Stroke

    .

    Source: Multiple ("The Little ICU Book" by Paul Marino), MKSAP 16/17, JAMA Rational Clinical Exam "does this patient have a stroke?"

    Introduction

    • National Institute of Neurological Disorders and Stroke defines "Stroke" as:
      • "An acute brain disorder of vascular origin accompanied by neurological dysfunction that persists for longer than 24 hours".
    • Transient Ischemic Attack (TIA)
      • "Acute episode of focal loss of brain function that is caued by ischemia and lasts less than 24 hours"
    • TIA vs. Stroke
      • Reversibility of clinical symptoms!
      • Radiologic reversibility is not necessary (1/3 of TIAs will have cerebral infarction)
    • TIME is KEY!
      • Each minute = 1.9 million neurons destroyed (7.5 miles of myelinated nerves)
      • Benefit of thrombolytic therapy is in the first 3 hours after sympton onset.

    Approach

    1. Has the patient had a stroke/TIA?
      • Take Focused History (Last Seen Normal (LSN), NIH Stroke Scale)
      • VS: BP, O2, HR
      • STAT CT brain
      • CBC, Lytes, Creatinine, INR, PTT, BG, 
      • Where is the lesion? what is the lesion?
    2. Make an etiologic diagnosis
      • Indications for MRI/MRA (or CTA)
        • Confirm diagnosis, type and possible etiology.
        • Evaluate extra- and intracranial vasculature
        • Suspition of vertebrobasilar stroke.
      • Indications for cerebral angiography
        • Interventional procedures, vasculitis, aneurisms, inconclusive non-invasive imaging of vessels.
      • Stroke investigations
        • Carotid Doppler USS
        • Transthoracic echocardiogram
        • 48hr Holter monitor
        • Lipid profile, fasting BG, HbA1c, liver enzymes, CK 
        • Hypercoagulable screen (if indicated, i.e. young stroke).
    3. Antiplatelet or anticoagulant therapy.
    4. Risk factor modification (medications and behavioural)
      • Diet, Exercise, smoking cessation
    5. Education --> Stroke, stroke prevention, warning symptoms of stroke.

     

    StrokeClassifcation.png

     

    • NIH Stroke Scale (NIHSS)
      • 11 Items to evaluate (LOC, Visual system, Motor system, sensory, language, etc... 
      • Score x/42.
      • 0 = no stroke.
      • 1-4 = mild stroke
      • 5-15 = moderate stroke
      • 15-20 = moderate-severe stroke
      • 21-42 = severe
      • Give tPA for score ≥6
    • ASPECT Score:
      • 10/10 is normal
        • Subtract 1 point for each abnormal structure on ischemic side (caudate, lentiform, insula, internal capsule, MCA 1,2,3,4,5,6)
      • <4/10 = high risk of bleed with tPA

    Ischemic Stroke

    Acute Management

    • Use NIH Stroke Scale to identify stroke severity
    • Main Question: tPA vs. no tPA
    • Generally, tPA if ≥6
    • NIHSSesmall.png
    • To tPA or not to tPA:

      Indication:

      Patient presents with disabling neurological symptoms with no sign of improvement, and onset is between 60 minutes and 4.5 hours.

       

      Exclusion Criteria for tPA:

      • Symptoms minor or improving rapidly
      • Seizure at onset
      • Past stroke/head trauma (in ≤3 mo)
      • BP > 180/110
      • Bleeding Diathesis
      • Major surgery in past 2 weeks.
      • INR > 1.7  ( 1.4 and PTT >40s?)
      • Plts < 100,000
         
      • Previous intracranial hemorrhage
      • Recent pericarditis
      • Gl or urinary hemorrhage within the past 21 d
      • Recent lumbar puncture or arterial puncture at noncompressible site
      • Patient is pregnant
      • Blood glucose < 2.8 or > 22 mmoi/L
      • Intracranial hemorrhage on CT or large volume infarct
      • Previously ADL dependent (clinical judgment)

       

       

       

     

