Doran Elisabeth, Kelly Albert, Stanila Raluca, Healy Laura, Doherty Colin P
Department of Neurology, St James's Hospital, Dublin, Ireland.
The Academic Unit of Neurology, Trinity College School of Medicine, Dublin, Ireland.
Epilepsia. 2025 Aug;66(8):2743-2753. doi: 10.1111/epi.18417. Epub 2025 Apr 18.
Following emerging evidence of autoimmune-associated seizures in medication-refractory epilepsy, we began offering a trial of immunotherapy to selected patients. Here, we review this approach's treatment response, predictive clinical features, and utility.
This was a retrospective single-center cohort study (2018-2022) of empiric, palliative immunotherapy in 31 adults with highly refractory, highly active epilepsy. Since 2018, in line with the International League Against Epilepsy's addition of "immune" as an etiology in the Classification of Epilepsy, we initiated immunotherapy after comprehensive antiseizure medication failures while at the same time screening for an autoimmune origin. The workup included assessing clinical features, serum autoantibody testing, cerebrospinal fluid testing (where feasible), magnetic resonance imaging (MRI), and electroencephalography. All patients received intravenous methylprednisolone or IV immunoglobulin according to previously published protocols, and follow-up was for at least 12 months.
Nine patients (29%) in this highly refractory cohort demonstrated a sustained treatment response, measured as a greater than 50% improvement in seizure frequency for at least 12 months. Three patients (10%) became seizure-free. Six patients (20%) were classified as partial responders and experienced an initial response that was not sustained. Apart from a trend toward a diagnosis of focal epilepsy, we did not identify any specific serological, clinical, electrodiagnostic, or imaging features with statistical significance that were predictive of treatment response.
This patient group demonstrated a reasonable response rate to an immunotherapy trial. These findings are surprising but support the consideration of an immunotherapy trial in patients with refractory epilepsy. Requirements for repeated courses of immunotherapy differed significantly between patients, and this is an area of interest for further research. The basis for response in this cohort remains unclear; in some cases, antiseizure medication changes may have contributed; however, without any apparent autoimmune features, we consider potential blood-brain barrier repair or a placebo effect as hypothetical alternative mechanisms of action for the response to immunotherapy.
随着难治性癫痫中自身免疫性相关癫痫发作的新证据不断出现，我们开始为部分患者提供免疫治疗试验。在此，我们回顾这种方法的治疗反应、预测性临床特征及效用。
这是一项回顾性单中心队列研究（2018 - 2022年），对31例高度难治性、高度活动性癫痫的成人患者进行经验性、姑息性免疫治疗。自2018年起，根据国际抗癫痫联盟在癫痫分类中将“免疫”列为病因，我们在全面的抗癫痫药物治疗失败后启动免疫治疗，同时筛查自身免疫性病因。检查包括评估临床特征、血清自身抗体检测、脑脊液检测（可行时）、磁共振成像（MRI）和脑电图检查。所有患者均按照先前发表的方案接受静脉注射甲泼尼龙或静脉注射免疫球蛋白，随访至少12个月。
在这个高度难治性队列中，9例患者（29%）表现出持续的治疗反应，即癫痫发作频率至少改善50%并持续至少12个月。3例患者（10%）实现无癫痫发作。6例患者（20%）被归类为部分反应者，经历了最初但未持续的反应。除了局灶性癫痫诊断有一定趋势外，我们未发现任何具有统计学意义的特定血清学、临床、电诊断或影像学特征可预测治疗反应。
该患者群体对免疫治疗试验表现出合理的反应率。这些发现令人惊讶，但支持在难治性癫痫患者中考虑进行免疫治疗试验。患者对重复免疫治疗疗程的需求差异很大，这是一个值得进一步研究的领域。该队列中反应的基础仍不清楚；在某些情况下，抗癫痫药物的改变可能起了作用；然而，在没有任何明显自身免疫特征的情况下，我们认为潜在的血脑屏障修复或安慰剂效应是免疫治疗反应的假设性替代作用机制。
