ISCHEMIC STROKE

• CEREBRAL ISCHEMIA IS CAUSED BY A REDUCTION IN BLOOD FLOW THAT LASTS LONGER THAN SEVERAL
SECONDS
• NEUROLOGIC SYMPTOMS ARE MANIFEST WITHIN SECONDS BECAUSE NEURONS LACK GLYCOGEN, SO
ENERGY FAILURE IS RAPID
PATHOPHYSIOLOGY
• ACUTE OCCLUSION OF AN INTRACRANIAL VESSEL CAUSES REDUCTION IN BLOOD FLOW TO THE BRAIN
REGION IT SUPPLIES
• MAGNITUDE OF FLOW REDUCTION DEPENDS ON THE FF:
• INDIVIDUAL VASCULAR ANATOMY
• THE SITE OF OCCLUSION
• SYSTEMIC BLOOD PRESSURE
PATHOPHYSIOLOGY

• DECREASE IN CEREBRAL BLOOD FLOW TO ZERO CAUSES DEATH OF BRAIN TISSUE WITHIN 4–10 MIN
• VALUES <16–18 ML/100 G TISSUE PER MINUTE CAUSE INFARCTION WITHIN AN HOUR
• VALUES <20 ML/100 G TISSUE PER MINUTE CAUSE ISCHEMIA WITHOUT INFARCTION UNLESS
PROLONGED FOR SEVERAL HOURS OR DAYS
PATHOPHYSIOLOGY

• ISCHEMIC PENUMBRA
• ISCHEMIC BUT REVERSIBLY DYSFUNCTIONAL TISSUE SURROUNDING A CORE AREA OF INFARCTION
• WILL EVENTUALLY PROGRESS TO INFARCTION IF NO CHANGE IN FLOW OCCURS
• SAVING THE ISCHEMIC PENUMBRA IS THE GOAL OF REVASCULARIZATION THERAPIES
PATHOPHYSIOLOGY

• FOCAL CEREBRAL INFARCTION OCCURS VIA TWO DISTINCT PATHWAYS

• NECROTIC PATHWAY
• CELLULAR CYTOSKELETAL BREAKDOWN IS RAPID, DUE PRINCIPALLY TO ENERGY FAILURE OF THE CELL
• APOPTOTIC PATHWAY
• CELLS BECOME PROGRAMMED TO DIE. ISCHEMIA PRODUCES NECROSIS BY STARVING NEURONS OF GLUCOSE AND
OXYGEN, WHICH IN TURN RESULTS IN FAILURE OF MITOCHONDRIA TO PRODUCE ATP.
ISCHEMIC STROKE

• CEREBRAL ISCHEMIA IS CAUSED BY A REDUCTION IN BLOOD FLOW THAT LASTS LONGER THAN SEVERAL
SECONDS
• NEUROLOGIC SYMPTOMS ARE MANIFEST WITHIN SECONDS BECAUSE NEURONS LACK GLYCOGEN, SO
ENERGY FAILURE IS RAPID
PATHOPHYSIOLOGY
• ACUTE OCCLUSION OF AN INTRACRANIAL VESSEL CAUSES REDUCTION IN BLOOD FLOW TO THE BRAIN
REGION IT SUPPLIES
• MAGNITUDE OF FLOW REDUCTION DEPENDS ON THE FF:
• INDIVIDUAL VASCULAR ANATOMY
• THE SITE OF OCCLUSION
• SYSTEMIC BLOOD PRESSURE
PATHOPHYSIOLOGY

