consciousness

› Prominent headache, nausea, and vomiting
› Retinal hemorrhages
› Nuchal rigidity
› Focal signs do not fit the anatomic pattern of
a single blood vessel

NEUROLOGY
Distinguishing Features:
Hemorrhagic vs Ischemic Stroke
 Ischemic Stroke
› Stepwise deterioration or progressive
worsening

› Waxing and waning of findings

› Focal neurologic impairments in the pattern

of a single blood vessel

NEUROLOGY
Common Stroke Subtypes in Asia

Intracerebral Hemorrhage
20-50% Asians vs.
10-15% in the West

Intracranial Atherosclerosis
40-50% Asians vs.
8% in the West

NEUROLOGY
Subtypes of Cerebral Infarction
Others rare cause: Arterial dissection, Moyamoya disease, Takayasu’s arteritis

Etiology Mechanism

Athero-
thrombotic Thrombus

Cardio- Embolism
embolic

Lacunar Small-vessel

NEUROLOGY
Subtypes of Cerebral Infarction
156 institutes, 16,922 cases 1995. 5～2000. 4. Yamaguchi T et al.

TIA

Others
6.4%
5.7%

Cardiogenic 36.3%
Lacunar
Embolism 20.4% Infarction

31.1%
Atherothrombotic
Infarction

Others rare cause: Arterial dissection, Moyamoya disease, Takayasu’s arteritis NEUROLOGY
Major risk factors are unevenly distributed
among stroke subtypes

Cardioembolism Elderly (>70 yr), low rate of

early stroke recurrence

Atherothrombotic (Large-vessel) Middle age (45-70 yr), high

rate of early stroke
recurrence
Highest male
preponderance

Lacunar (Small-vessel) Hypertension, DM,

hypercholesterolemia,
obesity

NEUROLOGY
Three Types of Ischemic Stroke

 Atherothrombotic

 Cardioembolic

 Lacunar

NEUROLOGY
 Atherothrombotic Stroke
(Large Vessel Disease)
 Usually develops at
night during sleep
 Symptoms felt in
the morning
 Suspect history of
atherosclerosis,
hypercoagulable
states and collagen
vascular diseases
NEUROLOGY
Macroangiography or Large
Vessel Disease

TOAST Criteria - Macroangiopathy is defined as

the presence of an occlusion or a stenosis with
50% diameter reduction of a brain-supplying
artery corresponding to clinical symptoms and
with location and morphology typical of
atherosclerosis on Doppler ultrasound or
angiography. Diagnostic studies had to exclude
potential sources of cardiogenic embolism.

NEUROLOGY
Usual Locations of Extracranial and
Intracranial Atherosclerosis

NEUROLOGY
Macroangiopathy (Large-
Artery Atherosclerosis)
Mechanism of Atherosclerotic Stroke in Large
Cerebral Arteries
1. Artery to artery embolism
2. Thrombotic occlusion
3. Hemodynamic infarction: watershed
infarction
Extracranial Atherosclerosis (ECAS) vs Intracranial Atherosclerosis
(ICAS)

• ECAS (e.g. carotid bifurcation atherosclerosis) has been

considered as the most common source of embolism among
Whites.
• ICAS is more common in Asian and Blacks than Whites.
• There is no proven treatment for ICAS. J Clin Neurosci. 2003;10(1):30-4
Cleve Clin J Med. 2004;71 Suppl 1:S47-9

NEUROLOGY
NEUROLOGY
NEUROLOGY
The genesis and evolution of the
atherosclerotic plaque: A closer look
Foam Fatty Intermediate Atheroma Fibrous Complicated
cells streak lesion plaque lesion/rupture

Endothelial dysfunction
From first decade From third decade From fourth decade
Smooth Thrombosis
Growth mainly by lipid accumulation muscle
hematoma
and collagen

NEUROLOGY
Pepine C. Am J Cardiol. 1998;82(Suppl 10A):23S-27S
 Clinical Manifestations
Anterior Cerebral Artery (ACA)
 ACA supplies the frontal lobe (logical
thought, personality, and voluntary
movement, especially the legs.
 Opposite leg weakness

