RESUMO
BACKGROUND: SARS-CoV-2 can affect the human brain and other neurological structures. An increasing number of publications report neurological manifestations in patients with COVID-19. However, no studies have comprehensively reviewed the clinical and paraclinical characteristics of the central and peripheral nervous system's involvement in these patients. This study aimed to describe the features of the central and peripheral nervous system involvement by COVID-19 in terms of pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings. METHODS: We conducted a comprehensive systematic review of all the original studies reporting patients with neurological involvement by COVID-19, from December 2019 to June 2020, without language restriction. We excluded studies with animal subjects, studies not related to the nervous system, and opinion articles. Data analysis combined descriptive measures, frequency measures, central tendency measures, and dispersion measures for all studies reporting neurological conditions and abnormal ancillary tests in patients with confirmed COVID-19. RESULTS: A total of 143 observational and descriptive studies reported central and peripheral nervous system involvement by COVID-19 in 10,723 patients. Fifty-one studies described pathophysiologic mechanisms of neurological involvement by COVID-19, 119 focused on clinical manifestations, 4 described neuropathology findings, 62 described neuroimaging findings, 28 electrophysiology findings, and 60 studies reported cerebrospinal fluid results. The reviewed studies reflect a significant prevalence of the nervous system's involvement in patients with COVID-19, ranging from 22.5 to 36.4% among different studies, without mortality rates explicitly associated with neurological involvement by SARS-CoV-2. We thoroughly describe the clinical and paraclinical characteristics of neurological involvement in these patients. CONCLUSIONS: Our evidence synthesis led to a categorical analysis of the central and peripheral neurological involvement by COVID-19 and provided a comprehensive explanation of the reported pathophysiological mechanisms by which SARS-CoV-2 infection may cause neurological impairment. International collaborative efforts and exhaustive neurological registries will enhance the translational knowledge of COVID-19's central and peripheral neurological involvement and generate therapeutic decision-making strategies. REGISTRATION: This review was registered in PROSPERO 2020 CRD42020193140 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020193140.
Assuntos
COVID-19/complicações , Doenças do Sistema Nervoso/virologia , Sistema Nervoso Periférico/fisiopatologia , Sistema Nervoso Periférico/virologia , Encéfalo , COVID-19/líquido cefalorraquidiano , Fenômenos Eletrofisiológicos , Humanos , Doenças do Sistema Nervoso/líquido cefalorraquidiano , NeuroimagemRESUMO
OBJECTIVE: To investigate the possibility of a viral agent in the central nervous system of patients with epidemic neuropathy. DESIGN: Virus isolation attempts, in cell cultures and suckling mice, from cerebrospinal fluid (CSF) of neuropathy patients and controls undergoing lumbar puncture for unrelated reasons. Serologic studies in patients, contacts, and controls. SETTING: An epidemic of optic and peripheral neuropathy affected more than 50,000 people in Cuba in 1991 through 1993. Illness was associated with dietary limitations and increased physical demands accompanying the shortages of food and fuel experienced in Cuba since 1989. Most patients responded to parenteral vitamin therapy, and the epidemic began to subside when oral vitamin supplementation was begun for the entire Cuban population. RESULTS: Coxsackievirus A9 (five isolates) and a similar, less cytopathic virus (100 isolates) were recovered from 105 (84%) of 125 CSF specimens from neuropathy patients. The strains with light cytopathic effect were antigenically related to Coxsackieviruses A9 and B4 by cross-neutralization and immunoblotting assays. Virus persisted in CSF of some patients for 1 to 12 months. Cerebrospinal fluid from patients and both types of virus from cell culture produced illness, including complete posterior flaccid paralysis, in newborn mice, and virus was reisolated from the mice. Mouse tissues and sural nerve biopsy specimens from patients were stained by immunoperoxidase and colloidal gold techniques using hyperimmune rabbit antisera against the virus with light cytopathic effect. CONCLUSIONS: Coxsackievirus A9 or an antigenically related agent with a light cytopathic effect was present in CSF of 84% of 125 patients with epidemic neuropathy. The role of these agents, probably in combination with nutritional factors, in the pathophysiology of the disease requires further investigation.