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: 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)
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
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 AIS1. 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)
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
Exclusion Criteria (2)• Combination of previous stroke and diabetes mellitus• Platelet count of less than 100,000 per cubic millimeter• Oral anticoagulant treatment
Distribution (shift) analysis* day 90 mRS score* 0 1 2 3 4 5 6 Alteplase 27.5 24.9 14.1 9.3 9.3 8.1 6.7 (n=418) p=0.024 Placebo 21.8 23.3 16.4 11.4 13.7 5.2 8.2 (n=403) Patients 0% 20% 40% 60% 80% 100%*stratified on Cochran–Mantel–Haenszel test,adjusted for baseline NIHSS scores and time-to-treatment onset *Lees et al. N Engl J Med 2006;354:588-600
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 Thrombolytic rate 25% 20% 15% 10% 5% 0% 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
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
What treatments are available for each etiology?• For most mechanisms of • class I treatment evidence cerebral infarction or TIA, – symptomatic carotid artery antiplatelet agents are stenosis greater than 70% with indicated. carotid endarterectomy (CEA) – diagnostic evaluation is aimed – anticoagulation for atrial at evaluating potential fibrillation mechanisms that would require – anticoagulants for a few something other than an additional cardioembolic antiplatelet agent, such as sources surgery, endovascular • For most other etiologies, intervention, anticoagulants, antiplatelet agents are antibiotics, or immunosuppressants. recommended
ASA/AHA Guidelines for prevention of stroke in patients with ischaemic stroke or TIA (2008) Class/Level of Recommendation Evidence*For patients with noncardioembolic stroke or TIA, antiplatelet agents rather thanoral anticoagulation are recommended to reduce the risk of recurrent stroke and Class I, Level Aother cardiovascular events.Aspirin (50 to 325 mg/d) monotherapy, the combination of aspirin and extended-release dipyridamole, and clopidogrel monotherapy are all acceptable options for Class I, Level Ainitial therapy.*The combination of aspirin and extended-release dipyridamole is recommended Class I, Level Bover aspirin alone.Clopidogrel may be considered over aspirin alone on the basis of direct-comparison Class IIb, Level Btrials.Addition of aspirin to clopidogrel increases the risk of haemorrhage and is notroutinely recommended for ischaemic stroke or TIA patients unless they have a Class IIIspecific indication for this therapy (ie, coronary stent or acute coronary syndrome).For patients allergic to aspirin, clopidogrel is reasonable. Class IIa, Level BFor 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- Adams et al. Stroke 2008; 39: 1647-1652.cardioembolic patients, no single agent or combination has been well studied inpatients who have an event while receiving aspirin.
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
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 inpatients with moderate-to-severe impairment, even years aftera stroke