Middle Cerebral Artery (MCA)

 MCA supplies the frontal lobe, lateral
surface of the temporal and parietal lobe.
 Speech disorder

NEUROLOGY
Clinical Manifestations

Posterior Cerebral Artery (PCA)

 PCA supplies the temporal and occipital
lobes.
 Color blindness, Verbal dyslexia,
homonymous hemianopsia

NEUROLOGY
NEUROLOGY
- Contralateral weakness of
leg > arm
- Sensory loss over leg, feet
- Urinary incontinence
- Frontal lobe release signs,
abulia, amnesia with
apathy
- Dyspraxia

NEUROLOGY
- Weakness of face & arm > leg
- Preferential gaze looking away
from the weakness
- Contralateral hemineglect
- Contralateral hemisensory
impairment
- Global aphasia (if dominant
hemisphere)
- Homonymous hemianopsia

NEUROLOGY
- Homonymous hemianopsia
with macular sparing
- Loss of color differentiation

NEUROLOGY
- Ipsilateral limb
ataxia
- Vertigo
- Nystagmus
- Dysarthria
- Gait ataxia

NEUROLOGY
 Top of the Basilar
- Somnolence
- Convergence
nystagmus
- Skew deviation
Locked In
- Vertical Gaze
- Quadriplegia
- paralysis
Horizontal gaze
paralysis
- Bifacial paralysis
- Tongue and
Mandibular Weakness

NEUROLOGY
- Ipsilateral dysmetria
- Hearing loss
- Horner’s syndrome
- Contralateral
thermoanalgesia
- Choreiform dyskinesia

NEUROLOGY
- Contralateral weakness
of arm and leg
- Hemisensory loss
- Ipsilateral tongue
Paralysis

NEUROLOGY
- Vertigo, nausea,
vomiting
- Ipsilateral facial
numbness and
dysmetria
- Horner’s syndrome
- Contralateral
thermoanalgesia
- Choreiform dyskinesia

NEUROLOGY
Natural Course

 45 intracranial stenosis in 21 patients

followed up in 26.7 months
› In those with ICA stenosis 20% progressed and
14% regressed
› In those with ACA, MCA, PCA stenosis, 61%
progressed and 28% regressed

Akins et al (Stroke 1998)

NEUROLOGY
Stroke rate in patients with
symptomatic intracranial disease
 Retrospective, nonrandomized review of
151 patients in several academic centers
in the US
 50-99% stenosis
 Treated with aspirin
 10.7/100 patients had stroke recurrence
WASID Neurology 1995

NEUROLOGY
 ICS (Intracranial Stenosis)
Symptomatic ICS is a dynamic process with frequent progression.
Progression of symptomatic stenosis predicted clinical recurrence.

MRA Progression

TCD Progression

Clinical events
Change of ICS
Yes (n = 18) No (n = 125)
Normalized (n = 42) 4.8% (2) 95.2% (40)
Stable (n = 88) 12.5% (11) 87.5% (77)
Progressed (n = 13) 38.5% (5) 61.5% (8)
NEUROLOGY
Wong et al. Stroke. 2002;33:532
Three Types of Ischemic Stroke

 Atherothrombotic

 Cardioembolic

 Lacunar

NEUROLOGY
 Embolic stroke
 Occurs at anytime
 Frequently during
periods of vigorous
activity
 History of atrial
fibrillation, valvular
vegetations, throm-
boembolism from
MI, etc
 Seizures in 20% of
cases

NEUROLOGY
Cardioembolism
• Embolism of thrombotic
material forming on the atrial
Infarction
or ventricular wall or the left
heart valve.
• The fragment of thrombus may
lyse quickly, producing only
TIA.
• Alternatively, the arterial
Embolus occlusion may last longer,
producing stroke.
Localization of emboli
• Frequently in MCA, PCA
• Infrequently in ACA

MCA: Middle Cerebral Artery

PCA: Posterior Cerebral Artery
ACA: Anterior Cerebral Artery

NEUROLOGY
Cardioembolism

TOAST criteria - Cardioembolism is defined

as the presence of a high- or medium-risk
source of cardiac embolism. Potential
large-artery atherosclerotic sources of
thrombosis or embolism had to be
absent.

