Ischemic stroke is an acute neurological condition caused by impaired cerebral blood flow (e.g., vascular occlusion or systemic hypoperfusion). The most important risk factors are chronic systemic hypertension and cardiovascular disease. Modifiable risk factors should be managed (e.g., , anticoagulation for patients with atrial fibrillation) for primary prevention of stroke. Clinically, ischemic stroke is characterized by the acute onset of focal neurological deficits, which are dependent on the cerebral territory covered by the relevant vessel. If ischemic stroke is suspected, a noncontrast head CT should immediately be performed to rule out intracranial hemorrhage and blood glucose should be measured as it is a stroke mimic. Revascularization of the vessels affected in ischemic stroke, e.g., via tissue plasminogen activator (tPA) or thrombectomy, can preserve brain tissue and improve outcomes if given early. Further treatment consists of supportive care, neuroprotective measures, management of underlying causes, and reducing subsequent stroke risk with antiplatelet therapy and other .
Risk factors for ischemic stroke
- Nonmodifiable risk factors 
Modifiable risk factors 
- Systemic hypertension
- Diabetes mellitus
- Cardiovascular disease
- Coagulopathy (e.g., protein C or S deficiency), hyperhomocysteinemia
- Heavy alcohol use
- Tobacco use
- Recreational drug use (e.g., cocaine can cause cerebral vasospasm)
- Oral contraceptive use
- Hormone replacement therapy
- Sedentary lifestyle
- Suboptimal diet (e.g., high salt intake, inadequate fruit and vegetable intake)
Epidemiological data refers to the US, unless otherwise specified.
- Most commonly affect the middle cerebral artery (MCA)
- Dislodged emboli can affect multiple cerebral vascular territories simultaneously.
- Cardiac emboli
- Infectious emboli: bacterial endocarditis
- Paradoxical embolism: venous thromboembolism (especially due to deep vein thrombosis) in patients with right-to-left cardiac shunt (e.g., persistent foramen ovale or atrial septal defect)
- Spectacular shrinking deficit: distal migration of the embolus leads to recanalization of the affected vessel and rapid clinical improvement after symptom onset
Thrombotic strokes (∼ 40%)
- Large vessel atherosclerosis (∼ 20%)
- Small vessel occlusion (e.g., ) (∼ 20%): see “Subtypes and variants” below.
Global cerebral ischemia
- Hypoglycemia: Repeated episodes of hypoglycemia (e.g., due to insulinoma) increase the risk of cerebral ischemia.
- Severe and/or chronic hypoxia: hypoxemia (e.g., due to respiratory arrest) → global tissue hypoxia in the brain
- Vasculitis (e.g., giant cell arteritis)
- Arterial dissection (e.g., due to trauma or fibromuscular dysplasia)
- Sudden onset of focal neurological deficits (e.g., weakness/paralysis, paresthesias, aphasia, dysarthria)
- Nonspecific symptoms (e.g., impaired consciousness, nausea, vomiting, headache, seizures)
- Symptoms depend on the location of the stroke (see “ ” and “ ”)
- Symptoms suggesting a specific etiology:
Subtypes and variants
Lacunar infarct 
- Definition: noncortical infarcts characterized by the absence of cortical signs (e.g., no aphasia, hemianopsia, agnosia, apraxia)
- Risk factors
- Clinical features
- Pathology: results in a pale infarction at the periphery of the cortex
- Treatment: same as for other ischemic strokes (see “Treatment”)
Infarction of the posterior limb of the internal capsule is the most common type of lacunar stroke and may manifest clinically with pure motor stroke, pure sensory stroke (rare), sensorimotor stroke, dysarthria-clumsy hand syndrome, and/or ataxic hemiparesis.
Watershed infarct 
- Definition: border-zone infarct in the region between the territory of two major arteries that supply the brain (watershed area)
- Etiology: sudden decrease in blood pressure or cessation of blood flow through both vessels → ischemia in the susceptible region between two vascular territories
- Signs of systemic hypoperfusion (e.g., tachycardia, low blood pressure, pallor, sweating)
- Diffuse neurological deterioration
- PCA-MCA watershed region: bilateral visual loss (cortical blindness)
- ACA-MCA watershed region: proximal limb weakness with sparing of the face, hands, and feet (“man-in-the-barrel syndrome”)
Clinical assessment and management should occur simultaneously with the goals of stabilizing the patient, keeping the door-to-neuroimaging time to a minimum, and identifying candidates for reperfusion therapy as soon as possible. 
- Airway management: Secure airway if airway protective reflexes are impaired, e.g., due to depressed level of consciousness or bulbar dysfunction.
