A randomized controlled trial of flunarizine as add-on therapy and effect on cognitive outcome in children with infantile spasms

Jonathan Y. Bitton, Hannelore C. Sauerwein, Shelly K. Weiss, Elizabeth J. Donner, Sharon Whiting, Joseph M. Dooley, Carter Snead, Kevin Farrell, Elaine C. Wirrell, Ismail S. Mohamed, Gabriel M. Ronen, Milagros Salas-Prato, Devendra Amre, Maryse Lassonde, Lionel Carmant

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Purpose: Cognitive impairment is observed commonly in children with a history of infantile spasms (IS). The goal of this study was to prospectively examine the effect on cognitive outcome of a neuroprotective agent used as adjunctive therapy during treatment of the spasms. Methods: In a randomized controlled trial, patients received a standardized therapy plus flunarizine or placebo. The standardized treatment consisted of vigabatrin as first-line therapy. Nonresponders were switched to intramuscular synthetic adrenocorticotropic hormone (sACTH depot) after 2 weeks and, if necessary, to topiramate after two additional weeks. The Vineland Adaptive Behavior Scale (VABS) and Bayley Scales of Infant Development (BSID) were used as outcome measures 24 months after the intervention. Key Findings: Sixty-eight of 101 children diagnosed over 3 years in seven centers in Canada received either adjunctive flunarizine or placebo. Sixty-five of the 68 children (96%) became spasm-free within 8 weeks and no late relapse occurred. Bayley and Vineland results were available at baseline and at 24 months in 45 children. There was no significant difference in the BSID developmental quotient between the flunarizine- and placebo-treated children at baseline (44.3 ± 35.5 vs. 30.9 ± 29.8; p = 0.18) or 24 months later (56.9 ± 33.3 vs. 46 ± 34.2; p = 0.29). However, the 10 flunarizine-treated children with no identified etiology had a better outcome than the eight controls at 24 months on both the Vineland Scale (84.1 ± 11.3 vs. 72.3 ± 9.8; p = 0.03) and the Bayley Scale (87.6 ± 14.7 vs. 69.9 ± 25.3; p = 0.07). Significance: Our study failed to demonstrate a protective effect of flunarizine on cognitive outcome in a cohort of children with IS. An analysis of subgroups suggested that flunarizine may further improve cognitive outcome in children with no identified etiology.

Original languageEnglish (US)
Pages (from-to)1570-1576
Number of pages7
Issue number9
StatePublished - Sep 2012


  • Calcium channel blocker
  • Cognition
  • Developmental outcome
  • Epileptic encephalopathy
  • Neuroprotection
  • Steroids
  • Synthetic adrenocorticotropic hormone
  • Vigabatrin
  • West syndrome

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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