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., ASCVD prevention, 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 secondary prevention strategies of ASCVD.
Transient ischemic attack, intracerebral hemorrhage, and subarachnoid hemorrhage are covered in separate articles. See also “Overview of stroke.”
- Cerebral infarction due to insufficient cerebral blood flow (hypoperfusion), which results in ischemia and neuronal injury
- See “Overview of stroke” for related conditions.
Ischemic strokes account for ∼ 85% of all strokes.
Risk factors for ischemic stroke
Nonmodifiable risk factors 
- Age ≥ 65 years
- Sex ♂ > ♀
- African Americans, Native Americans, Alaska Natives, and Hispanics are at higher risk.
- Family history of cardiovascular or cerebrovascular disease
- Genetic disorders (e.g., sickle cell disease)
- History of TIA
- Migraine with aura
- Low birth weight
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)
For both ischemic and hemorrhagic strokes, age is the most important nonmodifiable risk factor and arterial hypertension is the most important modifiable risk factor.
Epidemiological data refers to the US, unless otherwise specified.
Embolic strokes (∼ 20% of all strokes)
- Most commonly affect the middle cerebral artery (MCA)
- Dislodged emboli can affect multiple cerebral vascular territories simultaneously.
- Atrial fibrillation
- Atrial or ventricular thrombi
- Rheumatic heart disease
- Ventricular aneurysms
- Internal carotid artery
- Aortic arch (less common)
- 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%)
- Rupture of an atherosclerotic plaque and exposure of subendothelial collagen → formation of a thrombus
- Thrombus formation most commonly occurs at branch points in arteries (e.g., ; internal carotid artery bifurcation or where the MCA branches from the circle of Willis).
- Small vessel occlusion (e.g., lacunar infarct) (∼ 20%): see “Subtypes and variants” below.
Global cerebral ischemia
- Shock or bilateral large artery atherosclerosis (e.g., of carotid arteries) → decreased effective oxygen delivery to the whole brain
- Common during cardiac surgeries
- Can result in watershed infarct
- 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
- Inherited thrombophilia (e.g., factor V Leiden mutation, protein C deficiency)
- Hormonal contraceptive use
- Hormone replacement therapy
- Sickle cell disease
- 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 “Stroke symptoms by affected vessel” and “Stroke symptoms by affected region”)
- Symptoms suggesting a specific etiology:
- Aortic dissection: chest pain, hypotension, dyspnea
- Endocarditis: fever, heart murmur
- ICH/SAH: sudden, severe headache
Stroke should be ruled out in patients presenting with first-time epileptic seizures and subsequent neurological deficits, as the seizure may have been caused by an acute cerebral pathology.
Subtypes and variants
Lacunar infarct 
- Definition: noncortical infarcts characterized by the absence of cortical signs (e.g., no aphasia, hemianopsia, agnosia, apraxia)
- Most common: chronic hypertensive vasculopathy → lipohyalinosis of the small vessels → occlusion of small, penetrating arteries (e.g., lenticulostriate artery); → lacunar stroke resulting in specific lacunar syndromes (see “Lacunar syndromes”)
- Less common
- Cardioembolic event
- Microatheroma formation
- Microbleed (rare)
- Risk factors
- Acute transient focal neurological symptoms that often have a stuttering course
- Symptoms depend on the affected territory.
- See “Lacunar syndromes.”
Commonly affected areas
- Internal capsule, corona radiata
- Basal ganglia (striatum, putamen, globus pallidus, thalamus, caudate)
- Diagnosis: diffusion-weighted MRI
- 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
- Cortical border zones: territories between the anterior and middle cerebral arteries and between the middle and posterior cerebral arteries
- Internal border zones: territories between the superficial and deep branches of the MCA
- 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”)
Initial evaluation and acute stabilization
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.
- Provide oxygen therapy to keep SpO2 > 94%.
- Consider mechanical ventilation for respiratory failure.
- 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 risk factors for hemorrhagic stroke.
- Minimum neurological examination
- GCS score
- Pupillary examination
- Identification of lateralizing signs, e.g., hemiparesis, facial droop, pronator drift
- Screening for signs of cerebral herniation
- Focused neurological examination
- Attempt to localize lesion by identifying stroke symptoms by affected vessel.
- Perform severity assessment: e.g., NIHSS
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 reperfusion therapy for acute ischemic stroke (e.g., IV thrombolytics, mechanical thrombectomy)
- Identify inclusion and exclusion criteria.
- Lower BP to < 185/110 mm Hg prior to initiation.
- Initiate neuroprotective measures and supportive care for ischemic stroke.
- 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 “Diagnostics of ischemic stroke” and “Treatment of ischemic stroke.”
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. 
