Section 5.1: Cerebrovascular Disease (Stroke, TIA)

PANCE Clinical Significance

Cerebrovascular disease is a corner-stone of the PANCE neurologic blueprint. The exam expects candidates to rapidly differentiate between ischemic and hemorrhagic events, localize cortical deficits to specific vascular territories, master the temporal windows and contraindications for thrombolytic therapy, and properly risk-stratify transient ischemic attacks (TIAs).

Definitions, Pathophysiology, and Risk Factors

• Ischemic Stroke (85% of cases): Caused by focal cerebral hypoperfusion. Ischemic events are broadly classified into:
  • Thrombotic: Localized clot formation over an atherosclerotic plaque, most commonly at the bifurcation of the common carotid artery or within the middle cerebral artery (MCA).
  • Embolic: A blood clot, debris, or foreign body travels from a distant source to occlude a cerebral vessel. The most common source is cardiogenic, associated with Atrial Fibrillation, valvular heart disease, or a patent foramen ovale (PFO).
  • Pathophysiology: Hypoperfusion leads to cellular hypoxia and immediate depletion of adenosine triphosphate (ATP). The failure of energy-dependent sodium-potassium ATPase pumps results in sodium accumulation inside cells, drawing water in and causing cytotoxic edema. Rapid depolarization of the neuronal membrane triggers a massive release of glutamate into the synaptic cleft. Glutamate binds to NMDA receptors, causing a massive influx of calcium that activates intracellular enzymes (proteases, lipases, endonucleases), culminating in cell death. The central area of severe hypoperfusion undergoes irreversible necrosis (the infarct core), while the surrounding hypoperfused tissue (the ischemic penumbra) remains structurally intact but metabolically compromised. This penumbra is the primary target of urgent reperfusion therapy.
• Hemorrhagic Stroke (15% of cases): Caused by extravasation of blood into the brain parenchyma or subarachnoid space.
  • Intracerebral Hemorrhage (ICH): Most commonly caused by chronic hypertension. Hypertension damages small penetrating arteries (e.g., lenticulostriate arteries), leading to lipohyalinosis and the formation of Charcot-Bouchard microaneurysms, which are prone to rupture. In the elderly, cerebral amyloid angiopathy (deposition of beta-amyloid in cortical vessels) is a common cause of lobar hemorrhages.
  • Subarachnoid Hemorrhage (SAH): Extravasation of blood into the subarachnoid space, typically caused by the rupture of a saccular (berry) aneurysm. These aneurysms occur most commonly at arterial branch points in the Circle of Willis, particularly at the junction of the anterior communicating artery (ACom) and the anterior cerebral artery. Rupture is associated with sudden spikes in blood pressure (e.g., during physical exertion or drug use).
• Transient Ischemic Attack (TIA): A transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute tissue infarction on neuroimaging. Symptoms typically resolve within 1 hour. A TIA is a warning sign of an impending stroke; approximately 10-15% of patients will have a stroke within 90 days, with the highest risk in the first 48 hours.
• Risk Factors: Hypertension (the most significant modifiable risk factor), diabetes mellitus, hyperlipidemia, cigarette smoking, advanced age, male sex, family history, atrial fibrillation, and physical inactivity.

Clinical Presentation and Cortical Localization

The clinical presentation of stroke is sudden and focal. The specific deficits allow localization of the affected vascular territory:

