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Ischemic stroke in children: Management and prognosis

Ischemic stroke in children: Management and prognosis
Literature review current through: Jan 2024.
This topic last updated: Jan 05, 2024.

INTRODUCTION — While more common in older adults, stroke also occurs in neonates, infants, children, and young adults, resulting in significant morbidity and mortality.

An overview of the management and prognosis of arterial ischemic stroke in children one month of age or older is provided here. Other aspects of ischemic stroke in children and neonates are reviewed elsewhere:

Ischemic stroke in children and young adults: Epidemiology, etiology, and risk factors
Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis
Hemorrhagic stroke in children
Stroke in the newborn: Classification, manifestations, and diagnosis
Stroke in the newborn: Management and prognosis
Cerebral venous thrombosis: Etiology, clinical features, and diagnosis
Cerebral venous thrombosis: Treatment and prognosis

INITIAL MANAGEMENT — No randomized controlled trials of treatment in acute childhood stroke have been performed. In general, treatment of pediatric stroke is largely adapted from treatment of adult stroke. However, the treatment of children with stroke diverges from that of adults regarding the use of acute anticoagulation and the use of reperfusion therapies (intravenous thrombolysis and mechanical thrombectomy).

Our management recommendations for pediatric stroke are based on the clinical experience of experts, recommendations from consensus guidelines [1-3], clinical trials in adults, and the clinical experience of the authors.

Intensive care — Children with acute stroke are best managed initially in an intensive care unit, preferably one with experience in managing pediatric stroke [3]. For most children with suspected acute arterial ischemic stroke, the following supportive measures are recommended (algorithm 1) [3,4]:

Maintain airway, breathing, and circulation (ABCs). Aspiration precautions include initial nil per os (NPO, nothing by mouth) restriction until swallowing function is evaluated.

Maintain normoglycemia; persistent hyperglycemia is associated with worse outcomes. Therefore, it is reasonable to treat hyperglycemia, when present, to keep blood glucose levels between 140 and 180 mg/dL while avoiding hypoglycemia.

Maintain normothermia; identify and treat sources of fever (temperature >38°C) and use antipyretic medications to lower temperature in patients with fever.

Start normal saline intravenously at maintenance rate.

Allow modest hypertension; hypotension should be corrected aggressively with measures including intravenous fluids, keeping the head of bed flat, and use of pressors if needed.

Perform frequent neurologic checks.

Begin respiratory and oxygen saturation monitoring, along with oxygen supplementation as needed to keep oxygen saturation >95 percent.

Utilize cardiac monitoring for the first 24 hours after stroke onset to look for atrial fibrillation or other potentially serious cardiac arrhythmias.

Start venous thromboembolism prophylaxis with pneumatic compression device for patients restricted to bed with paralysis or diminished consciousness. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Approach to VTE prophylaxis'.)

Most children with acute ischemic stroke should be positioned as flat as possible in bed for at least the first 24 hours from stroke onset because of the high frequency of large vessel arteriopathies in childhood stroke, ideally with head-of-bed elevation kept close to 0 degrees, but 30 degrees if there is concern for nausea and vomiting. However, exacerbation of cerebral edema or elevated intracranial pressure (ICP) may occur with flat head-of-bed positioning. Significant aggravation of elevated ICP is unlikely in the first 24 hours after ischemic stroke onset but can occur after 24 hours. Thus, patients with large ischemic infarction of unknown onset or more than 24 hours since onset should be maintained at 30 degrees in bed, once hypovolemia and large vessel arteriopathies have been excluded.

Reperfusion with thrombolysis and thrombectomy

Approach to reperfusion in children — Recognizing that safety and efficacy data are lacking in patients younger than 18 years of age (see 'Experience in children' below), acute reperfusion therapies with intravenous thrombolysis and/or mechanical thrombectomy (where available at experienced centers) may be appropriate for selected children with arterial ischemic stroke. In all cases, decisions regarding reperfusion therapies should be made in consultation with neurologists who have expertise in the treatment of children with stroke [3,5,6].

