BACKGROUND Investigations of myelin oligodendrocyte glycoprotein (MOG) antibodies are usually focused on demyelinating syndromes, but the entire spectrum of MOG antibody-associated syndromes in children is unknown. In this study, we aimed to determine the frequency and distribution of paediatric demyelinating and encephalitic syndromes with MOG antibodies, their response to treatment, and the phenotypes associated with poor prognosis. METHODS In this prospective observational study, children with demyelinating syndromes and with encephalitis other than acute disseminated encephalomyelitis (ADEM) recruited from 40 secondary and tertiary centres in Spain were investigated for MOG antibodies. All MOG antibody-positive cases were included in our study, which assessed syndromes, treatment and response to treatment (ie, number of relapses), outcomes (measured with the modified Rankin scale [mRS]), and phenotypes associated with poor prognosis. We used Fisher's exact and Wilcoxon rank sum tests to analyse clinical features, and survival Cox regression to analyse time to antibody negativity. FINDINGS Between June 1, 2013, and Dec 31, 2018, 239 children with demyelinating syndromes (cohort A) and 296 with encephalitis other than ADEM (cohort B) were recruited. 116 patients had MOG antibodies, including 94 (39%) from cohort A and 22 (7%) from cohort B; 57 (49%) were female, with a median age of 6·2 years (IQR 3·7-10·0). Presenting syndromes in these 116 patients included ADEM (46 [68%]), encephalitis other than ADEM (22 [19%]), optic neuritis (20 [17%]), myelitis (13 [11%]), neuromyelitis optica spectrum disorders (six [5%]), and other disorders (nine [8%]). Among the patients with autoimmune encephalitis in cohort B (n=64), MOG antibodies were more common than all neuronal antibodies combined (22 [34%] vs 21 [33%]). After a median follow-up of 42 months (IQR 22-67), 33 (28%) of the 116 patients had relapses, including 17 (17%) of 100 diagnosed at first episode. Steroids, intravenous immunoglobulin, or plasma exchange were used in 100 (86%) patients at diagnosis, and 32 (97%) of 33 at relapses. Rituximab was mainly used at relapses (11 [33%]). 99 (85%) of 116 patients had substantial recovery (mRS <2) and 17 (15%) moderate to severe deficits (mRS >2; one died). Phenotypes of poor prognosis included ADEM-like relapses progressing to leukodystrophy-like features, and extensive cortical encephalitis evolving to atrophy. Time to antibody negativity was longer in patients with relapses (HR 0·18, 95% CI 0·05-0·59). INTERPRETATION The spectrum of paediatric MOG antibody-associated syndromes is wider than previously reported and includes demyelinating syndromes and encephalitis. Recognition of these disorders has important clinical and prognostic implications. FUNDING Mutua Madrileña Foundation; ISCIII-Subdirección General de Evaluación y Fomento de la Investigación Sanitaria; Fondo Europeo de Desarrollo Regional; Pediatrics Spanish Society; Departament de Salut, Generalitat de Catalunya; Marato TV3 Foundation; Red Española de Esclerosis Múltiple; La Caixa Foundation; and Fundació CELLEX.

中文翻译：

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小儿脱髓鞘和脑炎综合征与髓鞘少突胶质细胞糖蛋白抗体的关联：一项多中心观察性研究

背景髓鞘少突胶质细胞糖蛋白 (MOG) 抗体的研究通常集中在脱髓鞘综合征上，但儿童中 MOG 抗体相关综合征的全谱尚不清楚。在本研究中，我们旨在确定具有 MOG 抗体的小儿脱髓鞘和脑炎综合征的频率和分布、它们对治疗的反应以及与不良预后相关的表型。方法 在这项前瞻性观察性研究中，从西班牙 40 个二级和三级中心招募了患有脱髓鞘综合征和非急性播散性脑脊髓炎 (ADEM) 的脑炎儿童的 MOG 抗体。我们的研究包括所有 MOG 抗体阳性病例，该研究评估了综合征、治疗和对治疗的反应（即复发次数），结果（使用改良的 Rankin 量表 [mRS] 测量），以及与不良预后相关的表型。我们使用 Fisher 精确和 Wilcoxon 秩和检验来分析临床特征，并使用生存 Cox 回归来分析抗体阴性的时间。结果 2013 年 6 月 1 日至 2018 年 12 月 31 日期间，招募了 239 名患有脱髓鞘综合征的儿童（队列 A）和 296 名患有 ADEM 以外的脑炎的儿童（队列 B）。116 名患者有 MOG 抗体，包括队列 A 的 94 名（39%）和队列 B 的 22 名（7%）；57 (49%) 名女性，中位年龄为 6·2 岁 (IQR 3·7-10·0)。这 116 名患者中出现的综合征包括 ADEM (46 [68%])、ADEM 以外的脑炎 (22 [19%])、视神经炎 (20 [17%])、脊髓炎 (13 [11%])、视神经脊髓炎谱障碍（6 [5%]）和其他障碍（9 [8%]）。在 B 组的自身免疫性脑炎患者（n=64）中，MOG 抗体比所有神经元抗体的总和更常见（22 [34%] 对 21 [33%]）。中位随访 42 个月 (IQR 22-67) 后，116 名患者中有 33 名 (28%) 复发，其中 100 名首次发作时诊断出 17 名 (17%)。100 名 (86%) 患者在诊断时使用了类固醇、静脉注射免疫球蛋白或血浆置换，33 名患者中有 32 名 (97%) 在复发时使用。利妥昔单抗主要用于复发（11 [33%]）。116 名患者中有 99 名 (85%) 显着恢复 (mRS <2)，17 名 (15%) 中度至重度缺陷（mRS > 2；1 名死亡）。预后不良的表型包括 ADEM 样复发进展为脑白质营养不良样特征，以及广泛的皮质脑炎发展为萎缩。复发患者出现抗体阴性的时间更长（HR 0·18，95% CI 0·05-0·59)。解释 儿科 MOG 抗体相关综合征的范围比以前报道的更广，包括脱髓鞘综合征和脑炎。识别这些疾病具有重要的临床和预后意义。资助 Mutua Madrileña 基金会；ISCIII-Subdirección General de Evaluación y Fomento de la Investigación Sanitaria；Fondo Europeo de Desarrollo Regional；西班牙儿科学会；Departament de Salut, Generalitat de Catalunya; Marato TV3 基金会；Red Española de Esclerosis Múltiple; La Caixa 基金会；和 Fundació CELLEX。识别这些疾病具有重要的临床和预后意义。资助 Mutua Madrileña 基金会；ISCIII-Subdirección General de Evaluación y Fomento de la Investigación Sanitaria；Fondo Europeo de Desarrollo Regional；西班牙儿科学会；Departament de Salut, Generalitat de Catalunya; Marato TV3 基金会；Red Española de Esclerosis Múltiple; La Caixa 基金会；和 Fundació CELLEX。识别这些疾病具有重要的临床和预后意义。资助 Mutua Madrileña 基金会；ISCIII-Subdirección General de Evaluación y Fomento de la Investigación Sanitaria；Fondo Europeo de Desarrollo Regional；西班牙儿科学会；Departament de Salut, Generalitat de Catalunya; Marato TV3 基金会；Red Española de Esclerosis Múltiple; La Caixa 基金会；和 Fundació CELLEX。