Comment on “Anti-NMDA receptor encephalitis presenting as new onset refractory status epilepticus in COVID-19”

Abstract

Monti and colleagues [[1]Monti G. Giovannini G. Marudi A. Bedin R. Melegari A. Simone A.M. et al.Anti-NMDA receptor encephalitis presenting as new onset refractory statusepilepticus in COVID-19.Seizure. 2020; 81: 18-20https://doi.org/10.1016/j.seizure.2020.07.006Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar] described a patient who developed psychiatric symptoms followed by refractory status epilepticus caused by anti N-methyl-D-aspartate receptor (NMDAr) encephalitis. Despite the lack of lung involvement, the patient resulted positive for SARS-CoV-2 infection. Recently, another case of anti-NMDAr encephalitis with prominent psychiatric symptoms during symptomatic SARS-CoV-2 infection has been reported by Panariello and colleagues [[2]Panariello A. Bassetti R. Radice A. Rossotti R. Puoti M. Corradin M. et al.Anti-NMDA receptor encephalitis in a psychiatric Covid-19 patient: a case report.Brain Behav Immun. 2020; 87: 179-181https://doi.org/10.1016/j.bbi.2020.05.054Crossref PubMed Scopus (85) Google Scholar]. NMDAr encephalitis represents one of the most frequent cause of autoimmune encephalitis and, in a minority of patients, it may be triggered by viral infections, particularly Herpes Simplex Virus encephalitis [[3]Dalmau J. Armangué T. Planagumà J. Radosevic M. Mannara F. Leypoldt F. et al.An update on anti-NMDA receptor encephalitis for neurologists and psychiatrists: mechanisms and models.Lancet Neurol. 2019; 18: 1045-1057https://doi.org/10.1016/S1474-4422(19)30244-3Abstract Full Text Full Text PDF PubMed Scopus (294) Google Scholar]. The case reported in this issue may suggest that SARS-CoV-2 infection could represent a new trigger to NMDAr encephalitis, even though the underlying pathogenic mechanisms are still widely unknown. The probable role of the current strain of coronavirus in the development of central nervous system autoimmunity has been recently highlighted in a case series from the UCL Queen Square National Hospital for Neurology and Neurosurgery COVID-19 Study Group [[4]Paterson R.W. Brown R.L. Benjamin L. Nortley R. Wiethoff S. Bharucha T. et al.The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings.Brain. 2020; : 2-37https://doi.org/10.1093/brain/awaa240Crossref PubMed Scopus (598) Google Scholar]: in their cohort, two patients could be classified as a “probable autoimmune encephalitis” (limbic encephalitis, brainstem and cortical autoimmune encephalitis) and nine patients were diagnosed with acute disseminated encephalomyelitis (ADEM). Intriguingly, in those patients, SARS-CoV-2 PCR was negative in cerebrospinal fluid and none of the typical antibodies usually found in those syndromes (such as MOG, AQP-4, NMDAr, LGI1) was detected. Moreover, most of the patients in the UCL cohort, as well as the two with NMDAr encephalitis, had different degrees of improvement after receiving first-line immunotherapy (such as intravenous steroids, plasma exchange or immunoglobulins), thus further suggesting an autoimmune etiology. Although it seems that the virus is linked with an increased incidence of ADEM [[4]Paterson R.W. Brown R.L. Benjamin L. Nortley R. Wiethoff S. Bharucha T. et al.The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings.Brain. 2020; : 2-37https://doi.org/10.1093/brain/awaa240Crossref PubMed Scopus (598) Google Scholar], only time will tell us if COVID-19 pandemic will lead to an increase of central nervous system autoimmune disorders. We should not forget that, one century ago, the “pandemic flu” was followed by the outbreak of encephalitis lethargica [[5]Hoffman L.A. Vilensky J.A. Encephalitis lethargica: 100 years after the epidemic.Brain. 2017; 140: 2246-2251https://doi.org/10.1093/brain/awx177Crossref PubMed Scopus (98) Google Scholar], an elusive form of encephalitis that has been recently linked to NMDAr encephalitis [[6]Dale R.C. Irani S.R. Brilot F. Pillai S. Webster R. Gill D. et al.N-methyl-D-aspartate receptor antibodies in pediatric dyskinetic encephalitis lethargica.Ann Neurol. 2009; 66: 704-709https://doi.org/10.1002/ana.21807Crossref PubMed Scopus (181) Google Scholar].