背景:在过去的二十年中,已经出现了与新出现的冠状病毒有关的三种流行病。COVID-19大流行强调了与SARS-CoV-2感染相关的神经系统表现的存在,并提出了冠状病毒神经致病性的问题。这篇综述的目的是总结与人类冠状病毒相关的神经系统表现和疾病的最新数据。
方法:文章已通过截至2020年9月25日的PubMed和Google学者的搜索确定,使用冠状病毒和神经病学搜索词的组合,并在文章中添加相关参考文献。
结果:我们发现,在2533例COVID-19住院患者中,有5个队列提供了神经系统症状的患病率数据,和文章重点关注COVID-19患者的神经系统表现,包括总共580例患者。高达73%的COVID-19住院患者出现神经系统症状,主要是头痛,肌痛和意识受损。COVID-19报告的中枢神经系统(CNS)表现主要是非特异性脑病,占所有神经系统表现的13%至40%;感染后综合征,包括急性脱髓鞘性脑脊髓炎(ADEM,n=13),急性坏死性脑病(ANE,n=4),Bickerstaff脑炎(n=5),全身性肌阵鸣(n=3)和急性横贯性脊髓炎(n=7);其他脑炎,包括边缘叶脑炎(n=9)和放射学表现可变的杂性脑炎(n=26);急性脑血管疾病,包括缺血性中风(COVID-19患者的1.3%至4.7%),出血性中风(n=17),脑静脉血栓形成(n=8)和后部可逆性脑病(n=5)。在COVID-19中报告的周围神经系统(PNS)表现如下:格林-巴利综合征(n=31)和包括MillerFisher综合征(n=3)在内的变体,颅骨多发性神经炎(n=2)和面部瘫痪(n=2);孤立性动眼神经病变(n=6);危重病肌病(n=6)。COVID-19患者的神经病理学研究显示了不同的中枢神经系统损伤模式,大多是缺血性和出血性改变,很少有炎症损伤。只有1例提示SARS-CoV-2在内皮细胞和神经细胞中浸润。我们发现了10例病例报告或病例系列,描述了22例与其他人类冠状病毒相关的神经系统表现。其中我们发现了四名患有ADEM或Bickerstaff脑炎的MERS患者,两名患有脑炎的SARS患者,脑脊液中SARS-CoVPCR阳性,5名与SARS相关的缺血性中风患者,8名患有危重病神经肌病的MERS患者和1名患有格林-巴利综合征的MERS患者。对SARS-CoV患者的尸检研究表明,八名患者的大脑中存在该病毒。
结论:与SARS-CoV-2相关的广泛的神经系统表现和疾病与多种致病途径一致,包括感染后机制,败血症相关性脑病,凝血病或内皮炎。没有明确的证据支持SARS-CoV-2的直接神经致病性。
BACKGROUND: The past two decades have been marked by three epidemics linked to emerging coronaviruses. The COVID-19 pandemic highlighted the existence of neurological manifestations associated with SARS-CoV-2 infection and raised the question of the neuropathogenicity of coronaviruses. The aim of this
review was to summarize the current data about neurological manifestations and diseases linked to human coronaviruses.
METHODS: Articles have been identified by searches of PubMed and Google scholar up to September 25, 2020, using a combination of coronavirus and neurology search terms and adding relevant references in the articles.
RESULTS: We found five cohorts providing prevalence data of neurological symptoms among a total of 2533 hospitalized COVID-19 patients, and articles focusing on COVID-19 patients with neurological manifestations including a total of 580 patients. Neurological symptoms involved up to 73% of COVID-19 hospitalized patients, and were mostly headache, myalgias and impaired consciousness. Central nervous system (CNS) manifestations reported in COVID-19 were mostly non-specific encephalopathies that represented between 13% and 40% of all neurological manifestations; post-infectious syndromes including acute demyelinating encephalomyelitis (ADEM, n=13), acute necrotizing encephalopathy (ANE, n=4), Bickerstaff\'s encephalitis (n=5), generalized myoclonus (n=3) and acute transverse myelitis (n=7); other encephalitis including limbic encephalitis (n=9) and miscellaneous encephalitis with variable radiologic findings (n=26); acute cerebrovascular diseases including ischemic strokes (between 1.3% and 4.7% of COVID-19 patients), hemorrhagic strokes (n=17), cerebral venous thrombosis (n=8) and posterior reversible encephalopathy (n=5). Peripheral nervous system (PNS) manifestations reported in COVID-19 were the following: Guillain-Barré syndrome (n=31) and variants including Miller Fisher syndrome (n=3), polyneuritis cranialis (n=2) and facial diplegia (n=2); isolated oculomotor neuropathy (n=6); critical illness myopathy (n=6). Neuropathological studies in COVID-19 patients demonstrated different patterns of CNS damage, mostly ischemic and hemorrhagic changes with few cases of inflammatory injuries. Only one case suggested SARS-CoV-2 infiltration in endothelial and neural cells. We found 10 case reports or case series describing 22 patients with neurological manifestations associated with other human coronaviruses. Among them we found four MERS patients with ADEM or Bickerstaff\'s encephalitis, two SARS patients with encephalitis who had a positive SARS-CoV PCR in cerebrospinal fluid, five patients with ischemic strokes associated with SARS, eight MERS patients with critical illness neuromyopathy and one MERS patient with Guillain-Barré Syndrome. An autopsy study on SARS-CoV patients demonstrated the presence of the virus in the brain of eight patients.
CONCLUSIONS: The wide range of neurological manifestations and diseases associated with SARS-CoV-2 is consistent with multiple pathogenic pathways including post-infectious mechanisms, septic-associated encephalopathies, coagulopathy or endothelitis. There was no definite evidence to support direct neuropathogenicity of SARS-CoV-2.