Basics
Description
Acute CNS insult that causes objective evidence (e.g., radiographic, pathologic) of neurologic damage in a vascular territory and clinical symptoms lasting more than 24 hours. A stroke can be ischemic due to decreased arterial blood flow (acute ischemic stroke [AIS]), venous thrombotic (cerebral sinovenous thrombosis [CSVT]), or hemorrhagic. Acute neurologic dysfunction lasting less than 24 hours and not causing evidence of brain injury is a transient ischemic attack (TIA). Acute neurologic dysfunction lasting less than 24 hours with diffusion changes on MRI is an ischemic stroke. Acute hemiparesis, sensory loss, aphasia, cranial nerve deficits, or altered consciousness (especially if occurring together) should prompt rapid evaluation for possible stroke to prevent delays in diagnosis.
Epidemiology
Incidence
- The neonatal period is the highest risk period for pediatric stroke. Neonatal stroke occurs in approximately 1 in 4,000 live births.
- Incidence of AIS is 1.2 " 7.9 per 100,000 per year in children over a month of age.
- Hemorrhagic stroke incidence is estimated to be 0.5 " 5.1 per 100,000 children per year.
- CSVT occurs in 0.67 per 100,000 children per year.
Risk Factors
Genetics
Pediatric stroke occurs secondary to a plethora of etiologies as noted below. Some risk factors are genetic:
- Hemoglobin SS (Hgb SS, sickle cell disease): autosomal recessive (AR)
- Factor V Leiden mutation
- Prothrombin G20210A gene mutation
- Classic homocystinuria: CBS gene, AR
- Mitochondrial encephalomyopathy, lactic acidosis and stroke-like symptoms (MELAS): maternal inheritance
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADISIL): NOTCH-3, autosomal dominant (AD)
- Fabry disease: GLA gene, X-linked
- Ehlers-Danlos type IV: COL3A1 gene, AD
- Marfan syndrome: FBN1 gene, AD
Etiology
- Cardiac
- Congenital heart defects
- Cardiac rhabdomyoma or myxoma
- Infectious endocarditis
- Rheumatic heart disease
- Prosthetic heart valves
- Cardiomyopathy/myocarditis
- Vascular
- Congenital/genetic vasculopathies including Ehlers-Danlos type 4, Marfan syndrome, Sturge-Weber syndrome, PHACES, neurofibromatosis type I
- Fibromuscular dysplasia, moyamoya disease, postradiation vasculopathy, intracranial aneurysm, arterial agenesis or hypoplasia, traumatic dissection, transient cerebral arteriopathy, focal arteriopathy, arteriovenous malformation
- Vasculitis, inflammatory
- Systemic: systemic infections, varicella, lupus, hemolytic uremic syndrome, AIDS, Takayasu arteritis, drug abuse, Beh §et disease
- Primary angiitis of the CNS
- Cranial or cervical infections
- Hematologic/coagulation disorders
- Severe anemia, polycythemia, or thrombocytosis
- Hemoglobinopathies especially Hgb SS
- Primary thrombophilia: antithrombin III deficiency, factor V Leiden homozygous mutation, protein S and C deficiencies, prothrombin G20210A homozygous mutation, hemophilia A and B
- Acquired thrombophilia: disseminated intravascular coagulation, leukemia or other neoplasm, L-asparaginase treatment, anticardiolipin/antiphospholipid syndrome, oral contraceptives, nephrotic syndrome, pregnancy/postpartum period, inflammatory bowel disease, thrombotic thrombocytopenic purpura, warfarin/heparin use
- Trauma
- Blunt cervical or intraoral trauma
- Carotid ligation (e.g., with extracorporeal membrane oxygenation [ECMO])
- Fat, air, foreign body, amniotic fluid embolism
- Catheter angiography
- Chiropractic manipulation
- Metabolic disorders
- Hyperhomocysteinemia
- Mitochondrial disorders
- Fabry disease
- Miscellaneous
- Migraine
- Severe hypotension or hypertension
- Reversible vasoconstriction syndrome
- Cervical vessel compression
Diagnosis
History
- Timing and progression of symptoms, including last known time when patient was normal.
