Department of Neurology, Washington University Pediatric MS and Other Demyelinating Disease Center, St. Louis, MO, USA.
Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
Ann Neurol. 2023 Feb;93(2):271-284. doi: 10.1002/ana.26502. Epub 2022 Oct 4.
The purpose of this study was to determine the frequency of myelin oligodendrocyte glycoprotein (MOG)-IgG and aquaporin-4 (AQP4)-IgG among patients with pediatric-onset multiple sclerosis (POMS) and healthy controls, to determine whether seropositive cases fulfilled their respective diagnostic criteria, to compare characteristics and outcomes in children with POMS versus MOG-IgG-associated disease (MOGAD), and identify clinical features associated with final diagnosis.
Patients with POMS and healthy controls were enrolled at 14 US sites through a prospective case-control study on POMS risk factors. Serum AQP4-IgG and MOG-IgG were assessed using live cell-based assays.
AQP4-IgG was negative among all 1,196 participants, 493 with POMS and 703 healthy controls. MOG-IgG was positive in 30 of 493 cases (6%) and zero controls. Twenty-five of 30 patients positive with MOG-IgG (83%) had MOGAD, whereas 5 of 30 (17%) maintained a diagnosis of multiple sclerosis (MS) on re-review of records. MOGAD cases were more commonly in female patients (21/25 [84%] vs 301/468 [64%]; p = 0.044), younger age (mean = 8.2 ± 4.2 vs 14.7 ± 2.6 years; p < 0.001), more commonly had initial optic nerve symptoms (16/25 [64%] vs 129/391 [33%]; p = 0.002), or acute disseminated encephalomyelitis (ADEM; 8/25 [32%] vs 9/468 [2%]; p < 0.001), and less commonly had initial spinal cord symptoms (3/20 [15%] vs 194/381 [51%]; p = 0.002), serum Epstein-Barr virus (EBV) positivity (11/25 [44%] vs 445/468 [95%]; p < 0.001), or cerebrospinal fluid oligoclonal bands (5/25 [20%] vs 243/352 [69%]; p < 0.001).
MOG-IgG and AQP4-IgG were not identified among healthy controls confirming their high specificity for pediatric central nervous system (CNS) demyelinating disease. Five percent of those with prior POMS diagnoses ultimately had MOGAD; and none had AQP4-IgG positivity. Clinical features associated with a final diagnosis of MOGAD in those with suspected MS included initial ADEM phenotype, younger age at disease onset, and lack of EBV exposure. ANN NEUROL 2023;93:271-284.
本研究旨在确定髓鞘少突胶质细胞糖蛋白（MOG）-IgG 和水通道蛋白 4（AQP4）-IgG 在儿科发病的多发性硬化症（POMS）患者和健康对照者中的频率，确定血清阳性病例是否符合各自的诊断标准，比较 POMS 与 MOG-IgG 相关疾病（MOGAD）患儿的特征和结局，并确定与最终诊断相关的临床特征。
通过前瞻性 POMS 危险因素病例对照研究，在美国 14 个地点招募 POMS 患者和健康对照者。使用活细胞检测法评估血清 AQP4-IgG 和 MOG-IgG。
1196 名参与者中，AQP4-IgG 均为阴性，其中 493 名为 POMS 患者，703 名为健康对照者。MOG-IgG 阳性者 30 例（6%），无对照者阳性。30 例 MOG-IgG 阳性患者中，25 例（83%）为 MOGAD，而 30 例（17%）患者经记录重新审查后仍保持多发性硬化症（MS）的诊断。MOGAD 患者更常见于女性患者（21/25 [84%] vs 301/468 [64%]；p=0.044）、年龄较小（平均=8.2±4.2 岁 vs 14.7±2.6 岁；p<0.001）、更常首发视神经症状（16/25 [64%] vs 129/391 [33%]；p=0.002）或急性播散性脑脊髓炎（ADEM；8/25 [32%] vs 9/468 [2%]；p<0.001），首发脊髓症状较少（3/20 [15%] vs 194/381 [51%]；p=0.002）、血清 EBV 阳性（11/25 [44%] vs 445/468 [95%]；p<0.001）或脑脊液寡克隆带（5/25 [20%] vs 243/352 [69%]；p<0.001）。
健康对照者中未发现 MOG-IgG 和 AQP4-IgG，证实其对儿科中枢神经系统（CNS）脱髓鞘疾病具有高特异性。先前诊断为 POMS 的患者中有 5%最终诊断为 MOGAD，且均无 AQP4-IgG 阳性。在疑似 MS 患者中，与 MOGAD 最终诊断相关的临床特征包括首发 ADEM 表型、发病年龄较小以及无 EBV 暴露。ANN NEUROL 2023；93:271-284.
