Prospective Preliminary Analysis of the Development of Autism and Epilepsy in Children With Infantile Spasms

Abstract

The objective of this study was to compare the efficacy of corticotropin (ACTH) versus vigabatrin in treating infantile spasms and to determine which medication has a more favorable long-term outcome in terms of cognitive function, evolution of epilepsy, and incidence of autism. Patients with infantile spasms were included in the study if they were 3 to 16 months old, had hypsarrhythmia, and had no previous treatment with vigabatrin or corticosteroids. Patient evaluation included electroencephalographic and psychometric measures before and after treatment. Patients were stratified based on etiology (idiopathic or symptomatic) and sex and then randomized between the ACTH and vigabatrin treatment groups. Each of the treatment groups received either ACTH or vigabatrin for 2 weeks. At the end of 2 weeks of treatment, patients were considered responders if spasms and hypsarrhythmia resolved. Nonresponders were crossed over and treated with the alternate drug. Nine patients were included in the study. Three patients received ACTH, one of whom was a responder. Six patients received vigabatrin, three of whom were responders. The five nonresponders received both therapies. All patients had some degree of developmental plateau or regression before the initiation of treatment. Four patients with idiopathic infantile spasms showed improved cognitive function following treatment. The remaining five patients remained significantly delayed. Five patients with symptomatic infantile spasms had epilepsy following treatment; three of them were in the autistic spectrum. The small number of infants in this pilot study is insufficient to determine which of the two drugs is more effective. However, the following trends were identified: vigabatrin may be more effective for patients with symptomatic infantile spasms; patients with idiopathic infantile spasms tend to have a better cognitive outcome; and patients with symptomatic infantile spasms tend to develop both epilepsy and autism.

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

“…Two of the three were severely delayed in cognitive development on follow-up evaluations based on the Bayley Scales of Infant Development (the cognitive status of the third is unclear from the data). The other six patients in the cohort who did not develop ASD had, upon follow up assessment, variable cognitive outcomes, ranging from normal to significantly delayed development [68]. In a retrospective cohort of individuals with tuberous sclerosis complex (TSC)—a disorder of mTOR signaling caused by mutations in TSC1 and TSC2 and associated with IS and high prevalence rates of ASD (36%) [69]—IS occurrence predicted ASD development as determined by ICD-10 criteria in conjunction with review of ADI-R and ADOS testing [70].…”

Evidence-based guideline update: Medical treatment of infantile spasms [RETIRED]

“…A small Class III study (n ϭ 9) comparing highdose natural ACTH with VGB 29 showed no significant difference, with all patients in both treatment arms responding. All patients had resolution of clinical spasms and hypsarrhythmia after 2 weeks of either treatment arm, although 5 of the 9 patients continued to have moderate to severely abnormal EEGs and were crossed over to the alternate drug.…”

The role of a language scale for infant and preschool assessment

“…Studies have included children with or at risk for identified medical conditions/diagnoses, such as low birth weight [Msall and Tremont, 1997], birth hypoxia [Hopkins-Golightly et al, 2003], prenatal cocaine exposure [Espy et al, 1999], infantile spasms [Askalan et al, 2003], and isolated sagittal synostosis [Shipster et al, 2003], as well as inherited diseases, such as sickle-cell anemia [Gentry et al, 1997] and Fragile X syndrome [Jackson and Roberts, 1999;Kau et al, 2000]. Children identified with mental retardation [Cascella, 1999] and autism [Filipek, 1999] and children who are at risk for developmental delay [Costarides et al, 1998] have been studied extensively, using PLS-3 to assess receptive and expressive language skills.…”