Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial.
Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial.
复制标题
早期用氨己烯酸治疗不会减少结节性硬化症的局灶性癫痫发作或改善认知能力：预防试验。
DOI：
10.1002/ana.26778
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发表时间：
2023
影响因子：
11.2
通讯作者：
W
中科院分区：
文献类型：
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作者：
Bebin,ElizabethMartina;Peters,JurriaanM;Porter,BrendaE;McPherson,TarrantO;O'Kelley,Sarah;Sahin,Mustafa;Taub,KatherineS;Rajaraman,Rajsekar;Randle,StephanieC;McClintock,WilliamM;Koenig,MaryKay;Frost,MikeD;Northrup,HopeA;W
本研究旨在验证这一假设，即早期氨己烯酸治疗结节性硬化症（TSC）婴儿改善神经认知结果在24个月龄。MethodsA IIb期多中心随机双盲安慰剂对照试验进行氨己烯酸在第一次癫痫样脑电图（EEG）与氨己烯酸在癫痫发作发作的TSC婴儿。主要结局是24个月时的Bayley婴幼儿发育量表第三版（Bayley‐III）认知评估评分。次要结果是耐药性癫痫的患病率，额外的发展成果，和安全的氨己烯酸。ResultsOf 84名婴儿入组，12个筛选失败，4个直接开放标签氨己烯酸，12个没有随机（正常脑电图整个）。56人随机接受早期氨己烯酸（n = 29）或安慰剂（n = 27）。安慰剂组27例中有19例转换为开放标签氨己烯酸，随机化后中位延迟时间为44天。随机分配至氨己烯酸组或安慰剂组的受试者在24个月时的Bayley-III认知综合评分相似。此外，在24个月时的总体癫痫发病率和耐药性癫痫、随机化后至首次癫痫发作的时间和继发性发育结局方面，未发现组间存在显著差异。氨己烯酸组婴儿痉挛的发生率较低，随机分组后至痉挛的时间较晚。不良事件在各组之间相似。基于癫痫发作前EEG癫痫样活动的氨己烯酸解释性治疗不能改善TSC儿童24个月时的神经认知结局，也不能延迟发作或降低24个月时局灶性癫痫发作和耐药癫痫的发生率。氨己烯酸抑制剂与婴儿痉挛发作时间晚和发生率低有关。神经网络2024;95：15-26
ObjectiveThis 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.MethodsA 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.ResultsOf 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.InterpretationPreventative 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 2024;95:15–26