中国循证儿科杂志 ›› 2021, Vol. 16 ›› Issue (5): 351-356.

• 论著 • 上一篇    下一篇

不同血清型视神经脊髓炎谱系疾病双向队列研究

滕新岭, 常旭婷张捷李尚茹武元谢涵包新华张月华姜玉武吴晔
  

  1. 北京大学第一医院儿科 北京,100034
  • 收稿日期:2021-10-25 修回日期:2021-10-25 出版日期:2021-10-25 发布日期:2021-10-25
  • 通讯作者: 吴晔

Neuromyelitis optica spectrum diseases of different serology in children: A bidirectional cohort study

TENG Xinling,CHANG Xuting,ZHANG Jie,LI Shangru,WU Yuan,XIE Han,BAO Xinhua,ZHANG Yuehua,JIANG Yuwu,WU Ye   

  1. Department of Pediatrics,Peking University First Hospital,Beijing 100034,China
  • Received:2021-10-25 Revised:2021-10-25 Online:2021-10-25 Published:2021-10-25
  • Contact: WU Ye

摘要: 背景:视神经脊髓炎谱系疾病(NMOSD)根据血清学可分为AQP4-IgG阳性、MOG-IgG阳性和血清学阴性(2种抗体均阴性),目前对于不同血清型NMOSD患儿的临床表型及影像学特征的差异尚不明确。 目的:通过建立NMOSD患儿双向随访队列,比较不同血清型NMOSD临床表型差异,以利于临床识别。 设计:动态双向队列研究。 方法:2012年1月至2021年3月在北京大学第一医院儿科诊断为NMOSD患儿即进入队列,依据事先设计的临床观察量表进行临床特征信息收集,回顾性采集既往的临床资料(首次诊断收集发病以来的临床症状和体征,他院诊断的收集既往的诊疗经过),对临床特征进行随访观察,队列终点为起病至末次随访时间≥6个月。以AQP4-IgG阳性、MOG-IgG阳性和血清学阴性分为3组。 主要结局指标:不同血清型的临床特征。 结果:46例NMOSD患儿中,MOG-IgG阳性组、AQP4-IgG阳性组和血清学阴性组分别为21、12和13例,3组起病年龄、起病至末次随访中位病程和发作次数差异均无统计学意义,性别构成比差异有统计学意义,AQP4-IgG阳性组以女孩多见。首次发作的临床表型共74个,3组大脑综合征和脑干症状差异有统计学意义,大脑综合征在MOG-IgG阳性组(42.9%)和血清学阴性组(43.8%)常见,脑干症状在AQP4-IgG阳性组(33.3%)和血清学阴性组(23.1%)常见;病程中所有发作临床表型共196个,3组横贯性脊髓炎(TM)、大脑综合征、脑干症状和延髓最后区症状差异均有统计学意义,TM在AQP4-IgG阳性组占比最高(43.9%),大脑综合征在MOG-IgG阳性组(36.2%)和血清学阴性组(34.4%)常见,脑干症状在AQP4-IgG阳性组(17.1%)和血清学阴性组(18.0%)占比较高、延髓最后区症状在AQP4-IgG阳性组(12.2%)常见。头颅MR共收集到134个,主要受累部位为皮层下白质(59.0%)和脑干 (47.8%);脊髓MR共采集到42个,3组皮层下白质、脑室旁白质、胼胝体、丘脑、基底节、脑干差异均有统计学意义,皮层下白质在MOG-IgG阳性组和血清学阴性组占比较大,脑室旁白质在AQP4-IgG阳性组和血清学阴性组占比较大,胼胝体在AQP4-IgG阳性组中常见,丘脑在AQP4-IgG阳性组、MOG-IgG阳性组占比较大,基底节在MOG-IgG阳性组占比较大,脑干在AQP4-IgG阳性组占比较大。3组胸髓和长节段脊髓炎差异均有统计学意义,在3组中普遍受累,以AQP4-IgG阳性组更常见(94.1%和100%)。共收集94次急性期脑脊液和46次自身免疫性抗体数据,3组脑脊液有核细胞数、蛋白和不同自身免疫性抗体差异均无统计学意义。46例均得到了末次随访EDSS评分,中位数为1.5(0~4.5)分,3种不同血清型末次随访EDSS评分差异无统计学意义。 结论:AQP4-IgG阳性及血清学阴性NMOSD以女孩多见。大脑综合征常见于MOG-IgG阳性和血清学阴性NMOSD。延髓最后区症状常见于AQP4-IgG阳性患儿。皮质下白质受累在MOG-IgG阳性和血清学阴性患儿更常见,长节段脊髓炎在AQP4-IgG患儿中更常见。

