Acute focal neurologic deficit from arterial occlusion causing brain infarction.
Also known as: CVA, cerebral infarction, brain attack, thromboembolic stroke, large vessel occlusion, LVO
Overview
Acute focal neurologic deficit lasting >24 hours (or imaging-confirmed infarction at any duration) caused by interruption of cerebral arterial blood flow with resulting tissue ischemia and infarction.
Epidemiology
Fifth leading cause of death in the US and a leading cause of long-term disability. ~87% of all strokes are ischemic. Incidence rises sharply after age 55, doubling each decade.
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Other: hypercoagulable states (antiphospholipid syndrome, malignancy), oral contraceptives + smoking in women >35, cocaine/methamphetamine use, recent MI with mural thrombus, PFO (paradoxical embolism)
Pathophysiology
Occlusion of a cerebral artery by thrombus (in-situ atherosclerosis) or embolus (cardioembolic or artery-to-artery) reduces regional cerebral blood flow below the threshold for neuronal function (~20 mL/100 g/min) and then below the threshold for cellular integrity (~10 mL/100 g/min). The irreversibly infarcted core is surrounded by an ischemic penumbra of stunned but viable tissue maintained by collateral flow. Reperfusion within the therapeutic window can salvage the penumbra; without it the infarct expands.
Sudden onset focal deficit referable to a single vascular territory; NIHSS quantifies severity (0-42).
Differential diagnosis
Hemorrhagic stroke (ICH) — Indistinguishable clinically — non-contrast head CT differentiates; headache, vomiting, and rapidly declining consciousness more common with ICH
TIA — Same clinical syndrome but symptoms resolve completely, usually <1 hour; no infarction on imaging
Seizure with Todd paralysis — Postictal focal weakness lasting minutes to ~48 h; witnessed convulsion or tongue bite favor this
Hypoglycemia — Can mimic any focal deficit; fingerstick glucose mandatory before tPA — D50 if <60 mg/dL
Complex migraine (hemiplegic migraine) — Younger patient, headache prominent, spreading march of symptoms over minutes, prior similar episodes
Conversion disorder / functional — Inconsistent exam, non-anatomic distribution, normal imaging — diagnosis of exclusion
Brain tumor / abscess — Subacute progression over days-weeks; CT/MRI with contrast diagnostic
Bell palsy — Isolated peripheral CN VII palsy involving the forehead; central facial sparing involves lower face only
Diagnostic workup
Diagnostic criteria
Clinical syndrome of acute focal neurologic deficit with imaging evidence of infarction (CT hypodensity or MRI DWI restriction) and exclusion of hemorrhage.
Labs
Fingerstick glucose immediately (rule out hypoglycemia)
CBC, platelets, PT/INR, PTT, BMP, troponin
Lipid panel, A1c — for secondary prevention
Pregnancy test in women of childbearing age
Imaging
Non-contrast head CT within 20 min of arrival — excludes hemorrhage (essential before tPA)
CT angiography head and neck — identifies large vessel occlusion candidates for thrombectomy
CT perfusion or MR diffusion/perfusion — quantifies core vs penumbra for extended-window thrombectomy (DAWN, DEFUSE-3)
MRI with DWI — most sensitive for acute infarction (positive within minutes)
Carotid duplex, transthoracic or transesophageal echo, telemetry/Holter (AFib detection) for etiology
Diagnostic algorithm
flowchart TD
A[Acute focal deficit<br/>Last known well documented] --> B[Glucose + NIHSS]
B --> C[Non-contrast head CT<br/>≤20 min]
C --> D{Hemorrhage?}
D -->|Yes| E[Hemorrhagic pathway<br/>BP control, reverse anticoag]
D -->|No| F{Within 4.5 h<br/>+ no contraindications?}
F -->|Yes| G[IV alteplase 0.9 mg/kg<br/>or tenecteplase]
F -->|No| H[Aspirin 325 mg<br/>secondary prevention]
G --> I[CTA head/neck]
H --> I
I --> J{LVO present?}
J -->|Yes, ≤24 h + favorable imaging| K[Mechanical thrombectomy]
J -->|No| L[Stroke unit admission<br/>workup etiology]
K --> L
Acute ischemic stroke triage — time-critical pathway from arrival to reperfusion therapy.
Treatment
First-line
tPA dosing — alteplase 0.9 mg/kg IV (max 90 mg), 10% as bolus over 1 min, remainder over 60 min, if within 4.5 h of last known well and no contraindications (NINDS, ECASS III)
Tenecteplase 0.25 mg/kg IV bolus — increasingly used alternative, particularly with LVO bridging to thrombectomy
Mechanical thrombectomy for anterior circulation LVO within 6 h (standard) or up to 24 h if favorable perfusion imaging (DAWN, DEFUSE-3)
BP target: <185/110 before tPA; <180/105 for 24 h after tPA; otherwise permissive HTN <220/120 unless end-organ injury
Aspirin 325 mg within 24-48 h (delay 24 h after tPA)
DVT prophylaxis (mechanical immediately; chemical after 24 h if no hemorrhage)
Second-line / adjunct
Dual antiplatelet therapy (aspirin + clopidogrel) for 21-90 days after minor stroke/high-risk TIA (CHANCE, POINT) then aspirin monotherapy
Anticoagulation (warfarin, DOAC — apixaban, rivaroxaban, dabigatran, edoxaban) for cardioembolic stroke from AFib; typically start 4-14 days post-stroke based on infarct size
Carotid endarterectomy or stenting if ipsilateral carotid stenosis 70-99% (symptomatic) — within 2 weeks
BE-FAST: Balance, Eyes, Face, Arm, Speech, Time — public stroke recognition mnemonic.
tPA absolute contraindications: ICH ever, recent (<3 mo) head trauma/stroke/intracranial surgery, active bleeding, platelets <100k, INR >1.7, BP >185/110 refractory to treatment.
Wake-up strokes with favorable MRI mismatch (DWI positive, FLAIR negative — 'WAKE-UP' trial) may still be tPA candidates.
Posterior circulation stroke is frequently misdiagnosed as labyrinthitis; HINTS exam (Head Impulse, Nystagmus, Test of Skew) distinguishes central from peripheral vertigo.
Young stroke workup: hypercoagulable panel, vasculitis serologies, drug screen, echo with bubble study for PFO, vertebral artery dissection imaging.
References
AHA/ASA 2019 — Guidelines for the Early Management of Patients With Acute Ischemic Stroke (Powers et al., Stroke 2019, 2019 update)
NINDS Trial — Tissue Plasminogen Activator for Acute Ischemic Stroke (NINDS rt-PA Study Group, NEJM 1995)
ECASS III — Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke (Hacke et al., NEJM 2008)
DAWN Trial — Thrombectomy 6 to 24 Hours after Stroke with a Mismatch (Nogueira et al., NEJM 2018)
DEFUSE 3 — Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging (Albers et al., NEJM 2018)
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