Stroke: An update

Asst. Prof. Sombat Muengtaweepongsa, M.D.

Division of Neurology

Faculty of Medicine

Thammasat University

Holistic Stroke Approach

Primary Stroke

Prevention

Acute Stroke Management

Secondary Stroke

Prevention

Rehabilitation

Primary Stroke Prevention

UPDATE

Homocysteine, Folic Acid, and B Vitamins

• Homocysteine: a risk factor for stroke

• VITAmins TO Prevent Stroke (VITATOPS)

aimed to assess whether daily

administration of folic acid, vitamin B6, and

vitamin B12 in patients with recent stroke

or transient ischemic attack lowers

homocysteine and reduces major vascular

events.

VITATOPS: results

VITATOPS: conclusions

• B vitamins have no or at most a marginal

positive effect on reducing vascular

events.

Blood Pressure

• not only blood pressure levels, but also

blood pressure variability account for

stroke risk

• the ideal antihypertensive agent should

lower both blood pressure levels and

variation in blood pressure to reduce

stroke risk (currently do not have such

agents)

Acute Stroke Management

UPDATE

Transient Ischemic Attack

Definition

• time-based definitions of TIA were first advanced in the 1950s and 1960s

• In 1964, Marshall proposed 24 hours as the maximal duration of symptoms

• In the 1975 revision of the NIH classification document, a 24-hour limit for TIAs was adopted.

TISSUE BASED DEFINITION OF TIA

• Proposals have been made for a "tissue-based" definition of TIA that relies on the absence of end-organ injury as assessed by imaging or other techniques.

• A brief episode of neurologic dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting less than one hour, and without evidence of acute infarction

Copyright ©2004 American Heart Association

Purroy, F. et al. Stroke 2004;35:2313-2319

Graded risk of futures vascular events and the combination of TIA duration and DWI findings

Prognosis of TIA

Copyright ©2004 BMJ Publishing Group Ltd.

Coull, A J et al. BMJ 2004;328:326

Cumulative risk of stroke after a transient ischemic attack (TIA) or minor stroke

ABCD2 score

• Age 60 years = 1

• Blood pressure:

– systolic 140 mm Hg and/or diastolic 90 mm Hg = 1

• Clinical features:

– unilateral weakness = 2

– speech disturbance without weakness = 1

– other = 0

• Duration of symptoms in min

– >60 = 2

– 10–59 = 1,

– <10 = 0

• Diabetes = 1

EXPRESS study

Lancet. 2007 Oct 20;370(9596):1432-42.

• TIA patients should undergo neuroimaging

evaluation within 24 hours of symptom

onset, preferably with magnetic resonance imaging, including diffusion sequences

AHA Guidelines: TIA (Diagnostic)

• noninvasive imaging of the cervical vessels

should be performed and noninvasive imaging

of intracranial vessels is reasonable

• Electrocardiography should occur as soon as

possible after TIA and prolonged cardiac

monitoring and echocardiography are

reasonable in patients in whom the vascular etiology is not yet identified

AHA Guidelines: TIA (Treatment)

• It is reasonable to hospitalize patients

with TIA if they present within 72 hours and have an ABCD2 score ≥ 3.

June 2009

Standard treatment for AIS

1. Intravenous rt-PA within 3 hrs window

(NNT < 10)

2. Stroke unit (NNT 20-30)

3. ASA within 48 hrs (NNT 140)

4. Early decompressive surgery for malignant MCA infarction (NNT 2)

Copyright ©2003 American Heart Association

Graham, G. D. Stroke 2003;34:2847-2850

Symptomatic ICH rates ordered by decreasing sample size

Exclusion Criteria (1)

• Time of symptom onset unknown

• Symptoms improve rapidly/symptoms only

minor before infusion started

• Evidence of ICH by CT

• Severe stroke as assessed clinically (e.g.

NIHSS25) and/or imaging

• Seizure at the onset of stroke

• Symptoms suggestive of subarachnoid

haemorrhage, even if normal CT scanCT, computed tomography; ICH, intracranial haemorrhage;

NIHSS, National Institutes of Health Stroke Scale

• Combination of previous stroke and diabetes

mellitus

• Platelet count of less than 100,000 per cubic

millimeter

• Oral anticoagulant treatment

Exclusion Criteria (2)

*Lees et al. N Engl J Med 2006;354:588-600

*stratified on Cochran–Mantel–Haenszel test,

adjusted for baseline NIHSS scores and time-to-treatment onset

0% 20% 40% 60% 80% 100%Patients

p=0.024

Alteplase

(n=418)

mRS score*

Placebo

(n=403)

1 2 30 4 5 6

27.5

23.321.8 16.4

9.314.124.9

13.7

9.3

8.2

6.78.1

11.4 5.2

Distribution (shift) analysis* day 90

Thrombolytic Therapy (i.v. rtPA)

Guidelines Ischaemic Stroke 2008

Intravenous Thrombolysis

• rtPA should be administered to eligible patients who can be treated the time period of 3 to 4.5 hours after stroke (Class I Recommendation, Level of Evidence B).

