Research Centre and Division of Neurology, Department of Pediatrics, Sainte-Justine Hospital (CHU Sainte-Justine), Montreal, Quebec, Canada.
Epilepsia. 2012 Sep;53(9):1570-6. doi: 10.1111/j.1528-1167.2012.03623.x. Epub 2012 Aug 13.
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.
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.
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).
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.
婴儿痉挛症（IS）患儿常伴有认知障碍。本研究旨在前瞻性研究神经保护剂辅助治疗痉挛对认知结果的影响。
在一项随机对照试验中，患者接受标准化治疗加氟桂利嗪或安慰剂。标准化治疗包括氨己烯酸作为一线治疗。如果 2 周后无反应，患者换用肌肉注射合成促肾上腺皮质激素（sACTH 储库），如果有必要，再加用托吡酯。干预后 24 个月，采用适应行为量表（VABS）和贝利婴幼儿发育量表（BSID）作为结局测量。
在加拿大的 7 个中心，3 年内共诊断出 101 例患儿，其中 68 例接受了辅助氟桂利嗪或安慰剂治疗。68 例患儿（96%）在 8 周内痉挛消失，且无迟发性复发。45 例患儿在基线和 24 个月时，BSID 和 VABS 结果可用。氟桂利嗪治疗组和安慰剂治疗组患儿在基线时（44.3±35.5 vs. 30.9±29.8；p=0.18）和 24 个月时（56.9±33.3 vs. 46±34.2；p=0.29）的 BSID 发育商无显著差异。然而，氟桂利嗪治疗组中 10 例无明确病因的患儿在 24 个月时，在 VABS（84.1±11.3 vs. 72.3±9.8；p=0.03）和 BSID（87.6±14.7 vs. 69.9±25.3；p=0.07）上的结局均优于对照组的 8 例患儿。
本研究未能证明氟桂利嗪对 IS 患儿认知结局有保护作用。亚组分析提示氟桂利嗪可能进一步改善无明确病因患儿的认知结局。