    How to Remember NIH Stroke Scale

    • Acronym:
      • FLEAS Acronym
      • F- Face (Asymmetry)
        • Show Teeth
        • Puff Cheeks
      • L - LOC
        • aLert/Comatose?
        • Oriented to self (Age + Month) and me (neglecting one side?)
        • Command - "Close your eyes", "Squeeze My Hand"
      • E - Eyes
        • Fields, Nystagmus, gaze palsy
      • A - Arms/Legs (check each limb individually!!!)
        • Arm Drift (10s) (check for drift)
        • Legs  (5 seconds, 45° angle --> drift?)
        • Sensation to touch
        • Finger-to-Nose / Heel-to-Shin
      • S - Speech
        • Express (form words)
        • Articular (make sounds)

    tPA Protocol

    • Once decision to give tPA is made:
      • NO antiplatelet or anticoagulation for 24hrs until F/U CT head is performed to rule out intracerebral hemorrhage.
        • After 24hrs can start ASA and DVT prophylaxis with LMWH/Heparin
      • Acute Stroke Unit: Frequent vital sign & neuro exam
        • ASU reduces mortality in stroke
      • Control BP < 180/105  (ICH occurs in 6% of lyzed patients)
        • To reach target use IV labetalol or nicardipine
        • DO NOT use nitrates (can raise intracerebral pressure)
        • DO NOT use oral medicine (cannot titrate)

     

    Non-tPA Protocol

    • Admit to ASU (Acute Stroke Unit - reduces mortality)
    • ASA 325 (80mg in Canada)
      •  (Other anticoagulants such as heparins --> no benefit)
      • Even if new onset AFib --> continue ASA and bridge to warfarin later
    • c< 220/120 (keep BP high, discontinue anti-HTN agents)

     

    Evidence for tPA

    • Only thing that reduce mortality in acute stroke:
      • Acute Stroke Unit.
    • NINDS r-tPA Trial:
      • 11% absolute improvement in stroke outcome with r-tPA
      • Hemorrhage: 6.4%
      • Angioedema 1.3%
    • ECASS-III Trial (validated tPA use)
      • Good outcome: 52.4% vs. 45.2% pl.
      • Death 7.7% vs. 8.4% pl.
      • ICU 2.4% vs. 0.3% pl.
    • Pooled Data: Lees et al. Lancet 2010;375:1695
      • StrokeOutcomesLancet.png
      • NIH Stroke Scale predicts severity of stroke and outcome (correlates with MRI findings) based on JAMA Rational Clinical Exam review:
        • NIHss data.png
      • For Interest:

    Intravascular Intervention

    • ESCAPE trial and MRCLEAN Trials (4 major trials as of 2015) supporting use.
    • Becoming standard of care

     

    Etiology

    • TOAST Trial:
      • 30% - Small artery atherothrombosis
      • 25% - Cardioembolic
      • 20% - Large artery atheroembolism
      • 25-30% - Cryptogenic
      • 5% - Other
        • Dissection
        • Hypercoagulability
        • Vasculitis

    Risk Factors

    • Non-modifiable
      • Age
      • Gender
      • Race / Ethnicity
      • Heredity
      • Prior stroke or TIA
    • Modifiable
      • RiskFactorModification.png

     

    BP Targets

    • Ischemic Stroke < 220/120 (keep BP high, discontinue anti-HTN agents)
      • If over 220/120, reduce by 15% (not more than 25%) in first 24hrs, then gradual reduction afterwards
    • tPA Use Limit < 185/110
    • Ischemic post-tPA < 180/105
    • Source: CHEP 2016 guidelines

    Prevention of Ischemic Stroke

    • First line: ASA
    • If have stroke on ASA: then ASA + dipyridamole (superior to ASA alone)
    • Do not combine ASA + Plavix (incr. mortality in MATCH and SPS3 trials)

     

