- Clinical science
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.
- Transient ischemic attack: temporary, focal cerebral ischemia that results in brief neurologic deficits lasting < 24 hours (usually < 1 hour)
- Minor stroke: a stroke without debilitating neurologic deficits
- Stroke: : an acute neurologic condition caused by an acute cerebrovascular event
- Ischemic stroke: cerebral infarction due to insufficient cerebral blood flow (hypoperfusion), which results in ischemia and neuronal injury
- Hemorrhagic stroke: cerebral infarction due to hemorrhage; either intracerebral hemorrhage or subarachnoid hemorrhage
- Intracerebral hemorrhage: bleeding within the brain parenchyma.
- Intraventricular hemorrhage: bleeding within the ventricles
- Subarachnoid hemorrhage: bleeding into the subarachnoid space
- Stroke is the fifth leading cause of death and the leading cause of disability in the US.
Sex: ♂ > ♀
- Subarachnoid hemorrhage is an exception: ♀ > ♂ (3:2)
- Age: ∼ ⅔ of stroke patients are ≥ 65 years
- Race and ethnicity: higher risk in African Americans, Native Americans, Alaska Natives, and Hispanics
Epidemiological data refers to the US, unless otherwise specified.
Large artery atherosclerosis: secondary to hypertension (∼ 20% of cases)
- Embolic stroke (∼ 20% of cases)
Small vessel occlusion (∼ 20% of cases)
- Lipohyalinotic thickening of the small vessels; → occlusion of small, penetrating arteries that originate directly from large vessels (e.g., middle cerebral artery, anterior cerebral artery); → lacunar stroke resulting in specific lacunar syndromes (see below)
- Primarily due to hypertension and diabetes mellitus
- Systemic hypoperfusion results in Watershed stroke (see below)
- Coagulopathies (e.g., polycythemia or due to hormonal contraceptive use or hormone replacement therapy during/after menopause)
- Vasculitis (e.g., giant cell arteritis)
- Dissection (e.g., due to trauma, fibromuscular dysplasia)
- Sickle cell disease
- aura with
- Family history of cardiovascular or cerebrovascular disease
- Genetic disorders (e.g., sickle cell disease)
Age is the most important nonmodifiable risk factor! Arterial hypertension is the most important modifiable risk factor!
- Hypertension (most common cause of spontaneous ICH)
- Cerebral amyloid angiopathy (most common cause of spontaneous ICH in the elderly)
- Ruptured arteriovenous malformations (most common cause of spontaneous ICH in children)
- Coagulation disorders (e.g., anticoagulant use)
- Vasculitis (e.g., giant cell arteritis)
- CNS infections (e.g., herpes simplex virus) and septic embolisms
- Neoplasms (e.g., meningioma)
- Stimulants (e.g., cocaine and amphetamines)
- Infarction (venous sinus thrombosis)
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
- Berry aneurysm: (80% of cases of nontraumatic SAH)
- Ruptured arteriovenous malformation (AVM) (10% of cases of nontraumatic SAH)
- Other causes: cortical thrombosis, angioma, neoplasm, infection
- 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:
|Anterior cerebral artery (ACA)|
|Posterior cerebral artery (PCA)|| |
|Extracranial arteries||Internal carotid artery|| |
|Common carotid artery|
|Pure motor stroke|| |
|Pure sensory stroke|| |
|Sensorimotor stroke|| || |
|Ataxic hemiparesis|| || |
|Dysarthria-clumsy hand syndrome|| || |
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).
- 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
- Putamenal stroke: contralateral hemiplegia, hemisensory loss and gaze palsy, ipsilateral deviation of the eyes, stupor, and coma
- Cerebellar stroke: cerebellar signs (e.g., ataxia, nystagmus, slurred speech); , headache, vomiting, neck stiffness, gaze palsy, and facial weakness. No hemiparesis.
