Table_1_Epidemiology of Pediatric NMOSD in Germany and Austria.XLSX

Background: Neuromyelitis optica spectrum disorders (NMOSD) are severe inflammatory demyelinating disorders of the central nervous system mainly characterized by recurrent episodes of uni- or bilateral optic neuritis (ON), transverse myelitis (TM) and brainstem syndromes (BS). The majority of adult patients has serum antibodies directed against the water channel protein aquaporin 4 (AQP4-abs). In pediatric patients, AQP4-abs are less, while antibodies against myelin oligodendrocyte glycoprotein (MOG-abs) are more frequently detectable than in adults. Some children with NMOSD have neither AQP4- nor MOG-ab (double-seronegative).
Objective: Evaluation of epidemiological data regarding incidence and prevalence of pediatric NMOSD in Germany and Austria.
Methods: We recruited pediatric NMOSD patients between 1 March 2017 and 28 February 2019 with five different tools: (1) ESPED (Surveillance Unit for Rare Pediatric Disorders in Germany), (2) ESNEK (Surveillance for Rare Neurological Disorders during Childhood), (3) pediatric neurology working group within the Austrian Society of Pediatrics and Adolescent Medicine, (4) BIOMARKER Study and (5) NEMOS (Neuromyelitis optica Study Group). We requested data regarding clinical symptoms, antibody status, therapy regimen and response via a standardized questionnaire.
Results: During the 2-year recruitment period, 46 (both incidental and prevalent) patients with a suspected diagnosis of NMOSD were brought to our attention. Twenty-two of these patients did not fulfill the inclusion criteria. Of the remaining 24 children, 22 had a median age at onset of 11 (range 3–17) years and 16/22 were female (72.7%) (no data in two patients). Sixteen of 24 patients were AQP4-ab positive (67%), 4/24 MOG-ab positive (16.7%), three children were double-seronegative and in one patient no antibody testing was done. We calculated an incidence rate of 0.022 per 100,000 person-years for Germany, while there was no incidental case in Austria during the recruitment period. The prevalence rate was 0.147 and 0.267 per 100,000 persons in Germany and Austria, respectively.
Conclusion: Pediatric NMOSD, with and without associated antibodies, are very rare even considering the different limitations of our study. An unexpected finding was that a considerable proportion of patients was tested neither for AQP4- nor MOG-abs during diagnostic work-up, which should prompt to establish and disseminate appropriate guidelines.

背景：视神经脊髓炎谱系疾病（Neuromyelitis optica spectrum disorders, NMOSD）是一类严重的中枢神经系统炎性脱髓鞘疾病，主要以反复发作的单侧或双侧视神经炎（optic neuritis, ON）、横贯性脊髓炎（transverse myelitis, TM）以及脑干综合征（brainstem syndromes, BS）为特征。多数成人患者血清中可检测到针对水通道蛋白4的自身抗体（aquaporin 4 antibodies, AQP4-abs）。而儿童患者中AQP4-abs的检出率较低，但相较于成人，抗髓鞘少突胶质细胞糖蛋白抗体（myelin oligodendrocyte glycoprotein antibodies, MOG-abs）的检出更为常见。部分儿童NMOSD患者既无AQP4抗体也无MOG抗体，即双血清阴性（double-seronegative）。
研究目的：评估德国与奥地利儿童NMOSD的发病率与患病率相关流行病学数据。
研究方法：本研究于2017年3月1日至2019年2月28日期间，通过5种不同渠道招募儿童NMOSD患者：(1) 德国罕见儿科疾病监测单元（ESPED）；(2) 儿童罕见神经系统疾病监测项目（ESNEK）；(3) 奥地利儿科与青少年医学学会下属的儿神经病学工作组；(4) BIOMARKER研究；(5) 视神经脊髓炎研究组（NEMOS）。研究人员通过标准化问卷收集患者的临床症状、抗体状态、治疗方案及治疗应答相关数据。
研究结果：在为期2年的招募周期内，共计46例疑似NMOSD患者（包括偶发病例与现患病例）被纳入关注范围。其中22例患者不符合纳入标准，剩余24例儿童患者中，22例有明确发病年龄数据，发病年龄中位数为11岁（范围3~17岁），16例为女性（占比72.7%，2例患者无性别数据）。24例患者中，16例AQP4抗体阳性（占比67%），4例MOG抗体阳性（占比16.7%），3例为双血清阴性，另有1例患者未进行抗体检测。经计算，德国地区儿童NMOSD的发病率为0.022/10万人年；而奥地利在本次招募期内未发现偶发病例。德国与奥地利的患病率分别为0.147/10万人与0.267/10万人。
研究结论：即便考虑到本研究存在的各类局限性，伴或不伴相关抗体的儿童NMOSD仍属于极为罕见的疾病。本研究一项意外发现为：相当比例的患者在诊断流程中未接受AQP4抗体与MOG抗体检测，这一问题亟待通过制定并推广相关诊疗指南加以解决。