Ischemic Stroke

An ischemic stroke (also known as cerebrovascular accident) is an acute neurologic injury that occurs as a result of brain ischemia; this condition may be due to cerebral blood vessel occlusion by thrombosis or embolism, or rarely due to systemic hypoperfusion. The clinical presentation includes neurologic symptoms with varying degrees of motor and sensory loss corresponding to the area of the brain that is affected and the extent of tissue damage. Diagnosis is made by physical examination and imaging. Management is ideally with thrombolytic therapy to restore blood flow, depending on the time frame and clinical situation. Long-term rehabilitation with physical, occupational, and speech therapies is important after the acute event.

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Overview

Definition

An ischemic stroke is an acute neurologic injury that occurs as a result of brain ischemia; this condition may be due to cerebral blood vessel occlusion by thrombosis or embolism or, rarely, due to systemic hypoperfusion.

Epidemiology

  • Incidence: 800,000 cases per year in the US
  • 2nd leading cause of death worldwide
  • 2nd most common cause of disability in adults
  • Prevalence increases with age.
  • Approximately 80%–85% of all strokes are ischemic (15%–20% are hemorrhagic).
  • Of the ischemic strokes, approximately 80% are thrombotic (20% are embolic).
  • The most common embolic cause is atrial fibrillation with thromboembolism.

Etiology/classification

Thrombotic stroke:

  • Large-vessel occlusion: middle cerebral artery (MCA), posterior cerebral artery, anterior cerebral artery
    • Causes:
      • Atherosclerosis (most common cause) → large-vessel thrombosis due to a clot on an established plaque
      • Arteritis/vasculitis
      • Arterial dissection
      • Moyamoya disease (spontaneous occlusion of the arteries around the circle of Willis (rare))
    • Most common locations:
      • Bifurcation of the common carotid artery
      • MCA
      • Intracranial vertebral arteries proximal to the middle basilar artery
      • Origin of the vertebral arteries
    • Less common locations:
      • Origin of the common carotid artery
      • Posterior cerebral artery
      • Origin of the major branches of the vertebral basilar arteries
      • Origin of the branches of the anterior, middle, and posterior cerebral arteries
  • Small vessel occlusion = lacunar infarcts:
    • Causes:
      • Lipohyalinosis due to hypertension
      • Atherosclerosis at the origin of the small vessel or large parent artery
    • Least likely to have embolic occlusion
    • Location:
      • Small penetrating arteries that arise from the distal vertebral artery, basilar artery, stem of the MCA, or the circle of Willis
      • Most often in the deep penetrating vessels that reach the white matter and deep gray matter in the thalamus, basal ganglia, or pons

Embolic stroke:

  • Cardiac sources:
    • Left atrial thrombi/atrial fibrillation (most frequent isolated cause)
    • Left ventricular thrombus
    • Atrial fibrillation
    • Recent MI (< 1 month)
    • Rheumatic mitral or aortic valve disease
    • Bioprosthetic and mechanical heart valve emboli
    • Carotid atherosclerosis 
    • Bacterial endocarditis (septic emboli)
    • Patent foramen ovale
    • Arterial dissection (rupture of an arterial wall followed by thrombus formation and embolization)
  • Atherosclerosis may also be embolic (in addition to thrombotic).
    • Iatrogenic embolization after an angiogram or other vascular procedures
    • Emboli released during carotid artery surgery

Systemic hypoperfusion:

  • Usually global/bilateral and does not affect isolated regions
  • Watershed regions between major cerebral arteries are the most vulnerable.
  • Causes:
    • Heart failure with severely reduced cardiac output
    • Cardiac arrest or serious arrhythmia
Ischemic stroke in the brain

How an ischemic stroke can occur in the brain:
If a blood clot breaks away from plaque buildup in the carotid (neck) artery, it can travel to and lodge in an artery in the brain. The clot can block blood flow to a part of the brain, causing brain tissue death.