- Thalamic stroke: contralateral hemiparesis and hemisensory loss, miotic and unreactive pupils, upgaze palsy with gaze deviation away from the side of the lesion, a phenomenon known as “wrong way eyes”
- Lobar stroke: clinical features depend on the affected lobe
- Pontine stroke: decreased level of consciousness or coma , quadriplegia, ocular bobbing, facial palsy, dysarthria. A common cause of .
- Clinical assessment and history
- 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
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!
- Noncontrast cranial CT (gold standard and most important initial imaging): detects acute hemorrhage but cannot reliably identify early ischemia
- Identifies ischemia earlier than CT (within 3–30 minutes after onset)
- Detects hyperacute hemorrhage
- Evaluates reversibility of ischemic injury
- Perfusion-weighted imaging (PWI): visualizes areas of decreased perfusion and allows quantification of perfusion parameters, e.g., mean transit time (MTT), cerebral blood flow (CBF) and cerebral blood volume (CBV)
- Perfusion-diffusion mismatch MRI: allows identification of the penumbra (or “tissue-at-risk”)
- 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
- Hyperacute: hypodense lesion
- Hyperdense lesion
- Hypodense perifocal edema
- Possibly midline shift
- T1: hypointense
- T2: hyperintense
- T1: hypointense
- T2: hyperintense
- Acute: hypointense
- 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
- Definitive diagnostic test for SAH (indicated if a CT scan is inconclusive or negative but clinical suspicion for SAH is high)
Patterns of necrosis in ischemic stroke
- 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
- Definition: hypoxia-induced selective destruction of individual nerve cells with sparing of surrounding tissue
- 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)
- 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|| |
|>15 days|| |
Initial supportive management of ischemic and hemorrhagic stroke
- Acute stabilization/resuscitation and intensive care monitoring
- Control elevated intracranial pressure and/or cerebral edema; monitor for signs of brain herniation
Maintain sufficient cerebral perfusion
- Antihypertensive treatment (e.g., IV labetalol, nicardipine, enalapril, or hydralazine)
- Ischemic stroke: permissive hypertension; ; treat severe hypertension (> 220/120 mm Hg)
Hemorrhagic stroke: maintain BP < 160 mm Hg
- > 180 mm Hg systolic (or > 130 mm Hg MAP) without elevated ICP → consider modest reduction to 160 mm Hg systolic (or 110 mm Hg MAP)
- > 180 mm Hg systolic (or > 130 mm Hg MAP) and elevated intracranial pressure (ICP) → monitor ICP, lower blood pressure cautiously (if needed )
- > 200 mm Hg systolic (or > 150 mm Hg mean arterial pressure, MAP) → lower to ∼ 140 mm Hg systolic
- Always treat hypotension.
- Seizures should be treated pharmacologically
- Cardiac monitoring (for at least 24 hours)
Nitrates should be avoided since they may increase the intracranial pressure!
- 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
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!
- Intravenous recombinant tissue plasminogen activator (rtPA) alteplase
- Intracranial and extracranial hemorrhage
- Inclusion criteria
- Onset of symptoms ≤ 3 hours (therapeutic window of thrombolytic therapy )
- Age ≥ 18 years
- 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
- Preexisting conditions
- 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
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.
- Indicated in all ischemic stroke patients
- Contraindicated for 24 hours after thrombolytic therapy
- Drug of choice: aspirin
- Prevent complications.
- Early rehabilitation (physiotherapy, occupational and speech therapy) and mobilization
- Reverse anticoagulation
- Craniotomy and clot evacuation
Patients with signs of brain herniation should be operated on immediately!
- 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
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.
- Eliminate risk factors (see “Etiology” above).
- Prevention of specific causes: e.g., carotid endarterectomy (see )
- Cardiac dysfunction (arrhythmias, myocardial infarction)
- Deep vein thrombosis and pulmonary embolism
- Urinary tract infections
- Post-stroke bone fractures
- (Cushing triad)
- Persistent neurologic deficits (hemiparesis, aphasia)
- In ischemic stroke:
- Hemorrhagic transformation may occur.
- In hemorrhagic stroke