血清髓鞘少突胶质细胞糖蛋白抗体阳性的中枢神经系统脱髓鞘疾病患者的临床特征

Clinical Features of Central Nervous System Demyelinating Disease with Positive Serum Myelin Oligodendrocyte Glycoprotein Antibody

目的探讨血清髓鞘少突胶质细胞糖蛋白(MOG)抗体阳性的中枢神经系统脱髓鞘疾病患者的临床特征。方法回顾性收集自2018年1月至2021年1月在郑州大学第一附属医院儿科、眼科及神经内科收治的56例血清MOG抗体阳性患者的临床资料,包括发病年龄、性别、前驱感染病史、临床表现、实验室检查、影像学表现、治疗、扩展残疾状态评分(EDSS)、预后及随访等,并根据年龄分成未成年(<18岁)和成年(≥18岁)2个亚组。结果56例患者中,男27例,女29例;15例(26.79%)发病前出现前驱事件;20例(35.71%)首发症状为视物模糊;临床表型以急性播散性脑脊髓炎最常见(16例,28.57%)。56例行腰椎穿刺检查,其中14例(25.00%)压力升高,43例(76.79%)脑脊液白细胞升高,19例(33.93%)脑脊液总蛋白升高,20例(35.71%)白蛋白升高。7例(12.50%)合并抗N-甲基-D-天冬氨酸受体(NMDAR)抗体阳性。56例行头颅MRI,36例(64.29%)出现异常,见于皮质及皮质下(27例,75.00%)、脑干(13例,36.11%)、基底节和丘脑(9例,25.00%)、小脑(7例,19.44%)、室周(6例,16.67%)、胼胝体(4例,11.11%)、内囊和海马(各1例,2.78%)。43例行脊髓MRI,32例(74.42%)出现异常,其中颈髓(25例,78.13%)、胸髓(20例,62.50%)受累多见,17例(53.13%)出现长节段病灶。27例行视神经MRI,15例(55.56%)异常,其中球后段(11例,73.33%)受累多见。所有患者急性期接受糖皮质激素冲击或静脉注射丙种球蛋白或联合治疗,症状均减轻。随访过程中15例(26.79%)出现复发。按年龄分组,其中未成年组27例、成年组29例;两组比较,未成年组发热较成人组多见[10(37.04%)比4(13.79%),P=0.045]。未成年组最常见的是急性播散性脑脊髓炎(14例,51.85%),而成年组中最常见的是视神经炎和脊髓炎(各9例,31.03%),两组在疾病表型上的差异具有统计学意义(P=0.003)。成年组脑脊液白蛋白、总蛋白升高多于未成年组[15(51.72%)比5(18.52%),P=0.010;15(51.72%)比4(14.81%),P=0.004],而未成年组白细胞升高更常见[24(88.89%)比19(65.52%),P=0.038]。未成年组出现颅内病灶比率高于成年组[21(77.78%)比15(51.72%),P=0.042];基底节病灶仅见于未成年组(9例,42.86%)。结论MOG抗体阳性中枢神经系统脱髓鞘疾病男女发病比率类似,不同年龄组临床表型不同。患者可合并抗NMDAR抗体阳性。成年组可能存在更严重的血脑屏障破坏。未成年组更易出现颅内病灶,基底节病变可能是未成年患者特征性病变。患者经激素或者联合丙种球蛋白治疗效果好,加用免疫抑制剂可减少复发。

Objective To explore the clinical features of central nervous system demyelinating disease with positive serum myelin oligodendrocyte glycoprotein(MOG)antibody.Methods Clinical data of 56 cases with positive serum MOG antibody were retrospectively analyzed among Department of Paediatric,Ophthalmology and Neurology in the First Affiliated Hospital of Zhengzhou University from January 2018 to January 2021.Information about the age of onset,gender,history of prodromal infection,clinical manifestation,laboratory test,imaging manifestations,treatment,expanded disability status scale(EDSS),prognosis and follow-up data were collected.Patients were divided based on age:juvenile(<18 years)and adult(≥18 years).Results Among the 56 patients,27 were male and 29 were female.Fifteen cases(26.79%)had precursor events,20 cases(35.71%)with blurred vision as the primary clinical manifestation,the most common clinical phenotype was acute disseminated encephalomyelitis(16 cases,28.57%).Fifty-six cases underwent lumbar puncture examination,of which 14 cases(25.00%)had elevated pressure,43 cases(76.79%)had increased cerebrospinal fluid white blood cells,19 cases(33.93%)had elevated cerebrospinal fluid total protein,and 20 cases(35.71%)had elevated cerebrospinal fluid albumin.Seven cases(12.50%)were also positive for the anti-N-methyl-D-aspartate-receptor(NMDAR)antibody.Fifty-six cases underwent head MRI,and 36 cases(64.29%)were abnormal,including cortical and subcortical(27cases,75.00%),brain stem(13 cases,36.11%),basal ganglia and thalamus(9 cases respectively,25.00%),cerebellum(7 cases,19.44%),periventricular(6 cases,16.67%),corpus callosum(4 cases,11.11%),internal capsule and hippocampus(1 case respectively,2.78%).Spinal cord MRI was performed in 43 cases,32 cases(74.42%)had abnormalities,of which cervical spinal cord(25 cases,78.13%)and thoracic spinal cord(20 cases,62.50%)were more commonly involved.Seventeen cases(53.13%)had long-segment lesions.Twenty-seven cases underwent optic nerve MRI,15 cases(55.56%)were abnormal,of which the posterior segment(11 cases,73.33%)were more commonly involved.High-dose hormone,intravenous immunoglobulin or combination was effective in the acute phase.During the follow-up period,15 cases(26.79%)had relapsed.When stratifying by age subgroups,juvenile group was 27 cases and adult group was 29 cases.Compared with adult group,fever was more common in juvenile group[10(37.04%)vs.4(13.79%),P=0.045].Acute disseminated encephalomyelitis was the most frequent clinical phenotype in juvenile group(14 cases,51.85%),while optic neuritis and myelitis(9 cases respectively,31.03%)in adult group were more common.The difference between the two groups was statistically significant(P=0.003).The increase of albumin and total protein in cerebrospinal fluid of adult group was higher than those in juvenile group[15(51.72%)vs.5(18.52%),P=0.010;15(51.72%)vs.4(14.81%),P=0.004],while the increase of white blood cells in juvenile group was more common[24(88.89%)vs.19(65.52%),P=0.038].The rate of intracranial lesions in juvenile group was higher than that in adult group[21(77.78%)vs.15(51.72%),P=0.042].The lesions of basal ganglia were only found in juvenile group(9 cases,42.86%).Conclusion The incidence of MOG antibody positive central nervous system demyelination disease is similar in male and female.The most common clinical phenotype is different between juvenile group and adult group.Patients can co-exist with anti-NMDAR antibodies.The blood-brain barrier of adult group is more severely damaged.Intracranial lesions are more likely to occur in the juvenile group.Patients have a good effect on high-dose hormone therapy or combine with intravenous immunoglobulin,and the addition of immunosuppressants can reduce recurrence.