Stroke

Ischemic stroke (85%)

  • Large artery thromboembolic infarctions
  • Lacunar infarctions
    • Longstanding HTN, diabetes, smoking are risk factors
    • Locations: putamen/caudate/PLIC/thalamus, basis pontis
    • Prevention by BP control, prevention of microangiopathy, antiplatelet agents
  • Cardioembolic infarctions
    • Often large, multiple, wedge-shaped
    • Sudden, unheralded, focal deficits worse at onset
    • Atrial fibrillation and other arrhythmias
    • Valvular disease, subacute bacterial endocarditis, mechanical valves
    • Cardiomyopathy, myocardial infarction (esp first 1-3mo), congenital heart disease
    • Cardiac shunts, patent foramen ovale, atrial septal defect/aneurysm
    • Post CABG and other cardiac surgery (esp by POD#2)
    • Intracardiac tumours
  • Cryptogenic stroke
  • Nonatherosclerotic vasculopathies
    • Cervicocephalic dissection, traumatic cerebrovascular disease
    • Radiation vasculopathy
    • Moyamoya disease
      • Chronic, progressive, nonatherosclerotic, noninflammatory, nonamyloid occlusive intracranial vasculopathy of unknown cause
      • Fibrocellular intimal thickening, smooth muscle proliferation and elastin accumulation
      • Suzuki’s 6 angiographic stages: (1) stenosis of ICA bifurcation (2) moyamoya vessels at base of brain, dilated ACA/MCA/PCA (3) intensification of moyamoya vessels, small ACA/MCA (4) minimization of moyamoya vessels, small PCA (5) reduction of moyamoya vessels, absent ACA/MCA/PCA (6) disappearance of moyamoya vessels with extensive pial collaterals from external carotid branches
      • Imaging: lenticulostriate collaterals, Ivy sign, “puff of smoke”, narrowed ICA
      • Medical tx: ASA, acetazolamide (vasodilation)
      • Revascularization procedures:
        • Direct – superficial temporal artery to MCA bypass
        • Indirect
          • Encephalomyosynangiosis – muscle flap onto brain
          • Encephaloduroarteriosynangiosis – scalp artery to brain

 

 

    • Fibromuscular dysplasia
      • Segmental, nonatheromatous, dysplastic, noninflammatory angiopathy
      • Young-mid aged women
      • Subtypes: (1) intimal fibroplasia (2) medial hyperplasia (3) medial fibroplasias (4) perimedial dysplasia
      • Diagnosis by cerebral angiography – “string of beads” in extracranial carotid artery
    • Vasculitis
    • Migrainous infarction
      • Symptoms not resolved 7 days after imaging confirmation of infarction
  • Inherited and misc disorders
    • CADASIL
      • Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy
      • NOTCH3 mutation – chr 19 – granular osmiophilic material in vascular smooth muscle cells and pericytes (GOMs) see in EM
      • Ischemic episodes (lacunar), cognitive deficits, migraines, seizures, mood disorders
      • Anti-NOTCH3 Ab for diagnosis
    • MELAS
    • Homocystinuria or MTHFR mutation – more like AIS
    • Fabry disease
    • Marfan syndrome
    • Ehlers-Danlos syndrome
    • Pseudoxanthoma elasticum
    • Sneddon syndrome
      • Livedo reticularis and cerebrovascular accidents
    • Osler-Weber-Rendu syndrome
    • Lymphomatous angiomatosis
      • Multiple small/medium vessel occlusion by lymphoid neoplastic cells
    • Susac disease
      • Microangiopathy of brain, retina, inner ear – retinocochleocerebral vasculopathy
      • Encephalopathy, visual loss, vestibular dysfcn, tinnitus, vertigo, asymmetric hearing loss
      • Treatment with corticosteroids, immunosuppression, plasmapheresis, anticoagulation
    • Eales disease
    • Hypereosinophilic syndrome
    • Cerebral amyloid angiopathy
    • Arterial dolichoectasia
    • Emboli - air, fat, amniotic fluid, bone marrow, foreign body particle
    • Drug abuse – ephedrine, cocaine, amphetamine
  • Hypercoagulable states
    • Primary hypercoagulable states
      • Antithrombin III deficiency
        • Inhibits thrombin, IXa, Xa, XIa, XIIa
      • Protein C deficiency
        • Vitamin K-dependent anticoagulant
      • Protein S deficiency
        • Cofactor of protein C
      • Activated protein C resistance, factor V Leiden mutation
        • Send for mutation if APC resistance
      • Prothrombin 20210 (factor II) mutation
      • Fibrinogen disorders
      • Plasminogen disorders
      • Antiphospholipid antibody syndrome
        • Lupus anticoagulant and anticardiolipin antibodies
        • Arterial ischemic strokes, also CSVT, migraine, vascular dementia, chorea, transverse myelopathy, fetal loss, livedo reticularis
        • Warfarin with INR>3, during pregnancy use prednisone and low ASA