- Respiratory support
- Hemodynamic support: See “Blood pressure management in ischemic stroke.”
Rapid focused neurological assessment
- Determine the time of symptom onset or, if this is unknown, the time the patient was last seen well or at neurological baseline.
- Identify risk factors for ischemic stroke and .
- Minimum neurological examination
- Focused neurological examination
- Attempt to localize lesion by identifying .
- Perform severity assessment: e.g.,
Critical management steps 
- Check POC glucose and treat immediately if < 60 mg/dL or > 400 mg/dL to rule out stroke mimic.
- Arrange emergency neuroimaging, e.g., noncontrast CT head, to rule out intracranial hemorrhage.
Treat eligible patients with (e.g., IV thrombolytics, mechanical thrombectomy)
- Identify inclusion and exclusion criteria.
- Lower BP to < 185/110 mm Hg prior to initiation.
- Initiate and .
- Start ICP management if needed: Avoid steroids, hypothermia, and barbiturates.
Consults and disposition
- Consult neurology immediately if acute ischemic stroke is identified.
- Consult neurosurgery for any hemorrhagic transformation or if there are indications for ventriculostomy or decompressive craniectomy: e.g., cerebral edema with refractory ↑ ICP, large cerebellar infarction with obstructing hydrocephalus.
- Admit the patient to a dedicated stroke unit (or ICU) for at least 24 hours (arrange interfacility transfer if necessary).
- Next steps: See “ ” and “ .”
Only POC glucose and noncontrast neuroimaging (e.g., CT head or MR brain) are required prior to thrombolytic therapy. Do not delay treatment to complete the remainder of the diagnostic evaluation. A classic clinical presentation without evidence of a stroke mimic or intracranial bleeding on initial neuroimaging is typically enough to diagnose acute ischemic stroke in time-limited settings. 
Blood pressure management in acute ischemic stroke 
- Provide hypotension and hypovolemia for (see “Neurogenic shock”).
Treatment of hypertension in patients not undergoing reperfusion therapy
- BP < 220/120 mm Hg
- BP ≥ 220/120 mm Hg: Careful BP reduction, e.g., by ∼ 15% within the first 24 hours of stroke onset may be considered.
- Patients undergoing reperfusion therapy: Reduce BP to < 185/110 mmHg beforehand and keep BP < 180/105 mm Hg for the first 24 hours after treatment.
- Recommended agents: labetalol , clevidipine , or nicardipine
- Once the patient is neurologically stable, start (or restart) oral antihypertensive therapy if BP > 140/90 mm Hg.
The following scales can be calculated at initial presentation to guide treatment decisions and estimate prognosis, or repeated to monitor progression and response to therapy during admission, rehabilitation, and follow-up. They are also used as outcome measures in clinical trials.
National Institutes of Health Stroke Scale (NIHSS) 
- A severity score that quantifies neurological impairment for specific categories within the following broad domains:
- Scores between are assigned for each category are combined and totals can range from 0 (no impairment) to 42 (most severe).
|National Institute of Health Stroke Scale (NIHSS) |
1b: Orientation questions
Ask month and age.
Patient opens/closes eyes and makes a fist.
Patient follows examiner's finger in horizontal movements.
Present visual stimuli in the patient's visual field quadrants.
4: Facial palsy
Patient shows teeth, raises eyebrows, squeezes eyes shut.
5a: Motor: left arm
5b: Motor: right arm
Patient elevates each arm to 45° from a supine position or 90° if sitting with open palms facing downwards.
(Separate scores are given for left arm and right arm.)
6a: Motor: left leg
6b: Motor: right leg
Patient elevates each leg to 30° from a supine position.
(Separate scores are given for left leg and right leg.)
7: Limb ataxia
Patient performs finger-to-nose and heel-shin tests on both sides.
Test sensation of face, arms, and legs.
Patient names items, describes a picture, or reads a sentence.
Ask patient to read or repeat words.
11: Sensory extinction or inattention
Offer simultaneous tactile and visual stimuli.
Modified Rankin scale 
- A scale used to quantify the degree of disability and dependence in daily activities before and after cerebral stroke.
- The scale ranges from 0 (no symptoms) to 6 (death).
|Modified Rankin scale|
|Insignificant||Present, but not affecting usual activities||1|
|Slight||Affecting some activities, but not affecting independence||2|
|Moderate||Necessitating assistance for some ADLs, but not for walking||3|
|Moderately severe||Necessitating assistance for walking and most ADLs||4|
|Severe||Necessitating full-time care for all ADLs (e.g., bedbound, incontinent)||5|
Diagnostic approach 
as soon as possible.
