氨己烯酸早期治疗不能减少结节性硬化症的局灶性癫痫发作或改善认知功能：PREVeNT试验
Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial.
作者信息
Bebin Elizabeth Martina, Peters Jurriaan M, Porter Brenda E, McPherson Tarrant O, O'Kelley Sarah, Sahin Mustafa, Taub Katherine S, Rajaraman Rajsekar, Randle Stephanie C, McClintock William M, Koenig Mary Kay, Frost Mike D, Northrup Hope A, Werner Klaus, Nolan Danielle A, Wong Michael, Krefting Jessica L, Biasini Fred, Peri Kalyani, Cutter Gary, Krueger Darcy A
机构信息
Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
出版信息
Ann Neurol. 2023 Aug 28. doi: 10.1002/ana.26778.
OBJECTIVE
This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age.
METHODS
A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin.
RESULTS
Of 84 infants enrolled, 12 were screen failures, 4 went straight to open label vigabatrin, and 12 were not randomized (normal EEG throughout). Fifty-six were randomized to early vigabatrin (n = 29) or placebo (n = 27). Nineteen of 27 in the placebo arm transitioned to open label vigabatrin, with a median delay of 44 days after randomization. Bayley-III cognitive composite scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug-resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes. Incidence of infantile spasms was lower and time to spasms after randomization was later in the vigabatrin group. Adverse events were similar across groups.
INTERPRETATION
Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children, nor does it delay onset or lower the incidence of focal seizures and drug-resistant epilepsy at 24 months. Preventative vigabatrin was associated with later time to onset and lower incidence of infantile spasms. ANN NEUROL 2023.
目的
本研究旨在验证以下假设，即对结节性硬化症（TSC）婴儿早期使用氨己烯酸治疗可改善其24个月时的神经认知结局。
方法
开展了一项IIb期多中心随机双盲安慰剂对照试验，比较TSC婴儿在首次出现癫痫样脑电图（EEG）时使用氨己烯酸与癫痫发作时使用氨己烯酸的效果。主要结局为24个月时贝利婴幼儿发展量表第三版（Bayley-III）认知评估得分。次要结局包括耐药性癫痫的患病率、其他发育结局以及氨己烯酸的安全性。
结果
84名入组婴儿中，12名筛查未通过，4名直接进入氨己烯酸开放标签治疗组，12名未被随机分组（脑电图始终正常）。56名婴儿被随机分为早期氨己烯酸治疗组（n = 29）或安慰剂组（n = 27）。安慰剂组27名婴儿中有19名转为氨己烯酸开放标签治疗，随机分组后中位延迟时间为44天。随机接受氨己烯酸或安慰剂治疗的参与者在24个月时的Bayley-III认知综合得分相似。此外，两组在24个月时的总体癫痫发病率和耐药性癫痫、随机分组后首次发作时间以及次要发育结局方面均未发现显著差异。氨己烯酸组婴儿痉挛的发生率较低，随机分组后出现痉挛的时间较晚。各组不良事件相似。
解读
在癫痫发作前基于EEG癫痫样活动使用氨己烯酸进行预防性治疗，在24个月时并不能改善TSC儿童的神经认知结局，也不能延迟局灶性癫痫发作的发生或降低其在24个月时的发病率及耐药性癫痫的发生率。预防性使用氨己烯酸与婴儿痉挛发作时间延迟及发生率降低有关。《神经病学纪事》2023年。
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