儿童抗髓鞘少突胶质细胞糖蛋白免疫球蛋白G抗体相关疾病的表型特征及复发因素研究

doi:10.12114/j.issn.1007-9572.2022.0671

中国全科医学 ›› 2023, Vol. 26 ›› Issue (18): 2244-2249.DOI: 10.12114/j.issn.1007-9572.2022.0671

儿童抗髓鞘少突胶质细胞糖蛋白免疫球蛋白G抗体相关疾病的表型特征及复发因素研究

王欣¹^,^*(), 赵瑞斌², 杨花芳¹, 刘崇¹, 刘甜³, 路翠¹, 陈迪迪¹

1．050031　河北省石家庄市，河北省儿童医院神经内科
2．050031　河北省石家庄市，河北医科大学医学影像学院
3．050017　河北省石家庄市，河北医科大学基础医学院

收稿日期:2022-06-14 修回日期:2023-01-05 出版日期:2023-06-20 发布日期:2023-02-03
通讯作者: 王欣
作者贡献：王欣负责论文的研究思路、数据收集、论文起草、统计学分析、绘制图表等，负责最终版本修订，对论文整体负责；赵瑞斌负责入组病例影像学指导；刘崇、刘甜选取入组病例，数据处理，进行统计分析；路翠、陈迪迪数据收集；杨花芳进行核心督导，提供技术支持。
基金资助:
河北省医学科学研究课题计划(20220723，20230178); 2022年政府资助省级医学优秀人才项目(冀财预复[2022]180号)

Phenotypic Characteristics and Recurrence Factors of MOG-IgG Associated Disorders in Children

WANG Xin¹^,^*(), ZHAO Ruibin², YANG Huafang¹, LIU Chong¹, LIU Tian³, LU Cui¹, CHEN Didi¹

1. Department of Neurology, Children's Hospital of Hebei Province, Shijiazhuang 050031, China
2. School of Medical Imaging, Hebei Medical University, Shijiazhuang 050031, China
3. School of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China

Received:2022-06-14 Revised:2023-01-05 Published:2023-06-20 Online:2023-02-03
Contact: WANG Xin

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摘要/Abstract

摘要： 背景抗髓鞘少突胶质细胞糖蛋白（MOG）免疫球蛋白G抗体相关疾病（MOGAD）在儿童中的比例明显高于成人。目前在儿童中MOGAD相关表型的特征及与复发风险的联系仍未明确。目的观察儿童血清MOG免疫球蛋白G抗体（MOG-IgG）阳性的中枢神经系统（CNS）脱髓鞘疾病的表型特征及复发因素。方法对河北省儿童医院2017年12月至2021年12月确诊的54例MOGAD的儿童进行随访研究，回顾性分析每次发作时的临床表型、实验室检查、影像学特点、血/脑脊液的MOG-IgG滴度变化、疗效及复发高危因素。采用细胞转染免疫荧光法（CBA）检测MOG-IgG。随访截至2022-03-31。结果　54例患儿发病年龄为6.0（4.0，8.0）岁，男女比例为1∶1.07。血清MOG-IgG滴度为1∶10~1∶320。急性播散性脑脊髓炎（ADEM）为最常见的表型（44.4%，24/54），其次是视神经炎（ON）（25.9%，14/54）及非ADEM样脑膜/脑炎（20.4%，11/54）。10例（18.5%）患儿血及脑脊液MOG-IgG均呈阳性，2例（3.7%）脑脊液N-甲基-D-天冬氨酸受体（NMDAR）-IgG和血MOG-IgG为双阳性。在78次病程事件中，76.9%（60/78）事件的患儿脑MRI显示急性发作病灶，常见部位为皮质旁白质（66.7%，40/60）及视神经（35.0%，21/60）。40例（74.1%）患儿为单次病程，主要的临床表型为ADEM（57.5%，23/40）及非ADEM样脑膜/脑炎（25.0%，10/40）；14例患儿经历了2次及以上的复发病程（25.9%，14/54），主要的首发表型为ADEM-ON（57.1%，8/14）及单纯ON（21.4%，3/14）。未复发患儿首发表型为单纯ON、ADEM-ON比例明显低于复发患儿（P<0.05）。患儿首次发作均接受一线免疫调节治疗，14例复发患儿中2例（14.3%）经吗替麦考分酯治疗后好转，1例（7.1%）给予美罗华治疗后好转，11例（78.6%）经再次甲泼尼松冲击联合丙种球蛋白治疗后症状及影像学好转。复发患儿MOG-IgG滴度未见增加。经治疗28例（51.9%）患儿临床症状完全恢复，11例（20.4%）患儿有神经后遗症，视觉障碍（54.5%，6/11）是最常见的后遗症。结论 MOGAD的临床表型多样，儿童常见的表型为ADEM、ON及非ADEM样脑膜/脑炎。MRI损害部位广泛，以ADEM-ON及单纯ON为首发表型是复发的高危表型，大多患儿预后良好，部分可伴神经后遗症表现。

关键词: 脱髓鞘自身免疫疾病，中枢神经, 髓鞘少突胶质细胞糖蛋白, 儿童, 临床表型, 复发

Abstract:

Background

The prevalence of anti-myelin oligodendrocyte glycoprotein (MOG) -IgG associated disorders (MOGAD) is significantly higher in children than that in adults. The characteristics and associations of phenotypes and recurrence risk in children are still unclear.