Image: “The illustration shows how an ischemic stroke can occur in the brain” by National Heart Lung and Blood Institute (NIH). License: Public Domain

Risk factors

  • Hypertension (most important)
  • Diabetes mellitus
  • Smoking
  • Hyperlipidemia
  • Carotid stenosis
  • Previous history of stroke or transient ischemic attack (TIA)
  • Heart disease:
    • Atrial fibrillation
    • Valvular heart disease
    • Cardiomyopathy
  • Older age
  • Migraine with aura
  • Hypercoagulable states:
    • Antiphospholipid syndrome
    • Cancer/malignancy
    • Pregnancy
    • Oral contraceptive use (especially in women > 35 years who smoke)
  • Genetic conditions: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
  • Blood disorders:
    • Sickle cell disease
    • Protein C or protein S deficiency (usually congenital; can also be acquired)
    • Factor V Leiden (resistance to activated protein C)
    • Essential thrombocytosis
    • Polycythemia vera

Pathophysiology

A complete reduction in cerebral blood flow results in the death of brain tissue within 4–10 minutes:

  1. Occlusion of intracranial artery
  2. Reduction in blood flow to the region supplied by the vessel
  3. Cerebral tissue starts to undergo ischemia as neurons are deprived of glucose and oxygen → failure of mitochondria to produce ATP
  4. Membrane ion pumps stop functioning due to lack of ATP, and neurons depolarize → intracellular calcium increases and glutamate is released from the presynaptic terminals
  5. Excess extracellular glutamate induces greater uptake of calcium by neurons → neurotoxicity
  6. Free radicals are produced and accumulate within neurons → catalytic destruction of membranes
  7. Infarction or necrosis of brain tissue will occur if blood flow is not restored within a few minutes.
  8. An area of ischemic penumbra is produced around the area of infarction, where injury and corresponding neurological dysfunction are still reversible.
  9. Restoration of blood flow can induce the formation of more free radicals and reperfusion injury.
  10. Clinical neurological symptoms become apparent.

Clinical Presentation

History

  • The affected individual may or may not recall the time of onset of neurological symptoms.
  • Family members or caregivers may notice a sudden onset of a focal neurological deficit and call for transport to the ED.
  • Important to establish:
    • Amount of time passed since symptom onset (the last time seen as “normal”):
      • If the individual woke up with neurologic symptoms, the last time point considered “normal” is the night before.
      • Treatment decisions for reperfusion therapy are based on the time the affected individual was last seen without stroke symptoms.
    • Precise account of the event
  • Cardiovascular disease and other risk factors
  • Past episodes of TIAs
  • Medications

Physical examination

  • Neurological exam findings represent ischemia in different vascular territories:
    • Anterior cerebral artery:
      • Contralateral hemiparesis and sensory deficit
      • Lower extremity weakness and sensory loss
      • Limb apraxia
      • Incontinence
    • MCA:
      • Contralateral hemiparesis and sensory deficits
      • The face and upper limb are more profoundly affected than the leg.
      • Contralateral visual field reduction/hemianopsia
      • Aphasia: inability to understand and utilize language (dominant hemisphere)
      • Ataxic hemiparesis and dysarthria (also seen with lacunar stroke)
      • Hemianopsia
    • Posterior cerebral artery:
      • Contralateral homonymous hemianopia
      • Sensory loss
    • Posterior inferior cerebellar artery (PICA) = Wallenberg’s syndrome
      • Dysphonia (difficulty in phonating speech) and dysphagia (from cranial nerves IX and X being affected)
      • Ipsilateral ataxia with a tendency to fall to the affected side (inferior cerebellar hemisphere, spinocerebellar fibers, and cerebellar peduncle)
      • Horner syndrome: miosis, ptosis, and anhidrosis (sympathetic fibers)
      • Ipsilateral pain and numbness on the face (loss of facial sensation)
      • Contralateral numbness on the body
      • Dysarthria (difficulty in articulating speech)
      • Vertigo with nystagmus
      • Nausea and vomiting associated with vertigo; sometimes intractable hiccups
    • Small-vessel infarcts (lacunar infarcts): pure motor or sensory strokes
      • Pure motor hemiplegia: contralateral pons or internal capsule
      • Pure sensory stroke: lacunar infarct in the contralateral thalamus
  • Cardiovascular examination:
    • Cardiac arrhythmia (e.g., atrial fibrillation) 
    • Cardiac murmurs
    • Carotid bruits 
  • Ophthalmologic examination: fundoscopic signs of hypertensive or diabetic retinopathy

Diagnosis

Diagnosis is made with a suggestive history and clinical examination findings and confirmed by neuroimaging.

