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Diagnosis, Evaluation, and Treatment of Stroke Fariborz Khorvash, MD Assistant Professor of Neurology Topics Definitions Evaluation of Suspected Stroke Evaluation of TIAs Stroke Prevention Evaluation & Treatment of Ischemic Stroke Evaluation & Treatment of Hemorrhagic Stroke Case #1 62 year old woman presents after a abrupt onset of blindness in her left eye while shopping today. Sx resolved en route to ER via EMS about 20 minutes after they started. VS Afeb; BP 148/78; P 68 Exam unremarkable in ER What’s the diagnosis? Case #2 76 yo male, rehabbing at local NH after recent hip fx, has abrupt onset of slurred speech and left arm/leg weakness. Sx persistent in ER. Pt has no complaints. VS Afeb; BP 188/96; P 72 Head CT is “negative” What’s the diagnosis? Case #3 33 yo woman presents with “worst headache of her life”, abruptly starting 1 hour ago. On exam, she is mildly confused, has mild nuchal rigidity, but no other focal findings VS Afeb; BP 155/82; HR 58 What’s the diagnosis? Classification of Stroke 2 broad categories of stroke: • Ischemia • Inadequate blood supply (oxygen & nutrients) to an area of the brain • Hemorrhage- • Leakage of blood into the closed cranial cavity • Direct damage to tissue by compression/edema Epidemiology of Stroke Incidence in US 80-90% are ischemic Male:Female ratio 1.25:1 • ~700K per year (~200K are recurrent) • Ratio reverses after age 80 Higher rates in Blacks, Hispanics, & Native Americans Risk Factors Heart disease • AFib, Valvular Dz, MI, endocarditis Hypertension Smoking Diabetes/Metabolic Syndrome Dyslipidemia Pregnancy Drug Abuse/Meds Bleeding Disorders/Anticoagulant Use Ischemic Stroke Thrombosis • In situ arterial obstruction • Arteriosclerosis, dissection, FMD • Superimposed thrombosis Embolism • Arterial obstruction from debris from another source Systemic Hypoperfusion • Circulatory collapse • Multiorgan involvement Thrombosis Large Vessel Disease • • Common & Internal Carotids Circle of Willis & proximal branches Small Vessel Disease • • Penetrating arteries “Lacunar Stroke” “Stuttering” course Embolism Cardiac • Atrial fibrillation • Heart valves, atrial thrombus, recent MI, dilated CM, endocarditis, recent CABG Aortic Arterial (e.g. carotids) Other/Unknown Abrupt onset, rapid improvement • DVT- “Paradoxical embolus” Hypoperfusion Shock Sx are more diffuse/nonfocal “Border-zone regions” • Cardiogenic, septic, hypovolemic • Cortical blindness • Stupor • Proximal Weakness Hemorrhagic Stroke Intracerebral Hemorrhage (ICH) • • • • • Bleeding within the brain tissue Forms a hematoma Growth stopped by tamponade or leaking into the ventricles or CSF Headache, vomiting, delirium Progressive sx Causes of ICH HTN Trauma Bleeding Disorder • • Inherited Acquired, i.e. meds Amyloid Drug use • • Cocaine Amphetamines AVMs Bleeding into tumor Vasculitis Hemorrhagic Stroke Subarachnoid Hemorrhage (SAH) • • • • Bleeding into CSF on outer aspect of brain Quick rise in ICP Sudden onset headache in 97% Aneurysm & AVMs are most common cause Differential Diagnosis Seizure with Todd’s Paralysis Syncope Migraine Head Trauma Brain tumor Metabolic Causes • • • • • Hypoglycemia Hyponatremia Intoxication Uremia/ARF Hepatic Encephalopathy Conversion Disorder Initial Evaluation:Physical Exam Vital signs Pulses Carotid Bruit Cardiac Exam Funduscopic exam Skin exam Signs of trauma • Temperature, Pulse, Blood Pressure Initial Evaluation:Physical Exam Neurologic Exam • Level of consciousness/GCS • Language/Speech • Cranial nerves • Vertigo, diplopia, ataxia • Visual deficits • Weakness/Paralysis • Reflexes/ Babinski Initial Evaluation: Studies CBC with platelets Electrolytes, Bun, Cr Glucose LFTs PT/PTT O2 Sat ECG Chest XRay ESR Blood Cultures ANA Tox screen Alcohol level