Stroke

Stroke (Cerebrovascular Accident-CVA) Definition

• A reduced blood supply to the brain reduces oxygen supply, potentially causing brain death ("central nervous system infarction").
• Cerebral infarction: Brain, spinal cord, or retina cell death due to ischemia (lack of blood flow). Neurological evidence of permanent injury for at least 24 hours confirms diagnosis, excluding other causes.

Etiology & Pathophysiology Overview

• Ischemic Stroke: (3rd or 4th leading cause of death in developed countries). Occurs from thrombotic or embolic occlusion of cerebral arteries. Causes sudden focal neurological deficits.
• Hemorrhagic Stroke: Bleeding into brain tissue or other CNS spaces. Includes subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and subdural hematomas. Bleeding causes compression on brain tissue.

Risk Factors

• Non-Modifiable:*

• Age (males > females, >55 years)

• Race/ethnicity (American Indian, Alaska Natives, African American, Asian/Pacific Islander, Hispanic)

• Genetic predisposition/family history

• Low birth weight

• Modifiable:*

• Hypertension

• Cardiovascular diseases (e.g., atrial fibrillation, CHD)

• Diabetes

• Dyslipidemia

• Oral contraceptive use (estrogen content >50 mcg)

• Cigarette smoking

• Alcohol use

• Obesity

• Physical inactivity

• Drug abuse (cocaine, amphetamines, heroin)

Classification

• Transient Ischemic Attack (TIA): Transient neurological dysfunction from focal brain, spinal cord, or retinal ischemia, without acute infarction. No deficit remains after the attack.
• Ischemic Stroke: Neurological symptoms lasting 24 hours or more. Most common cause of adult disability. Tissue injury and infarction result.
• Hemorrhagic event: Sudden, severe headache, nausea, and vomiting

Clinical Presentation

• Ischemic Stroke:*

• Weakness on one side of the body. Inability to speak, loss of vision, vertigo, headache, or falling.

• Hemiparesis (facial droop, weakness on one side of the body)

• Hemisensory deficit (loss of sensation on one side of the body)

• Vertigo and double vision

• Slurred speech

• Altered level of consciousness

• Hemorrhagic Stroke:*

• Sudden severe headache.

• Nausea and vomiting.

• "Worst headache of my life"

• Photophobia

• Nuchal rigidity

Diagnosis

• No specific laboratory tests for stroke exist.
• CT scan (ideally within 20 minutes of symptom onset)
• MRI
• Carotid Doppler
• ECG
• Transthoracic echocardiogram (TTE)

Ischemic Stroke- Complication

• Cerebral edema (due to endothelial dysfunction)
• Increased intracranial pressure (ICP)
• Seizures
• Hemorrhagic conversion (ischemic stroke converted to hemorrhagic stroke)

Ischemic Stroke- Management

• Identification of stroke onset time and manner is critical for treatment.
• NIHSS score assessment.
• Supplementary oxygen (saturation >94%)
• Correct volume status and electrolytes.
• Check blood glucose; treat hypoglycemia and maintain blood glucose ≤180 mg/dL.
• Blood pressure (BP) check; Alteplase must be below 185/110 mmHg before use.
• Fibrinolytic therapy (Alteplase/rt-PA) in appropriate cases.

Ischemic Stroke- Fibrinolytic Therapy

• Alteplase (rt-PA) is the only FDA-approved agent for acute ischemic stroke. Administered within 3 hours (or up to 4.5 hours) after symptom onset.
• Timing is critical: Treatment should begin as soon as possible.
• Therapy benefit is time-dependent.

Ischemic Stroke- Fibrinolytic Therapy - Mechanism of Action

• activates plasminogen to plasmin, which degrades fibrin
• results in thrombus breakdown

Ischemic Stroke- Fibrinolytic Therapy - Administration

• Only after a brain imaging is completed
• Assess blood glucose levels
• Aim for door-to-needle time of 60 minutes. Dosing: 0.9 mg/kg (maximum 90 mg).
• First 10% as an IV bolus, rest infused over 1 hour

Inclusion and Exclusion Criteria for Alteplase (rt-PA)

• Inclusion:*

• Age 18 years or older.

• Clinical diagnosis of ischemic stroke, measurable neurological deficit.

• Onset time within 4.5 hrs of treatment.

• Exclusion:*

• Active internal bleeding

• Current anticoagulation therapy.

• LMWH within past 24 hours.

• NOAC within 48 hours.

• INR > 1.7.

• Platelets < 100 000/mm3.

• aPTT > 40 seconds.

• Blood glucose < 50 mg/dL (2.8 mmol/L)

• Previous stroke within 3 months

• History of subarachnoid or intracranial hemorrhage

• SBP > 185 mmHg or DBP > 110 mmHg at treatment time

Major Adverse Effects of Fibrinolytic Therapy (rt-PA)

• Bleeding, including ICH and systemic bleeding.
• Intracranial hemorrhage (ICH) may result in mental status changes and severe headaches.
• Angioedema.
• Systemic bleeding includes hematemesis, guaiac-positive stools, black tarry stools, hematoma formation, hematuria, gingival bleeding, and nosebleeds

Blood Pressure (BP) Recommendations for Ischemic Stroke (Alteplase-Eligible)

