Ischemic Stroke

Ischemic Stroke Overview

• Defined by the sudden loss of blood circulation to a brain region, resulting in neurological deficits.
• Typically caused by thrombotic or embolic occlusion of a cerebral artery.
• Ischemic strokes are more common than hemorrhagic strokes.

ICD-10-CM Classification

• Categorised as “cerebral infarction” under code I63.
• Includes occlusion and stenosis of cerebral and precerebral arteries.

World Health Organization Definition

• Stroke is described as a syndrome involving rapidly developing focal (or global) cerebral dysfunction.
• Symptoms last more than 24 hours or lead to death.
• Vascular origin is the primary cause.

TOAST Classification of Ischemic Stroke

Large artery atherosclerosis

• Thrombosis or embolism due to atherosclerotic changes in large arteries.

Cardioembolism

• Emboli originating in the heart, often associated with atrial fibrillation or cardiac anomalies.

Small vessel occlusion (lacunar stroke)

• Thrombosis in small penetrating arteries, commonly linked to hypertension or diabetes.

Stroke of other determined aetiology

• Rare causes such as arterial dissections, vasculitis, or hypercoagulable states.

Stroke of undetermined aetiology

• Cryptogenic strokes or those with multiple potential causes.

Non-modifiable Risk Factors

• Age: Increased risk with advancing age.
• Sex and Race: Variations in risk based on demographic factors.
• Genetic Factors: Family history of stroke or transient ischemic attack (TIA).
• Migraine with Aura: Particularly in younger women, significantly increases stroke risk.

Modifiable Risk Factors

• Hypertension: The most critical risk factor.
• Diabetes Mellitus: Promotes vascular disease and thrombosis.
• Cardiac Disease: Includes atrial fibrillation, heart failure, and valvular disorders.
• Hyperlipidemia: Increases atherosclerotic plaque formation.
• Lifestyle Factors: Smoking, excessive alcohol use, sedentary lifestyle, and obesity.
• Hormonal Factors: Oral contraceptives and postmenopausal hormone therapy.
• Sickle Cell Disease: Increases susceptibility to vascular stenosis and ischemia.

Atherosclerosis

• Driven by chronic inflammation and endothelial injury.
• Risk factors include oxidised low-density lipoprotein (LDL) cholesterol and smoking.

Genetic Mutations

• Mutations in F2, F5, and other genes (e.g., NOS3, ALOX5AP) increase susceptibility.
• Conditions like CADASIL and amyloid angiopathy are associated with genetic variants affecting vascular integrity.

Hyperhomocysteinemia

• Caused by mutations in the MTHFR gene or CBS deficiency.
• Elevated homocysteine levels are linked to vascular damage.

Mechanisms of Ischemic Stroke

General Pathogenesis

• Ischemic stroke results from events that limit or stop cerebral blood flow, such as:
  • Thrombotic embolism from extracranial or intracranial sources.
  • Thrombosis in situ within an affected artery.
  • Relative hypoperfusion due to systemic conditions like hypotension or heart failure.
• Neurons cease functioning as blood flow decreases, with irreversible neuronal damage occurring below 18 mL/100 g of tissue/min and cell death at rates below 10 mL/100 g of tissue/min.

Large Artery Occlusion

• Often results from embolisation of atherosclerotic debris from the carotid arteries or cardiac sources.
• Plaque ulceration and in situ thrombosis are additional contributors.
• Most commonly affects the middle cerebral artery (MCA) territory.

Lacunar Strokes

• Represent 13–20% of ischemic strokes, caused by occlusion of small penetrating arteries.
• Commonly associated with chronic hypertension, leading to lipohyalinosis, microatheroma, or fibrinoid necrosis.

Cardioembolic Strokes

• Account for up to 20% of ischemic strokes.
• Sources include valvular thrombi (e.g., mitral stenosis), mural thrombi, or atrial myxoma.
• Associated with conditions like atrial fibrillation and myocardial infarction.

Watershed Infarcts

• Occur in distal arterial territories due to embolic phenomena or severe hypoperfusion.
• Commonly found in border zones between major cerebral arteries.

Global Statistics

• Stroke is a leading cause of disability and a significant contributor to global mortality.
• Annually, 15 million people suffer from stroke worldwide, with 5 million deaths and 5 million left permanently disabled.