Malignant infarctions in the MCA territory or large PICA infarctions may require surgical intervention before edema reaches its maximum extent to prevent brain herniation. 
Blood pressure management in acute ischemic stroke 
- Provide immediate hemodynamic support for hypotension and hypovolemia (see “Neurogenic shock”).
Treatment of hypertension in patients not undergoing reperfusion therapy
- BP < 220/120 mm Hg
- Permissive hypertension: Moderate hypertension is tolerated within the first 48–72 hours with the goal of maintaining cerebral perfusion.
- Earlier BP reduction is indicated in patients with certain comorbidities, e.g., concomitant heart failure or aortic dissection, and after thrombolysis.
- BP ≥ 220/120 mm Hg: Careful BP reduction, e.g., by ∼ 15% within the first 24 hours of stroke onset may be considered.
- BP < 220/120 mm Hg
- 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:
- Level of consciousness, orientation, and ability to follow commands
- Cranial nerve palsies: e.g., visual impairment, facial droop
- Motor and sensory deficits or neglect
- Language impairment
- Scores between are assigned for each category are combined and totals can range from 0 (no impairment) to 42 (most severe).
The NIHSS is weighted towards anterior circulation strokes and underestimates stroke severity in the posterior circulation. 
|National Institute of Health Stroke Scale (NIHSS) |
|1a: Level of consciousness|| |
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 
- Prioritize neuroimaging for ischemic stroke 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 dissection of the carotid or vertebral arteries
Anterior circulation infarct
- Obtain noninvasive carotid imaging: e.g., CTA, MRA, or carotid artery duplex
- Consider noninvasive intracranial arterial imaging: e.g., CTA, MRA, transcranial doppler
- See also “Carotid artery stenosis diagnostics.”
- Posterior circulation infarct: Consider noninvasive imaging of intracranial and extracranial arteries (including vertebrobasilar circulation)
- Anterior circulation infarct
- 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 
- Serum troponin 
- Coagulation panel
Cardiac evaluation 
All patients with a suspected ischemic stroke should receive an initial ECG and cardiac monitoring.
- All patients
- ECG: to evaluate for atrial fibrillation, atrial flutter, or other cardiac conditions (e.g., acute myocardial infarction)
- Cardiac monitoring: indicated for a minimum of 24 hours to detect occult atrial fibrillation
- 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
- Lipid profile
- Fasting glucose or OGTT
- Hemoglobin A1C
- Pregnancy test
- Liver chemistries
- TSH 
- Evaluating underlying cause
- Thrombophilia screening: consider if patient is < 50 years of age and/or has a history of thrombosis 
- CNS infection screening: e.g., blood culture, CSF culture, HIV test, VDRL, RPR
- Toxicology screen: e.g., blood alcohol level, urine screen for cocaine or amphetamines 
- Electroencephalogram (EEG): Consider if there is a concern for seizures.
- Chest x-ray: Consider if cardiac or respiratory diseases are suspected.
Noncontrast CT head 
- Indication: all patients with a suspected acute stroke to rule out intracerebral hemorrhage 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
- Usually, no signs of infarction are visible.
- In a large artery occlusion, there may be hyperdense occluded vessels (e.g., hyperdense MCA sign, which indicates an acute thromboembolic occlusion of the MCA ).
< 6 hours after the event: in some cases, early signs of cytotoxic edema
- Hypodense parenchyma of infarcted region
- Loss of corticomedullary (i.e., gray-white matter) differentiation, especially in the basal ganglia and insula
- Effacement of the sulci: e.g., obscuring of the lateral sulcus (also known as Sylvian fissure) due to cortical swelling
- 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.
- < 2 hours after event
Infarctions in the cerebellum and brainstem may be harder to detect with noncontrast head CT than infarctions in other regions. 
MRI brain 
- If readily available, brain MRI may be performed instead of noncontrast head CT. 
- Unclear time of onset or wake-up stroke: to determine eligibility for thrombolysis
- Signs or symptoms of a posterior circulation infarct
- 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)
- Arterial enhancement or a hyperdense media sign may be visible.
- DWI: Ischemic lesion appears hyperintense within a few minutes (most sensitive modality).
- Late acute (6–24 hours after event)
- T1-weighted: Ischemic lesion appears hypointense.
- T2-weighted and FLAIR: Ischemic lesion appears hyperintense.
- Chronic infarcts can show variable signal intensity.
- Typical signal patterns can suggest an underlying etiology 
- Cardioembolic: multiple lesions in different vascular territories
- Large artery atherosclerosis: scattered lesions in one vascular territory
- Early acute (< 6 hours after event)
DWI-FLAIR mismatch indicates hyperacute ischemic stroke that occurred within the past 6 hours. 
