抗髓鞘少突胶质细胞糖蛋白抗体合并抗N-甲基-D-天冬氨酸受体抗体阳性患者临床特点分析

Analysis of clinical characteristics of patients with anti-myelin oligodendrocyte glycoprotein and anti-N-methyl-D-aspartate receptor antibody positive

目的分析抗髓鞘少突胶质细胞糖蛋白(MOG)抗体合并抗N-甲基-D-天冬氨酸受体(NMDAR)抗体双阳性患者的临床特点,提高临床医生对此类疾病的认识,并为其诊断提供参考。方法回顾性分析2017年3月至2020年3月于复旦大学附属华山医院神经内科住院的血清抗MOG抗体和脑脊液抗NMDAR抗体均阳性的18例患者(双抗体阳性组),并利用SPSS软件进行简单随机抽样,随机选取同期就诊的血清抗MOG抗体单阳性的20例患者(抗MOG组)和脑脊液抗NMDAR抗体单阳性的20例患者(抗NMDAR组)进行组间比较。收集并分析3组患者的临床特征、检查结果及预后差异。结果3组患者人口学资料差异无统计学意义(均P>0.05),双抗体阳性组患者的症状通过聚类分析分为两类症状群,分别与抗MOG组和抗NMDAR组聚类分析后得到的症状群相对应,通过对应分析再次验证亦然。双抗体阳性组与抗MOG组相比,癫痫发作(8/18比3/20,P=0.016)、精神行为异常(8/18比0/20,P=0.001)、视力障碍(8/18比17/20,P=0.016)、构音障碍/吞咽障碍(8/18比1/20,P=0.007)的发生率差异有统计学意义。双抗体阳性组与抗NMDAR组相比,精神行为异常(8/18比19/20,P=0.001)、共济失调(12/18比1/20,P<0.001)的发生率差异有统计学意义。组间两两比较,甲状腺过氧化物酶抗体合并率、甲状腺球蛋白抗体合并率、抗核抗体合并率、脑脊液压力、脑脊液白细胞计数、蛋白、氯化物、葡萄糖水平、寡克隆区带阳性率差异均无统计学意义(均P>0.017;应用Bonferroni校正进行多组间两两比较,以P<0.017为差异有统计学意义)。双抗体阳性组与抗NMDAR组相比,头颅磁共振成像有无病灶差异有统计学意义(18/18比8/20,P<0.001)。双抗体阳性组、抗MOG组和抗NMDAR组患者治疗前初始改良Rankin量表(mRS)评分差异有统计学意义[分别为(3.72±0.96)分、(2.75±0.97)分和(3.95±0.76)分,F=10.004,P<0.001],治疗后6个月mRS评分差异无统计学意义[分别为(1.22±1.44)分、(0.40±0.75)分和(1.20±1.24)分,F=3.153,P=0.051];疾病复发率在3组间差异有统计学意义(分别为8/18、14/20和5/20,P=0.017)。结论抗MOG抗体和抗NMDAR抗体可以同时存在,出现临床表型的重叠,为一种新的综合征——MOG抗体病合并抗NMDAR脑炎重叠综合征(MNOS)。MNOS患者病情多重于MOG抗体相关疾病(MOGAD)患者,但MNOS、MOGAD、抗NMDAR脑炎患者均对免疫抑制治疗反应良好。建议对MNOS和MOGAD患者早期应用二线免疫治疗降低复发率。

Objective To analyze the clinical characteristics of patients with double-positive anti-myelin oligodendrocyte glycoprotein(MOG)antibody and anti-N-methyl-D-aspartate receptor(NMDAR)antibody,so as to raise awareness of such diseases and improve the prognosis.Methods Eighteen patients(double positive group)with positive serum anti-MOG antibody and cerebrospinal fluid anti-NMDAR antibody in Huashan Hospital,Fudan University from March 2017 to March 2020 were retrospectively analyzed.Using the SPSS software for simple random sampling,anti-MOG group(20 cases)and anti-NMDAR group(20 cases)were randomly selected at the same time for comparison.The anti-MOG group referred to the patients only with positive serum anti-MOG antibody.While the anti-NMDAR group referred to the patients whose cerebrospinal fluid anti-NMDAR antibody was positive.The clinical characteristics,laboratory examination results,radiological characteristics and prognosis of the three groups were collected and analyzed.Results There was no statistically significant difference in demographic data among the three groups(P>0.05).The symptoms of patients in the double-positive group were divided into two categories by cluster analysis,which corresponded to the symptom groups obtained by cluster analysis of the anti-MOG group and the anti-NMDAR group,and the same result was verified by correspondence analysis.Compared with the anti-MOG group,the incidence of epilepsy(10/18 vs 3/20,P=0.016),psychosis and behavior change(8/18 vs 0/20,P=0.001),visual disturbances(8/18 vs 17/20,P=0.016),dysarthria/dysphagia(8/18 vs 1/20,P=0.007)was significantly different in the double-positive group(P<0.017).Compared with the anti-NMDAR group,the incidence of ataxia(8/18 vs 19/20,P=0.001),psychosis and behavior change(12/18 vs 1/20,P<0.001)was significantly different in the double-positive group.There was no statistically significant difference in the combination rate of thyroid peroxidase antibody,thyroglobulin antibody and antinuclear antibody between two groups,and the cerebrospinal fluid pressure,white blood cell count,protein,glucose,chloride and positive rate of oligoclonal band were also not statistically different between two groups(P>0.017;P<0.017 indicates statistically significant difference by Bonferroni corrected multiple comparisons).Compared with the anti-NMDAR group,whether the brain magnetic resonance imaging had lesions was different in double positive group(18/18 vs 8/20,P<0.001).The initial modified Rankin Scale(mRS)scores before treatment were different among the double positive group,anti-MOG group and anti-NMDAR group(3.72±0.96,2.75±0.97,3.95±0.76,respectively,F=10.004,P<0.001),but there was no statistically significant difference in the scores after six-month treatment(1.22±1.44,0.40±0.75,1.20±1.24,respectively,F=3.153,P=0.051),and the recurrence rate of the disease was different among the three groups(8/18,14/20,5/20,respectively,χ²=10.004,P=0.017).Conclusions Anti-MOG antibodies and anti-NMDAR antibodies could exist at the same time,showing clinical phenotype overlap,which was a new syndrome called the overlapping syndrome of myelin oligodendrocyte glycoprotein antibody-associated disease and NMDAR encephalitis,MNOS.The condition of MNOS patients was more severe than that of patients with MOG antibody-associated disease(MOGAD),but patients with MNOS,MOGAD,and anti-NMDAR encephalitis all responded well to immunosuppressive therapy.It was suggested that early second-line immunotherapy should be given to reduce the recurrence rate in patients with MNOS and MOGAD.