Stress is Associated with Severe Anti-NMDA Receptor Encephalitis: A Single-Center Retrospective Cohort Study

Abstract Background: Stress was reported to trigger and exacerbate a lot of autoimmune diseases. The underlying mechanisms include disturbed hormone homeostasis, dysregulated immune function, neuroinflammation by macrophages and microglia, and so on. There have been case reports of stress-induced anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis (anti-NMDARE). To elucidate the association between stress events and anti-NDMARE, we conducted a retrospective single-center cohort study.Materials and Methods: All severe anti-NMDARE patients admitted to neuro-intensive care unit (NICU) of Nanfang Hospital between September 2013 and July 2020 were screened. The stress events within 1 year before the onset were evaluated by a questionnaire survey using the Chinese Life Event Scale. The demographic information, clinical features, laboratory results and prognosis were collected and compared between patients with and without life stress events (LSE). Patients were further classified based on the existence of teratoma and herpes viruses in cerebrospinal fluid to investigate the association between stress and anti-NMDARE. Results: Of the 26 severe anti-NMDARE patients, 9 (34.6%) patients reported LSE. Among them, 5 (55.6%) had family stress, 3 (33.3%) had work stress and 1 (11.1%) had both family and work stress. No significant differences were observed in disease severity upon admission, NICU stay time, mechanical ventilation time or other laboratory results. The comorbid rate of teratoma and herpes virus was not significantly different between patients with and without LSE. However, 7 of the patients without teratoma and herpes virus (7/17, 41.2%) experienced LSE before the disease onset. The prognosis of patients with LSE was significantly better than that of patients without LSE (P=0.023).Conclusions: Up to 34.6% of severe anti-NMDARE patients had LSE within 1 year before the onset, which might even be underestimated. This study suggested that stress might be another risk factor for anti-NMDARE besides teratoma and herpes virus. Neurologists should pay attention to the stress of the patients and provide psychological therapy to the patients.