Andrea Pilotto1,2, Stefano Masciocchi1, Irene Volonghi1, Massimo Crabbio3, Eugenio Magni3, Valeria De Giuli4, Francesca Caprioli4, Nicola Rifino5, Maria Sessa5, Michele Gennuso6, Maria Sofia Cotelli7, Marinella Turla7, Ubaldo Balducci8, Sara Mariotto9, Sergio Ferrari9, Alfonso Ciccone10, Fabrizio Fiacco11, Alberto Imarisio1, Barbara Risi1, Alberto Benussi1, Enrico Premi12, Emanuele Focà13, Francesca Caccuri14, Matilde Leonardi15, Roberto Gasparotti16, Francesco Castelli13, Gianluigi Zanusso9, Alessandro Pezzini1, Alessandro Padovani1. 1. Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. 2. Parkinson's Disease Rehabilitation Centre, Fondazione Europea Ricerca Biomedica ONLUS, S. Isidoro Hospital, Trescore Balneario, Italy. 3. Neurology Unit, Poliambulanza Hospital, Brescia, Italy. 4. Neurology Unit, Istituti Ospedalieri, Azienda Socio Sanitaria Teritoriale di Cremona, Cremona, Italy. 5. Department of Neurology, Azienda Socio Sanitaria Teritoriale di Papa Giovanni XXII, Bergamo, Italy. 6. Neurology Unit, Crema Hospital, Crema, Italy. 7. Neurology Unit, Azienda Socio Sanitaria Teritoriale della Valcamonica, Esine, Brescia, Italy. 8. Neurology Unit, Azienda Socio Sanitaria Teritoriale di Chiari, Chiari, Italy. 9. Neurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy. 10. Department of Neurology and Stroke Unit, Carlo Poma Hospital, Azienda Socio Sanitaria Teritoriale di Mantova, Mantova, Italy. 11. Neurology Unit, Azienda Socio Sanitaria Teritoriale di Bergamo Est, Seriate, Italy. 12. Stroke Unit, Azienda Socio Sanitaria Teritoriale Spedali Civili di Brescia, Rescia, Italy. 13. University Division of Infectious and Tropical Diseases, University of Brescia and Azienda Socio Sanitaria Teritoriale di Spedali Civili Hospital, Brescia, Italy. 14. Microbiology Unit, Department of Molecular and Translational Medicine, University of Brescia and Azienda Socio Sanitaria Teritoriale di Spedali Civili Hospital, Brescia, Italy. 15. Neurology, Public Health, Disability Unit, Istituto di Ricerca e Cura a Carattere Scientifico Neurology Institute Besta, Milan, Italy. 16. Neuroradiology Unit, Department of Medical and Surgical Specialties, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy.
Abstract
BACKGROUND: Several preclinical and clinical investigations have argued for nervous system involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some sparse case reports have described various forms of encephalitis in coronavirus disease 2019 (COVID-19) disease, but very few data have focused on clinical presentations, clinical course, response to treatment, and outcomes. METHODS: The SARS-CoV-2 related encephalopaties (ENCOVID) multicenter study included patients with encephalitis with full infectious screening, cerebrospinal fluid (CSF), electroencephalography (EEG), and magnetic resonance imaging (MRI) data and confirmed SARS-CoV-2 infection recruited from 13 centers in northern Italy. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment, and outcomes were recorded. RESULTS: Twenty-five cases of encephalitis positive for SARS-CoV-2 infection were included. CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by reverse-transcription polymerase chain reaction resulted negative. Based on MRI, cases were classified as acute demyelinating encephalomyelitis (ADEM; n = 3), limbic encephalitis (LE; n = 2), encephalitis with normal imaging (n = 13), and encephalitis with MRI alterations (n = 7). ADEM and LE cases showed a delayed onset compared to the other encephalitis cases (P = .001) and were associated with previous, more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to those with other encephalitis. CONCLUSIONS: SARS-CoV-2 infection is associated with a wide spectrum of encephalitis characterized by different clinical presentation, response to treatment, and outcomes.
BACKGROUND: Several preclinical and clinical investigations have argued for nervous system involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some sparse case reports have described various forms of encephalitis in coronavirus disease 2019 (COVID-19) disease, but very few data have focused on clinical presentations, clinical course, response to treatment, and outcomes. METHODS: The SARS-CoV-2 related encephalopaties (ENCOVID) multicenter study included patients with encephalitis with full infectious screening, cerebrospinal fluid (CSF), electroencephalography (EEG), and magnetic resonance imaging (MRI) data and confirmed SARS-CoV-2 infection recruited from 13 centers in northern Italy. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment, and outcomes were recorded. RESULTS: Twenty-five cases of encephalitis positive for SARS-CoV-2 infection were included. CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by reverse-transcription polymerase chain reaction resulted negative. Based on MRI, cases were classified as acute demyelinating encephalomyelitis (ADEM; n = 3), limbic encephalitis (LE; n = 2), encephalitis with normal imaging (n = 13), and encephalitis with MRI alterations (n = 7). ADEM and LE cases showed a delayed onset compared to the other encephalitis cases (P = .001) and were associated with previous, more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to those with other encephalitis. CONCLUSIONS:SARS-CoV-2 infection is associated with a wide spectrum of encephalitis characterized by different clinical presentation, response to treatment, and outcomes.
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