AIS

CSVT

Hyperhomocysteinuria

Antiphospholipid antibody syndrome

Protein C deficiency (chr2)

Protein S deficiency (chr3)

Lipoprotein (a)

 

Prothrombin 20210 mutation (chr11, AD)

Antithrombin III deficiency (chr1)

Factor V Leiden mutation (chr1)

Protein C deficiency (chr2, AD)

Protein S deficiency (chr3, AD)

Antiphosholipid antibody syndrome

Hyperhomocysteinuria

 

 

 

 

 

 

 

 

 

·         Secondary hypercoagulable disorders

      • Malignancy
      • Pregnancy, puerperium, OCP use
      • Sickle cell disease
      • Polycythemia
      • Thrombocytopenia
        • HIT (heparin induced thrombocytopenia)
          • Type I – mild, benign condition with platelet counts 100,000/mcl
          • Type II – delayed onset (5-15d), severe, requires d/c heparin
            • Prevent by limiting exposure to <5d heparin
            • Daily platelet counts
        • TTP (thrombotic thrombocytopenic purpura)

 

Stroke risk factors

 

Non-modifiable factors

Modifiable factors

Age

  - strongest risk factor, 50% strokes >70 years age

Gender

Race/ethnicity

Family history

Genetics

Arterial hypertension

  - 3-4x increased risk, drop SBP by 10 or DBP by 5

Transient ischemic attacks

Asymptomatic carotic bruit/stenosis

Cardiac disease

Aortic arch atheromatosis

Diabetes mellitus

  - 2-4x increased risk, additive with age or BP

Dyslipidemia

  - high cholesterol, high LDL, low HDL

Cigarette smoking

  - 2-3x increased risk, baseline by 5 years of quitting

Alcohol consumption

  - 2 drinks/day good, >2 drinks/day bad

High fibrinogen

High homocysteine

Low folate

High anticardiolipin antibodies

Oral contraceptives

Obesity (esp. truncal obesity)

 

HOPE trial – controlling HTN in DM results in 1/3 RRR in stroke

 

4S (Scandinavian Simvastatin Survival Study) in cardiac patients – post-hoc ½ RRR in stroke, 1/3 RRR in TIA

 

CARE trial – statins in CAD patients 1/3 RRR in stroke

 

SPAF (Stroke Prevention in Atrial Fibrillation)

  • <65, no risk factors – ASA
  • 65-75, no risk factors – ASA or warfarin
  • >75 and anyone with risk factors – warfarin
  • Afib + ASA = 20% RRR
  • Afib + warfarin = 65% RRR

 

ACST (Asymptomatic Carotid Surgery Trial)

ACAS (Asymptomatic Carotid Atherosclerosis Study)

  • <75% stenosis – 1.3% risk of stroke
  • >75% stenosis – 10.5% risk fo stroke
  • Trials looked at >60% stenosis, medical vs. surgical management
  • Need very low risk perioperative mortality to go to surgery

 

NASCET (North American Symptomatic Carotid Endarterectomy Trial)

  • Risk of stroke after TIA – 8.5% at one week, 20% at 90 days (1/2 for retinal TIA)
  • With carotid stenosis (70-99%) and TIA – 25% at 90 days
  • Ontario data – 50% of strokes in first 90 days after TIA occurred within 48 hours

 

Antithrombotic Trialist Group (metaanalysis)

