10.1 Acute Ischemic Stroke: Syndromes & Reperfusion

Cerebrovascular diseases represent the leading cause of adult disability and the fifth leading cause of mortality in the United States. For the ABIM Internal Medicine examination, clinicians must demonstrate mastery of vascular neuroanatomy, rapid triage and contraindications for reperfusion therapies (intravenous thrombolysis and endovascular mechanical thrombectomy), acute blood pressure targets, anticoagulant reversal in hemorrhagic stroke, and the recognition and prevention of secondary neurovascular complications.

1. Acute Ischemic Stroke (AIS): Vascular Territories & Clinical Syndromes

Acute ischemic stroke results from focal cerebral hypoperfusion secondary to arterial thromboembolism or in situ thrombosis. Accurate localization based on bedside neurological examination is critical for guiding emergent vessel imaging and endovascular interventions.

Cerebral Vascular Territories

2. Emergency Evaluation & Reperfusion Therapies in Acute Ischemic Stroke

Time is brain: approximately 1.9 million neurons are lost every minute during untreated large-vessel ischemic stroke. Emergent care focuses on exclusion of hemorrhage, blood glucose correction, rapid initiation of intravenous thrombolytic therapy, and immediate triage for mechanical thrombectomy.

Initial Diagnostic Workup

1. Point-of-Care Blood Glucose: Must be performed immediately upon arrival. Hypoglycemia (<60 mg/dL [3.3 mmol/L]) is a frequent stroke mimic that can cause focal hemiparesis and aphasia; treat rapidly with IV 50% Dextrose (D50W).
2. Non-Contrast Head CT: The primary purpose is to rule out acute intracranial hemorrhage (ICH). It also detects early ischemic signs such as hyperdense MCA sign, loss of the insular ribbon, cortical sulcal effacement, and loss of gray-white matter differentiation. The ASPECTS (Alberta Stroke Program Early CT Score) evaluates 10 regions of the MCA territory; a score >=6 indicates a favorable small core appropriate for intervention.
3. NIH Stroke Scale (NIHSS): A validated 11-item quantitative assessment (scores 0-42) of stroke severity: 0 = no stroke; 1-4 = minor stroke; 5-15 = moderate stroke; 16-20 = moderate-to-severe stroke; 21-42 = severe stroke.

Intravenous Thrombolytic Therapy

• Pharmacological Agents:
  • Tenecteplase (TNK-tPA): 0.25 mg/kg IV single bolus over 5-10 seconds (maximum 25 mg). Preferred over alteplase in many stroke centers due to single-bolus convenience, higher fibrin specificity, and non-inferior (or superior) reperfusion rates.
  • Alteplase (rt-PA): 0.9 mg/kg IV (maximum 90 mg); 10% administered as an initial IV bolus over 1 minute, followed by the remaining 90% infused continuously over 60 minutes.
• Treatment Windows:
  • Standard Window (<=3.0 hours from Last Known Normal [LKN]): Indicated for all eligible patients without contraindications.
  • Extended Window (3.0 to 4.5 hours from LKN): Supported by the ECASS-III trial. Additional relative exclusions in the 3.0-4.5 hour window include: age >80 years, baseline NIHSS >25, combination of prior stroke and diabetes mellitus, or any oral anticoagulant use regardless of INR.
• Blood Pressure Management Surrounding Thrombolysis:
  • Pre-Thrombolysis Threshold: Systolic BP must be < 185 mmHg and diastolic BP must be < 110 mmHg BEFORE initiating thrombolytic infusion.
  • Post-Thrombolysis Threshold: Maintain BP < 180/105 mmHg for at least 24 hours following thrombolytic administration.
  • First-Line IV Antihypertensives:
    • Labetalol: 10 to 20 mg IV over 1-2 minutes; may repeat or double every 10-20 minutes up to a maximum cumulative dose of 300 mg, or infuse 2-8 mg/min.
    • Nicardipine: IV infusion starting at 5 mg/h, titrated by 2.5 mg/h every 5-15 minutes to a maximum of 15 mg/h.
    • Clevidipine: IV infusion starting at 1-2 mg/h, titrated by doubling every 2-5 minutes (maximum 21 mg/h).
• Absolute Contraindications to Intravenous Thrombolysis:
  • Evidence of intracranial hemorrhage on pretreatment non-contrast head CT.
  • Clinical presentation suspicious for subarachnoid hemorrhage even with normal head CT.
  • Prior history of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation (AVM), or intracranial aneurysm.
  • Significant head trauma or acute ischemic stroke within the preceding 3 months.
  • Gastrointestinal malignancy or active gastrointestinal bleeding within the preceding 21 days.
  • Major intracranial or intraspinal surgery within the preceding 3 months.
  • Persistent severe hypertension (SBP >=185 mmHg or DBP >=110 mmHg) refractory to emergent aggressive antihypertensive therapy.
  • Active therapeutic anticoagulation: Use of therapeutic Direct Oral Anticoagulants (DOACs: apixaban, rivaroxaban, dabigatran) within 48 hours (unless specific reversal agents are administered or calibrated anti-Xa/thrombin time assays are normal); therapeutic Low-Molecular-Weight Heparin (LMWH) within 24 hours; or Unfractionated Heparin (UFH) within 48 hours with elevated aPTT.
  • Coagulopathy: Platelet count < 100,000/mcL; International Normalized Ratio (INR) > 1.7; Prothrombin Time (PT) > 15 seconds; or aPTT > 40 seconds.

Endovascular Mechanical Thrombectomy (EVT)

Mechanical thrombectomy with stent retrievers and direct aspiration catheters has revolutionized the management of acute ischemic stroke caused by Large Vessel Occlusion (LVO) in the anterior circulation (intracranial Internal Carotid Artery [ICA] and Middle Cerebral Artery M1 segment) and basilar artery.

• Standard Window (<=6 Hours from LKN): Indicated for patients with: (1) Pre-stroke modified Rankin Scale (mRS) 0-1; (2) Causative LVO of the ICA or MCA M1 segment; (3) Age >=18 years; (4) NIHSS >=6; (5) ASPECTS score >=6. Note: Eligible patients should receive IV thrombolysis while being prepared for EVT without delaying groin puncture.
• Extended Window (6 to 24 Hours from LKN): Indicated in carefully selected patients with anterior circulation LVO who meet strict physiological mismatch criteria demonstrated by CT perfusion (CTP) or diffusion-weighted MRI (DWI):
  • DAWN Trial Criteria (6-24h): Disproportionate clinical deficit (NIHSS) relative to small ischemic core volume (e.g., age >=80 with NIHSS >=10 and core <21 mL; or age <80 with NIHSS >=20 and core <51 mL).
  • DEFUSE 3 Trial Criteria (6-16h): Initial ischemic core volume <70 mL, mismatch ratio (penumbra to core) >=1.8, and absolute penumbral volume >=15 mL.