NEUROLOGY
Cardioembolism

 Atrial fibrillation
› 2-4% risk for stroke annually

 Acute Myocardial Infarction (with left

ventricular thrombus)
› 5% risk for stroke within 2 weeks
› Risk higher with anterior than inferior infarcts
› May reach 20% in those with large
anteroapical infarcts
NEUROLOGY
 Cardiomyopathy
› EF 29-35% : 0.8% stroke rate/yr
› EF </=28% : 1.7% stroke rate/yr

 Prosthetic Heart Valves

› Annual percentage of occurrence of
systemic thromboembolism : 20%

NEUROLOGY
 Valvular Heart Disease
Annual Incidence of thromboembolism
No AF With AF
Prosthetic valve 20% Increased
Rheumatic mitral 7.7% 22%
Regurgitation
Rheumatic mitral stenosis 1.5-4% Inc by 7-8x
MV prolapse <2% Increased

NEUROLOGY
Three Types of Ischemic Stroke

 Atherothrombotic

 Cardioembolic

 Lacunar

NEUROLOGY
Microangiopathy (Small-Vessel
Disease or Lacunar Infarction)
Lacunar Infarction

• Very small infarctions.

• Occur only in small arterioles
(branch of large vessels) as the
lenticulostriate arteries.
• Can involve basal ganglia, thalamus,
internal capsule, corona radiata, and
brain stem.
• Almost always related to prolonged
uncontrolled hypertension
Lacunar
• 85% recovery
infarction

NEUROLOGY
Microangiography

 TOAST Criteria – Microangiopathy is

defined as the presence of one of the
traditional lacunar syndromes (eg, pure
motor stroke, pure sensory stroke,
sensorimotor stroke, ataxic hemiparesis,
and dysarthria-clumsy hand syndrome),
infarction(s) < 1.5 cm of diameter or
normal CT/MRI examination, and
absence of acute cerebral cortical
dysfunction.
NEUROLOGY
Microangiography

 Potential cardiac sources for embolism

should be absent, and evaluation of the
large extracranial arteries should not
demonstrate a stenosis of 50% in an
ipsilateral artery.

NEUROLOGY
Clinical Manifestations
Location of infarction Lacunar Syndrome

The poterior limb of the internal capsule

Pure Motor Hemiparesis
or basis pontis

Ventrolateral thalamus Pure Sensory Stroke

The base of pons Ataxic hemiparesis

The base of pons or The genu of the Dysarthria and a clumsy hand or
internal capsule arm

Leticulostriate branch Pure Motor Hemiparesis with

The anterior limb motor (Broca’s) aphasia

NEUROLOGY
Mechanisms of Lacunar Infarction
③ Embolism
① Lipohyalinosis

Penetrating artery

Large
artery

② Branch
Atheromatous plaque Microatheroma

NEUROLOGY
Transient Ischemic Attack

A focal neurological deficit lasting <24

hours
 Proposed new definition: “brief episode
of neurological dysfunction caused by a
focal disturbance of brain or retinal
ischemia, with clinical symptoms typically
lasting less than 1 hour, and without
evidence of infarction”

NEUROLOGY
TIA is an important predictor of
future strokes!
 90 day stroke risk 10.5%
(highest in the 1st week)

1st month 4-8%

1st year 12-13%
5 years 24-29%
2 years * >40%
*Hemispheric TIA and carotid stenosis >70%

NEUROLOGY
Transient Ischemic Attack (TIA)
Etiology of TIA is not different from definite stroke.
Atherosclerosis in the main arteries ＋Thrombus Formation

Emboli from Severe stenosis

larger blood clot or occlusion

TIA

Cardiogenic • Other causes

embolism • Subclavian steal syndrome
• Fibromuscular dysplasia
• Moyamoya disease
Heart Disease • Cervical Spinal Disease
• Essential thrombocythemia
• Multiple myeloma antiphospholipid syndrome
• Disseminated intravascular coagulation

The thickness of arrow indicates the frequency.

