Śmiałek Dominika, Kotulska Katarzyna, Duda Aleksandra, Jóźwiak Sergiusz
Department of Pediatric Neurology, Medical University of Warsaw, Warsaw, Poland.
Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland.
Neurol Ther. 2023 Jun;12(3):931-946. doi: 10.1007/s40120-023-00476-7. Epub 2023 Apr 21.
Mechanistic target of rapamycin (mTOR) inhibitors sirolimus and everolimus are an effective therapy for subependymal giant cell astrocytomas, cardiac rhabdomyomas, renal angiomyolipomas, and lymphangioleiomyomatosis associated with tuberous sclerosis complex (TSC). Everolimus was recently approved in the EU and the USA for the treatment of refractory focal-onset seizures. Despite frequent use of mTOR inhibitors, there are only a few studies on their effect on epilepsy control in children under 2 years of age. This study aims to assess the effect of adjunctive mTOR inhibitor treatment on seizure frequency in this age group.
We performed retrospective data analysis of medical records of patients with TSC who initiated sirolimus or everolimus under the age of 2 years. Participants' antiseizure medication was adjusted according to their epilepsy control independently from mTOR inhibitor administration. The data was assessed separately for patients treated with mTOR inhibitors before and after the onset of seizures. We also compared the treatment group with a matched control group. The follow-up duration was up to 24 months.
Twenty-one patients with TSC from two clinical centers were included in the study. Nine participants had no history of seizures before mTOR inhibitor initiation. Twelve reported active epilepsy in the month prior to treatment initiation. Most patients treated preventively with mTOR inhibitors did not report active epilepsy at the end of their follow-up. In the second group, the mean frequency of seizures decreased with time. According to the comparative analysis, seizure control was better in the groups treated with mTOR inhibitors.
Patients with TSC treated with mTOR inhibitors demonstrated better seizure control than individuals without this treatment. Adjunctive pharmacotherapy with mTOR inhibitors appears to have a beneficial effect on epilepsy outcome in young children. Further prospective clinical trials should be conducted to determine the efficacy of mTOR inhibitors on epilepsy in patients with TSC under the age of 2 years.
雷帕霉素机制性靶标（mTOR）抑制剂西罗莫司和依维莫司是治疗室管膜下巨细胞星形细胞瘤、心脏横纹肌瘤、肾血管平滑肌脂肪瘤以及与结节性硬化症（TSC）相关的淋巴管平滑肌瘤病的有效疗法。依维莫司最近在欧盟和美国被批准用于治疗难治性局灶性发作。尽管mTOR抑制剂使用频繁，但关于其对2岁以下儿童癫痫控制效果的研究却很少。本研究旨在评估辅助使用mTOR抑制剂治疗对该年龄组癫痫发作频率的影响。
我们对2岁以下开始使用西罗莫司或依维莫司的TSC患者的病历进行了回顾性数据分析。参与者的抗癫痫药物根据其癫痫控制情况独立于mTOR抑制剂给药进行调整。分别对癫痫发作前和发作后接受mTOR抑制剂治疗的患者数据进行评估。我们还将治疗组与匹配的对照组进行了比较。随访时间长达24个月。
来自两个临床中心的21例TSC患者纳入研究。9名参与者在开始使用mTOR抑制剂之前无癫痫发作史。12名在开始治疗前一个月报告有活动性癫痫。大多数预防性使用mTOR抑制剂治疗的患者在随访结束时未报告有活动性癫痫。在第二组中，癫痫发作的平均频率随时间下降。根据比较分析，接受mTOR抑制剂治疗的组癫痫控制更好。
接受mTOR抑制剂治疗的TSC患者比未接受该治疗的患者癫痫控制更好。mTOR抑制剂辅助药物治疗似乎对幼儿癫痫结局有有益影响。应进行进一步的前瞻性临床试验，以确定mTOR抑制剂对2岁以下TSC患者癫痫的疗效。
