ISCHEMIC STROKE

Pediatric stroke

David Goldemund M.D.
Updated on 08/10/2024, published on 13/09/2024

AHA/ASA (2019) – Management of Stroke in Neonates and Children

  • stroke in infants and children is increasingly recognized
  • while rare, it can have significant morbidity/mortality
    • greater brain plasticity in children may help mitigate the impact of stroke and increase the potential for recovery
    • despite that, stroke often results in substantial motor, behavioral, and neurocognitive impairment requiring long-term treatment [Kinney, 2018]   [DaVeber, 2000]
    • outcome must be evaluated with a developmental lens in mind; the full impact of the stroke may not be realized until adolescence or young adulthood
  • the pathophysiology of pediatric stroke differs from that of adults (often related to arteriolopathy and atherosclerosis) due to distinct and broader etiologic factors
    • understanding the etiology is key to appropriate acute treatment and prevention
  • symptoms can be subtle or mimic other pediatric conditions, delaying recognition
  • stroke in children has not been subjected to the depth and breadth of research that is available for adults
    • acute management strategies are extrapolated from adult studies due to the limited direct research in pediatric stroke; specific considerations of pediatric care are required
    • there is a lack of clarity regarding the timing of rehabilitation interventions, intensity of interventions, and duration of therapy in children

Classification of childhood

  • neonates (newborns): term birth to 1 month age
  • infancy: 1 month to 12 months
  • toddlerhood: 1 to 3 years
  • early childhood (preschool age): 3 to 5 years
  • middle childhood (school age): 6 to 12 years
  • adolescence: 13 to 18 years

Epidemiology

  • incidence
    • ischemic stroke –  1.2 to 2.4 per 100,000 children per year; higher incidence in neonates
      • ischemic stroke accounts for only 55% of all strokes (compared to ~ 80% in adults)
    • hemorrhagic stroke – 1.1 to 2.9 per 100,000 children per year; accounts for approximately 50% of all pediatric strokes, particularly in older children and adolescents
  • age distribution
    • neonatal period (0-28 days) – highest risk, incidence up to 25/100.000 births [Panagopoulos,2021]
    • beyond infancy – risk decreases but remains significant through childhood and adolescence
  • recurrence
    • ischemic stroke recurrence: ~ 10-20%
    • highest in patients with underlying arteriopathies, congenital heart disease, or prothrombotic disorders
  • morbidity
    • neurological sequelae such as hemiparesis, cognitive deficits, epilepsy, and speech/language impairments are common.
    • up to 60-70% of pediatric stroke survivors experience long-term neurological impairments
  • mortality
    • the mortality rate of pediatric stroke is lower than in adults (~ 3-6%); however, stroke remains among the top 10 causes of death in children  [Panagopoulos,2021]

Stroke subtypes

  • arterial ischemic stroke
    • the most common form of pediatric stroke
    • usually associated with arteriopathies, cardiac anomalies, and thrombophilia (prothrombotic disorders)
  • cerebral sinus venous thrombosis (CSVT)
    • risk factors include dehydration, infection, and hematologic disorders
  • hemorrhagic stroke

Etiopathogenesis

Neonates:

  • congenital heart disease (CHD)
  • perinatal asphyxia
  • infections (e.g., sepsis, meningitis)
  • coagulation disorders (e.g., protein C or S deficiency)
  • maternal complications (e.g., preeclampsia, chorioamnionitis)

Children (beyond the neonatal period):

  • arteriopathies (e.g., moyamoya disease, dissection, FCA)
  • cardiac disorders (e.g., congenital heart disease, arrhythmias)
  • hematologic conditions (e.g., sickle cell disease, thrombophilia)
  • infections (e.g., varicella-zoster virus, meningitis, endocarditis)
  • trauma (e.g., head or neck trauma leading to arterial dissection)
  • autoimmune diseases (e.g., systemic lupus erythematosus)
  • genetic disorders (e.g., mitochondrial diseases, MELAS syndrome)

Adolescents

  • arteriopathy, trauma
  • hypercoagulable states (e.g., hormonal contraceptive use in females with thrombophilia)

Cardiogenic causes

  • congenital heart disease (CHD)
  • cardiomyopathy
  • myocarditis
  • infective endocarditis – can lead to septic emboli
  • arrhythmias (e.g., atrial fibrillation)

Mechanisms of cardiogenic stroke

  • paradoxical embolism – right to left shunt (e.g., patent foramen ovale, atrial septal defect) allows venous thrombi to bypass the lungs and enter systemic circulation, leading to embolic stroke
  • cardioembolic stroke
    • thrombus formation in dilated or dysfunctional cardiac chambers (e.g., atrial fibrillation, ventricular dysfunction, cardiomyopathy, myocarditis).
    • mechanical prosthetic valves used in surgical correction increase the risk of thromboembolism
  • cerebral hypoperfusion:
    • chronic hypoxemia and reduced cerebral perfusion may lead to ischemic stroke, particularly in cyanotic CHD (e.g., Tetralogy of Fallot).
  • perioperative strokes due to embolization or hypoperfusion