    Evidence of Preventative Therapy

    • Anti-platelet Agents (Small or large vessel atherosclerosis and cryptogenic stroke (unknown etiology))
      • NOTE: Canadian CSN (Canadian Stroke Network) guidelines recommend ASA OR Dipyridamole/ASA (Aggrenox) OR plavix.  However, specific evidence is listed below:
      • ASA - 81mg ASA or 325mg daily
        • Meta-Analysis: 25% RRR of non-fatal recurrent stroke.
        • Discontinuation of ASA increases risk of stroke at the time when antiplatelet effect wears off (6-10 days) (odds ratio 3.4) [uptodate]
        • A review of 195 trials of secondary prevention by the ATC shows that low dose ASA (75-150mg) is equivalent in efficacy as high dose ASA (150-325)  [However criticism arises from the fact that higher doses were not as well assessed as lower doses, debate continues]
          • Laboratory evidence is consistent with this observation, as 30mg of ASA daily is enough to complete suppress thromboxane A2 production.
          • Higher dose increases bleeding risk.
        • Meta-Analysis: Antiplatelet Trialists’ Collaboration. BMJ. 1994;308:81
      • Dipyridamole / ASA (Aggrenox) 1 capsule daily
        • ESPS2, ESPRIT
        • ESPS2 Trial:
          • 25mg ASA BID vs. 200mg Dipyridamole ER (ext. rel.) BID vs. 25 ASA + 200mg Dipyridamole BID
          • OR of recurrent stroke were: 0.79, 0.81, and 0.59 (ASA + Dipyridamole)
          • Dipyridamole/ASA had RRR of 34% compared to ASA alone.
        • Meta-Analysis: ASA/Dipyridamole is better than ASA alone (OR 0.77)
        • Side Effects:
          • Headache (37%) much more common in women, that was not treated with Tylenol.  Headache incidence dropped to 20% with continued use.
          • Avoid in chronic stable angina - can cause coronary vessel dilatation.
      • Clopidogrel (Plavix) 75mg daily
        • Evidence:
          • CAPRIE Trial (19,185 pts) ASA 325 vs. clopidogrel 75.
            • Event rate 5.3 vs. 5.8 (ASA) - RRR 8.7% (ARR 0.5%/yr) of composite outcome with clopidogrel use (stroke, MI, vascular death)
          • MATCH, CHARISMA, SPS3 (ASA + Plavix)
            • NO BENEFIT in ASA + Plavix, combination increased hemorrhagic events.
            • MATCH trial showed slight benefit of ASA+Plavix combo in ischemic strokes, but higher bleeding risks.
            • Do not use combination
          • PRoFESS Trial (Plavix vs. Aggrenox)
            • NO DIFFERENCE in primary (recurrent stroke) or secondary outcomes (recurrent stroke /MI/vascular death)
            • Rate or heart failure was slightly higher in Aggrenox (1.4 vs. 1.8%)
            • Rate of discontinuation due to headache was higher in Aggrenox group (known s/e).
          • Therefore: Clopidogrel had a 7.3% RRR for recurrent stroke compared to ASA.
        • Concern over CYP1A2, CYP3A4, CYP2C19 polymorphisms and lack of efficacy of plavix in certain populations.  No evidence to suggest genetic screening of platelet activity ssays.
        • Side Effects compared to ASA
          • Slightly more rash and diarrhea.
          • Less GI upset and bleeding 
          • No neutropenia (seen with Ticlopidine)
    • Anticoagulation (LMWH, UH, Warfarin)
      • Only if there is indication (Heart valves, Afib, hypercoagulable states)
      • (WARSS trial, warfarin vs. aspirin for noncardioembolic ischemic small subcortical or lacunar strokes: equivalent)
      • Heparins:
        • Even patients presenting with stroke that you suspect is cardioembolic (has new AFib), use ASA and bridge to warfarin.  UFH and LMWH have no benefit 
        • Trial of Org 10172 in Acute Stroke Treatment (TOAST) and the IST, heparinoids did not show an overall benefit in preventing stroke; any beneficial effect on ischemic stroke is offset by risk of hemorrhagic stroke. In the Heparin in Acute Embolic Stroke Trial (HAEST), heparin was no better than than aspirin in preventing recurrent stroke at 14 days in patients admitted with acute ischemic stroke.
        • Acute anticoagulation for stroke only indicated in:
          • 1.  Mechanical valves
          • 2.  Atrial fibrillation with small infarcts after cardiac surgery
          • 3.  Cervicocephalic dissection.
    • Treat Hypertension
      • ACE-I, ARB, Diuretics, CCB
      • Targets - Canadian (www.hypertension.ca)
        • 140/90 - no diabetes
        • 130/80 - with diabetes
    • Treat Hyperlipidemia
      • SPARCL Study: statins reduced risk of recurrent stroke in pts with serum LDL > 2.59 mmol/L. (only enrolled pts >30 days post-stroke)
    • Other Prevention:
      • Control Diabetes
        • HbA1c < 7.0
      • Smoking Cessation
      • Healthy diet and lifestyle
        • Wait circumference: Men < 40in, women < 35in
      • Physical Activity
        • >30min daily.
    • Interventions
      • Carotid Endarterectomy (CEA)
        • NASCET Trial
          • 70-99% (NOT 100%)  - CEA Recommended
            • 17% absolute risk reduction, NNT = 8 with surgery (p<0.001)
          • 50-69% in select cases. (ARR=6.5%, NNT=15, p=0.045)
          • <50% ARR=3.8%, NNT=26, p=0.16.
        • Stenting --> high risk of intra-op strokes, not done (CREST trial)
    • Early Rehabilitation
      • IMPORTANT
      • STROKE UNITs decrease mortality (post-stroke care, prevention of complications, early rehab)

