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Objective. To analyze the spectrum and characteristics of neurological manifestations associated with SARS-CoV-2 infection. Methods. We conducted a nationwide, multicentric, retrospective study during the French COVID-19 epidemic in March-April 2020. All COVID-19 patients with de novo neurological manifestations were eligible. Results. We included 222 COVID-19 patients with neurological manifestations from 46 centers throughout the country. Median age was 65 years (IQR 53-72), and 136 patients (61.3%) were male. COVID-19 was severe or critical in almost half of the patients (102, 45.2%). Brain imaging was performed in 192 patients (86.5%), including 157 MRI (70.7%). Cerebrospinal fluid was analyzed in 97 patients (43.7%), with positive SARS-CoV-2 PCR in 2 out of 75 tested (2.7%). The most common neurological diseases were COVID-19 associated encephalopathy (CAE, 67/222, 30.2%), acute ischemic cerebrovascular syndrome (AICS, 57/222, 25.7%), encephalitis (21/222, 9.5%), and Guillain-Barre Syndrome (GBS, 15/222, 6.8%). Neurological manifestations appeared after first COVID-19 symptoms with a median delay of 6 days in CAE, 7 days in encephalitis, 12 days in AICS and 18 days in GBS. Around 25% of CAE and AICS were inaugural and 30% of CAE and encephalitis were diagnosed after discontinuation of sedation. Less common manifestations were also described, including meningitis and cranial neuropathy. The median follow-up of the patients was 24 days, with a particularly high short-term mortality rate in patients with CAE and AICS (19/124, 15.3%). Interpretation. Neurological manifestations associated with COVID-19 mainly included CAE, AICS, encephalitis and GBS. Clinical spectrum and outcomes were broad and heterogeneous, suggesting different underlying pathogenic processes.

Purpose. Data on encephalitis in the elderly remain scarce. We aimed to describe the characteristics, aetiologies, management, and outcome of encephalitis in patients older than 65 years. Methods.We performed an ancillary study of ENCEIF, a prospective cohort that enrolled all cases of encephalitis managed in 46 clinical sites in France during years 2016-2019. Cases were categorized in 3 age groups: i) 18-64; ii) 65-79; iii) ≥80 years.Results. Of the 494 adults with encephalitis enrolled, 258 (52%) were ≥65 years, including 74 (15%) ≥80 years. Patients ≥65 years were more likely to present with coma, impaired consciousness, confusion, aphasia, and rash, but less likely to present with fever, and headache (P<0.05 for each). Median cerebrospinal fluid (CSF) white cells count was 61/mm 3 [13-220] in 65-79 years, 62 [17-180] in ≥80 years, vs. 114 [34-302] in <65 years (P=0.01). The proportion of cases due to Listeria monocytogenes and VZV increased after 65 years (P<0.001), while the proportion of tick-borne encephalitis and Mycobacterium tuberculosis decreased with age (P<0.05 for each).In-hospital mortality was 6/234 (3%) in <65 years, 18/183 (10%) in 65-79 years, and 13/73 (18%) in ≥80 years (P<0.001). Age ≥80 years, coma on admission, CSF protein ≥0.8 g/L and viral encephalitis were independently predictive of 6-month mortality. Conclusion.The elderlies represent >50% of adult patients with encephalitis in France, with higher proportion of L. monocytogenes and VZV encephalitis, increased risk of death, and sequels. The empirical treatment currently recommended, aciclovir and amoxicillin, is appropriate for this age group.

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