Qiu Zhandong, Xu Fang, Zhang Mengyao, Yang Xixi, Han Yan, Li Dawei, Liu Liang, Chen Jia, Gao Lehong, Xue Qing, Hou Yue, Sun Ying, Di Li, Fan Chunqiu, Liang Junhua, Han Yue, Dong Huiqing, Hao Junwei, Liu Zheng
Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China.
CNS Neurosci Ther. 2025 Feb;31(2):e70237. doi: 10.1111/cns.70237.
To explore the clinical phenotypes, characteristics, immunotherapy response, and outcomes of glutamic acid decarboxylase-65 (GAD65) neurological autoimmunity.
We performed a retrospective review of patients diagnosed with GAD65 neurological autoimmunity in the Department of Neurology at Xuanwu Hospital over the past 6 years (2017-2023). The clinical and laboratory data, imaging, therapeutic response, and long-term prognosis of those patients were collected and analyzed.
Among the 37 patients displaying significant neurological impairment, there were 14 males (37.8%) and 23 females (62.2%), with a median age of onset of 41.5 (25-59) years and a median interval of 9 (1.5-36) months from onset to a definitive diagnosis. Clinical phenotypes included epilepsy (15, 40.5%), limbic encephalitis (7, 18.9%), brainstem dysfunction (2, 5.4%), parkinsonism (2, 5.4%), peripheral neuropathy (3, 8.1%), cerebellar ataxia (1, 2.7%), and overlap syndromes (7, 18.9%). Out of 36 patients who received immunotherapy, the median time from onset to initiation of immunotherapy was 8.5 (1.5-37.5) months. Four cases were lost to follow-up, leaving a median follow-up period of 20.5 (16-37.25) months among the remaining 32 patients. Most patients (26, 81.3%) responded positively to immunotherapy, with some showing mild improvement or no response. Some patients showed inadequate responses to treatments such as mycophenolate mofetil (MMF), but significant improvement is observed after switching to rituximab (RTX). The relationship between the timing of initiating immunotherapy and prognosis by Spearman's rank correlation only showed weak correlation.
The clinical spectrum of GAD65 neurological autoimmunity appeared highly diverse. Immunotherapy can benefit the majority of patients, and early treatment appeared to be associated with good prognosis. RTX may be more effective than MMF; however, this requires more rigorous prospective studies to explore.
探讨谷氨酸脱羧酶65（GAD65）神经自身免疫性疾病的临床表型、特征、免疫治疗反应及预后。
我们对过去6年（2017 - 2023年）在宣武医院神经内科诊断为GAD65神经自身免疫性疾病的患者进行了回顾性研究。收集并分析了这些患者的临床和实验室数据、影像学检查、治疗反应及长期预后情况。
在37例有明显神经功能损害的患者中，男性14例（37.8%），女性23例（62.2%），发病年龄中位数为41.5（25 - 59）岁，从发病到明确诊断的时间间隔中位数为9（1.5 - 36）个月。临床表型包括癫痫（15例，40.5%）、边缘叶脑炎（7例，18.9%）、脑干功能障碍（2例，5.4%）、帕金森综合征（2例，5.4%）、周围神经病（3例，8.1%）、小脑共济失调（1例，2.7%）及重叠综合征（7例，18.9%）。在36例接受免疫治疗的患者中，从发病到开始免疫治疗的时间中位数为8.5（1.5 - 37.5）个月。4例失访，其余32例患者的随访时间中位数为20.5（16 - 37.25）个月。大多数患者（26例，81.3%）对免疫治疗反应良好，部分患者有轻度改善或无反应。一些患者对霉酚酸酯（MMF）等治疗反应欠佳，但换用利妥昔单抗（RTX）后有显著改善。采用Spearman等级相关分析免疫治疗起始时间与预后的关系，结果显示相关性较弱。
GAD65神经自身免疫性疾病的临床谱表现高度多样。免疫治疗可使大多数患者获益，早期治疗似乎与良好预后相关。RTX可能比MMF更有效；然而，这需要更严格的前瞻性研究来探索。
