Cerebrovascular Diseases:Cerebrovascular Diseases:IschemicIschemic

Stroke Facts Stroke Facts

33rdrd leading cause of death leading cause of death Leading cause of long-term disabilityLeading cause of long-term disability >700,000 Americans suffer a new or >700,000 Americans suffer a new or

recurrent stroke each yearrecurrent stroke each year Cost : over $40 billion per yearCost : over $40 billion per year

Definition Definition

Stroke = cerebral infarctionStroke = cerebral infarction Sudden brain dysfunction related to blood Sudden brain dysfunction related to blood

vessel abnormality-low blood flowvessel abnormality-low blood flow Thrombo-Ebmoblism= Plugging of distal Thrombo-Ebmoblism= Plugging of distal

artery by a traveling blood-clot fragment artery by a traveling blood-clot fragment that originated more proximally in the that originated more proximally in the circulatory system circulatory system

80-85 % of all strokes are ischemic80-85 % of all strokes are ischemic

Pathophysiology Pathophysiology

Cerebral blood flow ( rCBF): changes after Cerebral blood flow ( rCBF): changes after acute ischemia seen by PET scanacute ischemia seen by PET scan

Normal = 40 to 50 ml/100 g/minNormal = 40 to 50 ml/100 g/min Anaerobic glycolysis= 35Anaerobic glycolysis= 35 Loss of synaptic transmission=20Loss of synaptic transmission=20 Anoxic depolarization of cell Anoxic depolarization of cell

membrane=15membrane=15 Necrosis <12Necrosis <12

PathophysiologyPathophysiology

Ischemic Ischemic PenumbraPenumbra : area of stunned : area of stunned parenchyma surrounding the ischemic parenchyma surrounding the ischemic corecore

Area of rCBF between 12 and 22 Area of rCBF between 12 and 22 ml/100gm/minml/100gm/min

Has the potential for recovery Has the potential for recovery ONLYONLY if if reperfusion is rapidly establishedreperfusion is rapidly established

The PenumbraThe Penumbra

Ischemic cascade Ischemic cascade

Risk factorsRisk factors

Non modifiable:Non modifiable: Advanced ageAdvanced age Family historyFamily history Race/ethnicityRace/ethnicity Geographic locationGeographic location Gender : Male>FemaleGender : Male>Female Post menopause : Female risk equals malePost menopause : Female risk equals male

Risk factorsRisk factors

Modifiable:Modifiable: Previous H/O stroke or TIAPrevious H/O stroke or TIA HypertensionHypertension: Most important modifiable risk : Most important modifiable risk

factorfactor DMDM Heart disease including Atrial fibrillationHeart disease including Atrial fibrillation HyperlipidemiaHyperlipidemia Cigarette SmokingCigarette Smoking Excessive alcohol consumptionExcessive alcohol consumption Cocaine and Amphetamine abuse Cocaine and Amphetamine abuse

Transient ischemic attacks (TIA’S)Transient ischemic attacks (TIA’S)

Episode of temporary low blood flow to a Episode of temporary low blood flow to a focal area of the brain without permanent focal area of the brain without permanent damagedamage

In essence ”Angina of the Brain”In essence ”Angina of the Brain” By definition TIA’S last less than 24 hrsBy definition TIA’S last less than 24 hrs This definition is arbitrary and outdatedThis definition is arbitrary and outdated Most cases : TIA symptoms last 5-20 minMost cases : TIA symptoms last 5-20 min Evidence on MRI brainEvidence on MRI brain

Why important to identify TIA’s?Why important to identify TIA’s?

10% of stroke pts have a preceding TIA10% of stroke pts have a preceding TIA 8% of pts with TIA will have stroke within 8% of pts with TIA will have stroke within

the next 1month the next 1month 30% within 5 yrs30% within 5 yrs TIA should be managed as stroke: same TIA should be managed as stroke: same

causes, treatment and investigationscauses, treatment and investigations

Classification by etiology Classification by etiology Atherosclerotic ArteriopathiesAtherosclerotic Arteriopathies : :Small vessel atherosclerotic- lacunarSmall vessel atherosclerotic- lacunarLarge vessel atherosclerosisLarge vessel atherosclerosis Nonatheroscelrotic ArteriopathiesNonatheroscelrotic Arteriopathies : :Noninflmmatory- dissection, moya-moya diseaseNoninflmmatory- dissection, moya-moya diseaseInflammatory infectious e.g. syphilisInflammatory infectious e.g. syphilisInflammatory noninfectiuos/Vasculitis e.g.: takayasu’s, lupusInflammatory noninfectiuos/Vasculitis e.g.: takayasu’s, lupus Embolism- Embolism- cardiac ,aortic arch, ICA,VA, artery-arterycardiac ,aortic arch, ICA,VA, artery-artery Generalized Hypoperfusion-Generalized Hypoperfusion- watershed infarction watershed infarction Hematological- Hematological- hypercoaguable state hypercoaguable state Drugs- Drugs- vasospasm, illicit drugs vasospasm, illicit drugs Cryptogenic stroke- Cryptogenic stroke- stroke of undetermined causestroke of undetermined cause