- Obtain initial noncontrast imaging without delay. 
- Consider advanced neuroimaging in consultation with a neurologist, but do not delay reperfusion therapy if indicated. 
- Identify any stroke mimics on neuroimaging: e.g., brain tumor, brain abscess
- Consider follow-up neuroimaging for patients with high clinical suspicion and equivocal initial CT and MRI.
- Order additional studies within the first 48 hours of symptom onset to determine the underlying etiology.
- Laboratory studies
- ECG and further cardiac evaluation (e.g., to identify atrial fibrillation)
- Neurovascular studies: to identify stenosis or
- Anterior circulation infarct
- Posterior circulation infarct: Consider noninvasive imaging of intracranial and extracranial arteries (including vertebrobasilar circulation)
- If etiology remains uncertain (i.e., cryptogenic stroke): Consider advanced studies, e.g., prolonged ambulatory ECG monitoring, evaluation for patent foramen ovale, screening for genetic diseases or vasculitides
Obtain noncontrast neuroimaging as soon as possible.
The decision to obtain advanced imaging should not delay the administration of thrombolytic therapy in appropriate candidates. 
Immediate laboratory studies 
Cardiac evaluation 
- All patients
- Select patients
- Consider prolonged cardiac monitoring (i.e., 30 days) for suspected intermittent atrial fibrillation or atrial flutter. 
Echocardiography: Consider in patients with suspected embolic stroke or symptoms of heart disease.
- TTE is the preferred initial modality.
- TEE may be added if the identification of a PFO , valvular disease, or aortic arch atherosclerosis will change management. 
- Possible findings include left atrial or ventricular thrombus, dilated or restrictive cardiomyopathy, patent foramen ovale (PFO), and cardiac tumor.
- Consider cardiac CT or cardiac MRI if embolic stroke of undetermined source (ESUS) is suspected.
Additional investigations 
Consider these in select patients, e.g., to identify the underlying cause, assess the risk of recurrence, and evaluate comorbidities or complications.
- Guiding treatment and secondary stroke prevention
- Evaluating underlying cause
Noncontrast CT head 
- Indication: all patients with a suspected acute stroke to rule out and potential stroke mimics (e.g., tumors) and detect early signs of stroke 
- Stroke protocols: can be paired with CTA head and neck in some centers.
Findings: may be normal or show evolving ischemic changes over time 
- < 2 hours after event
- < 6 hours after the event: in some cases, early signs of cytotoxic edema
- 12–24 hours after event; : Hypodense parenchyma starts becoming more clearly demarcated.
- 3–5 days after event: maximum extent of edema and mass effect 
- 2–3 weeks after event: Infarcted region appears isodense. 
- Chronic infarcts appear hypodense (isodense to cerebral spinal fluid) and well-demarcated, with negative mass effect.
MRI brain 
- Stroke protocols: includes T1-weighted, T2-weighted, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI).
Findings: The appearance of early ischemic lesions depends on the time and imaging sequence 
- Early acute (< 6 hours after event)
- Late acute (6–24 hours after event)
- Chronic infarcts can show variable signal intensity.
- Typical signal patterns can suggest an underlying etiology 
Neurovascular studies 
- Goal: visualize intracranial and/or extracranial vascular occlusions and collateral vessels 
- Confirming the diagnosis in patients with high clinical suspicion for ischemic stroke and equivocal noncontrast neuroimaging
- Identify candidates for vascular recanalization
- Large vessel revascularization (e.g., carotid endarterectomy): e.g., patients with nondisabling stroke (modified Rankin scale < 2) in the territory of the carotid arteries
- Mechanical thrombectomy: patients with acute ischemic stroke presenting in a late time window (6–24 hours since time last seen normal)
- Timing: within 24 hours if not already done at admission
Options: Choose modality based on individual patient risks and resource availability.
- Advanced neuroimaging
- Carotid artery duplex: to evaluate extracranial vasculature
- Transcranial doppler: to evaluate intracranial vasculature 
- Digital subtraction angiography (DSA): Invasive, catheter-based gold standard for cerebral vessel assessment 
- CTA/MR angiography 
- CT perfusion
- MR perfusion: A indicates the presence of a potentially salvageable penumbra.
If indicated, do not delay CTA to wait for creatinine or TSH levels, as the risk of and is relatively low, especially in patients with no known history of thyroid or renal abnormalities. 
- General: infarction → liquefactive necrosis; → cystic cavity formation
- Two main responses to brain tissue ischemia
- Irreversible neuronal injury begins ∼ 5 minutes after tissue hypoxia.
- See “ .”
