• Clinical science

Stroke (Cerebrovascular accident)

Abstract

Stroke is an acute neurological condition due to a focal cerebrovascular event, which may either be vascular occlusion (ischemic stroke) or rupture (hemorrhagic stroke). Hemorrhagic stroke is further classified into intracerebral hemorrhage, if the bleeding occurs within the cerebral parenchyma, and subarachnoid hemorrhage, if the bleeding occurs in the subarachnoid space. Hypertension, coagulation disorders, and cardiac diseases are common causes of both ischemic and hemorrhagic stroke. Stroke is characterized by the sudden onset of neurologic deficits, as well as nonspecific symptoms (headache, nausea, altered mental status). Distinguishing between ischemic stroke and hemorrhagic stroke is not usually possible based on clinical features. Subarachnoid hemorrhage, on the other hand, has a distinct clinical presentation. A detailed evaluation of the focal neurological deficits may provide a clue as to the affected cerebral vessel or region. Hemiparesis, aphasia, and hemianopsia are common. A noncontrast head CT is the most important diagnostic procedure, serving primarily to confirm or rule out intracranial hemorrhage. Further neurovascular imaging may be required in order to decide on treatment options. If an occluded vessel is responsible for the stroke, recanalization should be attempted as quickly as possible to salvage the greatest possible amount of tissue. The management of hemorrhagic stroke involves supportive measures and neurosurgery. Long-term management focuses on the elimination of risk factors.

Definition

References:[1][2][3]

Epidemiology

  • Stroke is the fifth leading cause of death and the leading cause of disability in the US.
  • Sex: >
  • Age: ∼ ⅔ of stroke patients are ≥ 65 years
  • Race and ethnicity: higher risk in African Americans, Native Americans, Alaska Natives, and Hispanics

References:[4][5][6][7]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[8]

Ischemic stroke

Etiology

Arterial hypertension is the strongest single predisposing factor for the development of both ischemic and hemorrhagic stroke!

Risk factors

Age is the most important nonmodifiable risk factor! Arterial hypertension is the most important modifiable risk factor!

References:[9][10][11][12][6][13][14][15][16][17][18][19][20][21]

Hemorrhagic stroke

Hemorrhagic stroke is due to intracerebral hemorrhage or subarachnoid hemorrhage. Both forms of bleeding can be traumatic or nontraumatic (spontaneous). Traumatic forms are discussed separately in traumatic brain injury.

Intracerebral hemorrhage (ICH)

Subarachnoid hemorrhage (SAH)

  • Ruptured aneurysm, usually in the circle of Willis
    • Berry aneurysm: (80% of cases of nontraumatic SAH)
      • Multifactorial etiology
      • Round, saccular aneurysms located at major branches of large arteries
      • Highest risk of rupture
    • Mycotic aneurysm: low risk of bleeding
      • Cause: septic embolisms (mostly due to bacterial endocarditis)
      • Shape: mushroom-shaped
      • Site: small, peripheral segments of cerebral vessels
    • Fusiform aneurysm: low risk of bleeding
      • Cause: arteriosclerosis
      • Shape: spindle-shaped
      • Site: straight nonbranching segments of cerebral arteries
  • Ruptured arteriovenous malformation (AVM) (10% of cases of nontraumatic SAH)
  • Other causes: cortical thrombosis, angioma, neoplasm, infection
  • Traumatic brain injury

References:[9][22][23][6][16][24][25]

Clinical features

  • Symptoms depend on the location of the stroke (see the sections below)
  • Sudden onset of focal neurologic deficits and nonspecific symptoms (impaired consciousness, nausea, vomiting, headache, and, less commonly, seizures)
  • Transient ischemic attack (TIA): temporary, focal symptoms of ischemic stroke that last < 24 hours
  • Subarachnoid hemorrhage is the only cause of stroke with distinct symptoms:
    • Sudden-onset “worst headache of my life”
    • Rapidly worsening nausea, vomiting, and cardiovascular deterioration
    • Unconsciousness or coma
    • Neck stiffness
    • Pupils are not reactive to light
    • > ⅓ of patients have prodromal symptoms caused by “sentinel leaks” (e.g., less severe headache).

