Stroke: An updateAsst. Prof. Sombat Muengtaweepongsa, M.D.             Division of Neurology              Faculty of Medic...
Holistic Stroke Approach             Acute Stroke             Management                  Rehabilitation Primary          ...
Primary Stroke Prevention         UPDATE
Homocysteine, Folic Acid, and B Vitamins• Homocysteine: a risk factor for stroke• VITAmins TO Prevent Stroke (VITATOPS)  a...
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 a...
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...
TISSUE BASED DEFINITION OF TIA• Proposals have been made for a  "tissue-based" definition of TIA that  relies on the absen...
Graded risk of futures vascular events and the combination of TIA duration and DWI                                       f...
Prognosis of TIA
Cumulative risk of stroke after a transient ischemic attack (TIA) or minor stroke                         Coull, A J et al...
ABCD2 score• Age 60 years = 1• Blood pressure:   – systolic 140 mm Hg and/or diastolic 90 mm Hg = 1• Clinical features: ...
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 resonan...
AHA Guidelines: TIA         (Diagnostic)• noninvasive imaging of the cervical vessels  should be performed and noninvasive...
AHA Guidelines: TIA         (Treatment)• It is reasonable to hospitalize patients  with TIA if they present within 72  hou...
Standard treatment for AIS1. Intravenous rt-PA within 3 hrs window   (NNT < 10)2. Stroke unit (NNT 20-30)3. ASA within 48 ...
Symptomatic ICH rates ordered by decreasing sample size                      Graham, G. D. Stroke 2003;34:2847-2850Copyrig...
Exclusion Criteria (1)       • Time of symptom onset unknown       • Symptoms improve rapidly/symptoms only         minor ...
Exclusion Criteria (2)• Combination of previous stroke and diabetes  mellitus• Platelet count of less than 100,000 per cub...
Distribution (shift) analysis* day 90             mRS score*             0                      1            2          3 ...
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....
Treatment rate   100 patients received i.v. rt-PA     59 patients got transferred from outside hospitals in      acute s...
Onset To Treatment and Door To Needle   Mean OTT 144 minutes (40 – 270)     Chulalongorn 137 (45 - 180) 1     Houston 1...
Hemorrhage   13 patients have intracerebral hemorrhage (13%),    Chulalongorn 11.8% 1, ECASS III 27% 3     11 asymptomat...
Functional outcomes at 3 months    NINDS        39%         21%         23%     17%                                       ...
Cerebrolysin• a compound consisting of free amino acids  and biologically active small peptides that  are products of the ...
Cerebrolysin for acute ischaemic stroke        The Cochrane Review• Review content: 7 January 2010.• one trial involving 1...
The Safety and Efficacy of Cerebrolysin in Patients      With Acute Ischemic Stroke (CASTA)• 10-day course of therapy with...
Secondary Stroke Prevention          UPDATE
What treatments are available for each etiology?• For most mechanisms of              • class I treatment evidence  cerebr...
ASA/AHA Guidelines for prevention of stroke  in patients with ischaemic stroke or TIA (2008)                              ...
Dual antiplatelet therapy• intracranial symptomatic atherosclerotic  stenosis, a short-term combination therapy  with clop...
Anticoagulation• Dabigatran: direct thrombin inhibitor  – equal or superior than warfarin to prevent    emboli but with lo...
Rehabilitation   UPDATE
After 36 weeks, robot-assisted and intensive therapy  had significantly improved motor function as compared  with standard...
Thank you for your attention
Stroke update 2011
Stroke update 2011
Stroke update 2011
Stroke update 2011
Stroke update 2011
Stroke update 2011
Stroke update 2011
Stroke update 2011
Stroke update 2011
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Stroke update 2011

  1. 1. Stroke: An updateAsst. Prof. Sombat Muengtaweepongsa, M.D. Division of Neurology Faculty of Medicine Thammasat University
  2. 2. Holistic Stroke Approach Acute Stroke Management Rehabilitation Primary Secondary Stroke StrokePrevention Prevention
  3. 3. Primary Stroke Prevention UPDATE
  4. 4. 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.
  5. 5. VITATOPS: results
  6. 6. VITATOPS: conclusions• B vitamins have no or at most a marginal positive effect on reducing vascular events.
  7. 7. 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)
  8. 8. Acute Stroke Management UPDATE
  9. 9. Transient Ischemic Attack
  10. 10. 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.
  11. 11. 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
  12. 12. Graded risk of futures vascular events and the combination of TIA duration and DWI findings Purroy, F. et al. Stroke 2004;35:2313-2319Copyright ©2004 American Heart Association
  13. 13. Prognosis of TIA
  14. 14. Cumulative risk of stroke after a transient ischemic attack (TIA) or minor stroke Coull, A J et al. BMJ 2004;328:326Copyright ©2004 BMJ Publishing Group Ltd.
  15. 15. 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
  16. 16. EXPRESS study Lancet. 2007 Oct 20;370(9596):1432-42.
  17. 17. • TIA patients should undergo neuroimaging evaluation within 24 hours of symptom onset, preferably with magnetic resonance imaging, including diffusion sequences
  18. 18. 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
  19. 19. 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
  20. 20. 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)
  21. 21. Symptomatic ICH rates ordered by decreasing sample size Graham, G. D. Stroke 2003;34:2847-2850Copyright ©2003 American Heart Association
  22. 22. 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. NIHSS25) 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
  23. 23. Exclusion Criteria (2)• Combination of previous stroke and diabetes mellitus• Platelet count of less than 100,000 per cubic millimeter• Oral anticoagulant treatment
  24. 24. 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
  25. 25. Thrombolytic Therapy (i.v. rtPA) Guidelines Ischaemic Stroke 2008
  26. 26. 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
  27. 27. 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
  28. 28. 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
  29. 29. 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
  30. 30. Functional outcomes at 3 months NINDS 39% 21% 23% 17% mRS 0-1 mRS 2-3 mRS 4-5Thammasat 42% 26% 18% 14% mRS 6 0% 20% 40% 60% 80% 100% 120%
  31. 31. 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
  32. 32. 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
  33. 33. 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
  34. 34. Secondary Stroke Prevention UPDATE
  35. 35. 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
  36. 36. 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.
  37. 37. 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
  38. 38. 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
  39. 39. Rehabilitation UPDATE
  40. 40. 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
  41. 41. Thank you for your attention

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