大坪孝一 ほか：脳卒中ハンドブック（片山泰朗 編集）, ｐ138, ヴァンメディカル, 2001

NEUROLOGY
 Intracerebral Hemorrhage
(ICH)
 Causes 15-30% of all strokes (higher in Asians)
 Results in higher mortality (30-40%) and worse
functional outcome than any other stroke
subtype

 To date no therapies have shown benefit in

randomized clinical trials

› Surgical evacuation
› Osmotic diuretics
› Glucocorticoids
NEUROLOGY
Sites of Spontaneous ICH
Thalamic
Hemorrhage
(20%)
Lobar
Subcortical
Hemorrhage
(25%)

Pontine
Hemorrhage
Putaminal (7%)
Hemorrhage
(35%)

Cerebellar
Hemorrhage
(8%)

Mayer SA, Rincon F. Lancet Neurol. 2005;4:662-672;

Qureshi AI, et al. N Engl J Med. 2001;344:1450-1460.
NEUROLOGY
Predictors of Outcome
ICH Volume
Ping-pong ball Overall
38.0 mm ICH (N=188) mortality
28.0 mL 44%

Mortality
0-29 cm3
19%

Mortality
30-60 cm3
20%-55%

Golf ball Mortality

≥60 cm3
1.68 in 91%
40.8 mL
Only 1 of 71 patients with ICH volume ≥30 cm3
functioned independently at 30 days

NEUROLOGY
Predictors of Outcome
The ICH Score
Component ICH score
points
30-day Mortality
3-4 2 100

GCS 5-12 1
80
13-15 0
ICH volume >30 1 60

(cc) <30 0
40
Intraventricular Yes 1
hemorrhage No 0 20

Infratentorial Yes 1 0
origin No 0 Overall 0 1 2 3 4 5
>80 1 ICH Score
Age (y)
<80 0
Total ICH score 0-6

NEUROLOGY
Diagnostic Methods
• History Examination
• General physical &
neurological investigation
• Structure of brain
- Computed Tomography
(CT scan)
- Computed tomographic
angiography (CTA) using
spiral CT

NEUROLOGY
Diagnostic Methods

› Magnetic Resonance Imaging (MRI)

including diffusion and perfusion studies
› Magnetic Resonance Angiography (MRA)
› Carotid and Transcranial Doppler Ultrasound
› Digital Subtraction Angiogram
› Single Photon Emission Computed
Tomography (SPECT)
› Positron Emission Tomography (PET)

NEUROLOGY
Computed Tomography

 Widely available
 Noninvasive
 Rapid
 Relatively inexpensive
 Relatively easy to interpret

NEUROLOGY
 Computed Tomography (CT)
Air
Bone • Isodense
(intermediate density)
Cerebrospinal Temporalis similar to brain tissue
fluid (CSF) muscle
• Hyperdense
(increased tissue density)
much lighter than
White matter brain tissue in CT
• Hypodense
Gray matter Skin of scalp
(decreased tissue density)
Subcutaneous fat
much darker than
Nonclotted blood brain tissue in CT
in blood vessel

• Distinguishes reliably between hemorrhagic and ischemic stroke

• May detect signs of ischemia as early as 2 hours after stroke onset
• Identifies hemorrhage almost immediately
• Helps to identify other neurological diseases (e.g. neoplasms)

NEUROLOGY
Computed Tomographic
Angiography (CTA)
 Requires spiral techniques and bolus
injection of a contrast agent
 Contraindication: Allergy to iodine and
renal dysfunction
 Visualizes obstruction of major intracranial
arteries, cortical veins, venous sinuses
 Reconstructs a 3-dimentional image of
an aneurysm