References:[26]

Clinical features by affected vessel

Arteries Clinical features

Middle cerebral artery (MCA) (most commonly affected vessel overall)

Anterior cerebral artery (ACA)
  • Contralateral paralysis in the lower limbs >> upper limbs
  • Minimal sensory loss in the lower limbs >> upper limbs
  • Dysarthria
  • Aphasia
  • Abulia (lack of motivation)
  • Limb apraxia
  • Urinary incontinence
Posterior cerebral artery (PCA)
Penetrating arteries
Vertebrobasilar
Extracranial arteries Internal carotid artery
Common carotid artery
Vertebral artery

References:[8][27][28][29][30][31][32][33][34]

Clinical features by affected region

Lacunar stroke

Lacunar strokes are noncortical infarcts and are characterized by the absence of cortical signs such as aphasia hemianopsia, agnosia, and apraxia.

Lacunar syndromes Location Feature
Pure motor stroke
  • Contralateral hemiparesis of the face, arm, and leg
Pure sensory stroke
  • Contralateral numbness and paresthesia of the face, arm, and leg
Sensorimotor stroke
  • Thalamocapsular area
  • Hemiparesis and ipsilateral sensory impairment
Ataxic hemiparesis
  • Ipsilateral impaired coordination (e.g., ataxia, gait instability) and weakness
Dysarthria-clumsy hand syndrome

  • Dysarthria, dysphagia, contralateral facial and hand weakness
Hemiballismus
  • Contralateral involuntary large and fierce flinging movements of the arm or leg

Watershed infarct

A watershed infarct is a border-zone infarct; in the region between the territory of two major arteries that supply the brain (i.e. the most distal tissue between the anterior, middle, and posterior cerebral artery territories).

  • Clinical features:
    • Signs of systemic hypoperfusion: tachycardia, low blood pressure, palor, sweating
    • Diffuse neurologic deterioration
    • Bilateral symptoms: visual loss (cortical blindness), proximal limb weakness with sparing of the face, hands, and feet

Neocortical syndromes

Others

References:[28][14][33][35][36][37][38][39][40][41]

Diagnostics

Initial evaluation

  • Clinical assessment and history
    • Identify risk factors for ischemic or hemorrhagic stroke.
    • Signs of the affected vessel or region
    • Signs of large vessel occlusion (e.g., carotid bruit)
    • Onset of symptoms → important for further treatment decisions
  • Rule out other causes of neurologic deficits (e.g., blood glucose level and oxygen saturation)
  • Rule out atrial fibrilliation via ECG and myocardial ischemia (e.g., ↓ left ventricular function) ↑ catecholamines and autonomic brain stimulation may lead to a myocardial infarction.
  • Laboratory studies
    • Complete blood count
    • Coagulation parameters (e.g., INR, APTT)
    • Electrolytes
    • Serum troponin in all patients (predicts neurological complications and outcome)


TIA is primarily a clinical diagnosis. However, patients with suspected TIA are at an increased risk of ischemic stroke and therefore also require immediate diagnostic work-up, including neuroimaging!

Neuroimaging

  • Noncontrast cranial CT (gold standard and most important initial imaging): detects acute hemorrhage but cannot reliably identify early ischemia
  • MRI
    • Identifies ischemia earlier than CT (within 3–30 minutes after onset)
    • Detects hyperacute hemorrhage
    • Evaluates reversibility of ischemic injury

CT findings

  • Ischemia
    • Acute
      • Hyperdense occluded vessels (e.g., hyperdense MCA sign )
      • Parenchymal hypodensity
      • Effacement of the sulci and loss of corticomedullary differentiation
    • After 12–24 hours: hypodense
    • After days: hyperdense
  • Hemorrhage
    • Hyperacute: hypodense lesion
    • Acute
      • Hyperdense lesion
      • Hypodense perifocal edema
      • Possibly midline shift

MRI findings

  • Ischemia
    • T1: hypointense
    • T2: hyperintense
  • Hemorrhage
    • Hyperacute
      • T1: hypointense
      • T2: hyperintense
    • Acute: hypointense

Neurovascular studies

  • CT or MRI angiography (CTA, MRA) : identify the exact location of the defect
  • Digital subtraction angiography (DSA): alternative to CTA/MRA, but invasive
  • Transcranial doppler sonography: less accurate than CTA and DSA

Lumbar puncture

  • Definitive diagnostic test for SAH (indicated if a CT scan is inconclusive or negative but clinical suspicion for SAH is high)
  • Findings
    • Yellowish (xanthochromia) or red discoloration
    • ↑ or ↔ opening pressure
    • Glucose normal
    • ↑↑ RBCs
    • WBCs
    • ↑ Protein (gamma globulin)


References:[23][42][13][19][21][43]

Pathology

Patterns of necrosis in ischemic stroke

Depending on the severity of ischemia, brain tissue responds to ischemia in two major ways: pan-necrosis and selective neuronal necrosis.

