Autoimmune Encephalitis - A comparison of patients with anti-GAD and anti-NMDAR antibodies

Autoimmune Encephalitis A comparison of patients with anti-GAD and anti-NMDAR antibodies Daníel Kristinn Hilmarsson, Radu Constantinescu Department of Medicine, University of Iceland, Reykjavík, Iceland; Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Neurology, Sahlgrenska University Hospital, Göteborg, Sweden. Introduction: Autoimmune encephalitis (AIE) comprises a group of disorders characterized by rapidly progressive short-term memory deficits, psychiatric symptoms and/or epileptic seizures. They are generally considered to be caused by immunological mechanisms, including autoantibodies directed against different neuronal antigens. The clinical presentation, effect of treatment and longterm outcome of these patients is variable and may differ between antibody groups. Results from recent studies indicate that early diagnosis and treatment may result in better recovery. In this study we compare AIE patients with anti-glutamic acid decarboxylase (GAD) antibodies and patients with anti-N-methyl-D-aspartate receptor (NMDAR) antibodies. Materials and Methods: Three follow-up periods were established; onset, a baseline visit and 12 months from the baseline visit. Onset was defined as the date of onset of symptoms and the associated hospital visit and baseline visit as the closest date of return for each patient (median: 86 days after onset, range: 4-435). Clinical data and lab results were collected retrospectively for these periods. Scores on the Karnofsky performance scale and the modified Rankin scale as well as ability to work were used to assess a patient's state and recovery. Fisher's exact test was performed with JMP for associations and Mann-Whitney U test was used to compare median values with RStudio. Results: Out of 41 AIE patients treated at Sahlgrenska University Hospital, five had anti-GAD antibodies, three had anti-NMDAR antibodies and one had both. These patients were subsequently classified into three groups, for comparison. The median age at disease onset was 38 years (range: 18-65), 78% were female (n=7). No patient was correctly diagnosed with AIE or given appropriate treatment measures at onset, making all of them return for the baseline visit. At that time, both groups had more severe symptoms and anti-NMDAR patients were more likely to have personality changes than patients with anti-GAD antibodies (p=0,0179). There were non-significant trends for anti-GAD patients to have AIE related abnormalities on brain magnetic resonance imaging (p=0,1964) and to respond better to immunosuppressive treatment (IST) (p=0,1964) compared to anti-NMDAR patients. Conclusions: The results of this study indicate that anti-GAD patients might respond better to IST than patients with anti-NMDAR encephalitis, as opposed to earlier published findings. However, our patient group was very small and data was collected retrospectively. Therefore, this investigation should be repeated prospectively, in a larger patient group, over a longer period of time. The way our results differ from earlier findings, as well as the fact that none of these patients got correctly diagnosed at onset, emphasises the need for further research of these different groups of AIE.