August 2009

Treatment rate

100 patients received i.v. rt-PA

59 patients got transferred from outside hospitals in

acute stroke network (59%)

21% of admissions with acute ischemic stroke

0%5%

10%15%20%25%

Thrombolytic rate

Thrombolytic rate

1 Suwanwela Clin Neurol Neurosurg, 2006

2 Grotta Arch Neurol, 2001

Onset To Treatment and Door To Needle

Mean OTT 144 minutes (40 – 270)

Chulalongorn 137 (45 - 180) 1

Houston 137 (30 – 180) 2

Mean Door to needle 54 minutes (15 – 90)

Chulalongorn 72 (20 - 150) 1

Houston 70 (10 – 129) 2

1 Suwanwela Clin Neurol Neurosurg, 2006

2 Grotta Arch Neurol, 2001

Hemorrhage

13 patients have intracerebral hemorrhage (13%),

Chulalongorn 11.8% 1, ECASS III 27% 3

11 asymptomatic or 11%

2 symptomatic (NIHSS worse > 4) with 1 fatal or 2%

(according to ECASS III definition)

NINDS 6.4% 2

Chulalongorn 5.9% 1

ECASS III 2.4% 3

1 Suwanwela Clin Neurol Neurosurg, 2006

2 NINDS N Engl J Med, 1995

3 ECASS III N Engl J Med, 2008

Functional outcomes at 3 months

42%

39%

26%

21%

18%

23%

14%

17%

0% 20% 40% 60% 80% 100% 120%

Thammasat

NINDS

mRS 0-1

mRS 2-3

mRS 4-5

mRS 6

Cerebrolysin

• a compound consisting of free amino acids

and biologically active small peptides that

are products of the enzymatic breakdown

of lipid free brain products

• Experimental models have demonstrated

neuroprotection although the mechanism

of action is unclear

Cerebrolysin for acute ischaemic stroke

The Cochrane Review

• Review content: 7 January 2010.

• one trial involving 146 participants

– no difference in death or adverse events

• not enough evidence to evaluate the effect

of cerebrolysin on survival and

dependency in people with acute

ischaemic stroke

The Safety and Efficacy of Cerebrolysin in Patients

With Acute Ischemic Stroke (CASTA)

• 10-day course of therapy with daily

intravenous administration of 30mL

Cerebrolysin

• Primary Outcome Measures:

– mRS, BI, NIHSS at 90 days

• Study location

– China, Hong Kong, Korea

• Being announced in WSC 2010

Secondary Stroke Prevention

UPDATE

What treatments are available for each etiology?

• For most mechanisms of

cerebral infarction or TIA,

antiplatelet agents are

indicated.

– diagnostic evaluation is aimed

at evaluating potential

mechanisms that would require

something other than an

antiplatelet agent, such as

surgery, endovascular

intervention, anticoagulants,

antibiotics, or

immunosuppressants.

• class I treatment evidence

– symptomatic carotid artery

stenosis greater than 70% with

carotid endarterectomy (CEA)

– anticoagulation for atrial

fibrillation

– anticoagulants for a few

additional cardioembolic

sources

• For most other etiologies,

antiplatelet agents are

recommended

ASA/AHA Guidelines for prevention of stroke

in patients with ischaemic stroke or TIA (2008)

RecommendationClass/Level of

Evidence*

For patients with noncardioembolic stroke or TIA, antiplatelet agents rather than

oral anticoagulation are recommended to reduce the risk of recurrent stroke and

other cardiovascular events.Class I, Level A

Aspirin (50 to 325 mg/d) monotherapy, the combination of aspirin and extended-

release dipyridamole, and clopidogrel monotherapy are all acceptable options for

initial therapy.*

Class I, Level A

The combination of aspirin and extended-release dipyridamole is recommended

over aspirin alone.Class I, Level B

Clopidogrel may be considered over aspirin alone on the basis of direct-comparison

trials. Class IIb, Level B

Addition of aspirin to clopidogrel increases the risk of haemorrhage and is not

routinely recommended for ischaemic stroke or TIA patients unless they have a

specific indication for this therapy (ie, coronary stent or acute coronary syndrome).Class III

For patients allergic to aspirin, clopidogrel is reasonable. Class IIa, Level B

For patients who have an ischaemic cerebrovascular event while taking aspirin,

there is no evidence that increasing the dose of aspirin provides additional benefit.

Although alternative antiplatelet agents are often considered for non-

cardioembolic patients, no single agent or combination has been well studied in

patients who have an event while receiving aspirin.

Adams et al. Stroke 2008; 39: 1647-1652.

Dual antiplatelet therapy

• intracranial symptomatic atherosclerotic

stenosis, a short-term combination therapy

with clopidogrel and aspirin was more

effective than aspirin alone in reducing

microembolic signals

• a short-term combination therapy with

cilostazol and aspirin may reduce

progression of intracranial stenosis

Anticoagulation

• Dabigatran: direct thrombin inhibitor

– equal or superior than warfarin to prevent

emboli but with lower or equal rates of major

hemorrhages

• Rivaroxaban: a factor Xa inhibitor

– noninferior to warfarin for the prevention of

stroke and noncentral nervous system

embolism

Rehabilitation

UPDATE

After 36 weeks, robot-assisted and intensive therapy

had significantly improved motor function as compared

with standard of care.

Potential long-term benefits of intensive rehabilitation in

patients with moderate-to-severe impairment, even years after

a stroke

Thank you for your attention