关键词: 儿童, 视神经脊髓炎谱系疾病, MOG-IgG, AQP4-IgG

Abstract: Background: Neuromyelitis optica spectrum disease (NMOSD) is divided into AQP4-IgG positive, MOG-IgG positive and serological negative cases according to the serology. The differences in clinical and imaging characteristics of patients with different serological NMOSD are not clear yet. Objective: We established a long-term follow-up cohort of pediatric patients to understand the differences among different serological NMOSD. Design: Dynamic bidirectional cohort study. Methods: Children diagnosed with NMOSD in the Department of Pediatrics, Peking University First Hospital from January 2012 to March 2021 were enrolled in the cohort, and information on clinical characteristics was collected based on a pre-designed clinical observation scale, with retrospective collection of previous clinical data (clinical symptoms and signs since the first diagnosis, and previous clinical characteristics for those diagnosed in other hospitals), and observation of clinical characteristics at hospital follow-up. The cohort endpoint was time from onset to last follow-up ≥6 months. The cohort was divided into 3 groups as AQP4-IgG-positive, MOG-IgG-positive and serologically negative (negative for both antibodies). Main outcome measures: Clinical characteristics of different serological NMOSD children. Results: Of the 46 cases of NMOSD, there were 21, 12 and 13 cases in the MOG-IgG-positive, AQP4-IgG-positive and serologically negative groups, respectively, with no statistically significant differences in age at onset, median disease duration from onset to final follow-up and number of episodes in the 3 groups, and statistically significant differences in sex composition ratios, with AQP4-IgG-positive being more common in females. There were 74 clinical phenotypes for the first attack, and the differences in cerebral syndrome and brainstem symptom in the 3 groups were statistically significant.Cerebral syndrome was common in the MOG-IgG-positive group (42.9%) and the serology-negative group (43.8%), and brainstem symptom was common in the AQP4-IgG-positive group (33.3%) and the serology-negative group (23.1%).During the course of the disease, there were 196 phenotypes in total, and the differences between the 3 groups were statistically significant for different serotypes of TM, cerebral syndrome, brainstem symptom, and postrema symptom, with TM being the most common phenotype in the AQP4-IgG-positive group (43.9%), brain syndrome common in the MOG-IgG-positive group (36.2%) and serology-negative group (34.4%), brainstem symptom common in the AQP4-IgG-positive group (17. 1%) and serologically negative group (18.0%), and postrema symptom common in the AQP4-IgG-positive group (12.2%). A total of 134 sites of brain MR involvement were acquired, mainly in the subcortical white matter (59.0%) and brainstem (47.8%) and a total of 42 sites of spinal MR involvement were acquired, with statistically significant differences in the subcortical white matter, paraventricular white matter, corpus callosum, thalamus, basal ganglia, and brainstem among the three groups with different serotypes.Subcortical white matter was more prevalent in the MOG-IgG-positive and serologically negative groups, paraventricular white matter was more predominant in the AQP4-IgG positive and serologically negative groups, corpus callosum was common in the AQP4-IgG positive group, thalamus was common in AQP4-IgG positive and MOG-IgG positive groups, basal ganglia was common in MOG-IgG positive group, and brainstem was common in AQP4-IgG positive group. Statistically significant differences were found among three groups with different serotypes of thoracic and longitudinally extensive transverse myelitis.The differences were statistically significant and were commonly involved in all 3 groups, with AQP4-IgG positive being more common (94.1% and 100%). A total of 94 acute cerebrospinal fluid and 46 autoimmune antibody data were collected, and the differences in number of nucleated cells of different serotypes, proteins and different autoimmune antibodies were not statistically significant in the 3 groups. Final follow-up EDSS scores were obtained from 46 cases with a median score of 1.5 (0-4.5) and no statistically significant differences were found among the 3 different serotypes. Conclusion: AQP4-IgG positivity was more common in females. Cerebral syndrome was common in MOG-IgG-positive and serologically negative NMOSD. Postrema syndrome was common in AQP4-IgG-positive children. Subcortical white matter involvement was the most common in MOG-IgG-positive and antibody-negative children, and longitudinally extensive transverse myelitis was the most common in children with AQP4-IgG-positive.

Key words: Children, Neuromyelitis optica spectrum diseases, MOG-IgG, AQP4-IgG