Selective neuronal necrosis
- Definition: selective destruction of nerve cells with sparing of glial cells
- Transient ischemia → subsequent reperfusion (e.g., resuscitation following cardiac arrest) → increased metabolic demand, release of toxic excitatory neurotransmitters → ischemic injury
- Certain neurons are more susceptible to ischemic injury.
- Histology: neuronal necrosis with viable glial cells (which can proliferate and cause a laminar or pseudolaminar tissue architecture)
- 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: cystic lesions and loss of tissue architecture
Histologic changes in the infarcted region 
|Time from start of ischemia||Histologic features|
|> 15 days|| |
- Areas and cells most vulnerable to hypoxia
The hippocampus, neocortex, Purkinje cells, and watershed areas are the areas most vulnerable to hypoxia: Vulnerable hippos Need PURe water.
Therapeutic approach 
- Treat all eligible patients with within recommended time frames.
- Continue including .
- Initiate secondary prevention of recurrent ischemic stroke.
- Monitor and treat any complications.
- Provide early rehabilitation and mobilization.
General principles 
- Identify eligible candidates and initiate treatment as soon as possible.
- Goal: to prevent further tissue ischemia and irreversible infarction
- Commonly used treatment options include intravenous thrombolytic therapy and mechanical thrombectomy.
- The effectiveness of intraarterial thrombolysis is unclear.
Time is brain! Reperfusion therapy should not be delayed. However, intracranial hemorrhage is a contraindication for reperfusion therapy and must be ruled out first.
Intravenous thrombolysis 
- Agents: intravenous recombinant tissue plasminogen activator (tPA)
- No evidence of stroke mimic or intracranial hemorrhage
- Acute disabling neurological symptoms
Time from onset of symptoms or last seen normal (or at baseline)
- < 3 hours: patients ≥ 18 years old with any disabling stroke (including mild disabling or severe stroke) 
- 3–4.5 hours: select patients (consult neurology)
- Unclear symptom onset > 4.5 hours from last known baseline state (e.g., wake-up stroke): MRI findings determine whether thrombolysis is indicated.
If a patient is unable to consent to treatment (e.g., altered mental status, aphasia) and a legal representative is not immediately present, IV alteplase can still be administered in eligible patients with disabling stroke symptoms. 
Do not wait on coagulation parameters before administering tPA in patients with no known history of coagulopathy or thrombocytopenia. Discontinue treatment if platelets are < 100,000/mm3, INR > 1.7 or PT is abnormally elevated. 
|Exclusion criteria for thrombolysis in acute ischemic stroke |
|Preexisting conditions|| |
|Acute findings|| |
Some conditions commonly misconceived as contraindications for thrombolysis therapy include antiplatelet therapy, end-stage renal disease, and concurrent MI. In patients with preexisting disability or dementia, treatment decisions should be based on prestroke functionality and quality of life. 
Complications of IV thrombolytic therapy 
Angioedema: can compromise airway
- Stop tPA infusion and any ACE inhibitors.
- Secure difficult airway: See “Management of angioedema.”
- Medication protocol: differs from standard .
- Intracranial hemorrhage: suspect if sudden neurological deterioration or headache
- Extracranial hemorrhage: Specific management depends on the site and severity of bleeding.
Additional measures after thrombolysis
- Check blood pressure and neurological status frequently.
- Avoid invasive procedures, if possible.
- Obtain a follow-up head CT (without IV contrast) or brain MRI 24 hours after thrombolysis, prior to starting anticoagulants or antiplatelet agents.
Mechanical thrombectomy 
- Description: physical retrieval or aspiration of the occluding thrombus via the femoral artery using a stent retriever and/or an aspiration catheter
Inclusion criteria 
- Age ≥ 18 years
- Acute large artery occlusion; causing a stroke: e.g., proximal artery occlusion in anterior cerebral circulation (M1) or occlusion of the internal carotid artery
- Disabling stroke symptoms (NIHSS ≥ 6)
- Limited affected area on CT (Alberta Stroke Program Early CT Score ≥ 6)
- Previously independent in ADLs (prestroke modified Rankin scale (mRS) ≤ 1)
- Patients with symptom onset within the past 6 hours or selected patients with symptom onset between 6 and 24 hours ago
Patients who are eligible for tPA should receive thrombolysis immediately, while mechanical thrombectomy is being considered. If indicated, mechanical thrombectomy should be performed without delay to assess the response to thrombolysis. 
- : treat any temperature > 38°C
- Blood pressure: see “Blood pressure management in acute ischemic stroke” for details.
- Dysphagia screening
VTE prophylaxis: in addition to antiplatelet therapy and hydration
- is preferred: intermittent pneumatic compression ( ).
