Chen Shimeng, Kessi Miriam, Tan Jielu, He Fang, Zhang Ciliu, Yin Fei, Yang Lifen, Peng Jing
Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Hunan Intellectual and Developmental Disabilities Research Center, Pediatrics, Changsha, People's Republic of China.
Immunotargets Ther. 2025 Apr 18;14:491-500. doi: 10.2147/ITT.S520026. eCollection 2025.
Although anti-GAD65 related epilepsy is rare, it needs more attention because it is refractory to the conventional therapies, has poor outcome and high relapse rate. In this study, we intended to report the efficacy of tocilizumab in the treatment of anti-GAD65 antibodies related refractory epilepsy based on our center's experience and literature review.
The clinical data of the patients managed with tocilizumab at Xiangya Hospital and those from the literature was collected and analysed.
A female child presented at our center with neuropsychiatric symptoms and generalized tonic-clonic seizures (including status epilepticus) at the age of 3 years. She had positive anti-GAD65 autoantibodies. Her initial electroencephalograph showed multi-focal epileptic discharges and an early brain magnetic resonance imaging demonstrated increased intensity in the bilateral hippocampi and right insular cortex. She received several anti-seizures medications (ASMs) and immunotherapies without significant improvement; however, she experienced significant clinical, electrographic and radiological improvement after receiving four cycles of the tocilizumab. Literature review unveiled two more female cases. The mean age of seizure onset for three cases was 7.72 years, and they presented with refractory seizures (n=3), neuropsychiatric symptoms (n=3), ataxia (n=2), and anti-GAD autoantibodies were elevated in both the serum and cerebrospinal fluid (n=3). All three cases tried several combinations of ASMs and immunotherapies before tocilizumab but they remained with refractory epilepsy. Following several cycles of the tocilizumab, all cases had significant positive changes: seizure freedom (n=1), seizure control (n=2), improved-normal cognition (n=3), improved neuropsychiatry symptoms (n=2) and controlled ataxia (n=2).
Tocilizumab seems to be an effective therapy for the refractory anti-GAD65 related epilepsy as it can control seizures, improve cognition and neuropsychiatric symptoms.
尽管抗GAD65相关癫痫较为罕见，但因其对传统治疗方法难治、预后差且复发率高，故而需要更多关注。在本研究中，我们旨在基于本中心的经验及文献综述，报告托珠单抗治疗抗GAD65抗体相关难治性癫痫的疗效。
收集并分析了在湘雅医院接受托珠单抗治疗的患者以及文献中的临床资料。
一名女童3岁时因神经精神症状和全面强直阵挛发作（包括癫痫持续状态）前来本中心就诊。她的抗GAD65自身抗体呈阳性。其初始脑电图显示多灶性癫痫放电，早期脑磁共振成像显示双侧海马和右侧岛叶皮质信号增强。她接受了多种抗癫痫药物（ASMs）和免疫治疗，但均无明显改善；然而，在接受四个周期的托珠单抗治疗后，她在临床、脑电图和影像学方面均有显著改善。文献综述又发现了另外两例女性病例。三例患者的平均癫痫发作起始年龄为7.72岁，均表现为难治性癫痫（n = 3）、神经精神症状（n = 3）、共济失调（n = 2），血清和脑脊液中的抗GAD自身抗体均升高（n = 3）。所有三例患者在使用托珠单抗之前都尝试了多种ASMs和免疫治疗的组合，但仍为难治性癫痫。经过几个周期的托珠单抗治疗后，所有病例均有显著的积极变化：癫痫发作停止（n = 1）、癫痫得到控制（n = 2）、认知改善至正常（n = 3）、神经精神症状改善（n = 2）以及共济失调得到控制（n = 2）。
托珠单抗似乎是治疗抗GAD65相关难治性癫痫的有效疗法，因为它可以控制癫痫发作，改善认知和神经精神症状。