Pan-necrosis

  • Definition: the death of all cell types in a given region of the brain, including neurons, glial cells, and vascular cells.
  • Mechanism: permanent ischemia
  • Histology: loss of tissue architecture and cystic lesions

Selective neuronal necrosis

  • Definition: hypoxia-induced selective destruction of individual nerve cells with sparing of surrounding tissue
  • Mechanism
    • Transient ischemia with subsequent reperfusion (e.g., resuscitation following cardiac arrest)
    • Increased metabolic demand and neurotoxicity due to the release of excitatory neurotransmitters (e.g., status epilepticus)
    • Certain neurons are more susceptible to ischemic injury as a result of cell-specific features (e.g., higher metabolic demand, absence of heat shock proteins)
      • Pyramidal cells of the hippocampus: damage causes anterograde amnesia
      • Purkinje cells of the cerebellum: damage causes intention tremor, nystagmus, and ataxia
      • Pyramidal cells of neocortex: symptoms depend on the affected brain region
  • Histology: neuronal necrosis with viable glial cells, which can proliferate resulting in a laminar or pseudolaminar tissue architecture

Changes in the infarcted region

Time from start of ischemia Histologic features
12–24 hours
  • Red neurons (eosinophilic cytoplasm + pyknotic nucleus)
1–3 days
3–5 days
5–15 days
>15 days
  • Glial scarring

Differential diagnoses

References:[13][44]

The differential diagnoses listed here are not exhaustive.

Treatment

Initial supportive management of ischemic and hemorrhagic stroke

Nitrates should be avoided since they may increase the intracranial pressure!

Additional measures

  • For ischemic stroke: Administer antipyretics (continuously, if needed) if body temperature rises above 38°C (100.4°F).
  • Experimental: mild hypothermia (33°C/91.4°F)
  • The use of a transnasal tube/nasogastric tube for providing nutrition should be considered.
  • Early treatment of infections with antibiotics, but prophylaxis is not generally recommended

References:[45][46][13][21][47][48][49][50]

Treatment of Ischemic stroke

Reperfusion therapy

Reperfusion therapy should not be delayed – time is everything! However, intracranial hemorrhage is a contraindication for reperfusion therapy and must always be ruled out first!

IV thrombolytic therapy

  • Intravenous recombinant tissue plasminogen activator (rtPA) alteplase
  • Complications
    • Intracranial and extracranial hemorrhage
    • Angioedema
  • Inclusion criteria
  • Exclusion criteria
    • Preexisting conditions
      • Previous intracranial hemorrhage
      • Head trauma or stroke (within the past 3 months)
      • Recent intracranial or intraspinal surgery
      • Arterial puncture at noncompressible site (within the past 7 days)
      • Intracranial neoplasm, arteriovenous malformation, or aneurysm
    • Current conditions

Intra-arterial thrombolysis

  • Indicated in patients who are not eligible for IV thrombolytic therapy
  • Procedure: intra-arterial administration of tPA close to the vessel occlusion within 6 hours of symptom onset

Mechanical thrombectomy

  • Indicated in patients with proximal large artery occlusion in the anterior cerebral circulation (usually in addition to IV thrombolytic therapy)
    • Rescue thrombectomy may also be considered if IV thrombolysis is ineffective.

Antiplatelet therapy

Further management

  • Prevent post-stroke complications.
  • Early rehabilitation (physiotherapy, occupational and speech therapy) and mobilization

References:[10][11][12][13][21][51][52][53]

Treatment of hemorrhagic stroke

Intracerebral hemorrhage

Patients with signs of brain herniation should be operated on immediately!

Subarachnoid hemorrhage

  • Reverse anticoagulation
  • Prevent vasospasm; (can cause ischemic stroke) with IV calcium channel blocker (i.e., nimodipine)
  • Neurosurgery (definitive treatment): surgical clipping or endovascular coiling should be performed early to prevent rebleeding
  • If hydrocephalus is present: ventricular drain, serial LPs, or permanent ventriculoperitoneal shunt

References:[8][45][26][54][48][49]

Prevention of ischemic stroke

All patients with a history of ischemic stroke or TIA require secondary prophylaxis, which should be initiated immediately (within one day of the ischemic event) to reduce the risk of reccurent stroke.

References:[11][15][44]

Complications

Medical complications

Neurologic complications

References:[10][12][55][56]

Prognosis