抗谷氨酸脱羧酶-65抗体相关神经免疫病九例临床特点分析

Clinical analysis of nine cases of neuroimmune disease with antibodies against glutamic acid decarboxylase 65

目的探讨抗谷氨酸脱羧酶-65(GAD65)抗体相关神经免疫病的临床特点、辅助检查结果、治疗及临床预后的情况。方法收集2018年10月至2020年10月就诊于首都医科大学宣武医院神经内科的9例GAD65抗体阳性患者的临床资料并进行回顾性分析。结果9例患者男女比例为1∶2,发病年龄为17~68(43.6±20.5)岁。有2例患者具有前驱感染史。首发症状以癫痫首发者4例,记忆力减退者2例,头晕者2例,肢体僵硬者1例。临床表型包括小脑性共济失调1例,单纯癫痫发作1例,边缘性脑炎5例,僵人综合征伴癫痫发作1例,脑干脑炎1例。9例患者中,合并甲状腺功能亢进1例,合并桥本氏甲状腺炎2例,血过氧化物酶抗体阳性5例。4例患者头颅磁共振成像表现为海马或颞叶异常信号,1例表现为海马萎缩。6例患者行脑电图检查均有癫痫样异常放电,放电区域在右侧额区2例,左侧或右侧颞区各2例。9例患者均接受免疫治疗,6例仅接受激素治疗,2例联合丙种球蛋白治疗,1例联合免疫抑制剂治疗。随访9例患者,其中失访2例,剩余7例随访时间为1.5个月至3年3个月不等,1例患者症状完全缓解,3例部分缓解,其中2例遗留痫性发作,1例遗留记忆力减退。其余3例症状未缓解。结论抗GAD65抗体相关神经免疫病以中青年女性最为常见,可表现为边缘性脑炎、僵人综合征等,临床以癫痫发作、肢体僵直、认知损害、小脑性共济失调等为主要表现,可出现症状重叠,血或脑脊液抗体检测为诊断的"金标准",整体预后不佳,早期及时的免疫治疗可改善患者预后,对以癫痫发作为核心症状的患者,免疫治疗效果最佳。

Objective To explore the clinical features,auxiliary examinations,therapies and prognoses of patients with antibodies targeting glutamic acid decarboxylase 65(GAD65).Methods The nine patients with anti-GAD65 neuroimmune disease,admitted to Xuanwu Hospital,Capital Medical University from October 2018 to October 2020,were analyzed,retrospectively.Results The onset age of nine cases was 17-68(43.6±20.5)years old,and six cases were female.Two cases had preceding infection.The data of initial symptoms were collected and analyzed,including epileptic onset in four cases,memory impairment in two cases,dizziness in two cases and limb stiffness in one case.As the disease continued to advance,one case developed cerebellar ataxia,one case presented with isolated epilepsy,five cases suffered from limbic encephalitis,one case had stiffman syndrome,one case had brainstem encephalitis.Five cases had antibodies against thyroid peroxidase.Brain magnetic resonance imaging scan showed abnormal signals of T2/fluid attenuated inversion recovery sequences in four cases,mainly involved bilateral temporal lobes or hippocampus.Epileptiform discharges of frontal or temporal regions of electroencephalography were observed in six cases.All cases received immunotherapy and long-term follow-up was performed in seven cases.Four cases benefited from the immunotherapy.Among the four patients,one fully recovered and returned to work,the other three cases developed neurologic sequelae,including seizures(two cases),and short-term memory loss(one case).The remaining three patients were unresponsive to treatment.Conclusions GAD65 antibody-mediated neuroimmune disease is a rare neurological disorder,presenting with various syndromes including limbic encephalitis or stiffman syndrome,which is more susceptible to young female.The clinical manifestations included epileptic onset,limb stiffness,cognitive impairment and cerebellar ataxia,etc.Detection of GAD65 antibody in serum or cerebrospinal fluid was gold standard.Early immunotherapy contributed to improving the prognosis of patients,especially for those patients with epileptic onset as the main symptom.