Standardized neurologic testing with the NIH stroke scale (NIHSS)

  • 0–42 points, > 25 is a severe stroke
  •  Note the time interval when the test is performed:
    • Baseline
    • 2 hours post-treatment
    • 24 hours post-onset of symptoms
    • 7–10 days
  • Administer in the order listed and record the performance in each category:
    • Level of consciousness
    • Best gaze-testing of horizontal eye movements
    • Visual fields
    • Facial palsy
    • Motor evaluation in arms and legs
    • Limb ataxia
    • Sensory exam
    • Evaluation of language comprehension
    • Evaluation of dysarthria

Labs

  • CBC including platelets
  • Urinalysis
  • Chemistries: electrolytes, glucose, BUN, and creatinine
  • Serum lipid profile: provides a baseline, but may not be accurate in acute emergencies
  • PT and PTT
  • Cardiac enzymes
  • Direct factor Xa activity assay, if the individual is taking direct thrombin inhibitor or direct factor Xa inhibitor and is a candidate for thrombolytic therapy

Other tests

  • Chest X-ray
  • ECG

Neuroimaging

  • Noncontrast head CT scan:
    • Only for differentiation between ischemic and hemorrhagic strokes
    • Acute ischemic zones are not visualized (can be mistaken for a normal scan).
    • Preferred emergency image modality
  • MRI brain:
    • Allows visualization of acute ischemia and ischemic penumbra = greater sensitivity
    • Greater resolution but longer time for imaging
    • Less availability
Ct scan of patient with middle cerebral artery stroke

Computed tomogram of an individual with middle cerebral artery stroke illustrating hypodense areas within the temporal and frontal lobes

Image: “CT scan of a patient with middle cerebral artery stroke” by 0475ramosk. License: CC BY-SA 4.0

Management

The goal of stroke management is to ensure prompt intervention and optimal outcomes. If possible, restoration of adequate blood flow to the injured regions and saving the ischemic penumbra from permanent injury should be attempted.

Initial management

  • Assess airway, breathing, and circulation (ABC).
  • Treat hypoglycemia or hyperglycemia accordingly (may masquerade as stroke).
  • IV fluids
  • Assess for reperfusion therapy: ideally administered within 60 minutes of arrival to the ED
  • Criteria for thrombolysis with the recombinant tissue plasminogen activator (tPA) alteplase or other agents:
    • Diagnosis of ischemic stroke causing neurologic deficits (and not improving)
    • < 4.5 hours after the onset of symptoms
    • ≥ 18 years of age
    • Absolute contraindications to thrombolytic therapy:
      • Intracranial hemorrhage on CT
      • Clinical presentation suggestive of subarachnoid hemorrhage
      • Neurosurgery, head trauma, or stroke in the previous 3 months
      • Uncontrolled hypertension (systolic blood pressure > 185 mm Hg or diastolic blood pressure > 110 mm Hg)
      • History of intracranial hemorrhage
      • Known intracranial arteriovenous malformation, neoplasm, or intracranial aneurysm
      • Active internal bleeding
      • Suspected or confirmed endocarditis
      • Known bleeding diathesis with platelet count < 100,000/μL
      • Elevated PTT with heparin administered in the last 48 hours or with the use of oral anticoagulants
      • Glucose < 50 mg/dL
    • Relative contraindications:
      • Recent GI or urinary tract bleeding (past 21 days)
      • Minor or rapidly improving stroke symptoms
      • Major surgery or serious nonhead trauma in the past 14 days
      • Seizure at stroke onset
      • Recent arterial puncture at a noncompressible site
      • Recent lumbar puncture
      • Post-MI pericarditis
      • Pregnancy
    • Other additional cautions:
      • Age > 80 years
      • History of prior stroke and diabetes
      • Use of any active anticoagulants (even with INR < 1.7)
      • NIHSS score > 25 (severe stroke)
      • CT with multilobar infarction (hypodensity > ⅓ of a cerebral hemisphere)
  • Continuous blood pressure monitoring:
    • < 180/105 mm Hg for the 1st 24 hours
    • If necessary, reduction of blood pressure with IV labetalol or other agents
  • Endovascular therapy:
    • Mechanical embolectomy or angioplasty using catheters
    • Indicated in occlusion of larger vessels (e.g., MCA) regardless of previous tPA administration
    • Indications for procedure initiation:
      • Must be within 6 hours of symptom onset
      • High baseline level of function prior to the stroke
      • NIHSS > 6 and minimal tissue damage on CT
  • Antithrombotic therapy if reperfusion is not feasible: Aspirin or other antiplatelet agents are given within 24–48 hours after symptom onset.
  • Compression socks to prevent deep vein thrombosis (DVT) and pulmonary embolism 
  • Urgent neurologic consultation
  • Neurosurgical consultation if evidence of brain edema or herniation

Rehabilitation

  • PT to improve neurologic function and reduce the risk of contractures
  • Occupational therapy:
    • Improves the quality of life
    • May need splinting of hands to prevent contractures
  • Swallowing assessment to prevent aspiration
  • Speech therapy
  • Careful attention to prevent complications due to immobility:
    • Pneumonia
    • Pressure ulcers
    • Limb contractures
  • Careful assessment of the ability to drive safely
  • Family and patient education:
    • Continuation of preventive measures at home
    • The FAST mnemonic is helpful for lay individuals to identify recurrence:
      • Facial droop
      • Arm weakness
      • Speech abnormality
      • Time

