Ischemic Stroke Overview and Mechanisms

Stroke Overview

• Stroke involves abrupt onset of focal neurologic dysfunction lasting at least 24 hours.
• Stroke can be ischemic or hemorrhagic.
• Transient ischemic attacks (TIAs) are focal ischemic neurologic deficits lasting less than 24 hours and usually less than 30 minutes.

Ischemic Stroke Pathophysiology

• Ischemic stroke (87% of all strokes) results from occlusion of a cerebral artery.
• Causes include local thrombus formation or emboli from a distant site.
• Atherosclerosis of large intracranial or extracranial arteries or small artery disease can lead to ischemic stroke.
• Emboli can originate from the heart (atrial fibrillation, valvular heart disease, or other prothrombotic heart problems) and are responsible for about 25% of ischemic strokes.

Ischemic Stroke Pathophysiology (Mechanism)

• Insufficient oxygen supply leads to ATP depletion, lactate buildup, intracellular Na and water accumulation, cytotoxic edema, and eventual cell lysis.
• Calcium influx activates lipases and proteases.
• Release of excitatory amino acids (e.g., glutamate, aspartate) causes neuronal damage and produces damaging substances (PG, leukotrienes, ROS).
• These processes occur within 2-3 hours of ischemia onset and lead to apoptosis and necrosis.

Ischemic Stroke Pathophysiology (Penumbra)

• Decreased cerebral blood flow leads to cerebral tissue infarction.
• The ischemic penumbra is the surrounding area with impaired blood flow, but the tissue maintains membrane integrity.
• The penumbra is a potentially salvageable area of brain tissue needing urgent pharmacological and endovascular interventions.

Hemorrhagic Stroke Pathophysiology

• Hemorrhagic strokes (13% of strokes) include subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH).
• Early hematoma expansion within 3 hours of onset worsens functional outcome and increases mortality.
• Secondary injury mechanisms include inflammation, cerebral edema, and damage from blood product degradation.

Clinical Presentation

• Stroke symptoms include unilateral weakness, inability to speak, loss of vision, vertigo, or falling.
• Ischemic stroke is not usually painful but some patients complain of headaches.
• Headaches are more common and severe in hemorrhagic strokes.

Clinical Presentation (Neurological Deficits)

• Neurological deficits on exam depend on the brain area involved.
• Hemi- or monoparesis and hemisensory deficits are common.
• Patients with posterior circulation involvement may experience vertigo and diplopia.
• Anterior circulation strokes commonly result in aphasia.
• Patients may have altered levels of consciousness.

Diagnosis

• General blood glucose, platelet count, and coagulation parameters are checked.
• CT and MRI head scans reveal areas of hemorrhage and infarction.
• Computed tomography angiography (CTA), carotid Doppler (CD), ECG, transthoracic echocardiogram (TTE), and transcranial Doppler (TCD) studies help diagnose.

Treatment Goals

• Reduce ongoing neurologic injury to decrease mortality and long-term disability.
• Prevent complications secondary to immobility and neurologic dysfunction.
• Prevent stroke recurrence.

Non-Pharmacological Treatment (Ischemic Stroke)

• Endovascular intervention and thrombectomy with retrievable stents are strongly recommended within 6 hours of symptom onset for anterior circulation occlusions.
• For posterior circulation occlusions, the benefit is less clear and should be evaluated on a case-by-case basis.
• Decompressive hemicraniectomy is brain surgery that removes a portion of the skull to reduce mortality and improve functional outcome in select patients.
• Carotid endarterectomy removes plaque buildup from stenotic carotid arteries to reduce stroke incidence.

Non-Pharmacological Treatment (Hemorrhagic Stroke)

• Early intervention (surgical clipping or endovascular coiling of vascular abnormalities) reduces mortality from rebleeding in subarachnoid hemorrhage (SAH).
• Early surgical intervention and hematoma removal are recommended for patients with cerebellar hemorrhage and neurologic deterioration, brainstem compression, or hydrocephalus.

Temperature Management

• Fever worsens outcomes in patients with both hemorrhagic and ischemic stroke.
• Source identification and pharmacologic/nonpharmacologic management is needed to maintain normothermia.

Pharmacologic Therapy (Ischemic Stroke)

• Adherence to a guideline protocol is essential for positive outcomes in ischemic stroke.
• Activation of the stroke team, obtaining a CT scan, treating the stroke as early as possible (within 4.5 hours), and meeting all inclusion criteria are crucial.
• Alteplase (0.9 mg/kg IV) is administered, with a 10% bolus over one minute followed by the rest over one hour.
• Avoid anticoagulants and antiplatelets for 24 hours after alteplase. Closely monitor BP, neurologic status, and hemorrhage.
• Aspirin (160-325 mg/day) within 24-48 hours of symptom onset reduces long-term disability, if no aspirin allergy or contraindications.
• Alternative antiplatelet agents may be used.
• For patients with high BP and alteplase eligibility, goal BP is <185/110 mm Hg prior to thrombolytic administration.
• In patients not needing IV thrombolysis, high BP (220/120 mm Hg) is often acceptable for the first 48-72 hours.

Pharmacologic Therapy (Hemorrhagic Stroke)

• Pharmacotherapy effectiveness in spontaneous intracerebral hemorrhage (ICH) is limited.
• Aggressive blood pressure lowering (IV infusion) is reasonable for patients with systolic BP > 220 mmHg
• Goal BP is 140 mmHg to improve functional outcome.
• For patients with subarachnoid hemorrhage (SAH) due to aneurysm rupture, target systolic BP is <160 mmHg during symptom onset to aneurysm obliteration.
• Use reversal agents if hemorrhage involves anticoagulant patients.

Evaluation of Outcomes

• Monitor bleeding with neurologic examination and blood pressure every 15 minutes during the first hour, every half-hour for 6 hours, then every hour for 17 hours and then once every shift thereafter.
• Daily monitoring for bleeding requires checking PT/INR and hemoglobin/hematocrit for patients on warfarin, aspirin, clopidogrel,. extended-release dipyridamole plus aspirin and other oral anticoagulants.

This quiz explores the key concepts of ischemic stroke, including its pathophysiology and mechanisms. Learn about the causes, effects, and consequences of ischemic strokes. Test your understanding of how oxygen deprivation impacts brain cells and leads to neurologic dysfunction.