  • Long-term risk reduction in cardiovascular events 22% risk reduction with antiplatelets
  • 2.5% ARR, 23% RRR in stroke after TIA/stroke with ASA

 

Weird syndromes:

  • Subclavian steal – reversal of flow of vertebral artery due to subclavian stenosis or occlusion of proximal vertebral artery or brachiocephalic artery, especially from left
  • Transient global amnesia – reversible anterograde/retrograde amnesia, lasting 3-6 hours, more in men >50 years, triggered by physical exertion, temperature, or sexual intercourse

 

Dr. Silver’s review session

 

  • Stroke prevention outcome is for disability and dementia, and not so much death as in MI
  • Stroke incidence increases with age, and is more common than MI

 

TIAs

  • 90 day risk of stroke after TIA is 10%
  • ABCD2 rule
    • A – age 60+ (1pt)
    • B – blood pressure SBP>140 (1pt)
    • C – TIA features – unilateral weakness (2pts), speech impairment w/o weakness (1pt)
    • D – duration of TIA – 10-59min (1pt), 60+min (2pt)
    • D – diabetes (1pt)
    • Low (0-3, 1% risk), moderate (4-5, 4% risk), high (6-7, 8% risk) stroke in 48hrs
  • MRI showing DWI lesion increases risk of re-stroke, if also vessel occlusion then 30% risk of restroke
  • EXPRESS trial – 2007 (UK)
    • Historical control compared to last few years of rapid workup and clopidogrel+ASA+ACEinh
    • Dramatic improvement in risk of restroke
  • Another trial in France showed that rapid work-up after TIA resulted in dramatic reduction in stroke rate

 

Acute Stroke

  • Neuroprotection and thrombolysis
  • Early CT signs of stroke
    • Hyperacute MCA sign, or other vessel
    • Subtle decreased grey-white differentiation
    • Early mass effect – sulcal effacement and shift
  • ASPECT scoring (Alberta Stroke Program Early CT scoring)
    • Lower cut – M1, M2, M3, Caudate, Lentiform nuclei, Internal Capsule, Insula
    • Upper cut – M4, M5, M6
    • Good prognosis if score >7
  • Perfusion/diffusion mismatch
    • Diffusion is area that is edematous
    • Perfusion is area that has less blood supply
    • >20% mismatch is significant – the penumbra
  • Neuroprotection
    • Hypothermia
    • Avoiding hypotension, hyperglycemia, fever, seizures
    • Retard ischemic cascade, e.g., glutamate antagonists, NOS antagonists, free radical scavengers?
    • Check American Heart Association guidelines for BP management
  • Hemicraniectomy (ideally 12-24 hours after event)
    • 30 day mortality of large MCA stroke is 80%
    • Edema peaks at 72 hours
    • Hyperventilation, mannitol, hypertonic saline – too short acting
    • Combination of 3 trials (93 patients), “good” outcome mRS 0-4
    • Limited inclusion criteria (<60yrs, NIHSS>15, 50%+ MCA involvement)
    • Mean time to treatment was about 15-30 hours
    • 55% RRR of poor outcome, for either hemisphere
  • NINDS trial (1995)
    • Inclusion criteria
      • <3 hours
      • clearly defined, stable deficit
      • CT no hemorrhage
      • No seizure at onset
      • BP<185-110
      • No recent surgery, hemorrhage, stroke
      • Informed consent (no longer necessary, now is standard of care)
    • Outcome
      • 11% absolute benefit
      • 55% relative benefit
      • 0.6 becomes 6.4% hemorrhage rate
      • NNT 10 for good outcome
    • tPA approved in Canada in 1999
  • PROACT II trial (1999)
    • Prourokinase, no longer available, tested in angiography-proven occlusions
    • NNT 7 for good mRS outcome, 15% patients reached independence
    • 6 hour treatment window, average 5.5 hour treatment, 2 hour treatment course
  • Pooled analysis of tPA 0-6 hours (2004)
    • 3000 patients, mean NIHSS 11, 1/3 treated
    • Favorable outcome of mRS 0-1
    • The longer you wait before treatment, the less probability of good outcome
    • 300 minutes when no risk improvement compared to controls
    • Delayed treatment NOT associated with risk of bleeding
    • Risk of death only after 270 minutes
  • IMS trials (Interventional management of stroke study)
    • IV rtPA 0.6mg/kg, 15% bolus, followed by angiography, up to 22mg IA rtPA over 2 hours
  • CASES trial (Canadian Activase for Stroke Effectiveness Study, 2005)
    • 4.6% symptomatic intracerebral hemorrhage
    • 1.3% anaphylactoid/angioedema reactions – swelling is ipsilateral to hemiplegia, more risk if patient of ACEinh
    • Atrial fibrillation as cause of stroke was found to be a good outcome predictor
  • SIT-MOST (Safety Implementation of Thrombolysis in Stroke)
  • Devices for mechanical thrombolysis
    • Merci – physically impressive, but unclear if good evidence of clinical efficacy
    • Ekos – transcranial Doppler during tPA helps activity of tPA (physical agitation)
  • FASTER
    • Clopidorel+ASA vs. ASA (also looked at simvastatin)
    • Trend towards combination therapy preventing more strokes
  • PRoFESS
    • Aggrenox vs. Plavix
    • Micardis vs. placebo
  • CREST
    • Carotid endarterectomy vs. stenting