Blood type & cross Urine/Serum HCG Hypercoaguability Profile Initial Evaluation: Imaging CT Scan • “R/O Bleed” • stroke Early signs (<6 hrs) • Sensitivity much better after 24 hrs for ischemic • May indicate worse prognosis CT Scans of Stroke Initial Evaluation: Imaging MRI • • • T1/T2 images, DWI Provides immediate evaluation of ischemia Not available for emergency use in many settings Further Evaluation: Carotids Carotid U/S for stenosis If ASVD, but no stenosis… If stenosis, consider… Vertigo & Syncope are not considered symptomatic • Risk Factor Modification • Carotid Endarterectomy • ?Carotid Stenting Treatment of Carotid Stenosis with Symptoms 100% occlusion • No treatment 70-99% occlusion • If good 5-yr survival & risks <6%, early CEA (within 2 weeks) 50-69% • • If above criteria & male, early CEA If female, medical mgt <50% • Medical management Further Evaluation: Echo Echocardiography indicated for • Patients who may need anticoagulation • Atrial fibrillation • Risk of atrial thrombus • Recent MI • Risk for Endocarditis TEE is more sensitive than TTE, but will it change management? Further Evaluation: Intracranial Not necessary for all patients Consider… CTA vs. MRA vs. TCD • Pts <50 without a clear source • Pts with recurrent stereotyped TIAs • Posterior circulation event without cardiac source • Prior to CEA Transient Ischemic Attack Sudden onset of neurologic dysfunction that lasts less than 24 hrs, brought on by presumed transient ischemia to a portion of the brain May be better to describe as sx <1 hr with no evidence of infarction May have infarct even with sx lasting a few hours (~50% of TIA patients have MRI evidence of ischemia) TSI? Transient Sx Associated with Infarction No established diagnostic criteria In one case series, 15% of TSI pts had a recurrent stroke in-hospital vs. 0% in TIA group. Hospitalize for TIAs? Could consider home if able to expedite urgent outpatient work-up AHA does not make a recommendation re: hospitalization One study suggested cost-effective if 24-hr stroke risk is >5% Risk of Stroke post-TIA NASCET trial suggested 90-day stroke risk of 20% with non-retinal TIAs (higher than for true stroke) 2000 JAMA study • • • 5% risk w/in 2 days 11% risk w/in 90 days Higher risk with age >60, DM, sx >10 min, weakness, speech impairment 2004 Neurology study: 21% risk of stroke/MI/death within 1 year of TIA ABCDs of TIAs Age >60 = 1 pt Blood Pressure >140/90 = 1 Clinical Features • • • Unilateral weakness = 2 Isolated speech deficit = 1 Other = 0 Duration • • • >60 minutes = 2 10-59 minutes = 1 <10 minutes = 0 Risk of “early stroke” Score ≤ 3: 0% 4: 1-9% 5: 12% 6: 24-31% Secondary Prevention of Stroke Risk factor modification Antithrombotic therapy Anticoagulant therapy Stroke Prevention: Risk Factors Hypertension • Goal <130/80 • SHEP Study, ISH in pts >60 • Dropped SBP from 155 to 143 • 36% reduction in stroke over 4 years • Pts >80 may not benefit as much & aggressive • BP lowering may increase mortality Diuretic +/- ACEI as 1st line Stroke Prevention: Risk Factors Smoking Diabetes • Stop it • Goal A1c <7, i.e. normoglycemic • Metabolic syndrome Stroke Prevention: Risk Factors Dyslipidemia • Evidence not as strong as may think, but still a • good idea, especially given other vascular disease SPARCL Study • Atorvastatin 80 mg/day in pts 1-6 months from CVA/TIA • Mean LDL reduction 56 • Endpoint was stroke: 16% RRR, but only 2.2% ARR (NNT ~50) Stroke Prevention: Risk Factors Dyslipidemia, continued • For average-risk patient, goal LDL <100 • For high-risk, goal <70 • Diabetes • Prior CAD • Multiple RFs with continued smoking Stroke Prevention: Risk Factors Lifestyle Modification Reduce alcohol intake, especially heavy drinkers ?Homocysteine • Weight loss • Exercise • Dietary changes • Consider B12, B6, Folate (MVI doses OK) Antiplatelet Therapy Aspirin • 20-25% reduction in stroke (& MI or other • • • vascular death) Standard doses of 81-325 mg as good as higher doses 81 mg dose just as good and less risk of bleeding ASA-non-responders? Antiplatelet Therapy Clopidogrel (Plavix) • 8% RRR vs. ASA for stroke/MI/Vasc death • 5.3% vs. 5.8%: NNT ~200 • All for only $100+/month • ?2nd-line therapy or ASA-allergic patients • No increased bleeding vs. ASA, but combo • should be avoided No neutropenia (like ticlopidine) Antiplatelet Therapy Dipyridamole • Alone 50-100 mg TID • Aggrenox (200mg ER-DP & 25mg ASA) BID • 2 studies have shown ~3% ARR (NNT 33) over • • ASA alone for stroke prevention Some guidelines are suggesting this a 1st line therapy over ASA alone for stroke prevention Cost >$100/month Anticoagulant Therapy Warfarin has only been proven effective in primary prevention of stroke in the setting of atrial fibrillation AF is responsible for 1/6th of all strokes in patients older than 60 Risk reduction “Low Risk” patients may consider ASA rx • Warfarin about 3 times as effective as ASA • Absolute annual risk reduction of ~3% Risk of AF-Related Stroke Annual Risk of Stroke 6% 5% 4% 3% 2% 1% 0% 50-59 60-69 70-79 Age 80-89 Risk Stratification for Stroke Highest Risk: Prior Stroke or TIA High Risk: Any of the following • Prior thromboembolism • Female >75 yo • SBP >160 • Heart failure/LV dysfunction Moderate Risk: None of above, but HTN Low Risk: None of the above, no HTN Choice of Medication Risk Category Annual Stroke Risk NNT Choice Highest: Prior CVA 10% 14 Warfarin High 6% 33 Warfarin Moderate 3% 66 Warfarin Low 1% >200 Aspirin Based on SPAF-III Trial, Lancet 1996 Treatment of Ischemic Stroke Thrombolysis Blood Pressure Management Antithrombotic Therapy Management of Medical Complications Thrombolysis of Acute Stroke Time-sensitive • Studies show that thrombolytics must be given within 3 hours of symptom onset Effective • NINDS- Complete or near-complete recovery at 3 • months post-event (38% vs. 21%, NNT=6) No difference in mortality Harmful • At least 6% risk of ICH Thrombolysis of Acute Stroke Alteplase (tPA) 0.9 mg/kg dose up to 90 mg • 10% as IV bolus, then 60 min infusion Multiple exclusion criteria Obtain informed consent (if possible) "There is a treatment for your stroke called alteplase that must be given within three hours after the stroke started. It is a 'clot-buster' drug that can lead to a complete or near-complete reversal of a stroke in about one of every three patients treated. However, it has a major risk, since it can cause severe bleeding in the brain in about one of every 15 patients. If bleeding occurs in the brain, it can be fatal. When used to treat large numbers of stroke patients, on average the potential benefits of this treatment outweigh the risks; however, in any individual patient it is a very personal decision." Exclusion Criteria for tPA Stroke/head trauma <3 mos Surgery <14 days GI Bleed <21 days Any prior ICH Acute MI or MI < 3 months LP < 7 days Arterial puncture @ noncompressible site <7d Rapidly improving or minor sx Seizure with postictal sx Sx of SAH, even if CT (-) BP >185/110 Pregnancy Active bleeding or trauma Platelets <100K Glucose <50, >400 INR >1.7 or elev PTT Hemorrhage on CT “Major” infarct on CT Thrombolysis of Acute Stroke 100 90 100 80 70 60 50 40 30 20 22 10 0 All Stroke Within 3 hrs 8 No Exclusions Thrombolytic Treatment Guidelines for In-Hospital Evaluation • Physician Evaluation: 10 minutes • Stroke Team Contact: 15 minutes • Imaging: 25 minutes • Interpretation: 45 minutes • Thrombolysis Started: 60 minutes • ?Coagulopathy- Don’t wait for labs unless on Coumadin, Heparin, or Dialysis Predictors of Success with tPA Early Treatment Less severe symptoms Younger Age Lack of systolic HTN