- Benefits of are unclear.
- Early rehabilitation and mobilization
Antiplatelet therapy 
- Starting within first 24–48 hours after symptom onset
Long-term antiplatelet therapy
- Indicated in patients with noncardioembolic stroke to reduce the risk of recurrence
- Choose an agent based on individual risk factors, e.g., aspirin , clopidogrel , or combination therapy.  
- Consult neurology for indication in patients with cardioembolic stroke and significant atherosclerosis. 
Wait at least 24 hours before initiating antiplatelet treatment after thrombolysis.
Management of underlying causes 
Large vessel disease
- Optimize medical management.
- Extracranial artery stenosis
- Intracranial artery stenosis
- Arterial dissection: treatment with antithrombotic agents for 3–6 months
or atrial flutter: anticoagulation with warfarin or direct oral anticoagulant is indicated regardless of frequency or persistence.
- Agents and dosages: See “Anticoagulation regimens in atrial fibrillation.”
- Timing: depends on risk of hemorrhagic conversion (specialist consultation advised)
- High risk (e.g., large infarct territory): Consider delaying > 14 days.
- Low risk: can start in 2–14 days
- Avoid concurrent oral anticoagulation and antiplatelet therapy, except in specific circumstances.
- Patent foramen ovale: Initiate antiplatelet therapy and refer to neurologist and cardiologist to consider PFO closure.
- LV thrombus or cardiomyopathy with left atrial thrombus: anticoagulation for 3 months
- Valvular heart disease and/or prosthetic valve
- or atrial flutter: anticoagulation with warfarin or direct oral anticoagulant is indicated regardless of frequency or persistence.
- Hypercoagulable states: See “Thrombophilia therapy.”
Treatment of modifiable risk factors 
See also “Management of ASCVD.”
Lifestyle modifications for ASCVD prevention
- Diet and exercise
- Smoking: Offer .
- Lipid-lowering therapy for ASCVD
Management of comorbidities
- Management of hypertension
- Management of diabetes mellitus; : glycemic control with antihyperglycemics as needed to maintain HbA1c < 7%
- Obesity: Weight loss is recommended.
- Substance use
- Obstructive sleep apnea (OSA): Consider screening in patients with , and CPAP therapy for established OSA.
- Perform primary survey.
- Determine the time of onset of symptoms and assess severity with NIHSS.
- Call for immediate neurology consult or activate stroke team.
- Establish IV access.
- Continuous cardiac monitoring
- Start supplemental O2 to keep SpO2 > 94%.
- Obtain POC glucose and treat immediately if < 60 mg/dL or > 400 mg/dL.
- Order immediate head CT (without contrast).
- Stabilize patient prior to neuroimaging as needed.
- Consider further imaging (e.g., MRI or CTA with or without perfusion protocol) without delaying reperfusion therapy.
- Evaluate inclusion and exclusion criteria for thrombolysis in consultation with neurology.
- If thrombolysis is indicated:
- Evaluate indications for mechanical thrombectomy in discussions with stroke specialists.
- Admit preferentially to stroke unit (medicine or neurology) or ICU for first 24 hours.
- Continue blood pressure management and other neuroprotective measures (e.g., euglycemia, normothermia).
- Perform serial neurological assessments.
- Identify and treat the underlying cause: ECG, laboratory studies, neurovascular studies.
- Ensure supportive care: e.g., NPO and dysphagia screening, VTE prophylaxis, physical and occupational therapy.
- Identify and treat any complications (e.g., seizures, neurogenic fever).
- Start secondary stroke prevention measures (e.g., antiplatelet therapy, statins).
- Obtain 24-hour follow-up imaging, if indicated (post thrombolysis).
Primary stroke prevention 
Most stroke risk can be attributed to modifiable risk factors, providing a significant opportunity for prevention. The following measures are applicable to individuals who have not experienced a stroke or TIA. 
- Perform screening for
- Perform an familial hypercholesterolemia or if LDL is < 190 mg/dL. in individuals without
- Individualize risk factors based on , e.g.:
Use shared decision-making to consider the initiation of low-dose aspirin for the primary prevention of ischemic stroke in patients aged 40–59 years with a low bleeding risk and a 10-year ASCVD risk ≥ 10%. 
Reduction of other risk factors for stroke 
|Strategies to reduce selected risk factors for stroke |
|Atrial fibrillation (Afib) |
|Valvular heart disease|| |
|Coronary artery disease or history of myocardial infarction|| |
|Carotid artery stenosis|| |
|Sickle cell disease|
|Obstructive sleep apnea (OSA)|
|Migraine with aura|
|Substance use|| |
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