Spatial and Ecological Factors Modulate the Incidence of Anti-NMDAR Encephalitis—A Systematic Review

Abstract

Anti-NMDAR encephalitis has been associated with multiple antigenic triggers (i.e., ovarian teratomas, prodromal viral infections) but whether geographic, climatic, and environmental factors might influence disease risk has not been explored yet. We performed a systematic review and a meta-analysis of all published papers reporting the incidence of anti-NMDAR encephalitis in a definite country or region. We performed several multivariate spatial autocorrelation analyses to analyze the spatial variations in the incidence of anti-NMDA encephalitis depending on its geographical localization and temperature. Finally, we performed seasonal analyses in two original datasets from France and Greece and assessed the impact of temperature using an exposure-lag-response model in the French dataset. The reported incidence of anti-NMDAR encephalitis varied considerably among studies and countries, being higher in Oceania and South America (0.2 and 0.16 per 100,000 persons-year, respectively) compared to Europe and North America (0.06 per 100,000 persons-year) (p < 0.01). Different regression models confirmed a strong negative correlation with latitude (Pearson’s R = −0.88, p < 0.00001), with higher incidence in southern hemisphere countries far from the equator. Seasonal analyses showed a peak of cases during warm months. Exposure-lag-response models confirmed a positive correlation between extreme hot temperatures and the incidence of anti-NMDAR encephalitis in France (p = 0.03). Temperature analyses showed a significant association with higher mean temperatures and positive correlation with higher ultraviolet exposure worldwide. This study provides the first evidence that geographic and climatic factors including latitude, mean annual temperature, and ultraviolet exposure, might modify disease risk.

NORSE seasonality may vary geographically in adults

“…5 In a mixed cohort comprising adults and children, Gopaul et al 7 linked the seasonal differences with AEs that have a higher reported prevalence in summer-autumn and in warmer months. 18,19 However, data from a Danish AE register did not suggest a strong seasonality of antibody detection in Denmark making a direct and substantial link between the seasonality of NORSE and AE less likely. It is a limitation that we used antibody positivity and not clinical diagnoses for this study and that the awareness of AE was lower before approximately 2010.…”

Antibody‐positive autoimmune encephalitis and paraneoplastic neurological syndrome: A Swedish case series

“…Like several other autoimmune disorders, such as multiple sclerosis (Koch-Henriksen & Sørensen, 2010), AE and PNS display some geographical variations, which have been attributed to both genetic and environmental factors (Alentorn et al, 2023;Binks et al, 2018;Mueller et al, 2018;Titulaer et al, 2013).…”