9.1 Stroke & Cerebrovascular Diseases

9.1 Stroke & Cerebrovascular Diseases

Acute stroke is a medical emergency requiring rapid clinical classification, urgent neuroimaging, and time-critical revascularization. In MRCPI General Medicine Part I, candidates are expected to demonstrate expert knowledge of stroke syndromes, thrombolysis and thrombectomy criteria, target hemodynamic parameters, anticoagulation reversal, cerebral venous sinus thrombosis, and secondary stroke prevention.

Oxford Community Stroke Project (OCSP) Classification

The Oxford Community Stroke Project (Bamford) classification categorizes ischemic strokes into four distinct clinical syndromes based on neurological signs at presentation. This classification correlates strongly with vascular anatomy, underlying pathology, infarct volume, and overall prognosis.

MRCPI Exam Pearl: A patient presenting with right hemiparesis and right homonymous hemianopia without dysphasia or spatial neglect is classified as PACS (2 of 3 criteria), not TACS. If motor deficit affects only one limb (monoparesis), it is also classified as PACS regardless of cortical signs.

Hyperacute Management of Ischemic Stroke

Emergency Revascularization

1. Intravenous Thrombolysis: • Medication & Dosage: IV Alteplase (0.9 mg/kg, maximum dose 90 mg; 10% given as IV bolus over 1 minute, remaining 90% infused over 60 minutes) or IV Tenecteplase (0.25 mg/kg, single bolus max 25 mg). • Time Window: Must be initiated within 4.5 hours of clear symptom onset (or time last seen well). • Efficacy: Number needed to treat (NNT) to achieve functional independence (mRS 0-1) at 90 days is 4.5 if treated within 90 minutes, expanding to 9.0 if treated between 3 and 4.5 hours. • Absolute Contraindications: Non-contrast CT showing intracerebral hemorrhage or acute extensive infarction (>1/3 MCA territory); arterial blood pressure persistently >185/110 mmHg despite antihypertensive therapy; active internal bleeding; platelet count <100,000/µL; INR >1.7 or therapeutic anticoagulation with DOAC taken within the preceding 48 hours (unless specific reversal agent given or drug-level assays normal); history of previous intracerebral hemorrhage or structural central nervous system lesion; acute head trauma or major surgery within the past 14 days.

2. Mechanical Thrombectomy: • Indications: Endovascular thrombectomy (EVT) is indicated for patients with acute ischemic stroke caused by a large vessel occlusion (LVO) in the anterior circulation (internal carotid artery or M1 segment of MCA), with baseline mRS 0-1 and NIHSS ≥6. • Time Window: Standard indication is within 6 hours of symptom onset. Selected patients with favorable perfusion imaging demonstrating salvageable ischemic penumbra (DAWN and DEFUSE-3 trials criteria) benefit up to 24 hours from time last seen well. • Efficacy: Extremely powerful intervention with an NNT of 2.6 for achieving functional independence at 90 days.

Acute Hemodynamic Parameters

• Non-Thrombolysed Patients: Permissive hypertension is maintained up to a systolic BP of 220 mmHg or diastolic BP of 120 mmHg during the first 24 to 48 hours to preserve collateral cerebral perfusion. Antihypertensive therapy is withheld unless blood pressure exceeds these thresholds or concomitant end-organ damage is present (e.g., acute aortic dissection, acute myocardial infarction, acute pulmonary edema). • Thrombolysed / Post-Thrombectomy Patients: Blood pressure must be maintained strictly below 180/105 mmHg for at least 24 hours following intravenous alteplase or mechanical thrombectomy to minimize the risk of secondary parenchymal hematoma transformation. Preferred intravenous agents include labetalol (10-20 mg IV bolus) or nicardipine infusion.

Acute Spontaneous Intracerebral Hemorrhage (ICH)

Intracerebral hemorrhage accounts for 15-20% of acute strokes and carries a 30-day mortality approaching 40%. Management centers on rapid blood pressure control, reversal of coagulopathy, and selective surgical evacuation.

1. Intensive Blood Pressure Lowering: • Rapid blood pressure lowering within 2 hours of presentation to a target systolic BP of 130-140 mmHg (INTERACT-2 trial) significantly reduces hematoma expansion without compromising cerebral perfusion. Systolic BP reductions below 110 mmHg should be avoided (ATTACH-2 trial).

2. Reversal of Anticoagulation: • Warfarin-Associated ICH: Immediate administration of 4-factor Prothrombin Complex Concentrate (PCC; 25-50 units/kg IV) plus IV Vitamin K 10 mg (slow infusion over 10 minutes). PCC reverses INR within 15-30 minutes, whereas fresh frozen plasma (FFP) requires large volumes and hours to infuse, placing patients at risk of volume overload. • Dabigatran-Associated ICH: IV Idarucizumab 5 g (two 2.5 g boluses). • Factor Xa Inhibitors (Rivaroxaban / Apixaban): IV Andexanet alfa or 4-factor PCC (50 units/kg).

