Ischemic Stroke

Definition and Epidemiology

Pathophysiology and Classification

• Large-vessel occlusion (LVO): Clot forms at ulcerated atherosclerotic plaque, especially at vessel bifurcations in the internal carotid artery (ICA) territory. Significant flow reduction occurs when stenosis exceeds 90% of vessel diameter.
• Small-vessel / lacunar strokes: Involve terminal small vessels; infarcts range from a few mm to 2 cm, located in the basal ganglia, thalamus, pons, and internal capsule. Strongly associated with hypertension (80-90% of cases) and diabetes. Caused by lipohyalinosis (hypertensive cerebral vasculopathy) or small emboli.

• Young stroke (age 15-45, ~3-4% of all strokes): Pregnancy, oral contraceptives, antiphospholipid antibody syndrome, sickle cell anemia, polycythemia, cocaine/amphetamines, fibromuscular dysplasia, prolonged migraine vasospasm, infectious vasculopathies (varicella, fungal meningitis)
• Carotid/vertebral dissection: Leading determined cause in the young; may follow mild trauma (sneezing), or be associated with fibromuscular dysplasia or connective tissue disorders - Rosen's Emergency Medicine, p. 1427

Clinical Presentation

Anterior Circulation (ICA, ACA, MCA)

Posterior Circulation (vertebrobasilar)

• Lateral medullary (Wallenberg) syndrome: Ipsilateral facial numbness, Horner's syndrome, hoarseness, dysphagia, ataxia + contralateral body pain/temperature loss
• Basilar artery occlusion: Locked-in syndrome, quadriplegia, coma

Temporal Patterns

• Stroke in evolution: Worsening deficits over minutes to hours (~20% anterior, ~40% posterior)
• TIA: Transient focal symptoms, fully resolving, no infarction on imaging - high risk of subsequent stroke

Differential Diagnosis

• Hypoglycemia - most important to exclude (may cause sustained focal deficits lasting days)
• Todd's postictal paralysis (post-seizure)
• Subdural/epidural hematoma (especially in elderly on anticoagulation)
• Brain tumor or abscess
• Wernicke encephalopathy (ophthalmoplegia, ataxia, confusion - mimics posterior fossa stroke)
• Complex migraine with focal aura
• Bell's palsy / vestibular neuronitis / labyrinthitis
• Giant cell arteritis (in elderly)
• Hypertensive encephalopathy
• Rosen's Emergency Medicine, p. 1430-1431

Diagnosis and Imaging

Initial Workup

• Immediate blood glucose (to rule out hypoglycemia)
• Non-contrast CT head (NCCT) - first-line, rapidly rules out hemorrhage
• ECG (identify AF, arrhythmias)
• Labs: CBC, BMP, coagulation studies, troponin

CT Findings

• Hyperdense artery sign - acute thrombus visible as focal hyperdensity in MCA ("hyperdense MCA sign") or dot sign in distal vessels
• Sulcal effacement and loss of the insular ribbon
• Loss of gray-white interface
• Acute hypodensity (appears by 6-12 hours)

Advanced Imaging

• CTA: Identifies LVO - essential for mechanical thrombectomy triage. Also detects dissection and stenosis.
• CT Perfusion (CTP): Identifies penumbra vs. core; most useful for extended time windows (6-24h). Should NOT delay tPA.
• MRI DWI with ADC mapping: Most sensitive for acute ischemia - detects restricted diffusion within minutes of onset. ADC helps distinguish true diffusion restriction from T2 shine-through. - Bradley and Daroff's Neurology, p. 701

NIHSS Scoring

Emergency Management

ABCs and Supportive Care

• Withhold oral intake until swallowing assessment (aspiration risk)
• Treat fever aggressively (even mild hyperthermia worsens neurologic injury; target normothermia)
• Correct hypoglycemia/hyperglycemia
• Cardiac monitoring for AF detection

Blood Pressure Management

• Rosen's Emergency Medicine, p. 1433-1434

Reperfusion Therapy

IV Thrombolysis

• Dose: 0.9 mg/kg IV (max 90 mg); 10% as bolus over 1 min, remainder over 60 min
• Time window: within 4.5 hours of clearly defined symptom onset
• Approved by FDA; remains standard of care based on NINDS trial
• ENCHANTED trial showed low-dose (0.6 mg/kg) non-inferior with fewer sICH events - currently standard only in Japan; AHA/ASA still recommends 0.9 mg/kg
• Symptomatic ICH rate: ~6.4% in treated patients

• Dose: 0.25 mg/kg IV (max 25 mg) as a single bolus - easier to administer
• Moderate-high quality evidence of non-inferiority to alteplase for functional outcome and sICH at 90 days
• EXTEND-IA TNK trial: tenecteplase showed higher reperfusion rates and better functional outcomes vs. alteplase when used before endovascular therapy
• Can be used in place of alteplase for patients also eligible for mechanical thrombectomy
• Rosen's Emergency Medicine, p. 1435

Mechanical Thrombectomy (Endovascular)

• Indicated for LVO in anterior circulation (ICA, MCA M1/M2)
• Standard time window: up to 24 hours with appropriate imaging selection (CTP or DWI/PWI mismatch)
• Key trials: MR CLEAN, DAWN, DEFUSE-3 established benefit
• A recent meta-analysis (2025) confirms thrombectomy benefit even in large ischemic core strokes
• Prior tPA should not be delayed in eligible patients who will proceed to thrombectomy
• BP target pre-thrombectomy (without prior tPA): ≤185/110 mmHg

Secondary Prevention

• Carotid endarterectomy (CEA) or stenting for symptomatic high-grade (>70%) carotid stenosis
• ESO guidelines (2024) address patent foramen ovale (PFO) closure after cryptogenic stroke

Key Stroke Mimics to Exclude Immediately

1. Hypoglycemia - check glucose first in every patient
2. Todd's paralysis - history of seizure
3. Subdural hematoma - history of falls, anticoagulant use
4. Wernicke encephalopathy - thiamine deficiency (give thiamine first)

Summary of Time-Critical Actions

• Thrombectomy for large ischemic core: Liu et al., Neurology 2025 (PMID 40245349) - systematic review/meta-analysis confirms benefit from EVT even in large-core strokes
• PFO after cryptogenic stroke: ESO Guidelines 2024 (PMID 38752755) - closure recommended in selected patients <60 years
• Chinese 2024 reperfusion guidelines: Xiong et al. 2025 (PMID 39832918) - tenecteplase recommended as an option over alteplase given ease of administration and non-inferiority data