United States

• Stroke ranks as the fifth leading cause of death and a major cause of long-term disability in the U.S.
• Approximately 795,000 strokes occur annually, with 610,000 being first-time events and 185,000 recurrent strokes.
• Ischemic strokes account for 87% of all strokes.
• Financial burden: Between 2018 and 2019, stroke costs totaled approximately $56.5 billion in healthcare, medication, and lost productivity.

United Kingdom

• More than 100,000 strokes occur annually, leading to 38,000 deaths.
• Stroke is a significant cause of disability and mortality, with increasing prevalence among individuals aged over 55.

Race, Sex, and Age Disparities

Race and Ethnicity

• In the U.S., African Americans have nearly double the risk of first stroke compared to White populations, with the highest mortality rates observed among non-Hispanic Black and Pacific Islander adults.
• Hispanic populations have a lower overall incidence but experience lacunar strokes more frequently and at younger ages.
• Indigenous populations in high-income countries face a higher stroke incidence compared to non-Indigenous groups.

Sex Differences

• Men have a higher stroke incidence compared to women; however, women experience higher mortality rates following stroke.

Age-Related Trends

• Stroke predominantly affects individuals aged over 65, with 75% of cases occurring in this demographic.
• However, one-third of strokes occur in individuals under 65 years of age.
• Incidence in younger adults is reportedly increasing, particularly in low- and middle-income countries.

Regional and Socioeconomic Patterns

Global Patterns

• Stroke burden disproportionately affects low- and middle-income countries, accounting for 86% of deaths and 89% of disability-adjusted life-years (DALYs).
• Highest risks for stroke are observed in East Asia, Central Europe, and Eastern Europe, while the lowest risks are in eastern sub-Saharan Africa.

High-Income Countries

• Stroke incidence and mortality rates have declined over recent decades due to advances in prevention and care.
• Socioeconomic factors, such as lower educational attainment, are linked to higher stroke prevalence.

Stroke Subtypes in Ischemic Cases

• Ischemic strokes are classified by pathophysiology:
  • Extracranial atherosclerosis: 10%.
  • Intracranial atherosclerosis: 10%.
  • Cardioembolic strokes: 25%.
  • Lacunar infarctions (small vessel disease): 15%.
  • Cryptogenic strokes (indeterminate aetiology): 30%.
  • Other defined causes: 10%.

Focused Medical History

Key Risk Factors:

• Hypertension, diabetes mellitus, tobacco use, high cholesterol.
• History of coronary artery disease, atrial fibrillation, or coronary artery bypass surgery.

In Younger Patients

• History of recent trauma, coagulopathies, illicit drug use (e.g., cocaine), migraines, and oral contraceptive use.

Presentation of Symptoms

• Sudden onset of acute neurologic deficits or altered level of consciousness.
• Common stroke symptoms include:
  • Hemiparesis, hemisensory deficits, facial droop, dysarthria.
  • Monocular or binocular visual loss, visual field deficits, diplopia.
  • Ataxia, vertigo, aphasia, and sudden decrease in consciousness.
• Symptoms may present alone or in combination.

Establishing Time of Symptom Onset

• Critical for considering fibrinolytic therapy.
• Time of onset is defined as the last known normal time or when the patient was last without symptoms.
• Input from family, coworkers, or bystanders may assist, especially in "wake-up" strokes.

Neurological 

Motor Deficits

• Hemiparesis or monoparesis typically involving the face, arm, or leg.
• Quadriparesis is rare and suggests a more severe condition.
• Lacunar syndromes like pure motor hemiparesis or ataxic hemiparesis may occur with small vessel occlusion.

Language Impairments

• Dysphasia indicates dominant hemispheric ischemia.
• Dysarthria often accompanies facial weakness or brainstem dysfunction.

Ataxia

• Suggests cerebellar ischemia or its connections.
• More common in posterior circulation strokes, often affecting fine motor coordination and gait.

Visual Disturbances

• Amaurosis fugax may indicate cervical carotid stenosis.
• Homonymous hemianopia involves vision loss in the same visual field of both eyes.
• Diplopia can occur in posterior circulation ischemia.

