Ischemic Stroke

Risk factors

• Non-modifiable: age, male sex (until later life), family history, prior stroke/TIA, sickle cell disease
• Modifiable: hypertension (strongest modifiable risk), diabetes, dyslipidemia, smoking, atrial fibrillation, carotid stenosis, obesity, OSA, physical inactivity
• 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.

Clinical presentation

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 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

Treatment

Complications

• Hemorrhagic transformation (especially after tPA, large infarct, or reperfusion)
• Cerebral edema with herniation (large MCA or cerebellar stroke; may need hemicraniectomy)
• Aspiration pneumonia (screen swallow before any oral intake)
• DVT/PE, UTI, decubitus ulcers from immobility
• Post-stroke depression, spasticity, seizures, vascular dementia
• Recurrent stroke (highest risk in first 90 days)

PANCE pearls

• 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)