Should you Use ACTH or Vigabatrin for Infantile Spasms? Or Why Not Use Both Together?

Abstract

COMMENTARYThe American Academy of Neurology and Child Neurology Society practice parameter published in 2004 (updated in 2012) concluded that adrenocorticotropic hormone (ACTH) and vigabatrin (VGB) should be considered standard treatments for infantile spasms; there was insufficient evidence to support use of other agents 1,2 . An update to these guidelines may be needed in light of newly published data including the study cited above.The National Infantile Spasms Consortium (NISC) recruited 230 children with infantile spasms from 22 US centers in a prospective study to assess early and sustained response to hormonal treatments (ACTH, oral steroids), VGB, and other treatments designated as nonstandard therapy 3,4 . Unlike the United Kingdom Infantile Spasm Study (UKISS), children with tuberous sclerosis (TS) were not excluded 5 . Dosing recommendations were provided for high-dose ACTH 150 units/m 2 for 2 weeks followed by a rapid taper over 2 weeks, prednisolone 40 mg/day for 2 weeks followed by taper over 2 weeks and VGB 50 mg/kg/day for 3 days, 100 mg/kg/day for 3 days, and then 150 mg/kg/day for an unspecified duration. Patients were not randomized, so their doctors could select which treatment and dose to use; dosing guidelines were followed in 80/96 (83%) children who received ACTH compared with 34/50 (68%) for prednisolone and 32/41 (78%) for VGB. Response was judged by cessation of spasms at 2 weeks and resolution of hypsarrhythmia at 3 months.Ninety-one of 198 (46%) of children receiving standard therapy responded versus only 3/32 (9%) of those who received nonstandard therapy. Response was seen in 53/97 (55%) of those received ACTH, 21/54 (39%) of those received OBJECTIVE: Infantile spasms (IS) represent a severe epileptic encephalopathy presenting in the first 2 years of life. Recommended first-line therapies (hormonal therapy or vigabatrin) often fail. We evaluated response to second treatment for IS in children in whom the initial therapy failed to produce both clinical remission and electrographic resolution of hypsarrhythmia and whether time to treatment was related to outcome. METHODS: The National Infantile Spasms Consortium established a multicenter, prospective database enrolling infants with new diagnosis of IS. Children were considered nonresponders to first treatment if there was no clinical remission or persistence of hypsarrhythmia. Treatment was evaluated as hormonal therapy (adrenocorticotropic hormone [ACTH] or oral corticosteroids), vigabatrin, or "other. " Standard treatments (hormonal and vigabatrin) were compared to all other nonstandard treatments. We compared response rates using chi-square tests and multivariable logistic regression models. RESULTS: One hundred eighteen infants were included from 19 centers. Overall response rate to a second treatment was 37% (n = 44). Children who received standard medications with differing mechanisms for first and second treatment had higher response rates than other sequences (27/49 [55%] vs. 17/69 [25%], p < 0.001). Children receiving fir...