Sensory Loss

• Unilateral sensory deficits may involve primary modalities or fine sensory processing.

Examination 

Objectives of the Physical Examination

• Detect extracranial causes of stroke symptoms.
• Differentiate stroke from stroke mimics.
• Document the degree of neurologic deficit for future comparison.
• Localise the lesion.
• Identify comorbidities and conditions influencing treatment, such as recent surgery, trauma, active bleeding, or infection.

General Physical Examination

Vital Signs

• May indicate clinical deterioration or assist in narrowing the differential diagnosis.
• Hypertension is common in stroke patients but often decreases spontaneously over time.

Head and Neck Examination

• Inspect for trauma, infection, or meningeal irritation.
• Auscultation for carotid bruits may reveal carotid disease.

Cardiac and Peripheral Vascular Examination

• Look for arrhythmias like atrial fibrillation, murmurs, or gallops, which are associated with embolic strokes.
• Unequal pulses or blood pressure differences in extremities may suggest aortic dissection.

Neurological Examination

Purpose

• Confirm the presence of a stroke syndrome.
• Establish a neurological baseline using tools like the NIH Stroke Scale (NIHSS).
• Assess stroke severity for prognosis and therapeutic decisions.

Key Components

Cranial Nerve Examination

• Assesses deficits that may help localise the lesion.

Motor and Sensory Function

• Detect hemiparesis, monoparesis, or sensory loss.

Cerebellar Function

• Evaluate for ataxia, which may indicate cerebellar involvement or posterior circulation ischemia.

Gait and Coordination

• Assess for abnormalities linked to stroke.

Language and Mental Status

• Identify expressive or receptive aphasia and cognitive impairments.

Consciousness

• Establish level of alertness and responsiveness.

National Institutes of Health Stroke Scale (NIHSS)

• A 42-point scale used to quantify stroke severity and localise the lesion.
• Focuses on six major areas:
  • Level of consciousness.
  • Visual function.
  • Motor function.
  • Sensory function and neglect.
  • Cerebellar function.
  • Language abilities.
• Scores correlate with outcomes:
  • <5: Minor stroke.
  • >10: High likelihood of proximal vessel occlusion.

Stroke Syndromes and Vascular Localisation

Middle Cerebral Artery (MCA)

• Symptoms: Contralateral hemiparesis (worse in arm and face), hemianopsia, aphasia (dominant hemisphere), neglect (non-dominant hemisphere).

Anterior Cerebral Artery (ACA)

• Symptoms: Leg weakness greater than arm, gait apraxia, impaired judgment, urinary incontinence.

Posterior Cerebral Artery (PCA)

• Symptoms: Visual disturbances (homonymous hemianopia), cortical blindness, memory impairment.

Vertebrobasilar Artery

• Symptoms: Cranial nerve deficits, ataxia, vertigo, dysarthria, and ipsilateral cranial nerve/contralateral motor deficits.

Lacunar Strokes

• Symptoms: Pure motor or sensory deficits without cortical signs (e.g., aphasia, neglect).

Additional Clinical Observations

Visual Disturbances

• Amaurosis fugax or transient monocular blindness may indicate carotid stenosis.
• Homonymous hemianopia suggests cortical involvement.

Dysarthria

• May accompany brainstem or cerebellar strokes.

Ataxia

• Points to posterior circulation or cerebellar involvement.

Vertigo

• Common in posterior circulation ischemia, often accompanied by nystagmus.

Nausea and Vomiting

• May reflect posterior circulation involvement or increased intracranial pressure.

Seizures

• More frequently associated with hemorrhagic stroke.

Primary and Essential Investigations

Non-Contrast CT (NCCT) Head

• Purpose: First-line imaging to differentiate ischemic from hemorrhagic stroke.
• Key Points:
  • Must be performed within 1 hour of arrival at the hospital.
  • Hypoattenuation and loss of gray-white matter differentiation are early ischemic signs.
  • Hyperattenuation indicates clot presence.
• Practical Considerations:
  • A normal CT does not exclude stroke, especially within the first few hours.
  • Requires immediate interpretation by trained personnel for critical treatment decisions.