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
- CTA head and neck (most common): often directly follows noncontrast CT head in many stroke neuroimaging protocols
- MR angiography head and neck
- Perfusion-weighted imaging: to assess the presence and size of the ischemic penumbra 
- 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 
- Advanced neuroimaging
CTA/MR angiography 
- Large vessel occlusion(s)
- Vascular dissection (e.g., dissection of the carotid or vertebral artery)
- Carotid artery stenosis
- CT perfusion
- Ischemic penumbra: reduced cerebral blood flow and blood volume
- Ischemic core: severely reduced cerebral blood flow and blood volume PLUS increased mean transit time
- MR perfusion: A perfusion-diffusion mismatch indicates the presence of a potentially salvageable penumbra.
- CTA/MR angiography 
In potential candidates for mechanical thrombectomy, perform CTA immediately following noncontrast CT. If indicated, thrombolysis can be performed simultaneously. 
If indicated, do not delay CTA to wait for creatinine or TSH levels, as the risk of iodine-induced hyperthyroidism and contrast-induced nephropathy is relatively low, especially in patients with no known history of thyroid or renal abnormalities. 
Patterns of necrosis in ischemic stroke 
- General: infarction → liquefactive necrosis; → cystic cavity formation
- Two main responses to brain tissue ischemia
- Selective neuronal necrosis: more likely to occur with transient ischemia
- Pannecrosis: more likely to occur with irreversible ischemia (e.g., infarction)
- Irreversible neuronal injury begins ∼ 5 minutes after tissue hypoxia.
- See “Cellular changes and adaptive responses.”
Infarction of brain tissue is typically followed by liquefactive necrosis, in contrast to the coagulative necrosis seen after infarction in other organs.
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.
- 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 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|
|3–5 days|| |
|5–15 days|| |
|> 15 days|| |
Areas and cells most vulnerable to hypoxia
- Purkinje cells (cerebellum)
- Watershed areas
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 reperfusion therapy for acute ischemic stroke within recommended time frames.
- Continue supportive care for ischemic stroke including neuroprotective measures.
Initiate secondary prevention of recurrent ischemic stroke.
- Start antiplatelet treatment with aspirin or clopidogrel within 24–48 hours after symptom onset.
- Treat underlying conditions: e.g., atrial fibrillation, carotid artery stenosis, carotid or vertebral artery dissection
- Reduce modifiable risk factors: e.g., smoking, hypertension, hyperlipidemia, diabetes
- 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 
Inclusion and exclusion criteria for thrombolysis are not strict and treatment decisions should be made in consultation with a neurologist taking into account multiple individual patient factors.
Agents: intravenous recombinant tissue plasminogen activator (tPA)
- OR tenecteplase 
- 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. 
Severe hypo- or hyperglycemia (glucose < 50 mg/dL or > 400 mg/dL) and severe hypertension > 185/110 mm Hg should be treated before tPA administration. 
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 treatment of bradykinin-mediated angioedema.
- Administer in rapid sequence.
- If edema progresses despite initial treatment: Administer epinephrine OR icatibant . 
Intracranial hemorrhage: suspect if sudden neurological deterioration or headache
- Stop tPA infusion and obtain immediate noncontrast head CT.
- Order urgent CBC, coagulation panel, fibrinogen level, blood type and screen, crossmatching.
- Consult neurosurgery and hematology.
- Administer cryoprecipitate .
- Administer tranexamic acid OR ε-aminocaproic acid .
- Maintain neuroprotective measures.
- See also “Intracerebral hemorrhage.”
- 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. 
Supportive care and neuroprotective measures
Follow standard measures, including the following specific targets for acute ischemic stroke: 
Targeted temperature management: treat any temperature > 38°C
- Goals: Maintain normothermia and avoid neurogenic fever.
- Hypothermia is not recommended in acute ischemic stroke.
Glucose management for secondary brain injury prevention
- Hypoglycemia: Treat if blood glucose is < 60 mg/dL.
- Hyperglycemia; : Treat to maintain blood glucose levels in a range of 140 to 180 mg/dL 
- Blood pressure: see “Blood pressure management in acute ischemic stroke” for details.
- Keep patient NPO until the risk of aspiration has been assessed.
- See “Dysphagia” for further information on diagnostics and management.
VTE prophylaxis: in addition to antiplatelet therapy and hydration
- Mechanical VTE prophylaxis is preferred: intermittent pneumatic compression (IPCs).
- Benefits of pharmacological VTE prophylaxis are unclear.
Early rehabilitation and mobilization
- Start normal enteral diet within 7 days if possible.
- Order physiotherapy, occupational therapy, and speech therapy. 
- Screen for depression. 
