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Background and objectives:Autoimmune encephalitis (AE) cases post-SARS-CoV-2 infection have been reported, but the frequency is unknown. We aimed to determine the frequency and diagnostic features of COVID-19 related AE.Methods:Residual sera from 556 consecutive Mayo Clinic Rochester patients (laboratory cohort) who underwent autoimmune encephalopathy neural IgG evaluation were tested for total antibodies against the SARS-CoV-2 spike glycoprotein using an FDA-authorized chemiluminescence assay (October 2019-December 2020). Clinical records from patients with a positive SARS-CoV-2 antibody result and available research consent were reviewed. This laboratory cohort was cross-referenced with the Department of Neurology’s COVID-related consultative experience (encephalopathy cohort, n=31).Results:Eighteen of the laboratory cohort (3%) were SARS-CoV-2 antibody positive (April-December 2020). Diagnoses were: AE, 2; post-acute sequelae of SARS CoV-2 infection [PASC], 3; toxic-metabolic encephalopathy during COVID-19 pneumonia, 2; diverse non-COVID-19 relatable neurological diagnoses, 9; unavailable, 2. Five of the encephalopathy cohort had AE (16%, including the 2 laboratory cohort cases which overlapped) representing 0.05% of 10,384 patients diagnosed and cared for with any COVID-19 illness at Mayo Clinic Rochester in 2020. The 5 patients met definite (n=1), probable (n=1), or possible (n=3) AE diagnostic criteria; median symptom onset age was 61 years (range, 46-63), 3 were women. All 5 were neural IgG negative and 4 tested were SARS-CoV-2 PCR/IgG index negative in CSF. Phenotypes (and accompanying MRI and EEG findings) were diverse (delirium [n=5], seizures [n=2], rhombencephalitis [n=1], aphasia [n=1], and ataxia [n=1]). No ADEM cases were encountered. The 3 patients with possible AE had spontaneously resolving syndromes. One with definite limbic encephalitis was immune therapy responsive but had residual mood and memory problems. One patient with probable autoimmune rhombencephalitis died despite immune therapy. The remaining 26 encephalopathy cohort patients had toxic-metabolic diagnoses.Discussion:We encountered occasional cases of AE in our 2020 COVID-19 experience. Consistent with sporadic reports and small case series during the COVID-19 pandemic, and prior experience of postinfectious AE, our cases had diverse clinical presentations and were neural IgG and CSF viral particle negative. Application of diagnostic criteria assists in differentiation of AE from toxic-metabolic causes arising in the setting of systemic infection.

Background and Objective:Severe attacks of myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disorder (MOGAD) and aquaporin-4 (AQP4)-antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) may require ventilatory support but data on episodes is limited, particularly for MOGAD. We sought to compare the frequency, characteristics, and outcomes of MOGAD and AQP4-NMOSD attacks requiring ventilatory support.Methods:This retrospective descriptive study identified Mayo Clinic patients (1/1/1996-12/1/2020) with MOGAD or AQP4-NMOSD and an attack requiring non-invasive or invasive ventilation at Mayo Clinic or an outside facility by searching for relevant terms in their electronic medical record. Inclusion criteria were: 1) Attack-related requirement for non-invasive (BiPAP or CPAP) or invasive respiratory support (mechanical ventilation); 2) MOG or AQP4 antibody positivity with fulfillment of MOGAD and AQP4-NMOSD clinical diagnostic criteria, respectively; 3) Sufficient clinical details. We collected data on demographics, co-morbidities, indication for and duration of respiratory support, MRI findings, treatments, and outcomes. The race of those with attacks requiring respiratory support were compared to those without such attacks in MOGAD and AQP4-NMOSD.Results:Attacks requiring ventilatory support were similarly rare in MOGAD (8/279, 2.9%) and AQP4-NMOSD patients (11/503, 2.2%) (p=0.63). The age at attack (median years [range]) (MOGAD, 31.5[5-47] vs AQP4-NMOSD, 43[14-65]; p=0.01) and percentage of female sex (MOGAD, 3/8[38%] vs AQP4-NMOSD, 10/11[91%]; p=0.04) differed. The reasons for ventilation differed between MOGAD (inability to protect airway from seizure, encephalitis or encephalomyelitis with attacks of: acute disseminated encephalomyelitis, 5[62.5%]; or unilateral cortical encephalitis, 3[37.5%]) and AQP4-NMOSD (inability to protect airway from cervical myelitis, 9[82%]; rhombencephalitis, 1[9%]; or combinations of both, 1[9%]). Median ventilation duration for MOGAD was 2 days (range, 1-7) versus 19 days (range, 6-330) for AQP4-NMOSD (p=0.01). All MOGAD patients recovered, but 2/11 (18%) of AQP4-NMOSD died from the attack. For AQP4-NMOSD, Black race was over-represented with attacks requiring ventilatory support versus those without these episodes (5/11[45%] versus 88/457[19%]; p=0.045).Discussion:Ventilatory support is rarely required for MOGAD and AQP4-NMOSD attacks and the indications differ. When compared to MOGAD, these attacks in AQP4-NMOSD may have higher morbidity and mortality and those of Black race were more predisposed, which we suspect may relate to socially mediated health inequality.