Department of Neuropediatrics, University Medical Center Schleswig-Holstein (UKSH, Campus Kiel), Arnold-Heller-Str. 3, Haus 9, 24105 Kiel, Germany.
Eur J Paediatr Neurol. 2013 Nov;17(6):631-8. doi: 10.1016/j.ejpn.2013.06.002. Epub 2013 Jul 8.
Tuberous Sclerosis Complex (TSC) is an often severe neurodevelopmental disorder caused by overactivation of the mTOR pathway due to mutations in either the TSC1 or TSC2 genes. Seizures are the primary cause of neurologic morbidity and often refractory. The mTOR inhibitor everolimus was recently approved for the treatment of giant cell astrocytomas and renal angiomyolipomas in TSC. Whether everolimus has any direct effect on epilepsy in TSC is not known.
Within the framework of a compassionate use trial, we evaluated the safety and efficacy of everolimus in seven patients with TSC and intractable epilepsy. We evaluated seizure frequency, seizure-free days and adverse effects including standard laboratory parameters. Seizure frequency was analysed in each patient using a non-parametric test for trend and using a Generalized Estimating Equations Model in the total patient group. The observation period was continued for nine months.
One patient discontinued the medication at the beginning of the observation period due to side effects (flushing). In the remaining 6 patients, we observed a reduction of seizures in 4/6 patients with a reduction of 25-100%. In addition, the percentage of seizure-free days increased in 3/4 of these patients. In 2/6 patients, no alteration of seizure frequency was noted. We observed an increase of mild infections and an increase of triglycerides and various liver function tests. We did not encounter life-threatening infections or other side effects of everolimus.
In some patients with TSC, everolimus may have an anticonvulsant effect with a reduction in seizure frequency and increase of seizure-free days. Everolimus was well tolerated, with adverse effects similar to those reported in previous studies.
结节性硬化症（TSC）是一种常伴有严重神经发育障碍的疾病，由 TSC1 或 TSC2 基因突变导致 mTOR 通路过度激活引起。癫痫发作是导致神经系统发病率的主要原因，且往往难以治疗。mTOR 抑制剂依维莫司最近被批准用于治疗 TSC 中的巨细胞星形细胞瘤和肾血管平滑肌脂肪瘤。依维莫司是否对 TSC 中的癫痫有直接作用尚不清楚。
在同情用药试验的框架内，我们评估了依维莫司在 7 例 TSC 伴难治性癫痫患者中的安全性和疗效。我们评估了癫痫发作频率、无癫痫发作天数和不良反应，包括标准实验室参数。在每个患者中，使用非参数趋势检验和总患者组中的广义估计方程模型分析癫痫发作频率。观察期持续 9 个月。
1 例患者因不良反应（潮红）在观察期开始时停止用药。在其余 6 例患者中，我们观察到 4/6 例患者的癫痫发作减少，减少幅度为 25-100%。此外，这些患者中有 3/4 的无癫痫发作天数增加。在 2/6 例患者中，未观察到癫痫发作频率的改变。我们观察到轻度感染增加，甘油三酯和各种肝功能检查增加。我们未遇到危及生命的感染或依维莫司的其他副作用。
在一些 TSC 患者中，依维莫司可能具有抗惊厥作用，可降低癫痫发作频率并增加无癫痫发作天数。依维莫司耐受性良好，不良反应与先前研究报道的相似。