• DECREASE IN CEREBRAL BLOOD FLOW TO ZERO CAUSES DEATH OF BRAIN TISSUE WITHIN 4–10 MIN
• VALUES <16–18 ML/100 G TISSUE PER MINUTE CAUSE INFARCTION WITHIN AN HOUR
• VALUES <20 ML/100 G TISSUE PER MINUTE CAUSE ISCHEMIA WITHOUT INFARCTION UNLESS
PROLONGED FOR SEVERAL HOURS OR DAYS
PATHOPHYSIOLOGY
• ISCHEMIC PENUMBRA
• ISCHEMIC BUT REVERSIBLY DYSFUNCTIONAL TISSUE SURROUNDING A CORE AREA OF INFARCTION
• WILL EVENTUALLY PROGRESS TO INFARCTION IF NO CHANGE IN FLOW OCCURS
• SAVING THE ISCHEMIC PENUMBRA IS THE GOAL OF REVASCULARIZATION THERAPIES
PATHOPHYSIOLOGY
• FOCAL CEREBRAL INFARCTION OCCURS VIA TWO DISTINCT PATHWAYS
• NECROTIC PATHWAY
• CELLULAR CYTOSKELETAL BREAKDOWN IS RAPID, DUE PRINCIPALLY TO ENERGY FAILURE OF THE CELL
• APOPTOTIC PATHWAY
• CELLS BECOME PROGRAMMED TO DIE. ISCHEMIA PRODUCES NECROSIS BY STARVING NEURONS OF GLUCOSE AND OXYGEN,
WHICH IN TURN RESULTS IN FAILURE OF MITOCHONDRIA TO PRODUCE ATP.
ETIOLOGY
• NEARLY 30% OF STROKES REMAIN UNEXPLAINED DESPITE EXTENSIVE EVALUATION.
• CLINICAL EXAMINATION SHOULD FOCUS ON THE
• PERIPHERAL AND CERVICAL VASCULAR SYSTEM (CAROTID AUSCULTATION FOR BRUITS AND BLOOD PRESSURE),
• THE HEART (DYSRHYTHMIA, MURMURS),
• EXTREMITIES (PERIPHERAL EMBOLI), AND
• RETINA (EFFECTS OF HYPERTENSION AND CHOLESTEROL EMBOLI [HOLLENHORST PLAQUES]).
• A COMPLETE NEUROLOGIC EXAMINATION IS PERFORMED TO LOCALIZE THE ANATOMIC SITE OF STROKE.
CARDIOEMBOLIC STROKE
• CARDIOEMBOLISM IS RESPONSIBLE FOR ~20% OF ALL ISCHEMIC STROKES.
• STROKE CAUSED BY HEART DISEASE IS PRIMARILY DUE TO EMBOLISM OF THROMBOTIC MATERIAL
FORMING ON THE ATRIAL OR VENTRICULAR WALL OR THE LEFT HEART VALVES.
• THESE THROMBI THEN DETACH AND EMBOLIZE INTO THE ARTERIAL CIRCULATION. THE THROMBUS MAY
FRAGMENT OR LYSE QUICKLY, PRODUCING ONLY A TIA.
CARDIOEMBOLIC STROKE

• EMBOLI FROM THE HEART MOST OFTEN LODGE IN THE INTRACRANIAL INTERNAL CAROTID ARTERY, THE
MCA, THE POSTERIOR CEREBRAL ARTERY (PCA), OR ONE OF THEIR BRANCHES; INFREQUENTLY, THE
ANTERIOR CEREBRAL ARTERY (ACA) IS INVOLVED
CARDIOEMBOLIC STROKE

