Eisele Amanda, Schwager Matthias, Bögli Stefan Yu, Reichen Ina, Dargvainiene Justina, Wandinger Klaus-Peter, Imbach Lukas, Haeberlin Marcellina, Keller Emanuela, Jelcic Ilijas, Galovic Marian, Brandi Giovanna
Department of Neurology and Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
Institute for Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland.
Epilepsia. 2023 Dec;64(12):e229-e236. doi: 10.1111/epi.17755. Epub 2023 Oct 5.
Most cases with new onset refractory status epilepticus (NORSE) remain cryptogenic despite extensive diagnostic workup. The aim of this study was to analyze the etiology and clinical features of NORSE and investigate known or potentially novel autoantibodies in cryptogenic NORSE (cNORSE). We retrospectively assessed the medical records of adults with status epilepticus at a Swiss tertiary referral center between 2010 and 2021. Demographic, diagnostic, therapeutic, and outcome parameters were characterized. We performed post hoc screening for known or potentially novel autoantibodies including immunohistochemistry (IHC) on rat brain with cerebrospinal fluid (CSF) and serum samples of cNORSE. Twenty patients with NORSE were identified. Etiologies included infections (n = 4), Creutzfeldt-Jakob disease (n = 1), CASPR2 autoimmune encephalitis (n = 1), and carotid artery stenosis with recurrent perfusion deficit (n = 1). Thirteen cases (65%) were cryptogenic despite detailed evaluation. A posteriori IHC for neuronal autoantibodies yielded negative results in all available serum (n = 11) and CSF (n = 9) samples of cNORSE. Our results suggest that neuronal antibodies are unlikely to play a major role in the pathogenesis of cNORSE. Future studies should rather focus on other-especially T-cell- and cytokine-mediated-mechanisms of autoinflammation in this devastating disease, which is far too poorly understood so far.
尽管进行了广泛的诊断检查，但大多数新发难治性癫痫持续状态（NORSE）病例仍病因不明。本研究的目的是分析NORSE的病因和临床特征，并调查病因不明的NORSE（cNORSE）中已知或潜在的新型自身抗体。我们回顾性评估了2010年至2021年期间瑞士一家三级转诊中心成年癫痫持续状态患者的病历。对人口统计学、诊断、治疗和结局参数进行了描述。我们对已知或潜在的新型自身抗体进行了事后筛查，包括对cNORSE的脑脊液（CSF）和血清样本进行大鼠脑免疫组织化学（IHC）检测。确定了20例NORSE患者。病因包括感染（n = 4）、克雅氏病（n = 1）、接触蛋白相关蛋白2（CASPR2）自身免疫性脑炎（n = 1）以及伴有反复灌注不足的颈动脉狭窄（n = 1）。尽管进行了详细评估，但仍有13例（65%）病因不明。对cNORSE所有可用血清（n = 11）和CSF（n = 9）样本进行的神经元自身抗体事后IHC检测结果均为阴性。我们的结果表明，神经元抗体不太可能在cNORSE的发病机制中起主要作用。未来的研究应更多地关注这种毁灭性疾病中其他特别是T细胞和细胞因子介导的自身炎症机制，目前对该疾病的了解还非常有限。
