Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Neurology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
Epilepsia. 2022 Sep;63(9):2173-2191. doi: 10.1111/epi.17315. Epub 2022 Jul 10.
Seizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4-NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune-associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4-NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)-like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM-like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4-NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most-updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4-NMOSD/MOGAD. Treatment cautions including drug-drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions.
癫痫发作是中枢神经系统炎症性脱髓鞘疾病的表现之一，主要包括多发性硬化症（MS）、水通道蛋白 4 抗体阳性视神经脊髓炎谱系疾病（AQP4-NMOSD）和髓鞘少突胶质细胞糖蛋白抗体相关性疾病（MOGAD）。MS/AQP4-NMOSD/MOGAD 继发的急性症状性癫痫发作发生在疾病的急性期，MOGAD 中更为常见。相反，复发性非诱发性癫痫发作主要归因于自身免疫相关的癫痫，发生在疾病的非急性期。MS/AQP4-NMOSD/MOGAD 中的癫痫发作大多为局灶性发作。伴有全身感染、发病较早和疾病活动度较高的 MS 患者更易发生癫痫发作，而 MS 严重程度较高、癫痫持续状态和皮质损伤等因素则表明发生癫痫的风险更大。在 MOGAD 中，皮质脑炎和急性播散性脑脊髓炎（ADEM）样表型（主要为 ADEM 和多相播散性脑脊髓炎）表明癫痫发作风险更高。MOGAD 患儿中具有 ADEM 样表型的多次复发预测癫痫发作。病理生理学上，MS 中的急性症状性癫痫发作与炎症和脱髓鞘引起的神经元过度兴奋有关。MS 中的慢性癫痫主要是由于神经胶质增生、神经元功能障碍和突触异常。MS/AQP4-NMOSD/MOGAD 继发癫痫发作的治疗主要包括免疫治疗和抗癫痫药物治疗。这篇评论性文章讨论了 MS/AQP4-NMOSD/MOGAD 中癫痫发作和癫痫的最新流行病学、临床相关性和炎症机制的证据。还概述了治疗注意事项，包括药物相互作用和治疗对疾病的影响。我们还强调了管理此类患者的困难和挑战，以及解决未解决问题的未来研究前景。