• NONRHEUMATIC ATRIAL FIBRILLATION IS THE MOST COMMON CAUSE OF CEREBRAL EMBOLISM OVERALL.
• THROMBUS FORMATION IN THE FIBRILLATING ATRIUM OR ATRIAL APPENDAGE, WITH SUBSEQUENT
EMBOLIZATION.
• PATIENTS WITH ATRIAL FIBRILLATION HAVE AN AVERAGE ANNUAL RISK OF STROKE OF ~5%.
ARTERY-TO-ARTERY EMBOLIC STROKE
• THROMBUS FORMATION ON ATHEROSCLEROTIC PLAQUES MAY EMBOLIZE TO INTRACRANIAL ARTERIES
PRODUCING AN ARTERY-TO-ARTERY EMBOLIC STROKE.
• LESS COMMONLY, A DISEASED VESSEL MAY ACUTELY THROMBOSE.
• APPEARS TO BE THE DOMINANT VASCULAR MECHANISM CAUSING LARGE-VESSEL BRAIN ISCHEMIA. ANY
DISEASED VESSEL MAY BE AN EMBOLIC SOURCE, INCLUDING THE AORTIC ARCH, COMMON CAROTID,
INTERNAL CAROTID, VERTEBRAL, AND BASILAR ARTERIES.
CAROTID ATHEROSCLEROSIS
• ATHEROSCLEROSIS WITHIN THE CAROTID ARTERY OCCURS MOST FREQUENTLY WITHIN THE COMMON
CAROTID BIFURCATION AND PROXIMAL INTERNAL CAROTID ARTERY;
• THE CAROTID SIPHON (PORTION WITHIN THE CAVERNOUS SINUS) IS ALSO VULNERABLE TO
ATHEROSCLEROSIS.
• MALE GENDER, OLDER AGE, SMOKING, HYPERTENSION, DIABETES, AND HYPERCHOLESTEROLEMIA ARE
RISK FACTORS FOR CAROTID DISEASE, AS THEY ARE FOR STROKE IN GENERAL
• CAROTID ATHEROSCLEROSIS PRODUCES AN ESTIMATED 10% OF ISCHEMIC STROKE.
TREATMENT
• FIRST GOAL IS TO PREVENT OR REVERSE BRAIN INJURY
• ATTEND TO THE PATIENT’S AIRWAY, BREATHING, AND CIRCULATION (ABCS)
• TREAT HYPOGLYCEMIA OR HYPERGLYCEMIA IF IDENTIFIED BY FINGER STICK TESTING
• PERFORM AN EMERGENCY NONCONTRAST HEAD CT SCAN TO DIFFERENTIATE BETWEEN ISCHEMIC
STROKE AND HEMORRHAGIC STROKE
• MORE DEPRESSED LEVEL OF CONSCIOUSNESS, HIGHER INITIAL BLOOD PRESSURE, OR WORSENING OF
SYMPTOMS AFTER ONSET FAVOR HEMORRHAGE
• DEFICIT THAT IS MAXIMAL AT ONSET, OR REMITS, SUGGESTS ISCHEMIA
MEDICAL SUPPORT

• IMMEDIATE GOAL :OPTIMIZE CEREBRAL PERFUSION IN THE SURROUNDING ISCHEMIC PENUMBRA

• SUBCUTANEOUS HEPARIN (UNFRACTIONATED AND LOW-MOLECULAR-WEIGHT) IS SAFE AND CAN BE
USED CONCOMITANTLY
• USE OF PNEUMATIC COMPRESSION STOCKINGS IS OF PROVEN BENEFIT IN REDUCING RISK OF DVT AND
IS A SAFE ALTERNATIVE TO HEPARIN
MEDICAL SUPPORT

• BLOOD PRESSURE SHOULD BE REDUCED IF IT EXCEEDS 220/120 MMHG, IF THERE IS MALIGNANT

HYPERTENSION, CONCOMITANT MYOCARDIAL ISCHEMIA, OR IF BLOOD PRESSURE IS >185/110 MMHG
AND THROMBOLYTIC THERAPY IS ANTICIPATED
• LOWERING THE HEART RATE WITH A Β1-ADRENERGIC BLOCKER (ESMOLOL) CAN BE A FIRST STEP TO
DECREASE CARDIAC WORK AND MAINTAIN BLOOD PRESSURE
MEDICAL SUPPORT
• FEVER IS DETRIMENTAL AND SHOULD BE TREATED WITH ANTIPYRETICS AND SURFACE COOLING
• SERUM GLUCOSE SHOULD BE MONITORED AND KEPT <10.0 MMOL/L (180 MG/DL) USING AN INSULIN
INFUSION IF NECESSARY, AND ABOVE AT LEAST 3.3 MMOL/L (60 MG/DL)
• WATER RESTRICTION AND IV MANNITOL MAY BE USED TO RAISE THE SERUM OSMOLARITY, BUT
HYPOVOLEMIA SHOULD BE AVOIDED
INTRAVENOUS THROMBOLYSIS