Intravenous thrombolysis – In view of case reports of good outcomes in children when following adult guidelines, evidence that the risk of symptomatic intracranial hemorrhage after tPA is low when given to children within 4.5 hours of symptom onset [7], and the obstacles to performance of clinical trials in children with this relatively uncommon clinical scenario, it is reasonable to offer intravenous thrombolysis with alteplase (recombinant tissue-type plasminogen activator, tPA) for adolescents (age ≥13 years) who otherwise fit eligibility criteria used for adults (table 1) [3]. However, intravenous alteplase is not approved in the United States by the US Food and Drug Administration for use in children less than 18 years of age with ischemic stroke. Although the use of tenecteplase is increasing for intravenous thrombolysis in adult stroke, there are few data regarding its safety or dosing in pediatric stroke [8].

Strict adherence to the accepted time limits and other eligibility criteria used in adults should be observed if thrombolytic therapy is employed for adolescents or children. Many pediatric stroke centers employ a higher threshold for offering intravenous thrombolysis in children compared with the adult guidelines, and include vascular imaging as part of hyperacute stroke imaging protocols to determine the presence of a vascular occlusion prior to offering treatment [9-11].

In order to exclude stroke mimics, we consider intravenous thrombolysis for older children (eg, ≥13 years of age) with confirmed arterial ischemic stroke (eg, as demonstrated by restricted diffusion on magnetic resonance imaging [MRI]) who have a persistent disabling neurologic deficit and evidence of partial or complete arterial occlusion on magnetic resonance (MR) angiography or computed tomography (CT) angiography in the territory of the ischemic stroke [3,12]. (See "Approach to reperfusion therapy for acute ischemic stroke".)

We suggest not using intravenous tPA for younger children (age <2 years) with stroke [9].

Mechanical thrombectomy – In general accord with a 2019 consensus statement from the American Heart Association/American Stroke Association, we suggest consideration of mechanical thrombectomy for children when the following criteria apply [3]:

Children with an acute ischemic stroke on neuroimaging (eg, as demonstrated by restricted diffusion on MRI or a large vessel occlusion on CT angiography in a child with a clinical stroke syndrome) who meet the time limits and other eligibility criteria used in adults (algorithm 2).

A persistent disabling neurologic deficit, with a Pediatric National Institute of Health Stroke Scale (table 2 and figure 1 and figure 2 and figure 3) score ≥6 at the time of intervention (algorithm 2).

A cerebral large artery occlusion confirmed by MR angiography or CT angiography in the territory of the ischemic stroke.

Small children may incur higher risks from thrombectomy compared with larger children due to the challenges associated with introducing catheters into small groin and cerebral arteries and size-based limitations on contrast dye and radiation exposure [3]. High-quality evidence to define the minimum size or age for the use of mechanical thrombectomy is lacking, but available data suggest that thrombectomy can be safe and beneficial even in small children when performed by experienced stroke neurointerventional radiologists. In a retrospective analysis of registry data from the Save ChildS cohort study, there were 73 children ranging in age from 0.7 to 18 years with acute arterial ischemic stroke who had endovascular recanalization with aspiration or stent retriever devices [13]. Stent retriever size was not associated with rates of recanalization, complications, or with outcomes, and there was no difference in these measures comparing use of first-pass aspiration with other endovascular methods (mainly stent retrievers). Overall neurologic outcomes were good while complication rates were low and did not differ between age groups.

Thrombectomy should be done by an interventionalist with experience both in treating children and in performing thrombectomy for adult patients with stroke [3,5]. Clinical experience with treating children is particularly important when deciding whether younger or smaller children may safely undergo thrombectomy, and when choosing catheters, radiation exposure, and use of intravenous contrast.

Experience in children — In adults, randomized controlled trials have established that intravenous thrombolytic therapy with alteplase improves functional outcome at three to six months when given within 4.5 hours of ischemic stroke onset for eligible patients, as discussed separately. (See "Approach to reperfusion therapy for acute ischemic stroke", section on 'Alteplase'.)

Similarly, there is compelling evidence from randomized controlled trials that early mechanical thrombectomy is effective for reducing disability in selected adult patients with acute ischemic stroke. (See "Mechanical thrombectomy for acute ischemic stroke".)

By contrast, there is only limited evidence regarding the use of these therapies for children. There are retrospective reports [14-21] and registry data [22-26] of intravenous or intra-arterial thrombolysis use in small numbers of children with acute arterial ischemic stroke. However, the effectiveness, safety and dose of alteplase for the treatment of children with arterial ischemic stroke have not been established [27]. Likewise, mechanical thrombectomy in children has not been rigorously tested, but limited observational data suggest safety when done by neuro-interventional radiologists with pediatric experience and careful selection of patients [5,13,28-33]. Safety of mechanical thrombectomy in children with inflammatory arteriopathy, moyamoya vasculopathy, or dissection is uncertain.