Normoglycemia Blood Pressure Management Blood flow in dilated, post-obstructive blood vessels is BP-dependent Aggressive BP lowering can increase mortality In one study, a fall in SBP >20 in first 24 hrs was the most likely factor associated with neurologic deterioration This does NOT apply to hemorrhagic stroke Blood Pressure Management Do not treat BP unless >220/120, unless Meds • Given thrombolytics (goal <180/105) • Acute coronary syndrome • Acute heart failure/pulmonary edema • Aortic Dissection • Labetalol • Nitroprusside • Avoid SA nifedipine Antithrombotic Therapy ASA – YES • IST- ASA 300 mg within 48 hrs • Reduced 14 day recurrent stroke (NNT=100) • Reduced nonfatal stroke & death (NNT=100) • CAST- ASA 160 mg within 48 hrs • Reduced mortality at 4 weeks (NNT=166) • Slight increased risk of hemorrhagic stroke • 2 per 1000 patients (11 ischemic strokes prevented) Clopidogrel & Dipyridamole not tested Antithrombotic Therapy Heparin (UFH or LMWH) • 2004 review of 23 trials, >23K patients • No clear benefit over ASA alone • Reduced recurrent ischemic strokes by 9/1000 patients, but increased hemorrhagic strokes by same number • ?Effective in some subsets • “Stroke-in-evolution” or “Progressive Stroke” • Many patients show neurologic deterioration in 1st 24 hrs • No studies effectively define this population or prove a benefit Antithrombotic Therapy Heparin for Atrial Fibrillation • IST • No difference between heparin & placebo in • • stroke/death at 2 weeks Reduction in new ischemic stroke (NNT=38) Increase in new hemorrhagic stroke (NNH=42) • Consider in patients with known intra-atrial clot or • • repetitive “showering” sx If used, no IV bolus ASA is of benefit, though (as stated before) Anticoagulant Therapy Warfarin for Atrial Fibrillation • Must r/o ICH • For small infarcts, start when medically stable • For large infarcts, consider after 2 weeks • Goal INR 2-3 • Consider ASA as bridging therapy until INR >2 Management of Medical Complications Acute Coronary Syndromes/Heart Failure Infections • • Aspiration pneumonia UTI Venous thromboembolism • Consider DVT prophylaxis for all patients • • SCDs for pts with bleeds Heparin or Lovenox SQ for others Malnutrition/Dehydration (consider Adv Directives) Decubitus ulcers Contractures CONSIDER EARLY MOBILIZATION IN ALL PATIENTS! Intracerebral Hemorrhage Accounts for ~8% of all strokes Presenting sx • Headache (~50%) • Seizures (7-9%) • Delirium/Altered LOC • Focal neuro sx (depends on area of brain) Intracerebral Hemorrhage Mortality 35-50% Prognosis • Half of deaths in 1st 24 hours • Size & location of hemorrhage • Age • Glasgow Coma Score • Comorbid conditions • Prior antiplatelet/anticoagulant therapy Treatment of ICH Neurosurgical ICU Constant monitoring Bedrest Pain control Reverse coagulopathies ICP control • Vitamin K, FFP, Platelets • Mannitol, Induced Coma, Hyperventilation Treatment of ICH Blood pressure management Surgery • Indicated for cerebellar bleeds >3 cm • Supratentorial bleeds more controversial • Depends on size, location, LOC, comorbidities rFVIIa therapy • Small studies show promise, but concern for prothrombotic effects Subarachnoid Hemorrhage High mortality rate, ~50% Prognostic Factors • 10% pre-hospital • 25% within 24 hrs • 45% within 30 days • Level of consciousness • Age • Amount of blood on CT Subarachnoid Hemorrhage Diagnosis • Head CT • (+) in 92% of cases w/in 24 hrs • Most sensitive in first 12 hrs • Lumbar Puncture • Not necessary for diagnosis but consider if clinical • • suspicion & negative head CT Elevated pressure & RBCs Xanthochromia: pink/yellow tint due to RBC breakdown Treatment of SAH Neurosurgical ICU Constant monitoring Bedrest Pain control Reverse coagulopathies DVT Prophylaxis (SCDs) Blood Pressure Management Management of Aneurysms/AVMs