• IV TPA (TISSUE PLASMINOGEN ACTIVATOR)

• FIRST TREATMENT PROVEN TO IMPROVE CLINICAL OUTCOMES IN ISCHEMIC STROKE AND IS COST-EFFECTIVE
AND COST-SAVING
EARLY SPECIFIC MANAGEMENT
1. THROMBOLYTIC THERAPY
• IV RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR (R-TPA)
• GIVE WITHIN 3 HOURS OF STROKE ONSET AT 0.9 MG/KG (MAX OF 90 MG), 10% OF TOTAL DOSE GIVEN AS IV
BOLUS THEN THE REST AS INFUSION OVER 60 MINUTES
• PATIENTS GIVEN R-TPA SHOULD NOT RECEIVE ANTIPLATELETS OR ANTICOAGULANTS WITHIN 24 HOURS OF
TREATMENT
• CONTRAINDICATIONS TO THROMBOLYTIC THERAPY (FROM SSP GUIDELINES 2014):
EARLY SPECIFIC MANAGEMENT
EARLY SPECIFIC MANAGEMENT
2. ANTITHROMBOTIC THERAPY
• NONCARDIOEMBOLIC ISCHEMIC STROKE OR TIA
• START ASA 160-325 MG/DAY AS EARLY AS POSSIBLE AND CONTINUE FOR 14 DAYS
• LONG-TERM ASA 80-100 MG/DAY MONOTHERAPY FOR SECONDARY STROKE PREVENTION
• ACCEPTABLE OPTIONS FOR INITIAL THERAPY:
• CLOPIDOGREL 75 MG OD
• ASPIRIN 25 MG PLUS EXTENDED RELEASE (ER) DIPYRIDAMPLE 200 MG BID
• CILOSTAZOL 100 MG BID
• TRIFUSAL 300 MG BID
EARLY SPECIFIC MANAGEMENT
2. ANTITHROMBOTIC THERAPY
• NONCARDIOEMBOLIC ISCHEMIC STROKE OR TIA
• CHOICE OF ANTIPLATELET SHOULD BE INDIVIDUALIZED
• PATIENTS WITH RECURRENT STROKE WHILE ON ANTITHROMBOTIC THERAPY SHOULD BE RE-EVALUATED FOR RISK
FACTORS (NO EVIDENCE THAT INCREASING THE DOSE WILL PROVIDE ADDITIONAL BENEFITS FOR THOSE WHO ARE
ALREADY TAKING ASPIRIN)
• USE OF LMWH AND HEPARINOIDS ASSOCIATED WITH SIGNIFICANT REDUCTION IN VENOUS THROMBOEMBOLISM BUT
NO SIGNIFICANT EFFECT ON MORTALITY AND DISABILITY AT 6 MONTHS
EARLY SPECIFIC MANAGEMENT
2. ANTITHROMBOTIC THERAPY
• CARDIOEMBOLIC STROKE
• COMPUTE FOR THE CHA2DS2-VASC AND HAS-BLED SCORE OF PATIENTS WITH AF
• BENEFIT OF ANTICOAGULATION IN ACUTE STROKE WITHIN THE FIRST 14 DAYS WOULD BE WEIGHED CAREFULLY AGAINST
THE RISK OF HEMORRHAGIC CONVERSION (LARGE INFARCTIONS, SEVERE STROKES OR NEUROLOGIC DEFICITS AND
UNCONTROLLED HPN)
EARLY SPECIFIC MANAGEMENT
3. NEUROPROTECTION (THE 5 “H” PRINCIPLE)
EARLY SPECIFIC MANAGEMENT

• 4. ROLE OF NEUROPROTECTIVE AND NEURORESTORATIVE DRUGS

• REMAINS A MATTER OF PREFERENCE OF THE ATTENDING PHYSICIAN
• EXAMPLES: CITICHOLINE, CEREBROLYSIN