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 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 non contrast head CT is the most important diagnostic procedure, serving primarily to confirm or rule
out intracranial haemorrhage. 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 haemorrhagic stroke involves supportive measures and neurosurgery.
Long-term management focuses on the elimination of risk factors.

Definition
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
Haemorrhagic stroke: cerebral infarction due to haemorrhage; either intracerebral haemorrhage or
subarachnoid haemorrhage
Intracerebral haemorrhage: bleeding within the brain parenchyma.
Intraventricular haemorrhage: bleeding within the ventricles
Subarachnoid haemorrhage: bleeding into the subarachnoid space.

Epidemiology
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

Ischemic stroke
Etiology
Large artery atherosclerosis: secondary to hypertension (∼ 20% of cases)
E.g., carotid artery stenosis
Embolic stroke (∼ 20% of cases)
Cardiac emboli
Atrial fibrillation (also see CHA2DS2-VASc score)
Myocardial aneurysms
Infectious emboli: bacterial endocarditis
Atheroemboli: internal carotid artery, aortic arch
Paradoxical embolism: in patients with right-to-left cardiac shunt (e.g., persistent foramen ovale
or ASD)
Small vessel occlusion (∼ 20% of cases)

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 - 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 Lacunar stroke below)
- Primarily due to hypertension and diabetes mellitus
Other causes
- Systemic hypoperfusion results in Watershed stroke (see border-zone infarct below)
- Cerebral venous sinus thrombosis
- 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
- Migraine with aura

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

Risk factors
Nonmodifiable
Age
Sex
Ethnicity
Family history of cardiovascular or cerebrovascular disease
Genetic disorders (e.g., sickle cell disease)
Modifiable
Arterial hypertension
Atherosclerosis
Hypercholesterolemia
Diabetes mellitus
Obesity and physical inactivity
Stress
High alcohol consumption
Tobacco use
Illicit drug use
Cardiovascular diseases
Disorders of coagulation
Hyperhomocysteinemia
Oral contraceptive use or postmenopausal hormone intake

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

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.

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Intracerebral hemorrhage (ICH)
- 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)
- Traumatic brain injury

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

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).

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Arteries Clinical features
Middle Contralateral sensory loss and paralysis in the arms, lower half of the face, and lower
cerebral artery limbs
(MCA) Gaze deviates towards side of infarction
(most Contralateral homonymous hemianopia without macular sparing
commonly Aphasia (left MCA territory; dominant hemisphere)
affected vessel Broca aphasia (lesion to inferior frontal gyrus, supplied by superior division of MCA)
overall) Wernicke aphasia (lesion to superior temporal gyrus, supplied by inferior division of
MCA)
Conduction aphasia (lesion to supramarginal gyrus, supplied by inferior division of
MCA)
Hemineglect (right MCA territory; nondominant hemisphere)

Anterior Contralateral paralysis in the lower limbs >> upper limbs

Minimal sensory loss in the lower limbs >> upper limbs
cerebral artery
Dysarthria
(ACA) Aphasia
Abulia (lack of motivation)
Limb apraxia
Urinary incontinence

Posterior Visual field defects: Contralateral homonymous hemianopia with macular sparing
Contralateral hemisensory loss: due to lateral thalamic involvement
cerebral artery
- Touch, pinprick, positional sense may be reduced
(PCA) Memory deficits
Vertigo, nausea
Left PCA territory: alexia without agraphia, anomic aphasia, visual agnosia
Right PCA territory: prosopagnosia
Thalamic syndrome
Penetrating Lacunar syndromes
arteries
Vertebasillar Vertebrobasilar insufficiency
- Ipsilateral cranial nerve deficits
arteries
- Vertigo, drop attacks, tinnitus, hiccups, dysarthria, dysphagia
- Visual deficits
- Gait ataxia
- Crossed paresthesias
- Crossed hemiplegia
Brainstem syndromes
- Wallenberg syndrome: lateral medullary syndrome (vertebral artery or posterior
inferior cerebral artery (PICA)
- Medial medullary syndrome: ipsilateral loss of function of the hypoglossal nerve
with contralateral hemiparesis
- Weber syndrome: ipsilateral loss of function of the oculomotor nerve with
contralateral hemiparesis
- Millard-Gubler syndrome (ventral pons syndrome): ipsilateral loss of function of
the facial and abducent nerves with contralateral hemiparesis

