Cytokine release syndrome-associated encephalopathy in patients with COVID-19
Cytokine release syndrome-associated encephalopathy in patients with COVID-19
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DOI：
10.1111/ene.14491
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发表时间：
2020-10-05
影响因子：
5.1
通讯作者：
Caillard, S.
中科院分区：
文献类型：
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作者：
Perrin, P.;Collongues, N.;Caillard, S.
背景与目的冠状病毒病(COVID)-2019的神经学表现可能对临床结果产生不利影响。严重的COVID-19和尿毒症是神经系统并发症的危险因素。然而，缺乏对其发病机制的了解，特别是关于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。本研究的目的是描述COVID-19患者的神经学表现，并获得有关CRS的病理生理学见解。方法在这项纵向研究中，我们对肾科收治的5例患者进行了广泛的临床、实验室和影像学表型分析。结果神经学表现包括精神错乱、震颤、小脑性共济失调、行为改变、失语、锥体综合征、昏迷、脑神经麻痹、自主神经异常和中枢性甲状腺功能减退。值得注意的是，神经障碍伴有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。脑磁共振成像结果包括急性脑白质炎（n = 3，其中1例有出血性）、模拟缺血性中风的细胞毒性水肿（n = 1）或正常结果（n = 2）。尝试用皮质类固醇和/或静脉注射免疫球蛋白治疗，导致两例神经障碍迅速恢复。在接受CSF逆转录pcr检测的90例COVID-19患者中，有88例检测不到SARS-CoV2。结论COVID-19患者可出现与嵌合抗原受体t细胞相关脑病具有相似临床、实验室和影像学表现的神经系统表现。病理生理基础似乎涉及CRS、内皮活化、血脑屏障功能障碍和免疫介导机制。
Background and purpose 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. Methods In this longitudinal study, we performed extensive clinical, laboratory and imaging phenotyping in five patients admitted to our renal unit. Results 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. Conclusions 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.