Prevention of recurrence

  • Lifestyle changes:
    • Healthy diet (e.g., Mediterranean diet)
    • Exercise as tolerated; weight loss if obese
    • Smoking cessation counseling if applicable
  • Risk-factor management with improved control of:
    • Diabetes
    • Hypertension
    • Hyperlipidemia
  • Medications:
    • Dual antiplatelet therapy unless contraindicated
      • Aspirin
      • Clopidogrel or extended-release dipyridamole
    • Statins (e.g., atorvastatin) in clinically important atherosclerotic disease
  • Treatment of underlying causes (e.g., atrial fibrillation) and anticoagulation as indicated

Complications and prognosis

Complications:

  • Cerebral edema:
    • Accumulation of water in the cerebral parenchyma if ischemic injury goes without management for the 1st few days
    • May lead to obstructing hydrocephalus or brain herniation
  • Adverse reactions to tPA thrombolysis:
    • Bleeding complications
    • Decline in neurologic status

Prognosis depends on these predictors of outcomes:

  • Stroke severity/extent of infarction
  • Age
  • Time elapsed from symptom onset to diagnosis and management
  • Length and intensity of therapy
  • Level of functioning before the event

Differential Diagnosis

  • TIA: a temporary episode of neurologic dysfunction caused by ischemia without evidence of infarction that resolves completely when blood supply is restored. No time limit is defined as was used previously. Causes may be small clots or thromboemboli imposed on blood vessels compromised by atherosclerosis, inflammation, or amyloid, or due to inadequate cerebral blood flow due to vasoconstriction or severe hypotension. Clinical presentation is with transient neurologic deficits that resolve spontaneously. Management includes risk-factor reduction to reduce the risk of a future stroke.
  • Hemorrhagic stroke: a stroke with resulting neurologic dysfunction caused by rupture and bleeding of an intracranial vessel. Hemorrhagic stroke is subdivided into intracerebral hemorrhage and subarachnoid (intracranial) hemorrhage. Clinically, hemorrhages are indistinguishable from ischemic stroke and require imaging for definitive diagnosis. Management may include mechanical ventilation, blood pressure control, reversal of anticoagulation, and risk-factor reduction for subsequent strokes.
  • Migraine: a common primary headache disorder characterized by episodic, moderate-to-severe headaches that may be associated with increased sensitivity to light and sound, and nausea and/or vomiting. Migraines may present as a “stroke mimic” with vasoconstriction, causing ischemia and neurologic deficits similar to those seen in an ischemic stroke, including hemiplegia. Diagnosis is by clinical history, physical exam, and imaging. Management includes medications to treat migraines and by avoiding triggers.
  • Intracranial tumor: can be a primary neoplasm derived from intracranial tissues (astrocytoma, oligodendroglioma, meningioma) or a metastatic process from other malignancies such as lung or breast cancer. As the mass grows, neurological presentations similar to those seen in ischemic stroke may develop. Diagnosis is by imaging, and management includes addressing the underlying cause.
  • Brain abscess: a life-threatening condition that involves the collection of pus in the brain parenchyma due to an infection or as a complication of trauma or surgery. The most common presentations include headache, fever with chills, seizures, and neurological deficits. Diagnosis is by MRI imaging and/or CT-guided aspiration of the contents for culture. Management requires surgical drainage and antibiotics.

References

  1. Hui, C., Tadi, P., Patti, L. (2021). Ischemic stroke. StatPearls. Retrieved August 4, 2021, from http://www.ncbi.nlm.nih.gov/books/NBK499997/ 
  2. Powers, W.J., et al. (2019). Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 50, e344–e418. https://doi.org/10.1161/STR.0000000000000211 
  3. Oliveira-Filho, J., Mullen, M.T. (2021). Initial assessment and management of acute stroke. UpToDate. Retrieved August 1, 2021, from https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke
  4. Kasner, S. (2021). Stroke and other cerebrovascular diseases. DeckerMed Medicine. Retrieved July 31, 2021. doi:10.2310/PSYCH.1027
  5. Edwardson, M.A. (2021). Overview of ischemic stroke prognosis in adults. UpToDate. Retrieved August 5, 2021, from https://www.uptodate.com/contents/overview-of-ischemic-stroke-prognosis-in-adults

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