Efforts to investigate thrombolysis and endovascular therapies for acute ischemic stroke in children have faced daunting obstacles. As an example, Thrombolysis in Pediatric Stroke (TIPS), the first multicenter prospective treatment trial in acute pediatric stroke, aimed to determine safety, dosing, and feasibility of intravenous tPA in children, but was closed in 2013 for lack of accrual [34]. Despite the obstacles, experts in the pediatric stroke community recognize the need for establishment of pediatric acute stroke centers and evidence-based guidelines for hyperacute stroke therapy in children [3,9,10,35,36].

Early antithrombotic therapy — For most children with acute arterial ischemic stroke, we suggest starting aspirin (3 to 5 mg/kg per day, maximum 325 mg daily) as soon as possible within 24 hours of confirming the diagnosis, in the absence of contraindications such as hemorrhagic transformation [1]. However, the approach to acute antithrombotic treatment varies, and some pediatric centers start with anticoagulation [37]. Note that aspirin, other antiplatelet agents, and anticoagulant agents should not be used for the first 24 hours after treatment with intravenous thrombolysis.

In adults with acute ischemic stroke, early initiation of aspirin has established efficacy. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'Efficacy of aspirin'.)

Seizures — Seizures are a common accompaniment of arterial ischemic stroke in children. In children with stroke and altered mental status, electroencephalographic (EEG) screening or monitoring can be useful to evaluate for subclinical seizures [3]. (See "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis", section on 'Clinical presentation' and "Seizures and epilepsy in children: Clinical and laboratory diagnosis".)

In the absence of acute seizures or a history of epilepsy, seizure prophylaxis is not indicated. For children who present with one or more seizures, antiseizure medication therapy (eg, levetiracetam) during the acute phase of stroke is reasonable. Continuation of antiseizure medications may not be necessary for most children after the acute period (eg, one to two weeks if seizures do not recur), as provoked seizures that occur with illness have a lower risk of recurrence than unprovoked seizures.

Cerebral edema — With ischemic stroke, large infarcts are associated with cerebral edema and increased ICP. Signs and symptoms of elevated ICP should be frequently assessed, particularly for children with large infarcts. These include the presence of positional headache, vomiting, irritability or combativeness, declining mental status, sixth nerve palsies, and papilledema. Cushing triad (ie, hypertension, bradycardia, and respiratory depression) is highly suggestive of elevated ICP but is typically a late finding.

For any neurologic deterioration, a brain imaging study (MRI or CT) should be obtained promptly to assess for worsening edema or herniation.

General measures for children with increased ICP include:

Rapid treatment of hypoxia, hypercarbia, and hypotension

Elevation of the head of the bed to at least 30 degrees

Maintenance of the head and neck midline to facilitate venous drainage

Aggressive treatment of fever with antipyretics and cooling blankets

Control of shivering in intubated patients with muscle relaxants (eg, vecuronium, rocuronium)

Maintenance of adequate analgesia to blunt the response to noxious stimuli

Additional medical interventions for management of increased ICP include hyperventilation to partial pressure of carbon dioxide (PCO2) of 25 to 30 mmHg (if the child is intubated) and hyperosmolar therapy with intravenous mannitol (bolus 1 g/kg, given as an intravenous infusion through an in-line filter over 20 to 30 minutes, followed by infusions of 0.25 to 0.5 g/kg as needed, generally every six to eight hours) or hypertonic saline to promote osmotic diuresis (see "Elevated intracranial pressure (ICP) in children: Management", section on 'Hyperosmolar therapy'). If hyperosmolar therapy is administered, close monitoring of plasma osmoles and electrolytes is required to avoid hypovolemia, hypotension, and renal failure.

Ultimately, these medical interventions are only temporizing measures, and decompressive craniectomy may be necessary to control refractory elevations in ICP and/or mass effect.

Malignant cerebral edema and herniation

Cerebral infarction – Children with acute infarction affecting the middle cerebral artery territory are at risk for developing malignant hemispheric infarction, which is a syndrome characterized by space-occupying cerebral edema leading to brain herniation. Medical interventions for cerebral edema (see 'Cerebral edema' above) have only a temporary effect, and decompressive craniectomy may be necessary to control refractory elevations in ICP and/or mass effect.

