• stroke is relatively rare in children but can lead to significant morbidity/mortality
  • the acute management strategies for pediatric stroke are extrapolated from adult studies, but they require specific considerations in the pediatric population (differences in etiology, pathophysiology, and clinical presentation between children and adults)
  • this approach is necessary due to the limited direct research on pediatric stroke

Specifics of stroke in pediatric population

  • stroke is relatively rare in childhood – the incidence is reported in the wide range of 1.2-13/100 000 children < 18 years (both ischemic and hemorrhagic)
    • the highest risk is observed in newborns – incidence up to 25/100.000 births [Panagopoulos,2021]
    • ischemic stroke accounts for only 55% of all strokes (compared to 80% in adults)
  • while occlusion of a major artery in adults is associated with significant morbidity and increased mortality, greater brain plasticity in children may help mitigate the impact of a stroke
  • nevertheless, stroke in children often results in substantial motor and/or neurocognitive impairment (in up to 60% of cases); these impairments require long-term management [Kinney, 2018]   [DaVeber, 2000]
  • 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 is often diagnosed later in children compared to adults
    • since stroke in children is relatively rare, the possibility of a stroke may be overlooked
    • additionally, pediatric stroke may have an atypical course, mimicking other diagnoses
    • lack of stroke protocols for pediatric emergencies may also contribute to late diagnoses
  • late diagnosis may delay or prevent the initiation of recanalization therapy
  • cardioembolism, dissection, or other focal vasculopathies and hematologic disorders predominate at younger ages
  • in ~ 50% of stroke cases, the exact etiology is not detected (cryptogenic stroke)

→ see Pediatric stroke etiology

  • 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]
  • examples of stroke mimics include:
    • Todd’s hemiparesis following a seizure
    • migraine headaches
    • functional (psychogenic) disorders (up to 20%!)  [DeLaroche, 2017]
    • methotrexate toxicity
    • PRES (Posterior Reversible Encephalopathy Syndrome)
    • demyelinating diseases
  • 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)
  • MRI is the optimal and preferred modality for the evaluation of suspected stroke in children
    • it detects early ischemia on DWI + occlusion on MRA and can help to exclude some stroke mimics
    • a rapid stroke protocol can be performed in 15-20 minutes (DWI/ADC, FLAIR or T2, GRE/SWI, MRA extra- and intracranial)
    • MR perfusion is optional
  • CT (if MRI is not available or the child is unstable)
    • optimally, perform NCCT+CTA (+CTP)
    • CTA is excellent for assessing occlusion and collateral circulation
    • disadvantages of CT: poor detection of early ischemia and mimics, radiation exposure, contrast agent toxicity
  • the relevance of CTP in children is unclear and remains under investigation
    • while CTP has demonstrated potential for assessing the ischemic penumbra and guiding reperfusion therapy, adult CTP cut-off values may not accurately reflect the pediatric context, particularly in very young children
    • currently, there are no strict rules for the indication of procedures beyond the conventional time window based on CTP in children
  • there is a lack of randomized data on the safety and efficacy of recanalization methods in children
  • retrospective cohort studies have provided evidence suggesting that both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) can be safely and effectively employed in this population
  • it is important to consider the risk-benefit balance; high-risk procedures may be less justified in children than in adults (although lower rates of sICH have been reported for both IVT and MT compared to adults)  [Sporns, 2020]
  • consider the specific causes of stroke in children (e.g., focal cerebral arteriopathy) as they may require personalized treatment approaches
  • a network of pediatric stroke centers should provide pediatric stroke care
  • centers should adhere to locally approved protocols that take into account the unique causes of a stroke in young patients and the potential for stroke mimics (confirmation of stroke through imaging is essential in these cases)
  • the legal aspects of providing care to minors must be carefully considered

Intravenous thrombolysis

  • children and young adults have been excluded from thrombolytic randomized controlled trials (RCTs); experience with their treatment is derived from case reports and smaller cohorts, which suggest that IVT is feasible and safe [Rambaud, 2020]
    • RCTs are unlikely to be conducted due to the challenges in patient recruitment (as evidenced by the prematurely terminated TIPS trial)
  • tissue plasminogen activator (tPA) is approved for patients aged 16-17 years (based on SITS-ISTR registry data) who meet adult inclusion criteria
    • contraindications and dosing are analogous to those in adults
    •  it is essential to exclude stroke mimics (typical clinical presentation + radiological parameters supporting stroke diagnosis) and follow the approved therapeutic protocol. In the TIPS study, the following was required:
      • negative CT/CT with mild early signs of ischemia + occlusion detected on CTA
      • detection of infarct tissue on DWI + occlusion on MRA  [Rivkin, 2015]
  • for children < 16 years of age, IVT is an off-label procedure; AHA-ASA 2018 guidelines recommend administering tPA at this age only within clinical trials
    • many international pediatric centers have in-house thrombolytic protocols for children ≥2 years of age; these protocols require positive imaging evidence of infarction +/- arterial occlusion  [Rivkin, 2016]
    • standard tPA dosing applies in younger age groups as well (the 0.9 mg/kg dose is considered too conservative, given the state of the fibrinolytic system in children) [Rivkin, 2016]
  • children with stroke should be managed in a pediatric ICU or pediatric stroke unit

Mechanical recanalization

  • children were excluded from randomized trials, and experience with MT is derived from case reports and smaller cohorts. According to them, MT appears to be feasible and safe [Sporns, 2020] [Adriaan, 2021]
  • thrombectomy can be indicated within 6h from onset of stroke symptoms; there are limited data on MT tailored by the advanced imaging
  • the pitfalls of thrombectomy in children:
    • cardioembolism and various vasculopathies are predominant causes of stroke in childhood; the safety and efficacy of MT in such conditions are unknown
    • chronic vasculopathies often develop robust collaterals; the risk of early neurological deterioration during LVO in these patients is unclear
    • numerous children with LVO are critically ill (e.g., on mechanical cardiac support, etc.) and require a multidisciplinary approach
    • thrombophilia and cardiac defects increase the risk of anesthesia and periprocedural thrombosis
    • basilar artery occlusion has a better prognosis with conservative therapy in children than in adults [Simonetti, 2012]
    • later initiation of treatment (due to delay in stroke recognition) is common, typically > 6h; radiological mismatch criteria are not well established in children (criteria from the adult population may not be reliable)
    • lack of comparative data in children with LVO who have been treated conservatively – at a minimum, a comparison with historical cohorts is required to assess the benefit of MT. An RCT would be optimal but is unlikely to be conducted  (similarly, recruitment to the TIPS trial with IVT failed)
  • a network of pediatric stroke centers should be established, and patient data should be collected in registries (e.g., International Pediatric Stroke Study)
  • the risk of MT appears to be relatively low [Sporns, 2020]
    • vasospasm (~ 5%)
    • risk of sICH: 1.3% (SAVEChildS trial) vs. 5% (HERMES meta-analysis in adults)

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Recanalization therapy in pediatric stroke
link: https://www.stroke-manual.com/recanalization-therapy-pediatric-stroke/