    Hemorrhagic Stroke

    • Primary ICH
      • By convention - a hypertensive hemorrhage.
      • Amyloid angiopathy (lobar)
    • Secondary Causes of ICH
      • ***Conversion of cerebral infarct (spontaneous)
      • ***Use of thrombolytics (6.4% risk - NINDS Trial)
      • Anticoagulation (2%/year)
      • Aneurysms, AVM
      • Neoplasms

     

    • Etiology:
      • Hypertension causes fibrinoid necrosis of arterial walls and Charcot-Bouchard microaneurysms.
        OR
      • Amyloid angiopathy causes weakening of arterial wall integrity (lobar vessels)
        Cause
      • Rupture of intracranial vessels --> hematoma
    • Typical Locations:
      • Thalamus
      • Putamen
      • Caudate
      • Cerebellum
      • Pons

    Evidence

    • >33% hematoma increase in 38% of pts with CT done <3h from stroke onset
    • Tried: 
      • Recombinant Factor VIIa -
        • Phase II studies
          • RRR 35% for mortality (18% vs. 29% placebo)
          • Improved 3 mo functional outcome.
        • FAST trial (phase III r-FVIIa) --> No clinical benefit.
      • PCC (Factors II, VII, IX, X, only)  (Intensive Care Medicine 2007;33:721, Hagen et al. Stroke. 2006;37:1465)
        • Decreased incidence/extent of hematoma growth
          • PCCs (19% vs. 44%)
          • FFP (33% vs. 54%)
          • Vit K (50% vs. 59%)
    • Spot sign on CT
      • SPOTLIGHT (Canada)
      • STOP-IT (Cincinnati)

     

    Risk Factors

    • High BP
    • Excessive EtOH use
    • Amyloid angiopathy

     

    Treatment if ICH

    • From figure in Broderick et al. Stroke. 2007;38;2001
    • Use labetalol! (does not increase ICP)
    • SBP > 200 mmHg

      or

      MAP > 150 mmHg

      Aggressive reduction of BP with continuous IV infusion.

      Monitoring BP q5min.

      SBP > 180 mmHg

      or

      MAP > 130 mmHg

      and

      Suspition of elevated ICP

      - Consider Monitoring ICP

      AND

      - Reducing BP with continuous or intermittent IV meds to

      keep CPP 60-80 mmHg.