3. Surgical Indications: • Emergency posterior fossa decompressive craniectomy and hematoma evacuation is indicated for cerebellar hemorrhage >3 cm in diameter, or cerebellar hemorrhage associated with brainstem compression or obstructive hydrocephalus. Direct surgical evacuation of supratentorial basal ganglia hemorrhages is generally not superior to medical management unless rapid clinical deterioration occurs.

Cerebral Venous Sinus Thrombosis (CVST)

Cerebral venous sinus thrombosis is a distinct cerebrovascular entity predominantly affecting young adults, women of childbearing age, and individuals with hypercoagulable states.

• Etiology & Risk Factors: Inherited thrombophilias (Factor V Leiden, Prothrombin G20210A, Antiphospholipid Syndrome), pregnancy, puerperium, combined oral contraceptive use, systemic inflammatory diseases (Behcet's, IBD), and local parameningeal infections (mastoiditis, otitis media, sinusitis). • Clinical Presentation: Progressive headache (90% of cases, occasionally presenting as thunderclap headache), focal or generalized seizures (40%), papilloedema, cranial nerve palsies (CN VI), and fluctuating altered mental status. • Neuroimaging Findings: Non-contrast CT shows "dense clot sign" in the sagittal sinus. Contrast CT Venogram (CTV) or MR Venogram (MRV) is the definitive diagnostic modality, classically demonstrating the "empty delta sign" (a central filling defect representing non-enhancing thrombus in the superior sagittal sinus surrounded by enhancing dura). • Management: Immediate administration of therapeutic anticoagulation with Subcutaneous Low-Molecular-Weight Heparin (LMWH) or IV Unfractionated Heparin. Crucially, anticoagulation is indicated even in the presence of venous hemorrhagic infarction on baseline imaging. Anticoagulation is continued for 3 to 6 months in provoked cases and indefinitely in unprovoked or recurrent thrombophilia.

Secondary Prevention & TIA Management

Transient Ischemic Attack (TIA) is defined as a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction on neuroimaging. Risk of stroke following TIA is stratified using the ABCD2 score: • Age ≥60 years (1 point) • Blood pressure ≥140/90 mmHg (1 point) • Clinical features: Unilateral weakness (2 points), Speech impairment without weakness (1 point) • Duration of symptoms: ≥60 minutes (2 points), 10-59 minutes (1 point) • Diabetes mellitus (1 point) (High risk = ABCD2 score ≥4, carrying an 8% 7-day stroke risk).

Secondary Prevention Regimens

1. Antiplatelet Regimens: • Minor Ischemic Stroke (NIHSS ≤3) or High-Risk TIA (ABCD2 ≥4): Initiate Dual Antiplatelet Therapy (DAPT) with Aspirin 75-100 mg daily plus Clopidogrel 75 mg daily (with a loading dose of Clopidogrel 300 mg) within 24 hours of onset, continued for 21 days (CHANCE and POINT trials), followed by Clopidogrel 75 mg daily monotherapy long-term. • Moderate-to-Severe Ischemic Stroke: Aspirin 300 mg daily for 14 days, followed by Clopidogrel 75 mg daily monotherapy.

2. Cardioembolic Stroke & Atrial Fibrillation: • Direct Oral Anticoagulants (DOACs: Apixaban 5 mg BD, Rivaroxaban 20 mg OD, Dabigatran 150 mg BD, or Edoxaban 60 mg OD) are superior to warfarin for non-valvular AF. • Timing of Anticoagulation Initiation ("Rule of 1-3-6-12 days"):

   • Day 1: TIA
   • Day 3: Mild stroke (NIHSS <8)
   • Day 6: Moderate stroke (NIHSS 8-15)
   • Day 12-14: Severe stroke (NIHSS >15 or large infarct occupying >1/3 MCA territory on neuroimaging, after repeating CT to exclude hemorrhagic transformation).

3. Lipid-Lowering & Hemodynamic Targets: • High-intensity statin therapy (Atorvastatin 80 mg daily) initiated regardless of baseline lipid profile, aiming for an LDL-cholesterol target <1.8 mmol/L (or <1.4 mmol/L in very high-risk vascular disease). • Long-term blood pressure target <130/80 mmHg using an ACE inhibitor (e.g., Ramipril) plus an indapamide-like thiazide diuretic or calcium channel blocker.

4. Carotid Endarterectomy (CEA): • Indicated for symptomatic carotid artery stenosis of 70% to 99% (NASCET measurement criteria) if performed within 14 days of TIA or non-disabling stroke (NNT = 3 to prevent 1 stroke at 5 years). • Marginal benefit for 50-69% stenosis; CEA is contraindicated for <50% stenosis or complete vessel occlusion.