• Before treatment: If SBP > 185 or DBP > 110, administer labetalol (10-20 mg IV over 1-2 minutes, repeat every 10 minutes) or nicardipine infusion (5 mg/hour) to reduce BP to ≤185/110 mm Hg.
• During/After Treatment: Reduce SBP and DBP to <180/105:
  • If SBP > 180 or DBP > 105: labetalol (10–20 mg IV over 1–2 min followed by infusion 2-8 mg/min) or nicardipine 5 mg/hour.
  • If uncontrolled or DBP > 140, nitroprusside 0.3-0.5 mcg/kg/min IV.
• Measure BP and neurological assessments
• every 15 min, 2hr duration of alteplase IV, then every 30 min for 6hrs, then hourly to 24hrs

Blood Pressure (BP) Recommendations for Ischemic Stroke (Not Alteplase-Eligible)

• SBP ≤ 220, DBP < 120: Observe for 2-3 days in absence of comorbidities; labetalol (10–20 mg IV over 1-2 minutes) or nicardipine 5mg/hour for 2-3 days
• SBP ≥ 220 or DBP ≥120 or comorbid conditions: use labetalol for at least 10 -20 minutes, and repeat every 10 minutes.
• If BP not controlled or DBP ≥ 140: use nitroprusside at 0.3-0.5 mcg/kg/min.
• Goal reduce BP by 15% within 24 hours.

Ischemic Stroke- Management (general)

• Fever control: Identify and treat fever source.
• Cardiac monitoring: Monitor for 24 hours for atrial fibrillation.
• Immobile Stroke Patients: use Intermittent pneumatic compression (IPC).
• Enteral diet introduction: Start within 7 days of hospitalization.
• Seizure treatment: Treat according to patient characteristics.
• Rehabilitation: Well-organized rehabilitation program for stroke patients.

Surgical Management

• Mechanical thrombectomy: In selected patients, within 24 hours of symptom onset.
• Carotid endarterectomy (CEA): Removal of a thrombus from the carotid artery.

Antiplatelet Agents

• Aspirin: Administered within 24–48 hours post-onset and continued indefinitely.
• Glycoprotein IIb/IIIa receptor inhibitors (GPIIb/IIIa): Not recommended.
• Minor Stroke: Patients with minor stroke often benefit from dual antiplatelet therapy (aspirin and clopidogrel) for up to 90 days post-symptom onset. (Avoid ticagrelor or prasugrel)
• Non-rt-PA Eligible Patients: Initiate aspirin (160-325 mg initial dose and 50-100 mg maintenance dose) within 48 hours.

Stroke Outlines

• Stroke definition/CVA.
• Stroke etiology, pathophysiology, and risk factors.
• Stroke classification and clinical presentation.
• Ischemic stroke definition and diagnosis.
• Ischemic stroke complications.
• Ischemic stroke management.
• Ischemic stroke prevention.
• Acute hemorrhagic stroke definition and treatment.
• Outcome evaluation.

Ischemic Stroke- Prevention

• Primary prevention:* Treatment of individuals with no history of stroke.
• Reduce all modifiable risk factors: Diabetes, hypertension, hyperlipidemia,smoking, weight reduction.
• Medications like statins and antiplatelets in eligible patients.
• Educate patients about stroke warning signs.
• Secondary prevention:* Treatment of individuals with history of stroke or TIA.
• Reduce all modifiable risk factors, including diabetes, hypertension, smoking cessation, and body weight reduction.
• Statin (high-intensity) use

Ischemic Stroke- Atrial Fib Treatment Intervention (CHA2DS2-VASc)

• If total score = 0 in men or 1 in women →no treatment.
• If total score ≥ 1 in men or ≥ 2 in women→ Give oral anticoagulant.

Anticoagulant and Stroke Prevention (atrial fibrillation treatment)

• Current guidelines recommend newer oral anticoagulants (NOACs) over Warfarin.
• HAS-BLED score to evaluate bleeding risk for patients with high risk.

Treatment of Acute Hemorrhagic Stroke

• Supportive Measures:
  • No proven treatment for ICH.
  • Manage increased ICP, seizures, glucose, infections, bleed prevention.
  • Manage BP to <180/140 mm Hg.
  • Prevention of hemorrhage extension.
• Deep vein thrombosis prophylaxis: Use of intermittent compression stockings and use of UH or LMWH, once stabilized.
• Calcium antagonists: Oral nimodipine for aneurysmal SAH to prevent delayed cerebral ischemia within 96 hours.

Potential Medication for Hemorrhagic Stroke

• Recombinant factor VIIa (rFVIIa) phase III trial for hemorrhagic stroke treatment remains inconclusive regarding efficacy.

Treatment of Acute Hemorrhagic Stroke - Blood Pressure Management

• Elevated SBP: Lower SBP to ≤ 220 mmHg (using nicardipine or labetalol).
• Gradually reduce to target range of 140–160 mmHg once the patient is clinically stable.

Treatment of Acute Hemorrhagic Stroke - Control of Intracranial Pressure (ICP)

• In patients with GCS 3–8, place an ICP monitor.
• Maintain ICP < 20 mmHg and cerebral perfusion pressure (CPP) at 50–70 mm Hg.
• Treatment options include ventricular drainage and 20% mannitol (osmotic diuretic). Hypertonic saline (3%, 7.5%, or 23.5% NS) may be used.

Treatment of Acute Hemorrhagic Stroke - Anticoagulant-Related Hemorrhage

• Discontinue anticoagulation immediately for IC patients to reverse.
• Rapid anticoagulant reversal with appropriate measures (Factor PCC or Vitamin K).