For children with large malignant middle cerebral artery territory stroke associated with mass effect, midline shift, and deterioration of consciousness, we suggest urgent decompressive hemicraniectomy. In this setting, some experts advise either early prophylactic hemicraniectomy within the first 24 hours or serial neuroimaging within the first 72 hours to monitor for swelling and the need for decompressive surgery [3]. Eligibility criteria for adults, provided in the table (table 3), are likely useful for children as well [3]. Published data for this procedure in children are limited but encouraging [38-40]. In the authors' experience, decompressive hemicraniectomy is both lifesaving and associated with good outcome in children.

Prolonged seizures and more severe stroke deficits may predict the development of the malignant middle cerebral artery territory infarction. In one retrospective report, all children at least two years of age with initial seizures lasting ≥5 minutes in the first 24 hours after stroke onset and a score ≥8 on the Pediatric National Institute of Health Stroke Scale (table 2 and figure 3 and figure 2 and figure 1) developed malignant middle cerebral artery territory infarction syndrome [41]. (See "Malignant cerebral hemispheric infarction with swelling and risk of herniation".)

In adults undergoing decompressive hemicraniectomy, the best outcomes were achieved when hemicraniectomy was done within 48 hours of stroke onset. (See "Malignant cerebral hemispheric infarction with swelling and risk of herniation".)

Cerebellar infarction – For children with cerebellar infarction who develop brainstem compression and neurologic deterioration despite maximal medical therapy, suboccipital craniectomy with dural expansion should be performed [42].

Identifying the etiology — The evaluation of children with arterial ischemic stroke should screen for the most common causes, including imaging of intracranial and extracranial cerebral arteries, assessment of heart structure and function, hypercoagulable testing, and evaluation of inflammatory markers [3].

The full evaluation is discussed in detail separately. (See "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis".)

TREATMENT FOR SPECIFIC CAUSES — There are no controlled trials or studies examining the effectiveness of specific treatments for different causes of arterial ischemic stroke in children. Thus, all of the recommendations that follow are based mainly upon extrapolation from studies involving adults, the clinical experience of the authors, and recommendations in consensus guidelines [1-3].

Arteriopathy — For children with arterial ischemic stroke related to arteriopathy (excluding adenosine deaminase 2 deficiency), we suggest treatment with aspirin (3 to 5 mg/kg per day, up to 81 mg daily) rather than anticoagulation. The evaluation for arteriopathy is reviewed separately. (See "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis", section on 'Arteriopathy evaluation'.)

In most cases, antithrombotic therapy (typically aspirin) is continued for two years, which is the time of highest risk for recurrent stroke [43]. However, the optimal duration of antiplatelet therapy is unknown, and treatment must be individualized. Patients with persistent arteriopathy may benefit from longer treatment.

Serial neurovascular imaging during the first year of follow-up is critical to monitor for progression among the common subtypes of childhood arteriopathy, including those with extracranial artery dissection, focal cerebral arteriopathy, and moyamoya [3]. When focal cerebral arteriopathy is suspected, we repeat neurovascular imaging three to seven days after initial imaging. In general, for other arteriopathies, we repeat imaging in one to three months after initial imaging and again at 12 months. MR angiography is the preferred method in most cases, since it avoids radiation exposure and contrast dye exposure that accompany CT angiography and conventional digital subtraction angiography.

For arterial ischemic stroke caused by an inflammatory arteriopathy, treatment is directed at the underlying condition. We generally use aspirin as initial therapy (3 to 5 mg/kg per day, up to 81 mg daily), but some centers treat with aspirin plus glucocorticoids if focal cerebral arteriopathy-inflammatory type (FCA-i) is suspected, particularly if rapidly progressive [44,45]. (See "Ischemic stroke in children and young adults: Epidemiology, etiology, and risk factors", section on 'FCA-inflammatory type (FCA-i)'.)

Long-term immunosuppressive treatment is generally required to treat primary vasculitides (eg, primary angiitis of the central nervous system, polyarteritis nodosa), while antibiotics are the mainstay of treatment for secondary vasculitides caused by infection (eg, bacterial meningitis, HIV infection). An overview of the treatment of vasculitis is discussed separately. (See "Vasculitis in children: Management overview".)

