Department of Nephrology and Transplantation, University Hospital, Strasbourg, France.
Fédération de Médecine Translationnelle (FMTS), Strasbourg, France.
Eur J Neurol. 2021 Jan;28(1):248-258. doi: 10.1111/ene.14491. Epub 2020 Oct 5.
Neurological manifestations in coronavirus disease (COVID)-2019 may adversely affect clinical outcomes. Severe COVID-19 and uremia are risk factors for neurological complications. However, the lack of insight into their pathogenesis, particularly with respect to the role of the cytokine release syndrome (CRS), is currently hampering effective therapeutic interventions. The aims of this study were to describe the neurological manifestations of patients with COVID-19 and to gain pathophysiological insights with respect to CRS.
In this longitudinal study, we performed extensive clinical, laboratory and imaging phenotyping in five patients admitted to our renal unit.
Neurological presentation included confusion, tremor, cerebellar ataxia, behavioral alterations, aphasia, pyramidal syndrome, coma, cranial nerve palsy, dysautonomia, and central hypothyroidism. Notably, neurological disturbances were accompanied by laboratory evidence of CRS. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was undetectable in the cerebrospinal fluid (CSF). Hyperalbuminorrachia and increased levels of the astroglial protein S100B were suggestive of blood-brain barrier (BBB) dysfunction. Brain magnetic resonance imaging findings comprised evidence of acute leukoencephalitis (n = 3, one of whom had a hemorrhagic form), cytotoxic edema mimicking ischaemic stroke (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted, resulting in rapid recovery from neurological disturbances in two cases. SARS-CoV2 was undetectable in 88 of the 90 patients with COVID-19 who underwent Reverse Transcription-PCR testing of CSF.
Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory and imaging similarities with those of chimeric antigen receptor T-cell-related encephalopathy. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.
新型冠状病毒病（COVID-19）的神经表现可能会对临床结局产生不利影响。COVID-19 重症和尿毒症是发生神经并发症的危险因素。然而，由于对其发病机制缺乏深入了解，特别是细胞因子释放综合征（CRS）的作用，目前阻碍了有效的治疗干预措施。本研究旨在描述 COVID-19 患者的神经表现，并深入了解 CRS 的病理生理学。
在这项纵向研究中，我们对 5 例入住我院肾内科的患者进行了广泛的临床、实验室和影像学表型分析。
神经表现包括意识障碍、震颤、小脑性共济失调、行为改变、失语、锥体束征、昏迷、颅神经麻痹、自主神经功能障碍和中枢性甲状腺功能减退。值得注意的是，神经紊乱伴有 CRS 的实验室证据。脑脊液（CSF）中未检测到严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）。高白蛋白血症和星形胶质蛋白 S100B 水平升高提示血脑屏障（BBB）功能障碍。脑磁共振成像（MRI）结果显示急性脑白质炎症（n=3，其中 1 例为出血性）、细胞毒性水肿类似缺血性卒中（n=1）或正常（n=2）。尝试了皮质类固醇和/或静脉注射免疫球蛋白治疗，其中 2 例患者的神经紊乱迅速恢复。对 90 例 COVID-19 患者的 CSF 进行逆转录聚合酶链反应（RT-PCR）检测，结果 88 例 SARS-CoV2 均为阴性。
COVID-19 患者可出现神经表现，其临床表现、实验室和影像学与嵌合抗原受体 T 细胞相关脑病相似。其病理生理学基础似乎涉及 CRS、内皮激活、BBB 功能障碍和免疫介导的机制。