NEUROLOGY
 Magnetic Resonance Imaging (MRI)
Air Cerebrospinal Cerebrospinal
fluid (CSF) Air fluid (CSF)
Bone
Bone
Gray matter Gray matter
Cerebrospinal
fluid (CSF)
Flowing
blood
White White
Fat and matter Fat and matter
water Flowing water Flowing
blood blood

T1-weighted T2-weighted
Water is dark/Fat is light Water is bright/Fat is dark
Anatomical detail best Good contrast

Morphological imaging Sensitive to edema

Brightness of MRI image is determined mainly by water and fat

content of the tissue.
NEUROLOGY
Advantages of Magnetic
Resonance Imaging
 Provides high-contrast, high-resolution
imaging of the nervous system with
striking anatomic detail

 Excellent images of the brainstem and

pituitary fossa not seen by CT scan due
to interference from bone

NEUROLOGY
Advantages: Magnetic
Resonance Imaging
 Detects early changes of ischemic brain
edema and may differentiate this from
normal and old ischemic lesions

 Used for atypical and problematic

cases where location or nature of brain
lesion is critical

NEUROLOGY
Disadvantages: Magnetic
Resonance Imaging
 Expensive with limited availability

 Low sensitivity for hemorrhage

 Contraindicated in those with

pacemakers

 Time: 45 minutes
NEUROLOGY
Diffusion Weighted Imaging (DWI) & Perfusion Weighted
Imaging (PWI)
Diffusion/Perfusion mismatch Final lesion volume

days-weeks

DWI
DWI PWI
DWI Ischemic Penumbra
Diffusion weighted images:
Core area of infraction
Mismatch
Perfusion weighted image:
Malperfused area
Tissue at Risk
PWI
Albers GW. Stroke 1999;30(10):2230-2237

NEUROLOGY
Magnetic Resonance Angiography
(MRA)
• MR scanner measures only
moving structures
• Shows only blood - no static
structure
• Generate 3-D image of
vasculature system
• Can be enhanced with contrast
agent (e.g. Gd-DTPA)

 Time of flight MRA through the circle of Willis demonstrates a high-grade stenosis
at the right middle cerebral artery

Types
• Time of flight (TOF) MRA: currently used most frequently, anatomic information
• Contrast enhanced MRA: reduction in the time and flow-related artifacts
• Contrast phase MRA: anatomic information, velocity and direction of blood flow

NEUROLOGY
Carotid duplex

 Relatively
inexpensive and available
 Detects candidates for endarterectomy
 Vulnerable to errors in technique
› Degree of narrowing can be over or
understimated
› Can not differentiate high-grade stenosis
from occlusion
› May supplement with MRA or conventional
angiogram

NEUROLOGY
Use of Transcranial Doppler Ultrasound to Predict
Outcome In Patients with Intracranial Large-Artery
Occlusive Disease

NEUROLOGY
Transcranial Doppler (TCD)
• Principle: Doppler uses ultrasound reflecting off moving red blood cells
to measure the velocity of blood flow.

• Purpose: Identify stenosis or occlusion, vasospasm, state of collaterals

and recanalization

Interpretation of Results
• Lack of blood flow  completely occluded blood vessel
• Increase of blood flow  narrowed blood vessel
Flow signal

Normal Stenotic Dampened Blunted Minimal Absent

Normal Partial occlusion Complete occlusion

NEUROLOGY
Flow velocity increases and then decreases with disappearance of turbulence

NEUROLOGY
TCD limitations

 Operator dependent
 Thick skull seen in 15-20% of elderly Asian
women

NEUROLOGY
World Stroke Campaign
Stroke Treatment and Prevention
Primary stroke prevention
modify risk factors to reduce primary stroke risk:
blood pressure lowering, statin therapy,
anticoagulation, behavioural modifications