Vascular causes

  • arterial dissection – trauma or spontaneous dissection of cerebral arteries can result in ischemic stroke
  • cerebral arteriopathy
  • intracranial atherosclerosis – rare, can occur in the context of genetic syndromes
  • vasculitis – inflammation of blood vessels, which can cause stenosis or occlusion

Hematological Conditions

  • Sickle Cell Disease (SCD) – can cause both ischemic and hemorrhagic strokes due to vaso-occlusive events.
  • polycythemia – elevated blood viscosity can contribute to thrombotic events
  • hypercoagulable states (inherited x acquired) – including Factor V Leiden mutation, protein C or S deficiency

Genetic and Metabolic Disorders

Cryptogenic stroke

  • in some cases, no definitive cause is identified (TOAST 5)

Clinical presentation

  • diagnosis is often delayed due to:
    • non-specific, subtle, and easily overlooked symptoms
    • lack of awareness among caregivers and healthcare providers
  • older children present with typical focal signs and symptoms, such as sudden-onset hemiparesis, speech or visual disturbances, altered consciousness, etc.
  • neonatal strokes may present with seizures, lethargy, poor feeding, irritability, or asymmetry in limb movements
  • late diagnosis may delay or preclude recanalization therapy

Diagnostic evaluation

Diagnosing stroke

  • medical history (neonatal history, congenital heart defects, recent infection or trauma, etc.)
  • rapid general and neurologic examination (NIHSS)
  • parenchymal and vascular imaging (preferably DWI)
  • EEG  – if seizures are present or to differentiate from epileptic events

→ Neuroimaging in pediatric stroke

Diagnosing stroke mechanism and etiology

  • family history (thrombophilia, genetic disorders, etc.)
  • lab tests
    • complete blood count (CBC) – identify anemia, polycythemia, or infection
    • electrolytes and metabolic panel
    • coagulation tests
    • thrombophilia screening – factor V Leiden, protein C and S levels, antithrombin III
    • additional test (tailored based on clinical clues)
      • CSF analysis
      • metabolic diseases screening (homocysteine, methionine, lactate, etc.)
      • genetic testing (inherited arteriopathies or metabolic disorders)
      • blood cultures (if infective endocarditis is suspected)
      • serology (varicella, HIV, borrelia, etc.)
  • vascular imaging (focused on the detection of vasculopathies)
  • cardiac evaluation
    • ECG
    • TransThoracic Echocardiogram (TTE) (screening for structural heart defects or intracardiac thrombi)
    • TransEsophageal Echocardiogram (TEE)

→ Etiologic classification of ischemic stroke

Differential diagnosis

  • the incidence of stroke mimics in children is relatively high (up to 44% according to the TIPS trial and over 70% according to other sources) [DeLaroche, 2017]
  • stroke mimics include:
    • post-ictal Todd’s paralysis
    • migraine
    • functional (psychogenic) disorders (up to 20%!)  [DeLaroche, 2017]
    • methotrexate toxicity
    • PRES (Posterior Reversible Encephalopathy Syndrome)
    • demyelinating diseases
    • infections
  • therefore, clear evidence of ischemic etiology is required to justify the indication of recanalization therapy (it is optimal to see a lesion on DWI + occlusion on MRA)

Management

  • management of pediatric stroke encompasses acute recanalization interventions, supportive care, rehabilitation, and secondary prevention

Acute stroke management

  • recanalization is a key aspect of acute stroke management, as it can significantly improve patient outcomes

→ Recanalization therapy in pediatric stroke

Supportive care and rehabilitation

Stroke prevention

  • preventive strategies depend on the underlying etiology
  • antiplatelet agents or anticoagulants
  • specific medication (like hydroxyurea in SCD)
  • some vascular or cardiac anomalies may require surgical intervention
    • the safety and efficacy of PFO closure procedures in children are less well-established compared to adults
    • bypass surgery in moyamoya

PFO in children

  • PFO closure may be considered for older children (age ≥16 years) who have had a cryptogenic stroke
  • evidence in children is weak, and a personalized approach is necessary (Saharan, 2022)
  • for children, especially younger ones, the careful evaluation of other stroke causes is needed
  • if a PFO is suspected to be causally related to the stroke, and if the child has had recurrent strokes despite adequate medical therapy, then closure might be considered

Prognosis

  • prognosis varies based on the cause and timeliness of intervention, with early diagnosis often leading to better outcomes.
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