Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität, Humboldt-Universität, Berlin Institute of Health, Berlin, Germany; Center for Chronically Sick Children, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität, Humboldt-Universität, Berlin Institute of Health, Berlin, Germany.
Institute of Medical Immunology and Labor Berlin - Charité Vivantes GmbH, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität, Humboldt-Universität, Berlin Institute of Health, Berlin, Germany.
Eur J Paediatr Neurol. 2020 Sep;28:159-166. doi: 10.1016/j.ejpn.2020.07.004. Epub 2020 Jul 30.
Anti-neuronal autoantibodies have been reported as the cause of several neurologic disorders other than encephalitis. Unfortunately, data are mostly based on serum analysis. Predictions about pathogenicity are thus limited. To determine the presence of so far unidentified autoantibody-derived neuroreactivity we analyzed cerebrospinal fluid (CSF) of children with neurological disorders other than encephalitis.
We did a retrospective analysis of CSF from 254 children with various neurologic diseases other than encephalitis and searched for reactivity against neuronal surface antigens by immunofluorescence on unfixed murine brain sections (tissue-based assay, TBA) and by commercial cell-based assays (CBA). A semi-quantitative fluorescence score classified our results and we described the clinical course of all positive patients with strong neuroreactivity.
Strong anti-neuronal IgG immunoreactivity of unknown antigen specificity was detected in CSF samples of 10 pediatric patients (4%, n = 10/254) with unsolved neurological disorders. CSF inflammatory markers were elevated. Most patients did not or only partly recover. Five screening-positive patients presented with a combination of headache and visual impairment due to optic nerve atrophy. Our data suggest to consider inflammatory, autoantibody-related etiologies, especially in cases without definite diagnoses.
We present an overview of CSF neuroreactivity in children with neurological disorders other than encephalitis, indicating the presence of unidentified anti-neuronal autoantibodies. As TBA enables screening for unknown autoantibodies, we suggest this method as a second step if commercial CBAs do not yield a result. Further studies are necessary to characterize such antibodies, evaluate pathogenicity, and answer the question whether positive CSF neuroreactivity should prompt an immunotherapeutic approach.
除脑炎外，抗神经元自身抗体已被报道为几种神经疾病的病因。遗憾的是，这些数据大多基于血清分析，因此对致病性的预测有限。为了确定是否存在目前尚未识别的自身抗体衍生的神经反应性，我们分析了 254 例除脑炎外的其他神经系统疾病患儿的脑脊液（CSF）。
我们对 254 例除脑炎外的各种神经系统疾病患儿的 CSF 进行了回顾性分析，并通过免疫荧光法在未经固定的鼠脑切片上（基于组织的测定法，TBA）和通过商业细胞测定法（CBA）检测神经元表面抗原的反应性。半定量荧光评分对我们的结果进行分类，并描述了所有具有强烈神经反应性的阳性患者的临床过程。
在 10 例（4%，n=10/254）原因不明的神经系统疾病患儿的 CSF 样本中检测到了未知抗原特异性的强烈抗神经元 IgG 免疫反应性。CSF 炎症标志物升高。大多数患者未完全恢复或仅部分恢复。5 例筛查阳性患者表现为头痛和视神经萎缩导致的视力障碍，后者是由于视神经萎缩。我们的数据表明，特别是在没有明确诊断的情况下，应考虑炎症、自身抗体相关病因。
我们介绍了除脑炎外的神经系统疾病患儿 CSF 神经反应性的概述，表明存在未识别的抗神经元自身抗体。由于 TBA 能够筛查未知的自身抗体，因此如果商业 CBA 未得出结果，我们建议将其作为第二步方法。需要进一步研究来描述这些抗体，评估其致病性，并回答阳性 CSF 神经反应性是否应该提示免疫治疗方法的问题。
