Association of Time to Clinical Remission With Sustained Resolution in Children With New-Onset Infantile Spasms

Abstract

Background and Objective:Standard therapies (ACTH, oral steroids, or vigabatrin) fail to control infantile spasms in almost half of children. Early identification of non-responders could enable rapid initiation of sequential therapy. We aimed to determine the time to clinical remission after appropriate infantile spasms treatment initiation and identify predictors of the time to infantile spasms treatment response.Methods:The National Infantile Spasms Consortium prospectively followed children aged 2-24 months with new onset infantile spasms at 23 US centers (2012-2018). We included children treated with standard therapy (adrenocorticotropic hormone (ACTH), oral steroids, or vigabatrin). Sustained treatment response was defined as having the last clinically recognized infantile spasms on or before treatment day 14, absence of hypsarrhythmia on EEG 2-4 weeks post-treatment, and persistence of remission to day 30. We analyzed the time to treatment response and assessed clinical characteristics to predict sustained treatment response.Results:Among 395 infants, clinical infantile spasms remission occurred in 43% (n=171) within the first two weeks of treatment, of which 81% (138/171) responded within the first week of treatment. There was no difference in the median time to response across standard therapies (ACTH: median 4 days, interquartile range (IQR) 3-7; oral steroids: median 3 days, IQR 2-5; vigabatrin: median 3 days, IQR 1-6). Individuals without hypsarrhythmia on the pre-treatment EEG (i.e., abnormal but not hypsarrhythmia) were more likely to have early treatment response than infants with hypsarrhythmia at infantile spasms onset (hazard ratio 2.23, 95% confidence interval 1.39-3.57). No other clinical factors predicted early responders to therapy.Conclusions:Remission after first infantile spasms treatment can be identified by treatment day 7 in most children. Given the importance of early and effective treatment, these data suggest that children who do not respond to standard infantile spasms therapy within 1 week should be reassessed immediately for additional standard treatment. This approach could optimize outcomes by facilitating early sequential therapy for children with infantile spasms.

Efficacy of vigabatrin in the treatment of infantile epileptic spasms syndrome: A systematic review and meta‐analysis

“…A total of 31 studies were assessed for eligibility by reading the full texts, of which eight studies could not extract the data that we needed. And there may be duplication of patient data in four studies: from the same consortium (The National Infantile Spasms Consortium, USA), hospitals (Nationwide Children's Hospital, The Ohio State University, Columbus), and research team 21–24 . In addition, all four studies 21–24 enrolled patients with new‐onset IESS between 2 months and 2 years of age, and data were collected between 2012 and 2018.…”

“…And there may be duplication of patient data in four studies: from the same consortium (The National Infantile Spasms Consortium, USA), hospitals (Nationwide Children's Hospital, The Ohio State University, Columbus), and research team 21–24 . In addition, all four studies 21–24 enrolled patients with new‐onset IESS between 2 months and 2 years of age, and data were collected between 2012 and 2018. The same data set in more than one publication likely will bias the aggregated effects in a meta‐analysis 25 .…”

“…The same data set in more than one publication likely will bias the aggregated effects in a meta‐analysis 25 . So we excluded three of the trials and included the latest study by Yuskaitis et al 21 with the largest number of patients. Finally, 20 studies 21,26–44 .…”

“…So we excluded three of the trials and included the latest study by Yuskaitis et al 21 with the largest number of patients. Finally, 20 studies 21,26–44 . appropriately covered the topics, met the eligibility criteria, and were included in this review.…”

“…The details of the 20 included articles are listed in Tables 1 and 2. Six RCTs and 14 OSs, including 2225 patients (1261 males, 56.7%), were published between 1996 and 2022 21,26–44 . Fourteen trials (five RCTs and nine OSs) 21,26–30,32–37,40,43 compared the efficacy of VGB vs hormonal monotherapy for IESS.…”