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 - Foville syndrome: facial nerve paralysis, internuclear ophthalmoplegia with
contralateral hemiparesis
Cerebellar syndromes
Locked-in syndrome: anarthria and paralysis of all voluntary muscles (except the
muscles for blinking and eye movement

Internal Ipsilateral amaurosis fugax

Numerous contralateral symptoms possible (e.g., hemiparesis, hemisensory loss,
carotid artery
homonymous hemianopsia)

Extracranial arteries

Common carotid artery Horner's syndrome

Paralysis of the hypoglossal nerve
Signs of middle cerebral artery infarction

Vertebral artery Wallenberg syndrome

Neck pain
Signs of posterior cerebral artery infarction (see carotid and vertebral artery
dissection)

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 Location Feature

syndromes
Pure motor stroke Most common type of lacunar stroke (> Contralateral hemiparesis of the face,
50%)
arm, and leg
Posterior limb or the angle of the internal
capsule
Often caused by occlusion of the
lenticulostriate artery
Pure sensory Thalamus, the posterior limb of the Contralateral numbness and
internal capsule, pontine paresthesia of the face,
stroke
tegmentum, or corona radiata arm, and leg
Sensorimotor Thalamocapsular area Hemiparesis and ipsilateral sensory
stroke impairment

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 Ataxic Corona radiata or the posterior limb of the Ipsilateral impaired coordination (e.g.,
ataxia, gait
hemiparesis internal capsule
instability) and weakness
Dysarthria-clumsy Base of the pons Dysarthria, dysphagia, contralateral
hand syndrome facial and hand
weakness
Hemiballismus Subthalamic nucleus 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

Frontal: lack of motivation, anosmia, Broca's aphasia

Temporal: mood changes, epilepsy, Wernicke's aphasia
Parietal: constructive apraxia, aphasia, neglect
Parasagittal cortex: sensorimotor paralysis of the lower limbs associated, in some cases, with bladder
dysfunction.

Others
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, phenomenon known as “wrong way eyes”.
Lobar stroke: clinical features depend on the affected lobe
Frontal lobe: contralateral weakness or paralysis of the leg with relative sparing of
the arm, gaze deviation to the same side of the lesion.
Parietal lobe: seizure, contralateral sensory loss
Occipital lobe: seizure, contralateral homonymous hemianopsia
Pontine stroke: decreased level of consciousness or coma , quadriplegia, ocular bobbing, facial palsy,
dysarthria. A common cause of locked-in syndrome.

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)

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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

1. Noncontrast cranial CT (gold standard and most important initial imaging): detects acute
haemorrhage but cannot reliably identify early ischemia.
2. MRI
- 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”)

CT findings

1. 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

2. 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

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Neurovascular studies

CT or MRI angiography (CTA, MRA) : identify the exact location of the defect
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)

Pathology
Brain tissue responds to ischemia in two major ways: pan-necrosis and selective neuronal necrosis.
The interplay of these mechanisms determines the
course of pathologic changes in stroke.

Pan-necrosis
Definition: Death of all cell types in a given tissue In the brain, this includes neurons, glial cells, and
vascular cells.
Occurrence: complete/permanent ischemia.
Histology: loss of tissue architecture, cystic lesions