Serum Glucose

• Purpose: Exclude hypoglycemia, a stroke mimic, and assess for hyperglycemia, which is associated with worse outcomes in ischemic stroke.
• Practical Considerations: Always check prior to administering thrombolytic therapy.

Electrocardiogram (ECG)

• Purpose: Identify arrhythmias like atrial fibrillation or ischemia that might suggest a cardioembolic source.
• Key Points:
  • Prolonged monitoring, including implantable loop recorders, may be needed in cryptogenic strokes.

Serum Electrolytes, Urea, and Creatinine

• Purpose: Evaluate for electrolyte imbalances and renal dysfunction, which can mimic stroke or impact treatment.

Prothrombin Time (PT), Partial Thromboplastin Time (PTT), and INR

• Purpose: Rule out coagulopathies and assess anticoagulation status.
• Practical Considerations: Do not delay thrombolysis unless anticoagulation history is known.

Full Blood Count (FBC)

• Purpose: Identify anemia or thrombocytopenia that could influence treatment options.

Cardiac Enzymes

• Purpose: Evaluate for myocardial infarction as a concurrent or contributing condition.

Advanced Imaging Techniques

MRI with Diffusion-Weighted Imaging (DWI)

• Purpose:
  • More sensitive than NCCT in detecting early ischemic changes and cerebral edema.
  • Provides greater anatomical detail and detects infarction earlier.
• Practical Considerations:
  • Contraindicated in patients with certain implants or pacemakers.
  • Limited availability in emergency settings compared to CT.

CT Angiography (CTA)

• Purpose:
  • Identify large vessel occlusions and assess suitability for thrombectomy.
• Practical Considerations:
  • Can be performed alongside NCCT without delaying thrombolysis.

Perfusion Imaging (CT or MRI)

• Purpose: Detect areas of salvageable brain tissue in delayed presentations or when considering thrombectomy (6–24 hours post-onset).
• Key Points:
  • Highlights mismatch between ischemic core and penumbra.

Carotid Ultrasound

• Purpose:
  • Identify critical stenosis or occlusion in patients considered for carotid intervention.
• Practical Considerations:
  • Often used for stroke patients evaluated for endarterectomy or stenting.

Echocardiography (TTE/TEE)

• Purpose:
  • Detect potential cardioaortic embolic sources like atrial thrombi, vegetations, or patent foramen ovale.

Laboratory Studies and Other Investigations

Toxicology Screen

• Purpose: Identify substance use (e.g., cocaine) mimicking stroke or causing ischemia/hemorrhage.

Cardiac Biomarkers

• Purpose: Assess for concurrent cardiac pathology.

Arterial Blood Gas (ABG):

• Purpose: Diagnose acid-base disturbances in suspected hypoxemic patients.

Coagulation Studies

• Purpose: Identify coagulopathies influencing stroke pathophysiology or treatment.

Practical Workflow and Tips

Immediate Actions

• Conduct NCCT within 1 hour of arrival and follow with CTA for thrombectomy candidates.
• Monitor glucose levels and assess coagulation before thrombolysis.

Communication

• Radiologist collaboration is crucial for timely imaging interpretation.
• Engage cardiology services for detailed cardiac evaluations in suspected embolic strokes.

Transient Ischemic Attack (TIA)

• Signs and Symptoms:
  • Sudden onset of focal neurological symptoms resolving within minutes to hours, usually within 24 hours.
  • Complete recovery is typical, with no residual deficits.
• Investigations:
  • Brain imaging (CT or MRI) may be normal or reveal evidence of previous infarcts.

Hypertensive Encephalopathy

• Signs and Symptoms:
  • Severe hypertension above baseline, accompanied by headache, confusion, visual changes, or reduced consciousness.
  • May present with signs of increased intracranial pressure.
• Investigations:
  • Brain imaging (CT or MRI) may show cerebral edema.

Intracerebral Hemorrhage

• Signs and Symptoms:
  • Presents with sudden headache, vomiting, reduced consciousness, and focal neurological deficits.
  • Increased intracranial pressure may be evident.
• Investigations:
  • Brain imaging (CT or MRI) demonstrates hyperattenuation consistent with hemorrhage.

