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      Neurologic manifestations in 1760 COVID-19 patients admitted to Papa Giovanni XXIII Hospital, Bergamo, Italy

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          Abstract

          Objectives

          Evidences from either small series or spontaneous reporting are accumulating that SARS-CoV-2 involves the Nervous Systems. The aim of this study is to provide an extensive overview on the major neurological complications in a large cohort of COVID-19 patients.

          Methods

          Retrospective, observational analysis on all COVID-19 patients admitted from February 23rd to April 30th, 2020 to ASST Papa Giovanni XXIII, Bergamo, Italy for whom a neurological consultation/neurophysiological assessment/neuroradiologic investigation was requested. Each identified neurologic complication was then classified into main neurologic categories.

          Results

          Of 1760 COVID-19 patients, 137 presented neurologic manifestations that manifested after COVID-19 symptoms in 98 pts and was the presenting symptom in 39. Neurological manifestations were classified as: (a) cerebrovascular disease [53 pts (38.7%)] including 37 ischemic and 11 haemorrhagic strokes, 4 transient ischemic attacks, 1 cerebral venous thrombosis; (b) peripheral nervous system diseases [31 (22.6%)] including 17 Guillain–Barrè syndromes; (c) altered mental status [49 (35.8%)] including one necrotizing encephalitis and 2 cases with RT-PCR detection of SARS-Cov-2 RNA in CSF; (d) miscellaneous disorders, among whom 2 patients with myelopathy associated with Ab anti-SARS-CoV-2 in CSF. Patients with peripheral nervous system involvement had more frequently severe ARDS compared to patients with cerebrovascular disease (87.1% vs 42%; difference = 45.1% 95% CI 42.0–48.2; χ 2= 14.306; p < 0.0002) and with altered mental status (87.1% vs 55.6%; difference = 31.5% 95% CI 27.5–37.5%; χ 2= 7.055; p < 0.01).

          Conclusion

          This study confirms that involvement of nervous system is common in SARS-CoV-2 infection and offers clinicians useful information for prevention and prompt identification in order to set the adequate therapeutic strategies.

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          Most cited references13

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          Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy

          Giacomo Grasselli, Alberto Zangrillo, Alberto Zanella … (2020)
          In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited.
          Article 0 comments Cited 2758 times – based on 0 reviews     Review now
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            Neurologic Features in Severe SARS-CoV-2 Infection

            Julie Helms, Stéphane Kremer, Hamid Merdji … (2020)
            To the Editor: We report the neurologic features in an observational series of 58 of 64 consecutive patients admitted to the hospital because of acute respiratory distress syndrome (ARDS) due to Covid-19. The patients received similar evaluations by intensivists in two intensive care units (ICUs) in Strasbourg, France, between March 3 and April 3, 2020. Six patients were excluded because of paralytic neuromuscular blockade when neurologic data were collected or because they had died without a neurologic examination having been performed. In all 58 patients, reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays of nasopharyngeal samples were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The median age of the patients was 63 years, and the median Simplified Acute Physiology Score II at the time of neurologic examination was 52 (interquartile range, 37 to 65, on a scale ranging from 0 to 163, with higher scores indicating greater severity of illness). Seven patients had had previous neurologic disorders, including transient ischemic attack, partial epilepsy, and mild cognitive impairment. The neurologic findings were recorded in 8 of the 58 patients (14%) on admission to the ICU (before treatment) and in 39 patients (67%) when sedation and a neuromuscular blocker were withheld. Agitation was present in 40 patients (69%) when neuromuscular blockade was discontinued (Table 1). A total of 26 of 40 patients were noted to have confusion according to the Confusion Assessment Method for the ICU; those patients could be evaluated when they were responsive (i.e., they had a score of −1 to 1 on the Richmond Agitation and Sedation Scale, on a scale of −5 [unresponsive] to +4 [combative]). Diffuse corticospinal tract signs with enhanced tendon reflexes, ankle clonus, and bilateral extensor plantar reflexes were present in 39 patients (67%). Of the patients who had been discharged at the time of this writing, 15 of 45 (33%) had had a dysexecutive syndrome consisting of inattention, disorientation, or poorly organized movements in response to command. Magnetic resonance imaging (MRI) of the brain was performed in 13 patients (Figs. S1 through S3 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). Although these patients did not have focal signs that suggested stroke, they underwent MRI because of unexplained encephalopathic features. Enhancement in leptomeningeal spaces was noted in 8 patients, and bilateral frontotemporal hypoperfusion was noted in all 11 patients who underwent perfusion imaging. Two asymptomatic patients each had a small acute ischemic stroke with focal hyperintensity on diffusion-weighted imaging and an overlapping decreased apparent diffusion coefficient, and 1 patient had a subacute ischemic stroke with superimposed increased diffusion-weighted imaging and apparent diffusion coefficient signals. In the 8 patients who underwent electroencephalography, only nonspecific changes were detected; 1 of the 8 patients had diffuse bifrontal slowing consistent with encephalopathy. Examination of cerebrospinal fluid (CSF) samples obtained from 7 patients showed no cells; in 2 patients, oligoclonal bands were present with an identical electrophoretic pattern in serum, and protein and IgG levels were elevated in 1 patient. RT-PCR assays of the CSF samples were negative for SARS-CoV-2 in all 7 patients. In this consecutive series of patients, ARDS due to SARS-CoV-2 infection was associated with encephalopathy, prominent agitation and confusion, and corticospinal tract signs. Two of 13 patients who underwent brain MRI had single acute ischemic strokes. Data are lacking to determine which of these features were due to critical illness–related encephalopathy, cytokines, or the effect or withdrawal of medication, and which features were specific to SARS-CoV-2 infection.
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              A first case of meningitis/encephalitis associated with SARS-Coronavirus-2

