Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine and Division of Child Neurology Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Ann Neurol. 2013 Nov;74(5):679-87. doi: 10.1002/ana.23960. Epub 2013 Sep 10.
Epilepsy is a major manifestation of tuberous sclerosis complex (TSC). Everolimus is an mammalian target of rapamycin complex 1 inhibitor with demonstrated benefit in several aspects of TSC. We report the first prospective human clinical trial to directly assess whether everolimus will also benefit epilepsy in TSC patients.
The effect of everolimus on seizure control was assessed using a prospective, multicenter, open-label, phase I/II clinical trial. Patients≥2 years of age with confirmed diagnosis of TSC and medically refractory epilepsy were treated for a total of 12 weeks. The primary endpoint was percentage of patients with a ≥50% reduction in seizure frequency over a 4-week period before and after treatment. Secondary endpoints assessed impact on electroencephalography (EEG), behavior, and quality of life.
Twenty-three patients were enrolled, and 20 patients were treated with everolimus. Seizure frequency was reduced by ≥50% in 12 of 20 subjects. Overall, seizures were reduced in 17 of the 20 by a median reduction of 73% (p<0.001). Seizure frequency was also reduced during 23-hour EEG monitoring (p=0.007). Significant reductions in seizure duration and improvement in parent-reported behavior and quality of life were also observed. There were 83 reported adverse events that were thought to be treatment-related, all of which were mild or moderate in severity.
Seizure control improved in the majority of TSC patients with medically refractory epilepsy following treatment with everolimus. Everolimus demonstrated additional benefits on behavior and quality of life. Treatment was safe and well tolerated. Everolimus may be a therapeutic option for refractory epilepsy in this population.
癫痫是结节性硬化症（TSC）的主要表现之一。依维莫司是一种哺乳动物雷帕霉素靶蛋白复合物 1 抑制剂，已被证明在 TSC 的多个方面具有益处。我们报告了首例直接评估依维莫司是否也将有益于 TSC 患者癫痫的前瞻性人体临床试验。
使用前瞻性、多中心、开放标签、I/II 期临床试验评估依维莫司对癫痫控制的影响。≥2 岁、确诊 TSC 且药物难治性癫痫的患者接受为期 12 周的治疗。主要终点是治疗前后 4 周内癫痫发作频率降低≥50%的患者比例。次要终点评估对脑电图（EEG）、行为和生活质量的影响。
共纳入 23 例患者，其中 20 例接受了依维莫司治疗。20 例中有 12 例患者的癫痫发作频率降低≥50%。总体而言，20 例中有 17 例患者的癫痫发作中位数减少了 73%（p<0.001）。在 23 小时脑电图监测期间，癫痫发作频率也降低了（p=0.007）。还观察到癫痫发作持续时间的显著缩短，以及父母报告的行为和生活质量的改善。共报告了 83 例不良事件，这些事件被认为与治疗有关，所有事件的严重程度均为轻度或中度。
在接受依维莫司治疗后，大多数药物难治性癫痫的 TSC 患者癫痫得到控制。依维莫司在行为和生活质量方面也有额外的获益。治疗安全且耐受良好。依维莫司可能是该人群中难治性癫痫的一种治疗选择。