Extracranial dissection — For children with ischemic stroke due to arterial dissection, we suggest treatment with aspirin (3 to 5 mg/kg per day) or anticoagulation with warfarin or low molecular weight heparin for three to six months after stroke onset, followed by long-term therapy with aspirin. The choice between antiplatelet and anticoagulant therapy should be guided by the clinical experience of the treating physician and by patient values and preferences, comorbid conditions, and tolerance of these agents. (See "Cerebral and cervical artery dissection: Treatment and prognosis".)

As already noted, serial neurovascular imaging during the first year of follow-up is critical to monitor for progression of childhood arteriopathy, including extracranial artery dissection. In most cases, antithrombotic therapy (typically aspirin) is continued for two years [43]. However, patients with persistent arteriopathy may benefit from longer treatment.

For patients with dissection of the V3 segment of the vertebral artery who have recurrent ischemic episodes despite antithrombotic treatment, we evaluate with dynamic angiography to look for rotational vertebral artery stenosis or occlusion. (See "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis", section on 'Multiple posterior circulation infarctions'.)

Some experts suggest consideration of surgical intervention (eg, vertebral artery sacrifice) in cases of unilateral vertebral artery involvement, C1-C2 posterior fusion in cases of bilateral involvement, or surgical exploration of the vertebral canal for possible debridement of fibrous tissue in cases of dynamic vertebral artery compression (ie, bow hunter syndrome) [3].

Moyamoya — Revascularization surgery is suggested for most children and young adult patients with symptomatic moyamoya disease, particularly considering the ineffectiveness of medical treatment. Although supporting evidence is limited and equivocal, long-term therapy with aspirin rather than no medical therapy is suggested for children and adults with asymptomatic or symptomatic ischemic moyamoya. These issues are discussed in greater detail elsewhere. (See "Moyamoya disease and moyamoya syndrome: Treatment and prognosis".)

In patients with moyamoya associated with other diseases, it is important to look for and treat the underlying condition when possible. The main example is sickle cell disease, where transfusion therapy is effective in primary and secondary stroke prevention. (See "Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease".)

Cardioembolic source — For children with a high initial clinical suspicion for cardioembolism as the etiology (such as those with complex congenital heart disease), we suggest short-term anticoagulation with low molecular weight heparin or unfractionated heparin until vascular imaging and echocardiography are obtained. Anticoagulation should then be stopped, and aspirin initiated if no indication (eg, a confirmed cardioembolic source) is identified by these investigations. (See "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis", section on 'Cardiac evaluation'.)

For children with arterial stroke due to a confirmed cardioembolic source, we suggest initial anticoagulation treatment (rather than aspirin). In this setting, we typically use intravenous unfractionated heparin (goal partial thromboplastin time [PTT] 60 to 85) or subcutaneous low molecular weight heparin (eg, enoxaparin [1 mg/kg dose every 12 hours] to achieve a goal anti-factor Xa level of 0.5 to 1.0 U/mL) for five to seven days, followed by treatment with low molecular weight heparin or warfarin for three to six months. In some cases, switching to a direct oral anticoagulant may be an option. Decisions for choice of anticoagulation should be made in conjunction with a hematologist.

Aspirin (3 to 5 mg/kg per day) should be given if there is a contraindication to anticoagulation.

Since chronic anticoagulation therapy may benefit children at high risk for recurrent cardiogenic embolism, we refer all children with a cardioembolic source other than atrial fibrillation to a pediatric cardiologist for risk assessment and consideration of long-term oral anticoagulation. We suggest long-term therapy with aspirin (3 to 5 mg/kg per day) if chronic anticoagulation is not employed.

For children with cardioembolic stroke due to atrial fibrillation, we suggest long-term oral anticoagulation treatment using warfarin, with an international normalized ratio (INR) goal of 2.5 (acceptable INR range 2 to 3).

Hypercoagulable state — For children with arterial stroke due to a confirmed hypercoagulable state (other than sickle cell disease), we suggest initial anticoagulation treatment (rather than aspirin) with intravenous unfractionated heparin (goal PTT 60 to 85) or subcutaneous low molecular weight heparin (eg, enoxaparin [1 mg/kg dose every 12 hours] to achieve a goal anti-factor Xa level of 0.5 to 1.0 U/mL) for five to seven days, followed by treatment with low molecular weight heparin or warfarin for three to six months. In some cases, a direct oral anticoagulant may be an option. As above, the choice of anticoagulation should be made in conjunction with a hematologist. Aspirin is used if there is a contraindication to anticoagulation.

