抗谷氨酸脱羧酶65抗体综合征的临床特征分析

Analysis of Clinical Characteristics of Anti-glutamic Acid Decarboxylase Antibodies(Anti-GAD65ab)Related Neurological Spectrum Disorders

目的分析探讨抗谷氨酸脱羧酶65(GAD65)抗体综合征相关的各种神经系统损害的临床特点,提高对抗GAD65抗体综合征的认识。方法回顾性收集2018年1月至2022年12月复旦大学附属中山医院及厦门分院收治的6例抗GAD65抗体阳性患者的临床、影像学、电生理和实验室检查资料,分析并总结抗GAD65抗体综合征的特征。结果6例抗GAD65抗体阳性患者,均为女性,平均年龄(55±12.7)岁,平均病程(23.6±15.3)个月。6例患者的神经系统损害包括:经典型僵人综合征2例,僵人综合征合并小脑性共济失调1例,颞叶癫癎1例,自身免疫性脑炎伴症状性癫间1例,小脑性共济失调伴重症肌无力1例。神经系统外损害:合并成人迟发型自身免疫性糖尿病3例,合并自身免疫性甲状腺炎2例,合并干燥综合征1例,合并恶性贫血2例,合并甲状腺癌1例。患者的血清抗GAD65抗体滴度均高于脑脊液,但临床症状严重程度、病程与抗GAD65抗体滴度高低无相关性。头颅影像学检查:1例自身免疫性脑炎患者提示右侧海马肿胀,1例小脑性共济失调患者提示双侧小脑半球显著萎缩。2例癫间患者脑电图提示一侧或双侧颞区高波幅尖波、尖慢复合波散在发放,3例僵人综合征患者的针电极肌电图提示腰椎椎旁肌、腹直肌同步的持续运动单位发放。4例患者进行了免疫抑制治疗,其临床症状明显改善。结论抗GAD65抗体综合征以女性多见,临床表现形式多样,常合并多种其他系统自身免疫性疾病,部分可能合并肿瘤;头颅MRI及神经电生理检查在本病的临床分型诊断中有特殊定位价值;血清抗GAD65抗体滴度高于脑脊液,但抗GAD65抗体滴度高低并不影响临床症状的严重程度;免疫调节治疗是最主要的治疗方法。

Aim To investigate the clinical symptoms and auxiliary examination of anti-glutamic acid decarboxylase antibodies(anti-GAD65 ab)related neurological spectrum disorders,and enhance clinical doctors'awareness of its diagnosis and treatment.Methods Clinical manifestation,MRI and electrophysiological characters,and laboratory examination data of 6 anti-GAD65 ab positive patients admitted to the department of neurology of Zhongshan Hospital and Xiamen Branch of Fudan University from January 2018 to December 2022 were retrospectively collected.The characteristics of anti-GAD65 antibody syndrome were analyzed and summarized.Results All the 6 patients were female,ages range from 38 to 74 years,and with an average age of 55 years.The median course was 30 months.Among the patients,two patients were diagnosed with classic stiff-person syndrome,one patient with stiff-person plus syndrome,one patient with temporal lobe epilepsy,one patient with autoimmune encephalitis and symptomatic epilepsy,and one with cerebellar ataxia(CA)combined with myasthenia gravis.Five patients were complicated with other autoimmune diseases,and one patient was complicated with thyroid cancer.The titers of anti-GAD65 ab in the serum of 6 patients were all higher than those in the cerebrospinal fluid.The severity of clinical symptoms in patients was not related to the duration of the disease or the level of anti-GAD65 ab titers(P>0.05).In term of head MRI,one patient with autoimmune encephalitis showed swelling of the right hippocampus,and one patient with cerebellar ataxia showed significant atrophy of both cerebellar hemispheres.In term of electrophysiological characteristics,EEG showed scattered high amplitude sharp slow complex waves in one or both temporal lobes in two patients of epilepsy.Needle electrode electromyography showed synchronous continuous motor unit activity in the paraspinal muscles and rectus abdominis in three patients of stiff-person syndrome.Four patients received immunomodulatory therapy,and the clinical symptoms improved significantly.Conclusion Anti-GAD65 ab related neurological spectrum disorders are more common in women,with various clinical manifestations,often accompanied by multiple autoimmune diseases,and some patients may also have tumors.Head MRI and electrophysiological examination have significant guiding value in the clinical classification diagnosis of this disease.The detection rate of anti-GAD65 ab in serum is higher than that in cerebrospinal fluid,and the titer of anti-GAD65 ab is not related to the severity of clinical symptoms.Immunomodulatory therapy is the main treatment method for the patients with anti-GAD65 ab related neurological spectrum disorders.