       

      SBP > 180 mmHg

      or

      MAP > 130 mmHg

      - Modest reduction of BP with continuous or intermittent

      IV meds

      I.E. Target (MAP 110 or BP 160/90 mmHg)

      - Clinically re-examine pt q15min

    •  

     

     

    Vascular Territories

    • ACA:
      • Total Anterior Circulation Stroke Syndrome:
        • 1. New Higher Cerebral Dysfunction (dysphasia, dyscalculia, visuospatial disorder).
        • 2. Homonymous visual field defect
        • 3. Ipsilateral motor or sensory deficit in at least 2 areas of face, arm and leg.
      • Generally:
        • Contralateral paresis (Leg >> face/arm)
        • Frontal signs: Akinetic mutism (do not move or speak), abulia (lack of initiative)
        • Mood Disturbance
        • Movement Disorders
        • (Sensory Loss?)
        • Urinary Incontinence: Hypertonic bladder
    • MCA
      • Superior Division:
        • Contralateral face/arm>>leg paresis and sensory loss.
        • Broca's (expressive) aphasia (if dominant hemisphere).
      • Inferior Division:
        • Occipital: Contralateral homonymous hemianopsia (esp inferiorly)
        • Parietal L: Apraxia, Alexia, Agraphia, Acalculia
        • Parietal R: Contralateral neglect (Extinction/Inattention)
        • Parietal: Contralateral agraphesthesia, astereognosis, anosognosia
        • Temporal/Parietal (Sylvian Fissure): Dominant Hemisphere: Wernicke's (receptive) aphasia
    • Internal Carotid
      • Transient monocular blindness (amaurosis fugax).
      • Could be asymptomatic or similar to MCA occlusion.
    • PCA  (Often few deficits, often misdiagnosed)
      • Headache
      • Contralateral homonymous hemianopsia (esp superior).
      • Midbrain Findings (vertical gaze palsy CN III palsy, INO)
      • Occipital Findings (Anomia, Alexia without agraphia, visual agnosia)
    • PICA  - Cerebellar Stroke (Lateral Medullary or Wallenburg Syndrome)
      • Based on JAMA RCE (Posterior Circulation Infarction Syndrome - PCIS)
        • Ispilateral cranial nerve palsy with contralateral motor or sensory deficit
        • Bilateral motor or sensory deficit
        • Cerebellar dysfunction w/o ipsilateral long-tract deficit (ataxic hemiparesis).
        • Isolated homonymous visual field defect.
      • Generally:
        • Headache, Nausea/vomiting
        • Vertigo, imbalance, Nystagmus
        • Normal Tone, Strength, Reflexes
        • Ipsilateral Ataxia (limb, trunk, and/or gait)
        • Brainstem signs (with edema/mass effect)
        • Others:
          • Ipsilateral Horner's
          • Ipsilateral Fascial Sensory Loss
          • Contralateral limb impairment of pain and temperature.
          • Dysphagia, Dysarthria, Hiccup
    • Lacunar Infarcts (Basal ganglia, thalamus, posterior limb of internal capsule)
      • Pure motor hemiparesis: contralateral arm, leg, face.
      • Pure sensory loss: (Thalamic infarct): hemisensory loss
      • Ataxic hemiparesis: ipsilateral ataxia, leg paresis.
      • Dysarthria-clumsy hand syndrome: dysarthria
      • Facial weakness, dysphagia, mild hand weakness, clumsiness.
    • Brain Stem Stroke
      • Crossed findings
        • Ipsilateral facial weakness or sensory loss
        • Contralateral hemiparesis
      • Bilateral sensorimotor deficits
      • CN III/IV/VI: Pupillary changes, diplopia, gaze palsies
      • CN VIII: Vertigo
      • H&N: Dysphagia, dysarthria
      • Depressed LOC

     

    Risk Stratification

    • ABCD2 score:

      • ABCD2.png

       

      • 6-7 --> High Risk (Admit for urgent evaluation and mgmt)
      • 4-5 --> Consider admission for evaluation
      • 0-3 --> Can likely be safetly managed as outpatients.
         

     

    Cerebral Aneurysms

    Source: MKSAP17

    • Risk of rupture = previous SAH + if >7mm aneurysm
    • If high risk of rupture is high --> esp if aneurysm is >12mm:
      •  
    • If low risk of rupture (no prev SAH and <7mm)
      • Annual neuroimaging to track changes
      • Risk factor modification:
        • Smoking cessation
        • Hypertension management (calcium channel blockers)

    Further Reading

    • "Primary and secondary prevention of ischemic stroke" Eur Neurol. 2010;63(5):267-78. doi: 10.1159/000285183. Epub 2010 Mar 27.
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