For decisions about long-term secondary stroke prevention, we refer children with arterial ischemic stroke and a hypercoagulable state to a pediatric hematologist, since long-term oral anticoagulation may benefit patients who have venous thrombosis, recurrent thrombotic events, or the antiphospholipid syndrome. Because the precise role of prothrombotic states in stroke pathophysiology remains unclear, clinical practice regarding screening for prothrombotic states and subsequent treatment varies by center. We suggest long-term therapy with aspirin (3 to 5 mg/kg per day) if long-term anticoagulation is not employed.

The evaluation and management of prothrombotic conditions is discussed in greater detail separately. (See "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis", section on 'Hypercoagulable evaluation' and "Antithrombin deficiency" and "Protein C deficiency" and "Protein S deficiency" and "Factor V Leiden and activated protein C resistance" and "Prothrombin G20210A" and "Overview of homocysteine".)

Sickle cell disease — For children with acute ischemic stroke resulting from sickle cell disease, management issues are reviewed in detail separately. (See "Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease" and "Prevention of stroke (initial or recurrent) in sickle cell disease".)

Deficiency of adenosine deaminase 2 — For patients with deficiency of adenosine deaminase 2 (DADA2), no proven treatment is available. Antithrombotic treatment should be stopped, given susceptibility to hemorrhagic stroke and hemorrhagic transformation of ischemic stroke. Limited data suggest that treatment with tumor necrosis factor inhibitors (etanercept, adalimumab, infliximab, or golimumab) is associated with a reduction in recurrent stroke, but further studies are needed to confirm safety and efficacy [46]. (See "Deficiency of adenosine deaminase 2 (DADA2)".)

Unknown etiology — Although data are limited and consensus opinions conflicting, we suggest aspirin 3 to 5 mg/kg per day rather than anticoagulation as initial therapy for most children with acute arterial ischemic stroke of unknown etiology (cryptogenic ischemic stroke). Exceptions to the use of any acute antithrombotic treatment (ie, aspirin or anticoagulation) are children with symptomatic hemorrhagic transformation. Children who are already anticoagulated at the time of ischemic stroke onset should not be treated acutely with aspirin.

In most cases, antithrombotic therapy (typically aspirin) is continued for two years, which is the time of highest risk for recurrent stroke [43]. However, the optimal duration of antiplatelet therapy is unknown, and treatment must be individualized.

Patent foramen ovale — In children with cryptogenic ischemic stroke, the presence of a patent foramen ovale (PFO) is of uncertain significance with respect to the stroke etiology or the risk of recurrence, and unlike adults, there are few data to guide management [3,47]. We suggest aspirin (3 to 5 mg/kg per day) rather than percutaneous PFO closure or anticoagulation in this setting. An exception is children with acute deep venous thrombosis or other venous thromboembolism, who are generally treated with anticoagulation for at least several months. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome".)

There is evidence that percutaneous PFO closure is more effective than medical therapy alone for select adults age ≤60 years with an embolic-appearing cryptogenic ischemic stroke (ie, no evident source of stroke despite a comprehensive evaluation). PFO closure may be considered for older children (age ≥16 years) on an individual basis. (See "Stroke associated with patent foramen ovale (PFO): Evaluation".)

RECURRENT ISCHEMIA — Recurrent cerebral ischemia, including stroke and transient ischemic attack (TIA), is common after childhood arterial ischemic stroke, particularly in children with arteriopathy. Estimates of stroke recurrence range from approximately 7 to 20 percent over several years of follow-up [43,48-52].

One of the largest reports, the multicenter VIPS study, prospectively followed 354 children with arterial ischemic stroke for a median follow-up of two years [43]. The cumulative ischemic stroke recurrence rates at one month and one year were 7 and 12 percent, respectively. Compared with idiopathic arterial ischemic stroke, index stroke with definite arteriopathy (eg, moyamoya, transient cerebral arteriopathy, dissection, or vasculitis) affecting the cervical or cerebral vessels had a significantly increased risk of recurrence (hazard ratio 5, 95% CI 1.8-14). Other reports suggest that recurrence is more common after posterior circulation arterial ischemic stroke in children compared with anterior circulation arterial ischemic stroke [53,54].

