Does treatment have an impact on incidence and risk factors for autism spectrum disorders in children with infantile spasms?

Abstract

SUMMARYObjective: Infantile spasms (IS) are a severe form of childhood epilepsy associated with autism spectrum disorders (ASD) in up to 35% of cases. The objective of this post hoc analysis of our randomized control trial was to determine whether rapid diagnosis and treatment of IS could limit the incidence of ASD while identifying risk factors related to ASD outcome. Methods: Patients with IS were randomized in a standardized diagnostic and treatment protocol. Clinical and electroencephalogram (EEG) evaluations were completed at all eight visits over 5 years, while cognitive evaluations were administered at 0, 6, 24 and 60 months, respectively. Autism was initially screened by means of the Checklist for Autism in Toddlers (CHAT) at 24 months, and formally assessed at the 30-and 60-month follow-ups using the Autism Diagnostic Observation Schedule-Generic (ADOS-G). Results: Of the 69 patients included in the study, 25 could not be assessed due to severe delay or death. Eleven of the 42 patients screened with CHAT, were found to be at risk of an ASD outcome. ADOS was performed in 44 and 10 were diagnosed with ASD. The CHAT proved to correlate highly with the ADOS (80% ppv). Only patients with symptomatic IS developed ASD (p = 0.003). Earlier diagnosis or successful treatment did not correlate with a reduced rate of ASD. Other risk factors were identified such as having chronic epileptic discharges in the frontotemporal areas after disappearance of hypsarrhythmia (p = 0.005 and p = 0.007) and being of nonwhite origin (p = 0.009). Significance: ASD was only observed in children with sympyomatic IS. Other clinical risk factors include chronic frontotemporal epileptic activity and being of non-white origin. Early diagnosis and treatment did not prevent ASD as an outcome of IS. However, patients at risk for ASD could be identified early on and should in the future benefit from early intervention to potentially improve their long-term outcome.

Autism spectrum disorder and epileptic encephalopathy: common causes, many questions

“…Among infants with new-onset IS treated rapidly with a standardized protocol and followed longitudinally, the incidence of ASD based on ADOS testing at >30 months was 23% [72]. The prevalence of ASD is 1.5% in the general population [73] and 9–35% in IS [67, 74–77], so this incidence of 23% falls within expected range, suggesting that early treatment of the spasms does not diminish ASD risk.…”

“…Such abnormalities can occur in the frontal [72] and temporal regions [72, 75]. Likewise, positron emission tomography (PET) studies show hypometabolism in these areas, in addition to the parietal lobe, in patients with IS who developed ASD [74, 78].…”

Comorbidity between epilepsy and autism from the point of view of ontogenesis

“…Отмечено, что РАС достоверно чаще развиваются при симптоматической этиологии ИС. Одним из существенных факторов риска для аутизма было сохранение региональной ЭА после блокирования приступов и паттерна гипсаритмии [14]. По данным крупного обзора, посвященного ИС и коморбидным состояниям, РАС наиболее характерны для небольшого ряда генетических синдромов, в клинической картине которых присутствуют ИС, -для туберозного склероза, атипичного варианта синдрома Ретта, синдрома FOXG1 и D-глицировой ацидурии [60].…”

“…У всех пациентов после хирургического вмешательства отмечено уменьшение психопатологической симптоматики вне зависимости от результата по шкале Engel (классификация исходов хирургического лечения эпилепсии в зависимости от уменьшения частоты приступов) [24]. В отдельных исследованиях предполагается влияние региональной ЭА в лобных отделах на риск развития РАС у детей с ИС [14], но так как в анализ были включены и пациенты в возрасте от 3 мес до 6,5 года, достоверность влияния выявленной ЭА на развитие аутизма в данном исследовании сомнительна.…”

“…Существенным доводом в пользу отсутствия прямой связи между эпилепсией и аутизмом является тот факт, что уменьшение аутистической симптоматики при лечении эпилепсии -редкое явление, частота которого, по данным крупного исследования, не превышает 8 % [52]. Отмечено, что ранняя диагностика синдромов с ИС и адекватное лечение с достижением клинической ремиссии не приводят к снижению частоты развития РАС [14]. В последнее время появляется все больше сообщений о наследственно обусловленном нарушении синаптогенеза.…”