Kilmer Jennifer, Ransley George, Murphy Elaine, Hanna Michael G, Pitceathly Robert D S, Rajakulendran Sanjeev, Pizzamiglio Chiara
UCL Queen Square Institute of Neurology, London, UK.
The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
Eur J Neurol. 2025 Jun;32(6):e70218. doi: 10.1111/ene.70218.
New-onset refractory status epilepticus (NORSE) is a diagnostically challenging and severe epileptic presentation in which aetiology is an important predictor of outcome. This retrospective study aimed to investigate the utility of metabolic screening to determine the underlying cause in 42 patients with suspected NORSE, admitted to The National Hospital for Neurology and Neurosurgery, London, between 2004 and 2021.
Demographic, clinical, biochemical, and molecular data were collected. Sixty-two per cent of the cohort was classified as cryptogenic (cNORSE), while 38% had symptomatic NORSE (sNORSE).
Despite extensive investigations (100 metabolic-related tests were performed among the 42 cases), inherited disorders of metabolism were not identified as causes for NORSE. Nevertheless, three patients with refractory status epilepticus (RSE), who did not fulfill the diagnostic criteria for NORSE, had a primary mitochondrial disease (PMD). These data help establish criteria that distinguish PMD-related RSE from cNORSE, including pre-existing multisystemic features, a positive family history and/or suggestive MRI findings.
The study highlights the challenges in diagnosing NORSE aetiology and the limited utility of extensive testing for inherited metabolic disorders in this patient population. Further research is required to refine diagnostic strategies and enhance our understanding of the heterogeneous aetiology of cNORSE.
新发难治性癫痫持续状态（NORSE）是一种诊断具有挑战性的严重癫痫表现，病因是预后的重要预测因素。这项回顾性研究旨在调查代谢筛查在确定2004年至2021年间入住伦敦国立神经病学与神经外科医院的42例疑似NORSE患者潜在病因方面的效用。
收集了人口统计学、临床、生化和分子数据。该队列中62%被归类为隐源性（cNORSE），而38%患有症状性NORSE（sNORSE）。
尽管进行了广泛的检查（42例患者共进行了100项与代谢相关的检测），但未发现遗传性代谢紊乱是NORSE的病因。然而，三名不符合NORSE诊断标准的难治性癫痫持续状态（RSE）患者患有原发性线粒体疾病（PMD）。这些数据有助于建立区分PMD相关RSE与cNORSE的标准，包括既往存在的多系统特征、阳性家族史和/或提示性的MRI表现。
该研究突出了诊断NORSE病因的挑战以及对该患者群体进行遗传性代谢紊乱广泛检测的有限效用。需要进一步研究以完善诊断策略并增进我们对cNORSE异质性病因的理解。