- Analysis of risk factors/etiology: Inquire about history of trauma, recent medication/drug use, cardiac history, infectious history, skin lesions (acute and chronic), other symptoms/signs of inflammatory disorders, and personal and family history of excessive bleeding or clotting.
Alert
Acute stroke may present with stuttering symptoms rather than abrupt onset of maximal deficits.
Physical Exam
- Note level of alertness, vital signs, presence of cough/gag and respiratory pattern as signs of possible increased intracranial pressure (ICP), and/or need for respiratory support/intubation.
- Age-appropriate neurologic examination including special attention to mental status, funduscopic exam for papilledema, cranial nerve abnormalities, and focal motor deficits. Pediatric National Institutes of Health (NIH) stroke scale use is encouraged.
- General examination: careful cardiac exam for murmurs or dysrhythmias; evaluate for neurocutaneous syndromes or connective tissue disorders
Diagnostic Tests & Interpretation
Lab
- Blood chemistry, particularly glucose
- CBC, prothrombin (PT), partial thromboplastin time (PTT), and fibrinogen
- Fasting lipid panel
- Thrombophilia screening (best to consult hematology): antithrombin III, protein C and S levels, factor V Leiden mutation, prothrombin G20210A mutation, and antiphospholipid screen
- More extensive testing in unexplained cases should be tailored to the individual patient and may include the following:
- Homocysteine
- Mitochondrial disorder: blood +/ ’ CSF lactate, genetic testing, muscle biopsy
- Connective tissue disorder gene testing
- Testing for systemic inflammatory disease (best done in consultation with rheumatology) such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antiphospholipid antibodies, antinuclear antibody, etc.
- Intracranial infection: lumbar puncture (after imaging) with opening pressure, cell counts, glucose and protein, viral studies, and cultures; blood cultures
- Consider drug screen.
Imaging
- After stabilization, prompt neuroimaging:
- Non " contrast-enhanced images to look for possible hemorrhage
- Gold standard for diagnosis of AIS is MRI with diffusion-weighted imaging.
- Contrast images (CT or MR) should be obtained if there is concern for infection.
- Consider vascular imaging (MR or CT) of the head and neck to evaluate for focal stenosis/thrombosis, dissection, vasculopathy, or congenital malformation.
- Perfusion imaging (CT or MRI) may be helpful in defining the penumbra to evaluate the possible benefit of endovascular procedures.
- More extensive testing in undiagnosed cases may include the following:
- ECG to assess for rhythm dysfunction
- Echocardiography with bubble study
- Conventional catheter angiography
Alert
CT scan may be normal in the first 24 hours after nonhemorrhagic stroke.
Differential Diagnosis
Several disorders may mimic an acute stroke:
- Hypoglycemia
- Complicated migraine (hemiplegic, basilar)
- Postepileptic paralysis (Todd paralysis)
- Alternating hemiplegia of childhood
- Posterior reversible encephalopathy syndrome
- Brain tumor
- Conversion disorder
- Metabolic encephalopathies
- Intoxication/toxins
- Syncope
- Acute vestibular disease
Treatment
Recommendations are extrapolated from adult stroke literature and expert opinion, as randomized control trials in pediatric stroke have only been conducted in sickle cell patients.
Medication
- Hyperacute treatment with tissue plasminogen activator (tPA) is recommended only in the setting of a clinical trial per American Heart Association (AHA) guidelines.
- Consider low-molecular-weight heparin or unfractioned heparin for CSVT, craniocervical dissection, or cardioembolic stroke.
- Avoid anticoagulation for intracranial dissection due to increased risk of subarachnoid hemorrhage.
- Avoid anticoagulation in large hemispheric strokes due to risk of hemorrhagic conversion.
- Antiplatelet therapy, such as aspirin 3 " 5 mg/kg/day, is reasonable in children whose strokes are not secondary to sickle cell disease, dissection, or cardioembolism.
Additional Therapies
General Measures
- Admit patients with acute stroke to the hospital for close monitoring for clinical deterioration and for workup for underlying etiology.
- Patients with diminished or fluctuating level of alertness, large hemispheric strokes, or posterior fossa strokes may require monitoring in an intensive care unit for respiratory deterioration or signs of increased ICP.