Acute ischemic stroke

intervention ameliorates the impact of stroke

• rt-PA therapy within 4.5 hours whenever appropriate

• Antiplatelet agents

Secondary stroke prevention

reduce risk of another event: Rehabilitation
antiplatelet therapy, anticoagulation, improve neurologic functioning
carotid revascularisation

Gorelick PB. Stroke. 2002;33(3):862-75

Goldstein LB et al. Circulation. 2001;103(1):163-82

NEUROLOGY
 Thrombolysis &
Recanalization Thrombectomy

Preserve Ischemic Tissue Neurorestoration&

(penumbra) Neuroprotection

Decompressive
Prevent neurologic worsening hemicraniectomy

Prevent early recurrent stroke/ Antithrombotics

Statins
Secondary stroke prevention
Anthypertensives

Prevent complications Stroke units

tissue that is at risk
but still salvageable and that is the
target of acute/subacute stroke
therapy
 With Neuroprotection Without Neuroprotection
Ischemic Damage minimized Permanent Ischemic Damage

Fisher M. Cerebrovasc Dis 2004; 17(suppl 1): 1-6

 Avoid Hypoxemia Avoid Hypotension

Avoid Hyperthermia Avoid Hyper / Hypoglycemia Neuroprotective drugs

 ISCHEMIC CASCADE Neuronal death

Hypoxia
Activation of lipases, NO synthase,
peroxidases
Na – K+ pump failure

 Intracellular Ca

K leak , Depolarization
Opening of
Citicoline Ca channels

Glutamate & Activation of NMDA, AMPA

neurotransmitter release receptors
 Neurorepair
ATP
Metabolic Acidosis
(Ca 2+)
Glutamate Release
Therapeutic Intervention

Free Radical Formation

Release Nitric Oxide
Inflammation
Gene Expression

Apoptosis
Ischemic Penumbra

3 hour 3 - 6 hours 6 hours - days

Time elapsed
 Stroke Interventions – Level I Evidence
Initial or
Intervention RRR ARR NNT
important study

Aspirin IST, CAST 1997 2.6 1.2 83

tPA NINDS 1995;ECASS 3 2008 9.8 5.5 7

Stroke Unit Langhorne et al, 1993 6.5 3.8 26

Hemicraniectomy Vahedi K et al, 2007 48.8 23.0 4

Endovascular MR Clean, ESCAPE, EXTEND
IA, SWIFT PRIME, REVASCAT 50 25 4
thrombectomy
• Based on IST and CAST

• Aspirin provides a reduction of 10

deaths or recurrent strokes per 1000 patients
during the first 2-4 weeks after acute ischemic
stroke
A. Aspirin : reduction in non-fatal stroke and death
a. International Stroke Trial (1997) : 300 mg ASA
b. Chinese Acute Stroke Trial (1997): 160 mg OD

B. Clopidogrel + Aspirin (FASTER trial, 2007) :

Recurrent stroke at 90 days:
Clopidogrel-ASA (7.1%), Aspirin alone (10.1%),

Absolute risk reduction of 3.8% p =0.19

Hemmorrhagic events were higher with the combination
treatment
International Stroke Trial (IST) Lancet 1997;349: 1569
Chinese Acute Stroke Trial (CAST) Lancet 1997;349: 1641
Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence FASTER,
Lancet Neurology 2007; 6: 961- 969)
 The oral administration of aspirin (325 mg) within 24 to 48
hours after stroke onset is recommended (IA)
 Aspirin should not be considered a substitute for other acute interventions for
treatment of stroke
 The administration of aspirin as an adjunctive therapy within 24 hours of
thrombolysis is not recommended
 The administration of clopidogrel alone or combination
with aspirin is not recommended for the treatment of acute
ischemic stroke
 Outside the setting of clinical trials, the intravenous administration of
antiplatelet agents that inhibit the glycoprotein IIb/IIIa receptor is not
recommended
 It is recommended that aspirin (160–325 mg loading dose) be
given within 48 hours after ischaemic stroke
 It is recommended that if thrombolytic therapy is planned or given,
aspirin or other antithrombotic therapy should not be initiated within 24
hours
 Use of other antiplatelet agents (single or combined) is not
recommended in acute stroke
 The administration of glycoprotein IIb/IIIa inhibitors is not recommended
 Early administration of UFH, LMWH or heparinoids is not recommended
for the treatment of patients with acute ischemic stroke
 Acute Ischemic Stroke: Aspirin
• For every 1000 patients treated,
• 12 avoid death or dependency,
• an extra 10 make a complete recovery
• risk of haemorrhage is low (1-2 per 1000) and is
outweighed by the benefits
• Should be given immediately after CT/MR has
excluded ICH
• In case rTPA was used, wait for 24 hours
before initiation
Intervention Outcome OR NNT
Death 0.81 21

