Early diagnosis and treatment of infantile spasms, particularly with adrenocorticotropic hormone, may lead to improved long-term developmental outcomes, according to an updated guideline from the American Academy of Neurology and the Child Neurology Society.
The evidence-based guideline update – the first since the guideline was issued in 2004 – focuses on the latest evidence with respect to treatment of the rare disorder and is published in the June 12 issue of Neurology. Members of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society undertook the review because of extensive variations in practice patterns with respect to the treatment of infantile spasms.
Dr. Cristina Y. Go
"Although the underlying etiology of infantile spasms is an important outcome determination (based on the literature review), we highlighted the importance of prompt diagnosis of infantile spasm to shorten the lag time to treatment and improve long-term developmental outcomes," said the lead author, Dr. Cristina Y. Go of the Hospital for Sick Children in Toronto, and her colleagues.
The committee members reviewed more than 1,900 articles from 2002 through 2012, including 68 that were selected for detailed review; 26 were included in the final analysis (Neurology 2012;78:1974-80).
Studies indicate that hormonal therapy using adrenocorticotropic hormone (ACTH) or prednisolone may lead to better neurodevelopmental outcomes in children with cryptogenic spasms, relative to the seizure drug vigabatrin (VGB), and that a shorter lag time to treatment – with either ACTH or VGB – "to possibly improve" long-term developmental outcomes, Dr. Go said in an interview.
This recommendation is based on findings from six studies published since the initial guideline was developed, including one large, randomized, controlled trial that provided class II evidence, and others that provided class II, III, and IV evidence for intermediate- to long-term outcomes.
A previous class III study and a newer class II study also demonstrated that shorter lag time to treatment improves long-term cognitive outcomes, according to the updated guidelines.
Low-dose ACTH should be considered in place of a high-dose because moderate (level B) evidence suggests that it is just as effective but with fewer side effects. However, questions remain regarding the optimal ACTH formulation, dose, and treatment duration.
The available evidence remains insufficient to recommend other therapies, including prednisolone, dexamethasone, and methylprednisolone as being as effective as ACTH for short-term treatment of infantile spasms, the authors said.
The available evidence also remains insufficient for recommending the use of other treatments or approaches, including valproic acid, vitamin B6, nitrazepam, levetiracetam, zonisamide, topiramate, the ketogenic diet, or other novel or combination therapies.
Additional studies with multiple treatment arms are needed to determine the most effective therapy for infantile spasms, the authors concluded, adding that these studies should include electroencephalograms, clinical seizure occurrence, and standardized development outcome measures.
Dr. Go and five of the six other authors reported having no disclosures. One author reported receiving honoraria from UCB Pharma, Jansen Cilag, and Sanofi-Aventis for presentations at industry-sponsored symposia.