- Consultation with neurology, hematology, and other pediatric subspecialists as clinically indicated (e.g., rheumatology, genetics)
Alert
- Obtain urgent hematology consult for children with sickle cell disease and AIS for exchange transfusion.
- Urgent neurosurgical evaluation is indicated for large hemispheric stroke, intracranial hemorrhage, or posterior fossa stroke for possible surgical decompression.
Inpatient Considerations
Initial Stabilization
- Immediately attend to airway, breathing, and circulation to avoid hypoxia and hypotension, which may cause secondary brain injury.
- Start empiric antibiotics if there is clinical concern for acute CNS infection.
- Maintain adequate hydration particularly in patients with CSVT.
- Avoid hypoglycemia.
- Aggressively treat fevers to avoid increased cerebral metabolic demand.
- Up to 25% of children have seizures with an acute stroke (may be the presenting sign). Treat seizures aggressively.
- Bedrest for at least the first 24 hours is recommended for patients with large territory strokes, stuttering symptoms, or increased ICP.
IV Fluids
Isotonic-based fluids, preferably 0.9 NS, should be used to avoid hyponatremia and brain edema.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Follow serial neurologic examinations.
- Initiate rehabilitation (physical, occupational, speech therapies) early.
- For patients with significant neurologic deficits, consider discharge to inpatient rehabilitation.
Diet
Strongly consider a swallow study in patients with facial weakness or cranial nerve involvement before allowing oral intake.
Prognosis
- More than half of children with AIS have residual neurologic deficits.
- Predictors of poor outcome after hemorrhagic stroke include Glasgow Coma Scale score ≤7 at admission, infratentorial hemorrhage, age <3 years, or large hemorrhage volume (Appendix, Tables 5 and 6).
Complications
- Acute complications include increased ICP/cerebral edema, seizures, dysphagia resulting in aspiration, and respiratory failure.
- Mortality from AIS is estimated to be 5 " 18% and from hemorrhagic stroke 7 " 54%.
Additional Reading
- DeVeber G, Andrew M, Bjornson B, et al. Cerebral sinovenous thrombosis in children. N Engl J Med. 2001;345(6):417 " 423. [View Abstract]
- Jordan LC, Hillis AE. Challenges in the diagnosis and treatment of pediatric stroke. Nat Rev Neurol. 2011;7(4):199 " 208. [View Abstract]
- Roach ES, Golomb MR, Adams R, et al. Management of stroke in infants and children: a scientific statement from a Special Writing Group of the American Heart Association. Stroke Council and the Council on Cardiovascular Disease in the Young. Stroke. 2008;39(9):264 " 291.
Codes
ICD09
- 434.91 Cerebral artery occlusion, unspecified with cerebral infarction
- 434.01 Cerebral thrombosis with cerebral infarction
- 431.00000 Intracerebral hemorrhage
- 434.11 Cerebral embolism with cerebral infarction
ICD09
- I63.9 Cerebral infarction, unspecified
- I63.50 Cereb infrc due to unsp occls or stenos of unsp cereb artery
- I61.9 Nontraumatic intracerebral hemorrhage, unspecified
- I63.40 Cerebral infarction due to embolism of unsp cerebral artery
- I63.8 Other cerebral infarction
SNOMED
- 230690007 Cerebrovascular accident (disorder)
- 371040005 Thrombotic stroke (disorder)
- 230706003 Hemorrhagic cerebral infarction (disorder)
- 422504002 ischemic stroke (disorder)
- 371041009 Embolic stroke (disorder)
FAQ
- Q: Will my child have another stroke?
- A: Overall risk of recurrence is estimated to be about 6.6 " 25%, but the risk primarily depends on the cause of the stroke. Children with Hgb SS and congenital heart defects have a higher risk for recurrence. Children with neonatal strokes without an identified risk factor are unlikely to have a second stroke.
- Q: Which therapies will help my child the most?
- A: Significant research is being conducted in rehabilitation after pediatric stroke, but there is no consensus on the best approach. Constraint-induced therapy has shown promising results. Therapies should not focus on just motor deficits but include cognitive and behavioral difficulties as well.