 

Secondary stroke prevention

  • NASCET trials
    • Carotid endarterectomy in symptomatic disease
    • Consider if >50% stenosis, definitely treat if 70-99%
    • Ideally treat within 2 weeks
  • Stenting with distal protection device
    • SAPPHIRE trial – stenting better than endarterectomy if including MI, stroke, mortality
      • Restenosis rate in stenting 20%, CEA 31%
    • EVA-3S trial – stenting
      • Outcome worse, but also ? experience of interventionalists
    • SPACE trial
      • No difference between stenting and endarterectomy
    • CREST trial (NIH-Canada)
      • Ongoing trial of carotid endarterectomy and stenting
      • Both symptomatic and asymptomatic patients included
    • Warfarin in A fib
      • 80% RRR of use of warfarin in patients with a. fib
      • In patients >80 years, 25% strokes due to a fib
      • CHADS score
        • CHF (1pt)
        • Hypertension (1pt)
        • Age >75 (1pt)
        • Diabetes (1pt)
        • Stroke/TIA (2pts)
        • 0 (low), 2 (moderate), 4+ (high) risk
    • Antiplatelet agents
      • ASA
      • Dipyridamole
      • Ticlopidine
      • Clopidogrel
      • GpIIb/IIIa antagonists
      • Combination therapies
        • Aggrenox (diapyridamole+ASA)
        • Clopidogrel+ASA
      • Irreversible inhibition of platelet activation and aggregation (except dipyridamole)
      • Antithrombotic Trialists’ Collaboration (2000)
        • Antiplatelet agents result in strong protection against re-stroke
        • Dose of ASA not important (minimum 30mg/day)
      • CAPRIE trial
        • Clopidogrel 75mg vs. ASA 325mg
        • Stroke, MI, peripheral
        • Small improvement in reduction rate of events – 9% RRR
        • Decreased risk of bleeding
      • MATCH trial
        • Clopidogrel/ASA vs. Clopidogrel
        • No significant difference, trend to helpfulness in acute (7d) setting
        • Increase in bleeding longterm treatment
      • CHARISMA trial
        • Clopidogrel/ASA vs. ASA
        • No significant benefit
      • Aggrenox
        • Containts a tartaric acid core, dipyridamole requires acid environment to be absorbed, thus issue in patients on H+ blockers
        • ESPS trial (European)
          • ASA vs. dipyridamole vs. combo vs. placebo
          • Clear improvement in stroke-free survival with treatment, esp combo
        • ESPRIT trial (European/Australasian, 2006)
          • ASA vs. dipyridamole/ASA
          • 20% RR with combination treatment, decreased bleeding
      • Warfarin
        • WARSS trial
          • Warfarin vs. ASA in noncardioembolic stroke
          • No benefit, more complications
        • WASID trial
          • Warfarin vs. ASA for symptomatic intracranial arterial stenosis
          • Stopped due to increased harm
      • Anticoagulation
        • Cardioembolic stroke
        • Acute arterial dissection
        • Progressive stroke with documented large artery occlusive disease, e.g., basilar
        • Sinovenous thrombosis
      • Risk factor modification
        • ACE inhibitor or ARB (+BP control)
          • PROGRESS trial – perindopril + indapamide
        • Quit smoking
        • Manage diabetes
        • Statins
          • SPARCL study – significant reduction in LDL
            • 16%RR of stroke despite unintended treatment of placebo patients with statins
            • 35% RR coronary events despite CAD patients being excluded from trial
        • Folic acid