• Middle Cerebral Artery (MCA) Syndrome (Most Common):
  • Deficits: Contralateral motor and sensory deficits affecting the face and upper extremity significantly more than the lower extremity (face/arm > leg).
  • Visual: Contralateral homonymous hemianopia.
  • Hemispheric Findings:
    • Dominant hemisphere (usually left): Aphasia. This can be expressive (Broca's aphasia, localized to the posterior inferior frontal gyrus) or receptive (Wernicke's aphasia, localized to the posterior superior temporal gyrus).
    • Non-dominant hemisphere (usually right): Hemispatial neglect of the contralateral side, anosognosia (unawareness of the deficit), and flat affect.
• Anterior Cerebral Artery (ACA) Syndrome:
  • Deficits: Contralateral motor and sensory deficits affecting the lower extremity significantly more than the upper extremity and face (leg > arm/face).
  • Associated signs: Urinary incontinence (due to damage to the cortical micturition center), dysarthria, abulia (apathy, slow responses, and lack of willpower), and contralateral primitive reflexes (e.g., grasp reflex).
• Posterior Cerebral Artery (PCA) Syndrome:
  • Deficits: Contralateral homonymous hemianopia with macular sparing (the macula is spared due to collateral supply from the MCA to the occipital pole).
  • Associated signs: Alexia without agraphia (inability to read but retaining the ability to write), visual agnosia (inability to recognize objects), and contralateral sensory loss (if the thalamus is involved).
• Vertebrobasilar (Posterior Circulation) Syndrome:
  • Deficits: Characterized by crossed signs (ipsilateral cranial nerve palsies with contralateral motor or sensory deficits of the body).
  • The "Ds": Dysphagia (difficulty swallowing), Dysarthria (difficulty speaking), Diplopia (double vision), Dizziness/Vertigo, ataxia, and nystagmus.
• Hemorrhagic Stroke Features:
  • ICH: Gradual progression over minutes to hours of headache, vomiting, altered mental status, and focal neurologic deficits, often accompanied by severe hypertension.
  • SAH: Sudden onset of an excruciatingly severe headache, classically described as the "worst headache of my life" or a "thunderclap headache". Associated symptoms include vomiting, brief loss of consciousness, meningeal signs (nuchal rigidity, photophobia, positive Kernig and Brudzinski signs), and preretinal hemorrhages (Subhyaloid hemorrhages).

Diagnostic Workup

• Initial Test of Choice: Non-contrast Head CT. It must be performed emergently to rule out hemorrhage (which appears hyperdense or white on CT) before any fibrinolytic or antiplatelet therapy is initiated. In the first 6 hours of an ischemic stroke, the non-contrast head CT is often normal, although subtle signs like the "hyperdense MCA sign" (indicating a fresh thrombus) or loss of insular ribbon definition may be present.
• Gold Standard (Ischemic Stroke): Diffusion-weighted MRI (DWI). It has the highest sensitivity and specificity for acute ischemic stroke and can detect ischemia within 15-30 minutes of onset (appearing as hyperintense/white areas due to restricted diffusion).
• Subarachnoid Hemorrhage Workup Protocol:
  1. Non-contrast Head CT: Highly sensitive (98% in the first 6 hours).
  2. Lumbar Puncture (LP): Performed if the head CT is negative but clinical suspicion remains high. Diagnostic findings include xanthochromia (yellow-pink supernatant resulting from enzymatic breakdown of hemoglobin to bilirubin, which requires 2-12 hours to develop) and a high, non-clearing RBC count from tube 1 to tube 4.
• Secondary Workup:
  • CT Angiography (CTA) or MR Angiography (MRA): To identify large vessel occlusions (LVO) suitable for mechanical thrombectomy.
  • ECG and Telemetry: To evaluate for atrial fibrillation.
  • Echocardiogram (ECHO): To screen for cardiac thrombi, patent foramen ovale (PFO), or valvular disease.
  • Carotid Duplex Ultrasound: To evaluate for carotid artery stenosis.

