A systematic review of neurological manifestations of SARS-CoV-2 infection: the devil is hidden in the details

Background: We systematically reviewed available evidence for reports of neurological signs and symptoms in Coronavirus disease (COVID)-19 patients to identify cases with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection or immune-mediated reaction in the nervous system. Methods: We followed PRISMA guidelines and used the MEDLINE, EMBASE, Google Scholar, MedRxiv and ChinaXiv databases to search for papers on COVID-19 and nervous system involvement which were published from January 1st to April 24th 2020. Data on design, sample size, neurologic assessment and related work-up were extracted. Biases were assessed with the Newcastle-Ottawa scale. Results: We analysed 27 publications on potential neuroinvasive or parainfectious neurological complications of COVID-19. The reports focused on smell and taste (n=5) and evaluation of neurological symptoms and signs in cohorts (n=5). There were cases of Guillain-Barr\ue9 syndrome/Miller-Fisher syndrome/cranial neuropathy (7 cases), meningitis/encephalitis (9 cases) and various other conditions (5 cases). Patients with cerebrospinal fluid (CSF) examination and in particular SARS-CoV-2 PCR was negligible. Amongst, two had a positive SARS-CoV-2 PCR exam of CSF specimen. The study of potential parenchymal involvement with magnetic resonance imaging was rare. Only 4 reports received a rating for the highest quality standards. Conclusion: This systematic review failed to establish comprehensive insights to nervous system manifestations of COVID-19 beyond immune-mediated complications as aftermath of respiratory symptoms. The authors therefore provide guidance for more careful clinical, diagnostic and epidemiological studies to characterize the manifestations and burden of neurological disease caused by SARS-CoV-2 on behalf of the Infectious Disease Panel of the European Academy of Neurology