Lacunar infarctionLacunar infarction Small, deep infarcts caused by occlusion of penetrating Small, deep infarcts caused by occlusion of penetrating

brain arteriesbrain arteries The small arteries that penetrate deeper brain structures The small arteries that penetrate deeper brain structures

(e.g., basal gray nuclei, internal capsule, thalamus, (e.g., basal gray nuclei, internal capsule, thalamus, pons) are especially susceptible to degenerative pons) are especially susceptible to degenerative changes caused by hypertension: changes caused by hypertension: Medial hypertrophyMedial hypertrophy, , fibrinoid changesfibrinoid changes, and , and lipohyalinosislipohyalinosis gradually narrow gradually narrow the lumens of these arteries, impeding blood flow. the lumens of these arteries, impeding blood flow.

Plaques within arteries, blocking or extending into the Plaques within arteries, blocking or extending into the orifices of penetrating arteries, andorifices of penetrating arteries, and microatheromasmicroatheromas are are more common among patients with diabetes. more common among patients with diabetes.

Clinical presentation Clinical presentation

Motor-weaknessMotor-weakness Sensory-numbness, parasthesiasSensory-numbness, parasthesias Speech-slurred speech, languageSpeech-slurred speech, language Visual-field deficits, loss of visionVisual-field deficits, loss of vision Dizziness/vertigoDizziness/vertigo Double visionDouble vision UnsteadinessUnsteadiness Difficulty walking Difficulty walking

Circle of willisCircle of willis

Case 1Case 1

55 Y.O lady with H/O inferior wall MI 2 months 55 Y.O lady with H/O inferior wall MI 2 months prior to her presentation, treated with aspirin.prior to her presentation, treated with aspirin.

C/O gradual onset of headache while watching C/O gradual onset of headache while watching TV followed by R arm tingling and weakness. TV followed by R arm tingling and weakness. She tried calling her daughter over phone but She tried calling her daughter over phone but her speech was slurred and she was not able to her speech was slurred and she was not able to produce certain wordsproduce certain words

Daughter called 777 and an ambulance Daughter called 777 and an ambulance transferred patient to nearest hospitaltransferred patient to nearest hospital

Case 1Case 1

In ER: pt lethargic, easily arousedIn ER: pt lethargic, easily aroused BP 160/90 HR 150 irregularBP 160/90 HR 150 irregular Dysarthric , has L gaze preferenceDysarthric , has L gaze preference Unable to name or repeatUnable to name or repeat M. power : R arm 2/5 with decreased M. power : R arm 2/5 with decreased

sensationsensation R leg 4+/5R leg 4+/5 R upgoing plantarR upgoing plantar

Case 1Case 1

What’s your diagnosis? Clinical What’s your diagnosis? Clinical localization?localization?

Initial CT brain : normalInitial CT brain : normal Repeat CT in 24 hrs: L frontoparietal Repeat CT in 24 hrs: L frontoparietal

hypodensityhypodensity

L MCA infarctionL MCA infarction

Clinical localization Clinical localization MCAMCA: C/L Hemiparesis &sensory loss : C/L Hemiparesis &sensory loss (face and arm- more involved)(face and arm- more involved) C/L hemianopsiaC/L hemianopsia AphasiaAphasia Gaze abnormalityGaze abnormality Neglect /inattentionNeglect /inattention ApraxiaApraxia ACAACA: C/L Hemiparesis & sensory loss : C/L Hemiparesis & sensory loss

(leg-more involved)(leg-more involved) Disconnection syndromeDisconnection syndrome Abulia, Akinetic MutismAbulia, Akinetic Mutism

Clinical localizationClinical localization PCAPCA: C/L hemianopsia with macular sparing, cortical : C/L hemianopsia with macular sparing, cortical

blindnessblindness Subcortical regionsSubcortical regions e.g. internal capsule, thalamus e.g. internal capsule, thalamus Face=arm=legs equally involved Face=arm=legs equally involved Absence of cortical signs: no aphasia, seizures, neglect, Absence of cortical signs: no aphasia, seizures, neglect,

gaze deviationgaze deviation C/L weakness: pure motor lacunar syndromeC/L weakness: pure motor lacunar syndrome C/L sensory loss: pure sensoryC/L sensory loss: pure sensory Combination of sensory& motor: sensorimotor Combination of sensory& motor: sensorimotor With involvement of cerebellar connection: ataxic-With involvement of cerebellar connection: ataxic-

hemiparesis lacunar syndromehemiparesis lacunar syndrome

Case 2Case 2

70 Y.O male with H/O HTN,DM II and 70 Y.O male with H/O HTN,DM II and TIA’s (recurrent attacks of vertigo and TIA’s (recurrent attacks of vertigo and double vision)double vision)

Brought by family because of sudden Brought by family because of sudden onset of collapse with unresponsiveness onset of collapse with unresponsiveness and generalized weakness.and generalized weakness.