Hypoglycemia

• Signs and Symptoms:
  • Often associated with diabetes and the use of insulin or hypoglycemic agents.
  • Symptoms include confusion, altered consciousness, or focal neurological deficits mimicking stroke.
• Investigations:
  • Low serum glucose levels during symptom onset confirm diagnosis.

Complicated Migraine

• Signs and Symptoms:
  • History of similar events with preceding aura and positive symptoms, such as visual or sensory disturbances.
  • Negative symptoms, such as weakness or numbness, are more typical of stroke.
• Investigations:
  • MRI excludes infarction.

Seizure and Postictal Deficits

• Signs and Symptoms:
  • History of seizures or witnessed convulsions followed by transient neurological deficits.
  • Wrong-way eye deviation (gaze away from the side of the lesion) may occur.
• Investigations:
  • Electroencephalogram confirms seizure activity.
  • MRI excludes infarction.

Functional Neurological Disorder

• Neurological symptoms inconsistent with vascular territories.
• May lack cranial nerve deficits or show multiple inconsistent signs.
• Psychological comorbidities like anxiety and depression are common.
• Investigations:
  • MRI is normal, with no evidence of infarction.

Brain Tumor

• Signs and Symptoms:
  • Gradual onset of neurological symptoms.
  • May present with a history of known malignancy or systemic cancer.
• Investigations:
  • CT or MRI shows space-occupying lesions.

Wernicke’s Encephalopathy

• Signs and Symptoms:
  • History of alcohol abuse or malnutrition.
  • Presents with confusion, ataxia, and ophthalmoplegia.
• Investigations:
  • Low blood thiamine levels.
  • Improvement with thiamine administration supports the diagnosis.

Ingestion of Toxic Substances

• Signs and Symptoms:
  • History of alcohol or drug use, with symptoms mimicking stroke.
• Investigations:
  • Positive toxicology screen for alcohol or drugs.

Stroke as an Emergency

• "Time is brain" underscores the need for rapid intervention to minimise neurological damage.
• Early reperfusion strategies, including intravenous thrombolysis and mechanical thrombectomy, improve outcomes when initiated within 4.5 hours of symptom onset.

Stabilisation

• Airway and Breathing:
  • Endotracheal intubation is recommended for patients with a Glasgow Coma Scale (GCS) score ≤8 or those unable to protect their airway.
  • Supplemental oxygen is indicated only when oxygen saturation drops below 93%; higher saturation targets (>96%) may increase mortality risk.
• Circulation:
  • Blood pressure management is critical but should only be actively reduced in hypertensive emergencies, such as hypertensive encephalopathy, cardiac failure, or aortic dissection.

Hospital Admission and Monitoring

• All suspected stroke patients should be admitted directly to a hyperacute stroke unit within 4 hours of hospital arrival to enable early thrombolysis and prevent complications.
• Monitor for elevated intracranial pressure (ICP), presenting as worsening consciousness, severe headache, or abrupt hypertension. Prompt imaging and neurosurgical referral are required for suspected ICP.

Reperfusion Therapy

Intravenous Thrombolysis

• Administer alteplase within 4.5 hours of symptom onset for eligible patients after excluding contraindications (e.g., intracranial hemorrhage or coagulopathy).
• Thrombolysis with tenecteplase is a potential alternative (off-label in the UK).
• Do not delay thrombolysis awaiting additional tests unless contraindications are suspected.

Mechanical Thrombectomy

• Perform within 6 hours of symptom onset for proximal anterior circulation occlusions.
• For wake-up strokes or those presenting 6–24 hours after symptom onset, thrombectomy is indicated if imaging demonstrates salvageable brain tissue, such as perfusion mismatch.
• Consider thrombectomy alone in patients ineligible for thrombolysis, such as those on anticoagulants or with recent surgery.

Secondary and Supportive Care

Antiplatelet Therapy

• Start aspirin within 24 hours of excluding intracerebral hemorrhage, delaying its use if thrombolysis was performed. A repeat CT scan is required to rule out post-thrombolysis bleeding.
• Dual antiplatelet therapy (aspirin and clopidogrel or ticagrelor) is recommended for 21–30 days in minor strokes (NIHSS ≤3), transitioning to single therapy for long-term prevention.

