In this cohort of 42 patients with mild COVID19 we found a unique clinical feature of acute anosmia and dysgeusia in more than third of patients. Median onset of these features was 3.3 days after onset of illness (range 0-7) with rapid recovery in most patients. Article Summary Line: Anosmia and dysgeusia appeared early in third of our patients with mild SARS-CoV-2 infection and were short-lived in most patients.

Background and Objectives Antileucine-rich glioma-inactivated 1 (anti-LGI1) autoimmune encephalitis was first described in 2010 and is today the most common type of limbic encephalitis. During the course of the disease, 60%–88% of the patients develop hyponatremia. The etiology of the sodium disorder is unclear, often presumed to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Other electrolyte abnormalities have not been reported in association with anti-LGI1 antibody encephalitis. Due to the presence of hypomagnesemia and hypophosphatemia in our patients, we set out to try to find the expression of LGI1 protein in the kidney as an explanation for these abnormalities. Methods We reviewed the medical files of all patients diagnosed with anti-LGI1 antibody encephalitis, at the Department of Neurology in the Tel Aviv Medical Center between January 2011 and December 2020, exploring for electrolyte abnormalities. Using tissue staining, Western blot, mass spectrometry, and RNA expression techniques, we tried to demonstrate the expression of LGI1 protein in the human kidney. Results We identified 15 patients diagnosed with anti-LGI1 antibody encephalitis. Their average age was 65 years (44–80), and 9 were male individuals. Thirteen of the 15 patients (87%) developed varying degrees of hyponatremia. Laboratory studies demonstrated low serum osmolality, low serum blood urea nitrogen, and low uric acid, with a high urinary sodium and inappropriately high urine osmolality, supporting the presumable diagnosis of SIADH. One patient with hyponatremia that was tested, had high levels of copeptin, supporting the diagnosis of SIADH. In addition to hyponatremia, 7 patients (47%) exhibited other electrolyte abnormalities; 5 patients (33%) had overt hypophosphatemia, 4 patients (27%) had overt hypomagnesemia, and 2 other patients (13%) had borderline low magnesium levels. Western blot analysis of human kidney lysate, mass spectrometry, and qRT-PCR failed to demonstrate the expression of LGI1 protein in the kidney. Discussion Hyponatremia in patients with anti-LGI1 antibody encephalitis is due to SIADH as previously assumed. Other electrolyte abnormalities such as hypomagnesemia and hypophosphatemia occur in at least 40% of patients and may be another clue for the diagnosis of anti-LGI1 antibody encephalitis. Because we failed to demonstrate LGI1 expression in the kidney, the results of our study suggest that renal losses lead to these disturbances, most probably due to SIADH.

Objectives: The incidence of autoimmune encephalitis (AIE) has risen in the last decade, yet recent studies are lacking. We compared the epidemiology of autoimmune and infectious encephalitis cases in Tel‐Aviv Sourasky Medical Center (TASMC) between 2010 and 2020.Methods: All encephalitis cases, aged 18 and above, admitted to TASMC between the years 2010 and 2020 were reviewed for demographic, clinical, laboratory, and imaging data and categorized based on etiology.Results: Two hundred and twenty‐five patients with encephalitis were identified. The most common identifiable cause was viral (42%), followed by autoimmune encephalitis (35%), bacterial (18%), and fungal/parasitic (5%). The incidence of AIE cases out of the yearly admitted cases increased substantially, from 3.8/100 K in 2010 to 18.8/100 K in 2020. The incidence of viral cases also increased while those of bacterial and fungal/parasitic infections remained stable. Patients with AIE were younger compared to infectious patients (p‐value <0.001) and had lower markers of systemic and cerebrospinal fluid inflammation (p‐value for all <0.001). Seizures were more common among AIE patients (p‐value <0.001), yet one‐year mortality rates were higher among infectious patients (p‐value <0.001).Interpretation: AIE incidence has risen significantly in our institution during the past decade, with current rates comparable to those of all infectious causes combined. Based on this cohort, clinical clues for an autoimmune etiology include a non‐inflammatory cerebrospinal fluid profile, the presence of seizures, and temporal lobe imaging abnormalities (also common in herpetic encephalitis). In light of its rising incidence and the importance of early treatment, AIE should be considered in the differential diagnosis of all encephalitis cases.

The Mayo Clinic institutional review board approved this study. In the past 30 years, Mayo Clinic’s Neuroimmunology Laboratory identified 650 PCA-1-IgG-seropositive patients3; 8 (1.2%) were men (online supplementary table 1a), with PCA-1-IgG specificity confirmed by western blot with purified human cerebellar degeneration-related protein 2 (CDR2, the PCA-1 antigen; Euroimmun, Lubeck, Germany). Clinical information was obtained for seven by case record review and physician telephone interviews. A PubMed literature search (1990–2015) identified 10 previously published PCA-1-IgG-positive male cases (online supplementary table 1b).