Selective neuronal necrosis

Definition: hypoxia-induced selective destruction of individual nerve cells with sparing of
surrounding tissue
Occurrence:
- Hypoxic/ischemic damage of brain tissue with subsequent reperfusion (incomplete
ischemia), as a result of temporary cardiac arrest
- Epilepsy (hippocampal sclerosis)
Histology
- Glial cells and blood vessels remain viable; astroglial cells proliferate within the defect.
- Laminar or pseudolaminar configuration is possible
- Brightening (reduced dye affinity) in the damaged layers is macroscopically visible.
Ischemic injury: : Certain regions of the brain are more susceptible to ischemic injury as a result of
tissue-specific features (e.g., absence of heat shock proteins) rather than vascular territory.
- Pyramidal cells of hippocampus: damage causes anterograde amnesia
- Purkinje cells of cerebellum: damage causes intention tremor, nystagmus, and ataxia
- Pyramidal cells of neocortex: symptoms depend on affected brain region
Differential diagnoses
Seizures
Metabolic disorders (hyponatremia, hypoglycemia)
Migraine aura
Systemic infection
Brain tumor
Psychiatric conversion disorders
Peripheral vestibulopathy
Traumatic intracranial haemorrhage

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Treatment
Initial supportive management of ischemic and hemorrhagic stroke
Acute stabilization/resuscitation and intensive care monitoring
Fluid replacement
Maintain sufficient oxygen supply and consider intubation if the patient shows signs of
increased intracranial pressure (e.g., altered mental
state).
Maintain blood glucose levels within 140–180 mg/dL
Analgesia
Control elevated intracranial pressure and/or cerebral edema; monitor for signs of brain herniation.
Head elevation (30°)
Hyperventilation (if intubated)
Administer IV mannitol
Stool softeners
No glucocorticoids!
Severe cases require decompression surgery
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)
- Patients who do not undergo thrombolytic therapy: Reduce blood pressure by ∼ 15%
within the first 24 hours after stroke onset.
- Patients who undergo thrombolytic therapy: ≤ 185 mm Hg/≤ 100 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 mmHg 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!

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
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

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 Intracranial and extracranial hemorrhage
Angioedema
Inclusion criteria
Onset of symptoms ≤ 3 hours (therapeutic window of thrombolytic therapy )
Age ≥ 18 years
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
Intracranial bleeding
Active internal bleeding or bleeding diathesis
Hypertension > 185/110 mm Hg
Anticoagulation (prolonged PTT or INR > 1.7)
Low platelet count (< 100,000/mm3)
Hypoglycemia < 50 mg/dL or hyperglycemia > 400 mg/dL
Minor stroke or TIA

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
- Indicated in all ischemic stroke patients
- Contraindicated for 24 hours after thrombolytic therapy
- Drug of choice: aspirin

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

Treatment of hemorrhagic stroke

Intracerebral hemorrhage
- Reverse anticoagulation
- Craniotomy and clot evacuation
Indications
- Signs of brain herniation (e.g., Cushing triad)
- Brainstem compression
- Obstructive hydrocephalus
- Hemorrhage extension > 3 cm
- Patients with hemorrhage in the basal ganglia or the internal capsule should generally not
undergo surgical clot removal.

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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 VP shunt

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 recurrent stroke.
- Eliminate risk factors (see “Etiology” above).
- Antihypertensive treatment
- Antiplatelet drugs (e.g., aspirin or clopidogrel)
- Statins
- Anticoagulation in patients with AF
- Prevention of specific causes: e.g., carotid endarterectomy (see carotid artery stenosis)

Complications
Medical complications
Cardiac dysfunction (arrhythmias, myocardial infarction)
Aspiration pneumonia
Deep vein thrombosis and pulmonary embolism
Urinary tract infections
Post-stroke bone fractures
Depression

Neurologic complications
Elevated intracranial pressure and brain herniation (Cushing triad)
Seizures
Persistent neurologic deficits (hemiparesis, aphasia)
In ischemic stroke:
Hemorrhagic transformation may occur.
Vascular dementia
In hemorrhagic stroke
Recurrent hemorrhage
Intraventricular hemorrhage
Hydrocephalus
Vasospasms after SAH (typically occur 5–7 days after SAH) → may result in ischemic stroke
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

Prognosis
Hemorrhagic stroke has a worse prognosis than ischemic stroke.
Persistent neurologic deficits and disability are common in survivors.

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