Blood Pressure Management

• For thrombolysis candidates, target a blood pressure of ≤185/110 mmHg before treatment.
• In non-thrombolysis patients, reduce blood pressure cautiously (>220/120 mmHg) to avoid abrupt declines.

Glycemic Control

• Maintain blood glucose between 4–11 mmol/L to prevent complications.

Statins

• Initiate high-intensity statin therapy 48 hours after stroke if atherosclerosis is confirmed.
• Adjust or continue existing statin regimens as needed.

Temperature Regulation

• Treat fever with antipyretics. Avoid therapeutic hypothermia as it does not reduce secondary brain damage.

Swallowing and Nutrition

• Assess swallowing before oral intake. Provide tube feeding for patients unable to swallow adequately and address malnutrition when present.

Neurosurgical Interventions

Decompressive Hemicraniectomy

• Consider for large middle cerebral artery infarcts meeting imaging and clinical criteria, such as decreased consciousness (GCS ≤8) or infarcts involving >50% of the MCA territory.
• Perform within 48 hours of symptom onset to reduce mortality and prevent herniation.

Preventing and Managing Complications

• Monitor for signs of ICP elevation, including altered consciousness and headache.
• Surgical options include ventriculostomy for cerebellar infarctions or decompressive craniectomy for malignant MCA syndrome.

• Treat with anticonvulsants such as levetiracetam or sodium valproate. Consult specialists for uncontrolled seizures or status epilepticus.

• Use intermittent pneumatic compression devices. Low-molecular-weight heparin is an option if contraindications to compression exist.

Rehabilitation and Long-Term Management

Early Mobilisation

• Begin light mobilisation (e.g., sitting or standing) 24–48 hours after symptom onset if clinically appropriate.
• Avoid high-intensity mobilisation in the first 24 hours.

Long-Term Anticoagulation

• Start anticoagulation in patients with atrial fibrillation or cardioembolic stroke once bleeding risks are addressed.

Overview 

• Prognosis is influenced by stroke type, severity, pre-existing comorbidities, treatment response, and post-stroke complications.
• Clinical tools like the National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and imaging studies are key for predicting outcomes.

Mortality and Survival Rates

• Approximately 19% of patients with ischemic stroke die within 30 days, and 77% survive at one year.
• Cardiogenic emboli have the highest one-month mortality among stroke subtypes.

Predictive Models

• NIHSS: High scores indicate greater early mortality and poorer outcomes.
• CT Findings: Early evidence of infarction correlates with worse outcomes and higher hemorrhagic transformation risk.
• Mortality Prediction Score:
  • Developed using data from Austrian stroke registries.
  • Factors include age, NIHSS score, pre-stroke functional status, diabetes, heart disease, and stroke subtype.
  • Scores ≥10 predict a 35% mortality risk within seven days.

Functional Outcomes

• Recovery varies:
  • Some patients achieve full or near-full recovery with timely and intensive rehabilitation.
  • Moderate to severe strokes often result in persistent motor, cognitive, or sensory impairments.
• Stroke remains a leading cause of long-term global disability.

Impact of Acute Interventions

• Intravenous Thrombolysis:
  • Alteplase improves functional outcomes when given within 4.5 hours of symptom onset.
  • While it increases intracerebral hemorrhage risk, long-term mortality or dependency rates are not significantly affected.
• Tenecteplase:
  • Non-inferior to alteplase for achieving functional independence (90-day mRS 0–1).
  • May be superior for moderate disability outcomes (90-day mRS 0–2).
  • Not advised for wake-up strokes without advanced imaging confirmation.

Common Complications

• Include aspiration pneumonia, depression, and deep vein thrombosis, which contribute to poorer outcomes.

Hyperglycemia

• Associated with larger infarct sizes and worse functional recovery.

Hemorrhagic Transformation:

• Occurs in 5% of ischemic strokes without fibrinolysis.
• Can range from small petechial hemorrhages to significant hematomas.

Rehabilitation and Recovery

• Physiotherapy improves outcomes, even when initiated late.
• Specialised stroke units with early, intensive rehabilitation enhance recovery and reduce disability.

Global Burden

• Stroke accounted for 6.5 million deaths globally in 2019 and remains a major cause of long-term disability.
• Early interventions like thrombolysis and specialised stroke care are proven to improve outcomes.

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