Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2023-08-28 DOI:10.1002/ana.26778

Elizabeth Martina Bebin MD, MPA, Jurriaan M. Peters MD, PhD, Brenda E. Porter MD, PhD, Tarrant O. McPherson PhD, Sarah O'Kelley PhD, Mustafa Sahin MD, PhD, Katherine S. Taub MD, Rajsekar Rajaraman MD, Stephanie C. Randle MD, William M. McClintock MD, Mary Kay Koenig MD, Mike D. Frost MD, Hope A. Northrup MD, Klaus Werner MD, PhD, Danielle A. Nolan MD, Michael Wong MD, PhD, Jessica L. Krefting RN, BSN, Fred Biasini PhD, Kalyani Peri MS, Gary Cutter PhD, Darcy A. Krueger MD, PhD, the PREVeNT Study Group

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Abstract

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 2024;95:15–26

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Vigabatrin的早期治疗不能减少结节性硬化综合征的局灶性癫痫发作或提高认知能力：PREVeNT试验。

目的：本研究旨在验证以下假设，即早期使用Vibabatrin治疗结节性硬化综合征（TSC）婴儿可改善24岁时的神经认知结果几个月大。方法：对患有TSC的婴儿进行IIb期多中心随机双盲安慰剂对照试验，在第一次癫痫样脑电图（EEG）时使用维巴他林，而在癫痫发作时使用维巴他林。主要结果是Bayley婴幼儿发展量表，第三版（Bayley III）认知评估评分为24分月。次要结果是抗药性癫痫的患病率、额外的发育结果和vigabatrin的安全性。结果：在入选的84名婴儿中，12名筛查失败，4名直接使用开放标签vigabatrin，12名未随机分组（脑电图始终正常）。56名患者被随机分为早期维那他林组（n = 29）或安慰剂（n = 27）。安慰剂组27人中有19人过渡到开放标签的维巴替林，中位延迟为44 随机化后几天。Bayley III在24岁时的认知综合得分随机分配给维巴替林或安慰剂的参与者的月数相似。此外，在24岁时，各组的癫痫总发病率和耐药性癫痫没有发现显著差异月、随机分组后首次癫痫发作的时间以及继发性发育结果。婴儿痉挛的发生率较低，随机分组后出现痉挛的时间较晚。各组的不良事件相似。解释：在癫痫发作前，根据脑电图癫痫样活动，使用维巴他林进行预防性治疗并不能改善24岁时的神经认知结果在TSC儿童中，它也不会延迟发作或降低24岁时局灶性癫痫和耐药性癫痫的发生率月。预防性维那巴特林与婴儿痉挛的发病时间较晚和发病率较低有关。ANN NEUROL 2023。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.