Clinical Management and Pharmacotherapy

• Acute Ischemic Stroke:
  • Thrombolytic Therapy: Intravenous alteplase (tPA) or tenecteplase is indicated if administered within 3 hours of symptom onset (or up to 4.5 hours in select patients under 80 years old without a history of both stroke and diabetes, and not on oral anticoagulants).
  • Blood Pressure Management:
    • For thrombolysis candidates: Blood pressure must be lowered to < 185/110 mmHg before tPA is administered and kept < 180/105 mmHg for 24 hours afterward. Intravenous labetalol or nicardipine are the preferred agents.
    • For non-thrombolysis candidates: Permissive hypertension is allowed up to 220/120 mmHg to maintain cerebral perfusion to the penumbra. Blood pressure should not be lowered unless it exceeds this threshold or if there is another compelling indication (e.g., acute coronary syndrome, aortic dissection, acute renal failure).
  • Mechanical Thrombectomy: Indicated for patients with a documented large vessel occlusion (LVO) in the anterior circulation within 6 to 24 hours of their last known normal, regardless of whether they received tPA.
  • Antiplatelet Therapy: Aspirin 325 mg is initiated within 24-48 hours of stroke onset. If tPA was administered, aspirin must be held for 24 hours. For minor ischemic stroke (NIHSS <= 3) or high-risk TIA (ABCD2 >= 4), Dual Antiplatelet Therapy (DAPT) with aspirin and clopidogrel is started within 24 hours and continued for 21 to 90 days.
• Absolute tPA Contraindications (High Yield):
  • Active internal bleeding or bleeding diathesis.
  • Platelet count < 100,000/mm³, INR > 1.7, or elevated aPTT due to recent heparin use.
  • Current use of direct thrombin inhibitors or factor Xa inhibitors with elevated sensitive lab assays.
  • History of previous intracranial hemorrhage, intracranial neoplasm, aneurysm, or arteriovenous malformation.
  • Recent intracranial or intraspinal surgery, or serious head trauma within 3 months.
  • Ischemic stroke within the past 3 months.
  • Uncontrolled blood pressure (>185/110 mmHg) despite aggressive medical therapy.
• Hemorrhagic Stroke Management:
  • Intracerebral Hemorrhage (ICH): Rapidly lower systolic blood pressure to a target of 140 mmHg using IV nicardipine or labetalol. Immediately reverse anticoagulation (e.g., Vitamin K and Prothrombin Complex Concentrate [PCC/Kcentra] for warfarin; Idarucizumab for dabigatran; Andexanet alfa for apixaban/rivaroxaban). Elevate the head of the bed to 30 degrees, manage increased intracranial pressure (ICP) with mannitol or hypertonic saline if needed, and consult neurosurgery.
  • Subarachnoid Hemorrhage (SAH): Prevent cerebral vasospasm (a major cause of delayed morbidity) by administering Nimodipine (oral calcium channel blocker) within 96 hours of symptom onset, continued for 21 days. Endovascular coiling or surgical clipping of the ruptured aneurysm should be performed within 24 hours.
• TIA Risk Stratification (ABCD2 Score):
  • Used to predict the risk of stroke in the 2 days following a TIA:
    • Age >= 60 years (1 point)
    • Blood Pressure >= 140/90 mmHg at presentation (1 point)
    • Clinical features: Unilateral weakness (2 points) OR Speech disturbance without weakness (1 point)
    • Diabetes mellitus history (1 point)
    • Duration of symptoms: >= 60 minutes (2 points) OR 10-59 minutes (1 point)
  • Patients with an ABCD2 score of >= 4 have a moderate-to-high risk of stroke and should be admitted for urgent workup and initiation of DAPT.

Classic PANCE Traps & Clinical Pearls

• The "Last Known Normal" Trap: The window for tPA is calculated from the patient's "last known normal" time, not when the symptoms were first noticed. If a patient wakes up with stroke symptoms, the last known normal is when they went to sleep, which often disqualifies them from tPA.
• The Aggressive BP Lowering Trap: Do not lower blood pressure in an acute ischemic stroke patient who is not a tPA candidate unless it is >220/120 mmHg. Lowering blood pressure decreases cerebral perfusion pressure, causing the ischemic penumbra to convert into completed infarcted tissue.
• The Negative Head CT Trap in SAH: A normal non-contrast head CT does not rule out subarachnoid hemorrhage. If the clinical presentation is suggestive of SAH (e.g., sudden onset of thunderclap headache), a lumbar puncture is mandatory.