In cases of unexplained recurrent ischemic stroke or TIA, it is important to identify the etiology, focusing on known causes with a relatively high risk of recurrence, which includes various types of arteriopathy, cardiogenic embolism, and hypercoagulable states. (See "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis", section on 'Evaluation for etiology'.)

In the setting of recurrent ischemic stroke or TIA in children on aspirin therapy, we suggest changing therapy to either clopidogrel or anticoagulation (with low molecular weight heparin or warfarin). Consensus guidelines make similar recommendations [2].

PROGNOSIS

Mortality — A study of national registry data from the United States reported that in-hospital mortality after arterial ischemic stroke in children ages 30 days to 18 years was approximately 5 percent [23]. Similarly, among 612 children with arterial ischemic stroke in an international database, the mortality rate prior to hospital discharge was 3 percent [37]. In young adults, mortality is approximately 4 to 6 percent in the first year after ischemic stroke [55,56]. Compared with matched controls, long-term mortality in children is increased beyond 20 years after ischemic stroke [57].

Disability — Despite the neural plasticity present in children, the majority of children with stroke have persistent disability [58].

In a study of 90 children with ischemic stroke followed for a median duration of three years, disability that interfered with daily life was present in 60 percent, while a good outcome was present in 40 percent [59].

In a report of 67 children with arterial ischemic stroke and follow-up of one year or more, there was no residual disability in 17 patients (25 percent), mild residual disability in 17 patients (25 percent), and severe residual disability in 33 patients (49 percent) [60].

In another study of 123 children with ischemic stroke followed for a mean duration of two years, 37 percent were normal, 20 percent had mild deficits, 26 percent had moderate deficits, 16 percent had severe deficits, and 13 percent developed epilepsy [61].

Social functioning may be impaired after pediatric stroke. In a study of 36 pediatric stroke patients compared with 15 controls with asthma (to control for effects of a hospital admission and chronic illness), children with stroke had poorer adaptive behavior and social functioning despite similar measures of intelligence quotient (IQ) and processing speed. Stroke severity was associated with greater impairment of social adjustment [62].

Long-term outcomes after ischemic stroke appear to be similar for children and younger adults. A prospective cohort study compared outcomes of 95 subjects who had arterial ischemic stroke in childhood (ages one month to 16 years) with 154 subjects who had stroke in young adulthood (ages 16 to 45 years) [63]. At a median follow-up of 6.9 years, there were no significant differences between the groups for mortality, disability, or quality of life.

Epilepsy — Epilepsy appears to be a long-term risk for neonates and children who have had a stroke [64-66]. Epilepsy is common and may be a predictor of lower quality of life. In the population-based Kaiser Pediatric Stroke Study, the cumulative risk of epilepsy was 13 percent by five years and 30 percent by 10 years after a childhood stroke [64]. In a study of 59 patients with perinatal or childhood stroke, those who developed epilepsy had lower scores on quality of life measures compared with children with stroke who did not develop epilepsy [65].

Predictors of poor outcome — In various reports of children with ischemic stroke, predictors of poor outcome have included the following:

Young age [60,67]

Age between 28 days and one year [68]

Large infarct size [67,69,70]

Altered consciousness at presentation [37,71,72]

Seizures at onset [73]

Fever at presentation [60]

Right middle cerebral artery territory infarction [60]

Bilateral ischemia [37]

Arteriopathy [37,74]

Hyperglycemia during the acute phase [70]

Severe persisting deficit one year after stroke onset predicted poor outcome in adulthood [75]

In an observational study of 29 children with unilateral stroke in the middle cerebral artery territory, abnormal signal in the descending corticospinal tract (DCST) was seen on diffusion weighted magnetic resonance imaging (MRI) in 20 (69 percent) within two weeks of stroke onset, and correlated with poor motor outcome [76]. In seven children with poor motor outcome, the abnormal DCST signal was either contralateral to the acute stroke or was bilateral, an unexpected and unexplained finding.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in children".)

SUMMARY AND RECOMMENDATIONS

Early management – Children with suspected acute arterial ischemic stroke are best managed in an intensive care setting with supportive care measures. (See 'Intensive care' above.)