              Takeshi Moriguchi, Norikazu Harii, Junko Goto … (2020)
              Highlights • Novel coronavirus (SARS-Coronavirus-2:SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly. • This is the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance. • The specific SARS-CoV-2 RNA was not detected in the nasopharyngeal swab but was detected in a CSF. • This case warns the physicians of patients who have CNS symptoms.
              Article 0 comments Cited 1025 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Maria Sessa:
                ORCID: http://orcid.org/0000-0002-9589-0290
                msessa@asst-pg23.it
                Journal
                Journal ID (nlm-ta): J Neurol
                Journal ID (iso-abbrev): J Neurol
                Title: Journal of Neurology
                Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )
                ISSN (Print): 0340-5354
                ISSN (Electronic): 1432-1459
                Publication date (Electronic): 7 October 2020
                Pages: 1-8
                Affiliations
                [1 ]GRID grid.7563.7, ISNI 0000 0001 2174 1754, University of Milano-Bicocca, ; Milan, Italy
                [2 ]GRID grid.460094.f, ISNI 0000 0004 1757 8431, Department of Neurology, , Papa Giovanni XXIII Hospital, ; Piazza OMS 1, 24127 Bergamo, Italy
                [3 ]GRID grid.460094.f, ISNI 0000 0004 1757 8431, Department of Neuroradiology, , Papa Giovanni XXIII Hospital, ; Bergamo, Italy
                [4 ]GRID grid.419450.d, Department of Neurology, , Cremona Hospital, ; Cremona, Italy
                [5 ]GRID grid.460094.f, ISNI 0000 0004 1757 8431, Department of Laboratory Medicine, , Papa Giovanni XXIII Hospital, ; Bergamo, Italy
                Author information
                http://orcid.org/0000-0002-9589-0290
                Article
                Publisher ID: 10251
                DOI: 10.1007/s00415-020-10251-5
                PMC ID: 7539268
                PubMed ID: 33026520
                SO-VID: 3d78b89e-8f90-46fb-baac-679126cd97ad
                Copyright © © Springer-Verlag GmbH Germany, part of Springer Nature 2020
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 21 July 2020
                Date revision received : 22 September 2020
                Date accepted : 29 September 2020
                Categories
                Subject: Original Communication

                ScienceOpen disciplines: Neurology
                Keywords: covid-19,infectious diseases,cerebrovascular diseases,peripheral neuropathies,altered mental status
                Data availability:
                ScienceOpen disciplines: Neurology
                Keywords: covid-19, infectious diseases, cerebrovascular diseases, peripheral neuropathies, altered mental status

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