Objective

To examine the phenotypic features and recurrence factors of MOG-IgG positivity in central nervous system inflammatory demyelinating diseases in children.

Methods

A follow-up study on 54 children with MOGAD diagnosed in Children's Hospital of Hebei Province from December 2017 to December 2021 was performed. Phenotypic features at each demyelinating attack, laboratory tests, imaging characteristics, MOG-IgG titers in serum/cerebrospinal fluid (CSF), efficacy, and high risk factors for recurrence were analyzed. The MOG-IgG was tested using cell-based immunofluorescence assay. All patients were followed up until March 31, 2022.

Results

In our study, the median age of onset was 6.0 (4.0, 8.0) years and the male to female ratio was 1∶1.07. Serum MOG-IgG titers were 1∶10-1∶320. Acute disseminated encephalomyelitis (ADEM) was the most common phenotype (44.4%, 24/54), followed by optic neuritis (ON) (25.9%, 14/54) and non-ADEM-like meninges /encephalitis (20.4%, 11/54). Ten cases (18.5%) were positive for MOG-IgG in serum and CSF, and 2 (3.7%) were positive for both NMDAR-IgG in CSF and MOG-IgG in serum. Brain MRI showed new lesions during the 76.9% (60/78) of the 78 attacks in total, and the most common locations were cortical white matter (66.7%, 40/60) and optic nerve (35.0%, 21/60). Forty patients (74.1%, 40/54) experienced one episode, the main phenotypes were ADEM (57.5%, 23/40) and non-ADEM-like meninges/encephalitis (25.0%, 10/40). Fourteen patients (25.9%, 14/54) had two or more episodes, and the initial phenotype of them was ADEM with ON (57.1%, 8/14) or ON (21.4%, 3/14). Compared with recrudescent cases, non-recrudescent cases had much lower prevalence of ON or ADEM with ON as the primary phenotype (P<0.05). All the children received first-line immunoregulation therapy at the time of the initial attack. Of the 14 relapsed cases, 2 (14.3%) were improved after mycophenolate mofetil treatment, one (7.1%) was better after rituximab treatment, and the other 11 (78.6%) had improved symptoms and imaging manifestations after being treated with methylprednisone pulse therapy combined with gamma globulin again. MOG-IgG titers were not increased in the recurrent children. After treatment, 28 (51.9%) children were completely improved, while 11 (20.4%) children had various neurological sequelae, among which visual dysfunction〔54.5% (6/11) 〕 was the most common.

Conclusion

The clinical phenotypes of MOGAD in children are diverse, among which the common phenotypes are ADEM, ON and non-ADEM-like meninges/encephalitis. Brain damages detected by MRI are extensive. The initial phenotypes of ADEM with ON and ON are prone to relapse. Most children have a good prognosis, but some may be accompanied by neurological after effects.

Key words: Demyelinating autoimmune diseases, CNS, Myelin oligodendrocyte glycoprotein, Child, Clinical phenotype, Recurrence

王欣,赵瑞斌,杨花芳,等. 儿童抗髓鞘少突胶质细胞糖蛋白免疫球蛋白G抗体相关疾病的表型特征及复发因素研究[J]. 中国全科医学, 2023, 26(18): 2244-2249. DOI: 10.12114/j.issn.1007-9572.2022.0671.
WANG Xin,ZHAO Ruibin,YANG Huafang, et al. Phenotypic Characteristics and Recurrence Factors of MOG-IgG Associated Disorders in Children[J]. Chinese General Practice, 2023, 26(18): 2244-2249. DOI: 10.12114/j.issn.1007-9572.2022.0671.

图/表 2

图1 MOGAD的MRI表现注：图中箭头所指部位病变分别为脑干（A），双侧小脑（B），顶叶白质（C），内囊后肢及脑室旁（D），皮质旁白质（脑白质营养不良样（E），丘脑（F），视神经（G），脊髓（H）；MOGAD=抗髓鞘少突胶质细胞糖蛋白免疫球蛋白G抗体相关疾病

Figure 1 Brain MRI lesions of children with MOGAD

表1 54例患儿单相及复发情况比较〔n（%）〕

Table 1 Comparison of the initial phenotype and clinical manifestations in 54 children by the prevalence of recurrence

项目	例数	起病的临床表型					首发临床表现
项目	例数	ADEM	单纯ON	ADEM-ON	脊髓炎	非ADEM样脑膜/脑炎	发热	脑病	癫痫发作	肢体无力	视力下降
未复发	40	23（57.5）	2（5.0）	1（2.5）	4（10.0）	10（25.0）	11（27.5）	21（52.5）	3（7.5）	3（7.5）	6（15.0）
复发	14	1（7.1）	3（21.5）	8（57.2）	1（7.1）	1（7.1）	8（57.2）	10（71.4）	5（35.7）	3（21.5）	8（57.2）
χ²值		—	—	—	—	—	—	—	—	—	—
P值		0.333	0.010	<0.001	0.320	0.706	0.343	0.124	0.529	0.574	0.308

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儿童抗髓鞘少突胶质细胞糖蛋白免疫球蛋白G抗体相关疾病的表型特征及复发因素研究

Phenotypic Characteristics and Recurrence Factors of MOG-IgG Associated Disorders in Children

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