Stroke Death or dependency 0.75 14

Unit Death or 0.71 15
institutionalization
46 Stroke Units /1856 Hospitals =
2.47%
46 Stroke Units out 456 Tertiary
Hospitals = 10.08%
Why Thrombolysis Works?
 Why the RUSH?
• Simply reducing onset to needle gives the best outcome in
terms of cost-benefit analysis
• Number Needed to Treat increases 1 per 20min with rTPA
• Penumbra dying + clot resistance to tPA increasing

Muchada et al Stroke 2014 Kim et al Stroke 2015

The recommended dose of Actilyse is 0.9 mg.kg (not to exceed 90-mg total
dose) infused over 60 minutes with 10% of the total dose administration as an
initial intravenous bolus over 1 minute.

Hospitals should ensure that Actilyse is readily

available in the ED or in the CT scanner area.
Basic Neuroimaging Needed
 The GOLDEN HOUR
Rapid intervention is crucial in the management of AIS Door to treatment in ≤60 minutes is the standard of care
recognized in the treatment of Acute Ischemic Stroke.

Door to treatment < 60 min

Complete initial MD
Suspected stroke Notify stroke team Give Actilyse
Evaluation, including Initiate CT scan Interpret CT scan and
Patient arrives Patient history and
(including neurologic bolus
At ED Expertise) labs Review patient, And initiate
Time last known
Well/symptom onset eligibility infusion
Initiate labwork For Activase In eligible*
Assess using NIHSS patients
 Effectiveness of IV thrombolysis:
• 2 positive studies (NINDS2, ECASS3) with absolute risk
reduction for death & disability of 7 and 13%
• All other studies were negative
• Combined analysis of all randomized IV lysis studies
shows no positive effect within 6 hours
• Today less than 10% of all patients are treated
• In reality, IV lysis helps less than 1% of stroke patients

Why so few?
 Effectiveness of IV thrombolysis:
• About 30% of acute ischemic stroke patients do not
have arterial occlusions at treatment onset
• These patients have a good outcome in 60%,
regardless of treatment or not
• In patients with major artery occlusion, IV lysis
leads to recanalization in about 50% only (IMS-3)
• IV lysis is only effective if thrombus length is <8mm
 Intravenous recombinant TPA …..

BENEFIT RISK

30 % MORE LIKELY to have Higher rate of symptomatic ICH

minimal or no disability at 3 months
Therapy for the Secondary Prevention of Stroke

Ischemic stroke

Non-cardioembolic stroke Cardioembolic stroke

Atrial fibrillation
Atherothrombotic stroke
Left ventricular thrombi
Lacunar stroke
Acute myocardial infarction
Cryptogenic stroke
Prosthetic heart valve

Antiplatelet therapy Anticoagulant therapy

Aspirin
Ticlopidine/Clopidogrel Warfarin
Aspirin +Dipyridamole Novel Oral Anti-
Cilostazol Coagulants

S Uchiyama, 2003

NEUROLOGY
Treatment of all types is specific
for the individual patient!

 It
is imperative that we recognize the
cause of each person’s stroke.

 We can and should individualize

treatment depending on the specific
problems and conditions present in that
patient.

NEUROLOGY
NEUROLOGY