Acute reperfusion – Acute reperfusion therapies with intravenous thrombolysis and/or mechanical thrombectomy (where available at experienced centers) may be appropriate in selected children with confirmed arterial ischemic stroke. Decisions regarding reperfusion therapies should be made in consultation with neurologists who have expertise in the treatment of children with stroke. (See 'Reperfusion with thrombolysis and thrombectomy' above.)

Early aspirin – For most children with acute arterial ischemic stroke, we suggest starting aspirin as soon as possible within 24 hours of confirming the diagnosis (Grade 2C). However, aspirin and antithrombotic agents should not be used for the first 24 hours after treatment with intravenous thrombolysis. (See 'Early antithrombotic therapy' above.)

Monitoring for seizures – Seizures may accompany arterial ischemic stroke in children. In children with stroke and altered mental status, electroencephalographic (EEG) screening or monitoring can be useful to evaluate for subclinical seizures. In the absence of acute seizures or a history of epilepsy, seizure prophylaxis is not indicated. (See 'Seizures' above.)

Large infarcts – Children with large infarcts should be monitored for signs and symptoms of symptomatic cerebral edema and elevated intracranial pressure (ICP). For any neurologic deterioration, a brain imaging study (magnetic resonance imaging [MRI] or computed tomography [CT]) should be obtained promptly to assess for worsening edema or herniation. Medical interventions for management of symptomatic cerebral edema and increased ICP are reviewed in the algorithm (algorithm 3).

For children with large malignant middle cerebral artery territory stroke associated with mass effect, midline shift, and deterioration of consciousness, we suggest urgent decompressive hemicraniectomy (Grade 2C). (See 'Cerebral edema' above and 'Malignant cerebral edema and herniation' above.)

Treatment for specific causes – Antithrombotic therapy varies according to stroke mechanism.

Arteriopathy – For most children with arterial ischemic stroke related to arteriopathy (excluding deficiency of adenosine deaminase 2), we suggest treatment with aspirin (3 to 5 mg/kg per day) rather than anticoagulation (Grade 2C). For inflammatory arteriopathy, treatment is directed at the underlying condition; we generally use aspirin as initial therapy, but some centers treat with aspirin plus glucocorticoids and acyclovir if focal cerebral arteriopathy-inflammatory type (FCA-i) is suspected, particularly if rapidly progressive. (See 'Arteriopathy' above.)

Dissection – For extracranial arterial dissection, initial treatment with either aspirin or anticoagulation (warfarin or low molecular weight heparin) is reasonable. (See 'Extracranial dissection' above.)

Moyamoya – For moyamoya, revascularization surgery is the mainstay of treatment. (See 'Moyamoya' above and "Moyamoya disease and moyamoya syndrome: Treatment and prognosis".)

Cardiogenic embolism or hypercoagulable state – For children with arterial ischemic stroke due to a confirmed cardioembolic source or hypercoagulable state (other than sickle cell disease), we suggest anticoagulation treatment with intravenous unfractionated heparin or subcutaneous low molecular weight heparin for five to seven days rather than aspirin, followed by treatment with low molecular weight heparin or warfarin (Grade 2C). Aspirin (3 to 5 mg/kg per day) should be given if there is a contraindication to anticoagulation.

We refer children with cardioembolic stroke to a pediatric cardiologist, and children with hypercoagulable source to a pediatric hematologist for discussion of long-term anticoagulation. (See 'Cardioembolic source' above and 'Hypercoagulable state' above.)

Sickle cell disease – Management is reviewed separately for children with ischemic stroke from sickle cell disease. (See "Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease" and "Prevention of stroke (initial or recurrent) in sickle cell disease".)

Unknown etiology – For most children with acute arterial ischemic stroke of unknown etiology, we suggest aspirin 3 to 5 mg/kg per day rather than anticoagulation as initial therapy (Grade 2C). (See 'Unknown etiology' above.)

Outcomes – Recurrent cerebral ischemia affects up to 20 percent of children after childhood arterial ischemic stroke. In cases of unexplained recurrent ischemic stroke or transient ischemic attack (TIA), it is important to identify the etiology, focusing on known causes with a relatively high risk of recurrence, which include various types of arteriopathy, cardiogenic embolism, and hypercoagulable states. (See 'Recurrent ischemia' above.)

Despite the neural plasticity present in children, the majority of children with stroke have persistent disability. (See 'Prognosis' above.)

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Topic 6215 Version 31.0

References

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