 

Cerebral sinovenous thrombosis

 

Hemorrhagic infarct

  • Etiologies:
    • Amyloid angiopathy - lobar
    • Hypertensive angiopathy – thalamus, basal ganglia, brainstem, cerebellum
    • Cocaine
    • Malignant hypertension
  • Reversal of coagulopathy
    • Protamine sulphate to reverse heparin
    • Vitamin K to reverse warfarin
    • FFP to normalize INR
  • Surgical decompression in 12-24 hours for:
    • Cerebellar/brainstem hemorrhage >3cm
    • Clots causing hydrocephalus
    • Superficial location

 

 

CT appearance

» heterogeneous

­

­­

­ (enhancing edge, fluid-fluid level)

― (hemosiderin-lined, calcification)

 

Vascular malformations

  • Vascular malformations without AV shunts
    • Developmental venous anomalies (DVA)
      • Venous structure, no arterial involvement
      • Arrest of fetal venous development
      • Usually incidental finding, can be seen in seizures/headache
      • “Caput medusa” appearance on imaging from radial draining veins
    • Capillary telangiectasia
      • Small groups of abnormally dilated capillaries, often in pons
      • Rarely hemorrhage, found only postmortem
    • Venous cavernoma
      • Majority are clinically silent and undetectable by angiography
      • Can present with seizures or focal neurological deficits, 2-3%/yr risk hemorrhage
      • “Popcorn” appearance on MRI
  • Vascular malformations with AV shunts
    • Cerebral (subpial) AV malformation
      • Commonly present 20-30 years
      • High flow AV shunting resulting in arterial hypotension
      • Wedge-shaped tangle of arteries and veins without intervening capillaries
      • Common presentation: hemorrhage, seizures, headache
      • Can show focal deficits, progressive cognitive decline, cardiomegaly, hydrocephalus
      • Natural history:
        • Annual risk of hemorrhage – 2-4%
        • Mortality from 1st bleed – 5-15%
        • Risk of bleed recurrence – 6% in first year, 2-4% annually
        • Mortality from 2nd bleed – 5%
      • Surgical options:
        • Stereotactic radiosurgery – for small, deep, highly vascular AVMs, 2yr to effect
        • Endovascular embolization – for larger AVMs, immediate effect
    • Dural AV fistula
    • Vein of Galen malformation
      • High pressure vascular communication between major cerebral arteries and vein of Galen
      • Fistulous connection between primitive choroidal vessels and embryonic median prosencephalic vein of Markowski
      • Causes high-output congestive heart failure, failure to thrive, hydrocephalus
      • Treatment: endovascular embolization

Intracranial aneurysms

  • 80-85% anterior circulation
    • Internal carotid, anterior communicating, posterior communicating arteries
    • Trifurcation of MCA
  • Posterior circulation
    • Bifurcation of basilar artery
    • Vertebral artery/PICA junction
  • 0.5-2% annual risk of rupture, 2% risk of new aneurysm after rupture
  • Risk factors:
    • Connective tissue disorders:
      • AD polycystic kidney disease
      • Ehlers-Danlos type IV
      • NF type 1
      • Marfan syndrome
    • Familial aneurysms – higher risk of rupture and new aneurysms
    • Smoking – via alpha-1-antitrypsin inhibition
    • Hypertension
    • Moderate-high alcohol consumption
    • Post-menopausal without HRT
  • Presentation:
    • Subarachnoid or intracranial hemorrhage
    • Sudden severe headache, loss of vision, nausea/vomiting, loss of consciousness, CN3 palsy
  • Management:
    • Early surgical clipping decreases risk of recurrence and ischemia from vasospasm
    • Endovascular coiling