Reducing subsequent stroke risk
Further therapeutic goals consist of identifying and treating risk factors and underlying conditions to prevent recurrent stroke. 
Antiplatelet therapy 
Starting within first 24–48 hours after symptom onset
- OR clopidogrel
- Dual antiplatelet therapy (DAPT): Consider starting 21-day course in patients with minor stroke symptoms (e.g., NIHSS ≤ 3–5), aspirin AND clopidogrel 
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
- Carotid artery stenosis: Consider carotid endarterectomy or carotid artery stenting patients with relevant ipsilateral stenosis within 2–7 days of the event.
- Vertebral artery stenosis: intensive medical therapy advised (see “Treatment of modifiable risk factors”)
- Intracranial artery stenosis
- 70–99%: Consider adding clopidogrel to aspirin for up to 90 days
- Routine angioplasty, stenting, and bypass surgery are discouraged.
- Arterial dissection: treatment with antithrombotic agents for 3–6 months
Atrial fibrillation 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
- Valvular AF: anticoagulation with warfarin
- Mechanical valve (mitral) and stroke prior to surgery: aspirin PLUS warfarin
- Other valvular diseases without another indication for anticoagulation: antiplatelet therapy typically preferred.
- Atrial fibrillation 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 
ASCVD: See also “Secondary prevention of ASCVD.”
- Diet and exercise
- A heart-healthy diet is preferred over a low-fat diet.
- Patients who can exercise
- Moderate intensity: minimum 10 minutes 4 times/week
- High intensity: minimum 20 minutes 2 times/week
- Patients who cannot exercise: Refer to physical therapy and rehabilitation.
- Reduce sodium intake by at least 1 g/day
- Recommend lifestyle changes for managing hypertension.
Antihypertensives: for patients with known hypertension or sustained average BP ≥ 130/80 mm Hg
- Target BP < 130/80 mm Hg 
- Preferred agents: thiazide diuretics, ACE-Is, ARBs
- Optimize agent and dosage on an individual basis.
- Diabetes mellitus; : glycemic control with antihyperglycemics as needed to maintain HbA1c < 7% (See “Treatment” in “Diabetes mellitus.”)
Hyperlipidemia; : Initiate statin therapy (see also “Treatment” in “Lipid disorders”).
- No coronary artery disease or cardioembolic source and LDL cholesterol > 100 mg/dL: Start atorvastatin.
- Other ASVCD present: lipid-lowering therapy with statin ± ezetimibe to a target LDL cholesterol < 70 mg/dL
- See also “Treatment of hypertriglyceridemia in adults.”
Smoking: Offer counseling on smoking cessation.
- Advise smoking cessation or reduction for those who cannot discontinue tobacco.
- Avoid second-hand smoke exposure.
- Consider pharmacotherapy: e.g., nicotine replacement (gums, patches), varenicline, bupropion
Obesity: Weight loss is recommended.
- Screen BMI of all patients.
- Provide directed counseling on weight and diet changes and referral to comprehensive weight loss program.
- Diet and exercise
- Substance use
- Alcohol consumption: Eliminate OR reduce to ≤ 2 drinks/day for men and ≤ 1 drink/day for women.
- Provide counseling on substance use disorders and rehabilitation referrals for the following:
- Patients using CNS stimulants
- Patients with infectious endocarditis due to IV substance use
- Obstructive sleep apnea (OSA): Consider screening in patients with risk factors for OSA, and CPAP therapy for established OSA.
- Substance use
The single most important treatable risk factor for secondary stroke prevention is hypertension.
Acute management checklist
- 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.
- Intubation and mechanical ventilation for airway protection or respiratory failure
- Blood pressure management for acute ischemic stroke for shock or hypertensive emergency
- Begin ICP management for cerebral herniation syndromes.
- 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:
- Lower blood pressure to < 185/110 mm Hg.
- Administer thrombolytic therapy (per neurologist).
- 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).
The differential diagnoses listed here are not exhaustive.
- See “Complications” in “Overview of stroke.”
- Embolic strokes are more likely to undergo hemorrhagic conversion than thrombotic strokes.
We list the most important complications. The selection is not exhaustive.
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. 
General reduction of risk for ASCVD 
- Perform age-appropriate screening for traditional ASCVD risk factors, e.g.:
- Perform an ASCVD risk assessment in individuals without familial hypercholesterolemia or if LDL is < 190 mg/dL.
Initiate ASCVD prevention strategies based on risk factors, e.g.:
- Lifestyle changes
- Management of comorbidities
- Statin and antiplatelet therapy
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|| |
In individuals with chronic HFrEF, antithrombotic therapy for stroke prevention is not recommended, unless high-risk factors (e.g., VTE, A-fib, cardioembolic source) are present. 
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