Immediately transported to ERImmediately transported to ER Found to have BP 200/120 HR 80 regularFound to have BP 200/120 HR 80 regular B.sugar 14 mmol/lB.sugar 14 mmol/l

O/E: unresponsiveO/E: unresponsive Not localizing to painful stimuliNot localizing to painful stimuli Pupils pinpointPupils pinpoint Eyes not aligned (skew deviation) with Eyes not aligned (skew deviation) with

failure to abduct bilaterally on failure to abduct bilaterally on oculocephalic reflexoculocephalic reflex

B/L upgoing plantars B/L upgoing plantars

What’s your diagnosis? Clinical What’s your diagnosis? Clinical localization?localization?

DX: Acute Basilar artery thrombosisDX: Acute Basilar artery thrombosis Localization: brainstem ischemiaLocalization: brainstem ischemia Initial CT Brain: normalInitial CT Brain: normal Next Step??Next Step?? Urgent cerebral angiography for possible Urgent cerebral angiography for possible

intervention (in reality does not happen!!)intervention (in reality does not happen!!)

Repeat CT in 24 hrs: hypodensities in L Pons Repeat CT in 24 hrs: hypodensities in L Pons and B/L Thalamiand B/L Thalami

Pt deteriorated and required mechanical Pt deteriorated and required mechanical ventilation ventilation

48 hrs later: no signs 48 hrs later: no signs

Of brainstem functionOf brainstem function 72 hrs later:72 hrs later:

Pt pronounced deadPt pronounced dead

Clinical localizationClinical localization

BrainstemBrainstem::Hemiparesis/quadreparesisHemiparesis/quadreparesisCrossed signsCrossed signsDiplopia, dysconjugate gaze, gaze palsyDiplopia, dysconjugate gaze, gaze palsyDysarthria, DysphagiaDysarthria, DysphagiaVertigo, tinnitusVertigo, tinnitusNausea, vomitingNausea, vomitingHiccups, abnormal respirationHiccups, abnormal respirationDecreased LOCDecreased LOC

Management Management

Time is Brain-save the penumbraTime is Brain-save the penumbra Concept of acute brain attack: Treat acute Concept of acute brain attack: Treat acute

stroke as emergencystroke as emergency CVA :not an accident !! PreventableCVA :not an accident !! Preventable (promotes inappropriate nothing-to-do (promotes inappropriate nothing-to-do

attitude)attitude) Determine the causeDetermine the cause Avoid hyperglycemia, hyperthermia & Avoid hyperglycemia, hyperthermia &

sedatives :all harmful to the penumbra sedatives :all harmful to the penumbra

Acute brain attackAcute brain attack

NINDS t-pa TrialNINDS t-pa Trial: NEJM 1995: NEJM 1995 Thrombolytic therapy given within first Thrombolytic therapy given within first 3 hours3 hours of of

onsetonset Beyond: high risk of hemorrhagic infarction, has Beyond: high risk of hemorrhagic infarction, has

to meet inclusion and exclusion criteria to meet inclusion and exclusion criteria Pts treated with tpa has Pts treated with tpa has 30%30% greater chance of greater chance of

being free of disability in 3 monthsbeing free of disability in 3 months Slight increase in hemorrhagic conversion: Slight increase in hemorrhagic conversion: 6%6% The benefit of tpa The benefit of tpa outweighoutweigh its riskits risk

Differential DiagnosisDifferential Diagnosis

Sudden cerebral dysfunction( non traumatic):Sudden cerebral dysfunction( non traumatic): Partial seizures with post-ictal weakness (Todd’s Partial seizures with post-ictal weakness (Todd’s

paralysis)paralysis) Hypoglycemia Hypoglycemia Toxic-metabolic insult with old cerebral lesionToxic-metabolic insult with old cerebral lesion Brain Tumor with bleed or seizureBrain Tumor with bleed or seizure Brain abscess Brain abscess Migraine with auraMigraine with aura Demylinating Disease- M.SDemylinating Disease- M.S

BP management in acute strokeBP management in acute stroke

Natural for BP to increase during first few Natural for BP to increase during first few hours after stroke& spontaneously decline hours after stroke& spontaneously decline within first 24 hrswithin first 24 hrs

In chronic HTN :shift of autoregulatory BP In chronic HTN :shift of autoregulatory BP curve to the rightcurve to the right

