抗谷氨酸脱羧酶抗体相关僵人综合征33例临床与预后分析  

Clinical characteristics and prognosis of stiff-person syndrome associated with glutamic acid decarboxylase 65 antibodies: a case series from China

作　　者：柏琳 关鸿志[1] 范思远[1] 任海涛[1] 管宇宙[1] 杨英麦[1] 朱以诚[1] 崔丽英[1] Bai Lin;Guan Hongzhi;Fan Siyuan;Ren Haitao;Guan Yuzhou;Yang Yingmai;Zhu Yicheng;Cui Liying(Department of Neurology,Peking Union Medical College Hospital,Peking Union Medical College and Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院神经科,北京100730

出　　处：《中华神经科杂志》2024年第9期993-999,共7页Chinese Journal of Neurology

基　　金：中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-003);北京协和医院中央高水平医院临床科研专项-免疫与炎症性神经疾病的精准诊疗技术应用与临床规范(2022-PUMCH-B-120)

摘　　要：目的:分析抗谷氨酸脱羧酶(GAD)抗体相关僵人综合征(SPS)患者的临床特点和预后。方法:回顾性分析北京协和医院2015年1月至2023年7月诊治的抗GAD抗体相关SPS患者的人口学特征、临床表现、辅助检查结果、治疗和预后。结果:共33例患者,其中女性26例(78.8%),男性7例(21.2%),起病年龄(42±12)岁,病程24.0(10.5,37.5)个月。合并肿瘤2例(6.1%),包括侵袭性胸腺瘤和小细胞肺癌各1例。29例(87.9%,29/33)患者表现为躯干及四肢近端僵硬,14例(42.4%,14/33)患者呈发作性痉挛,18例(54.5%,18/33)患者由声光等刺激诱发。神经科体格检查发现33.3%(11/33)的患者巴宾斯基或夏道克征阳性。部分患者(36.4%,16/33)合并边缘性脑炎/癫痫或小脑性共济失调(称为复杂型SPS)。脑脊液白细胞计数中位数为2×10 6/L[四分位数:1×10 6/L,6×10 6/L;范围:(0~30)×10 6/L],28.0%(7/25)的患者脑脊液白细胞轻度升高。66.7%(14/21)的患者多通道表面肌电图检查结果提示在放松状态下主动肌与拮抗肌同步收缩。极期改良Rankin量表(mRS)评分为4(3,4)分。全部患者均接受苯二氮?类药物或巴氯芬对症治疗。30例(90.9%,30/33)患者接受一线免疫治疗,3例(9.1%,3/33)患者接受利妥昔单抗二线免疫治疗,14例(42.4%,14/33)患者接受吗替麦考酚酯长程免疫治疗。随访时间16(10,42)个月,最佳中位mRS评分为2分,66.7%(22/33)的患者功能预后良好(mRS评分≤2分),复发率30.0%(9/30),末次随访中位mRS评分为2分,53.3%(16/30)的患者预后良好。患者预后与性别、年龄、临床类型、脑脊液白细胞水平均无显著相关性(均 P>0.05)。 结论:SPS为抗GAD抗体相关神经免疫病的主要表型之一,以中年女性多见,呈慢性病程。合并肿瘤者罕见。临床可分为单纯型SPS和复杂型SPS,确诊依靠典型的症状体征、抗GAD抗体检测和肌电图检查。免疫治疗对本病有效,初始免疫治疗效果良好,复发患者的预后欠佳。Objective:To analyze the clinical characteristics and prognosis of patients with stiff-person syndrome(SPS)associated with glutamic acid decarboxylase(GAD)antibodies.Methods:A retrospective analysis was conducted on demographic characteristics,clinical manifestations,auxiliary examination results,treatment,and prognosis of patients with GAD antibody-related SPS treated at Peking Union Medical College Hospital from January 2015 to July 2023.Results:A total of 33 patients were included,comprising 26 females(78.8%)and 7 males(21.2%),with an onset age of(42±12)years and a disease duration of 24.0(10.5,37.5)months.Two cases(6.1%)were diagnosed with tumors,including 1 case with invasive thymoma and 1 case with small cell lung cancer.The majority of patients(87.9%,29/33)presented with stiffness of trunk and proximal limb muscles,42.4%(14/33)of patients exhibited episodic spasm,and 54.5%(18/33)of patients were triggered by stimuli such as sound and light.Babinski or Chaddock reflexes were elicited in 33.3%(11/33)of patients.Some patients(36.4%,16/33)had concurrent limbic encephalitis/epilepsy or cerebellar ataxia(referred to as complex SPS).The median cerebrospinal fluid(CSF)white blood cell count was 2×106/L[quartile:1×106/L,6×106/L;range:(0-30)×106/L],with mild elevation in 28.0%(7/25)of patients.Multi-channel surface electromyography in 14 out of 21 cases(66.7%)suggested synchronous contraction of agonist and antagonist muscles in a relaxed state.The modified Rankin Scale(mRS)score during the acute phase was 4(3,4).All patients received treatment with benzodiazepines or baclofen.Thirty patients(90.9%,30/33)received first-line immunotherapy,3 patients(9.1%,3/33)received second-line immunotherapy with rituximab,and 14(42.4%,14/33)received mycophenolate mofetil as long-term immunotherapy.The follow-up period was 16(10,42)months,with a median best mRS score of 2;66.7%(22/33)of patients had a favorable functional prognosis(mRS score≤2),and the recurrence rate was 30.0%(9/30).At the last follow-up,the median mRS scor

关 键 词：谷氨酸脱羧酶 僵人综合征 免疫疗法 抗神经抗体 

分 类 号：R741[医药卫生—神经病学与精神病学]