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


RESULTS
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).


CONCLUSIONS
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.
Research Centre and Division of Neurology, Department of Pediatrics, Sainte-Justine Hospital (CHU Sainte-Justine), Montreal, Quebec, Canada.
Jonathan Y
JY
Bitton
Hannelore C
HC
Sauerwein
Shelly K
SK
Weiss
Elizabeth J
EJ
Donner
Sharon
S
Whiting
Joseph M
JM
Dooley
Carter
C
Snead
Kevin
K
Farrell
Elaine C
EC
Wirrell
Ismail S
IS
Mohamed
Gabriel M
GM
Ronen
Milagros
M
Salas-Prato
Devendra
D
Amre
Maryse
M
Lassonde
Lionel
L
Carmant
D000927:Anticonvulsants / Q000008:administration & dosage*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000453:epidemiology* / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005444:Flunarizine / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D008297:Male; D013036:Spasms, Infantile / Q000188:drug therapy* / Q000453:epidemiology* / Q000523:psychology; D016896:Treatment Outcome
D000927:Anticonvulsants; D005444:Flunarizine