In acute ischemia: impaired autoregulation In acute ischemia: impaired autoregulation so CBF varies directly with systemic BP so CBF varies directly with systemic BP

BP management in acute strokeBP management in acute stroke

Recommendations :Recommendations : Avoid precipitous drop in BP (do not use Avoid precipitous drop in BP (do not use

sublingual formulation!!)sublingual formulation!!) When to treat more aggressively:When to treat more aggressively: A.A.SBP>220 & DBP>130SBP>220 & DBP>130 B. B. End organ damage :HTN End organ damage :HTN

encephalopathy, ARF, CHFencephalopathy, ARF, CHF C. C. Post thrombolytics (r-tpa) withPost thrombolytics (r-tpa) with

SBP>180 & DBP >105SBP>180 & DBP >105

Investigations Investigations BloodBlood: glucose, electrolytes, creatinine, CBC, ESR, syphilis titer, lipid profile, : glucose, electrolytes, creatinine, CBC, ESR, syphilis titer, lipid profile,

coagulation profile, cardiac enzymescoagulation profile, cardiac enzymesUrineUrine toxicology screen toxicology screenHypercoaguable state W/uHypercoaguable state W/u:: in selected cases in selected casesECGECGCXRCXRBrain imagingBrain imaging:: CTCT Brain: should be done first in all cases( R/O bleed) Brain: should be done first in all cases( R/O bleed) MRIMRI Brain: with Diffusion-weighted imaging (DWI), detects ischemia early Brain: with Diffusion-weighted imaging (DWI), detects ischemia earlyUltrasoundUltrasound :Carotid ultrasound:Carotid ultrasound TCD- transcranial doppler ultrasoundTCD- transcranial doppler ultrasoundEchocardiogramEchocardiogram:: Transthoracic, Transesophageal Transthoracic, Transesophageal To look for cardiac source of embolism To look for cardiac source of embolism With bubble study to check for PFOWith bubble study to check for PFO

CT Brain MRI BrainCT Brain MRI Brain

Treatment Treatment

Antiplatelets:Antiplatelets: Aspirin: 81 mg to 325 mgAspirin: 81 mg to 325 mg DipyridamoleDipyridamole Ticlopidine Ticlopidine ClopidogrelClopidogrel Aggrenox ( Extended release dipyridamole+ASA) Aggrenox ( Extended release dipyridamole+ASA) Anticogulation :Anticogulation : HeparinHeparin LMWHLMWH Warfarin Warfarin

Neuroprotection Neuroprotection

NeuroprotectionNeuroprotection

Evidence from clinical trials is Evidence from clinical trials is disappointingdisappointing

Major problem is side effectsMajor problem is side effects Promising treatment : HypothermiaPromising treatment : Hypothermia Undergoing evaluationUndergoing evaluation

Rehabilitation Rehabilitation

Aim: Integrates pts in community ,Aim: Integrates pts in community ,

minimize disability and contracturesminimize disability and contractures Physiotherapy:Physiotherapy: focus on limb weakness, focus on limb weakness,

abnormal tone (flaccid or spastic) and balance abnormal tone (flaccid or spastic) and balance Occupational therapy:Occupational therapy: take the lead in teaching take the lead in teaching

independence in activities of daily livingindependence in activities of daily living Speech therapy: Speech therapy: deal with communication and deal with communication and

motor production of speech, as well as chewing motor production of speech, as well as chewing and swallowing and swallowing

Stroke complicationsStroke complications

DepressionDepression Cognitive impairment Cognitive impairment Spasticity Spasticity Urinary incontinence Urinary incontinence Post stroke pain/neuralgiaPost stroke pain/neuralgia Sexual dysfunction Sexual dysfunction

Stroke preventionStroke prevention

Venous infarctionVenous infarction

Hemorrhagic infarcts due to venous thrombosis Hemorrhagic infarcts due to venous thrombosis (Superior sagittal sinus)(Superior sagittal sinus)

Most cases : Hypercoaguable state (cancer, Most cases : Hypercoaguable state (cancer, drugs, pregnancy/postpartum, hereditary)drugs, pregnancy/postpartum, hereditary)

Presentation : depressed LOC, focal Presentation : depressed LOC, focal neurological deficits, focal seizures neurological deficits, focal seizures

Treatment : Anticoagulation even if there’s Treatment : Anticoagulation even if there’s evidence of hemorrhage (Exception to the rule!!)evidence of hemorrhage (Exception to the rule!!)

Stroke in the young Stroke in the young 5% of all strokes5% of all strokes Age < 45 yrsAge < 45 yrs Most common causes:Most common causes:

cardiac, hematological,cardiac, hematological,

dissectiondissection

Dissection :tear in intimaDissection :tear in intima

Vertebral artery Vertebral artery

dissection dissection