Anti-NMDA Receptor Encephalitis Disproportionately Impacts Black, Hispanic, and Asian Populations, Study Shows

Annette Langer-Gould, MD, PhD

Using data from a retrospective cohort of more than 10 million person-years of observation from members of Kaiser Permanente Southern California (KPSC), results showed a significantly higher incidence of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis among Black, Hispanic, and Asian/Pacific Island (PI) populations. Above all, these data raise questions about why minoritized individuals, particularly female individuals, in the United States may be more prone to aberrant humoral immune responses.

Published in Neurology, the study used KPSC’s complete electronic health records (HER), which include all inpatient and outpatient encounters, laboratory and imaging tests, diagnoses, medications, and demographic characteristics. KPSC provides comprehensive health care to more than 4.8 million members, representing approximately 20% of the general population in Southern California. From January 2011 to December 2022, 70 patients were identified who met diagnostic criteria for anti-NMDAR encephalitis. Of these, 67 had definite cases, defined by positive cerebrospinal fluid (CSF) antibodies, and 3 had probable anti-NMDAR encephalitis with missing CSF results.

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The median age at diagnosis was 23.8 years (range, 2.5-68.2 years), and 45 (64%) were female patients. After adjusting for age and sex, the risk of anti-NMDAR encephalitis was 7.01 (95% CI, 2.63-18.70; P <.0001) high in Black, 4.36 (95% CI, 1.58-12.00; P = .0044) higher in Asian/PI, and 4.28 (95% CI, 1.82-10.11; P = .0009) higher in Hispanic individuals compared with that in White persons (reference group). The age-standardized incidence rate was significantly higher among Black (incidence risk ratio [IRR] = 16.28, 95% CI 3.57–74.32, P = 0.0003), Asian/PI (IRR = 9.73, 95% CI 2.06–45.82, P = 0.0040), and Hispanic (IRR = 7.21, 95% CI 1.70–30.48, P = 0.0073) individuals compared with White female patients.

Senior author Annette Langer-Gould, MD, PhD, regional lead for Clinical and Translational Neuroscience at Southern California Permanente Medical Group, concluded, "We speculate that racial/ethnic disparity in anti-NMDAR encephalitis in the United States may at least partly be attributable to the embodiment of socioeconomic and environmental factors including poverty, racial discrimination, substandard health care, and earlier exposure and more vigorous responses to common childhood infections. These factors and their potential influence on immunologic dysregulation and epigenetic changes that could predispose individuals to anti-NMDAR encephalitis should be examined in future studies."

In comparison with White male patients, age-standardized incidence was similar between Black and Asian/PI patients but higher in Hispanic (IRR, 2.86; 95% CI, 0.95-8.56; P = .0609), although this finding did not reach statistical significance. After considering the racial/ethnic distribution of the US population, investigators estimates that approximately 400 individuals will be newly diagnosed with anti-NMDAR encephalitis per year in the United States.

In terms of limitations, the study had a relatively small number of cases, particularly among White individuals and in the youngest and oldest age groups, as well as limited data on the variation in timing and type of EEGs and MRIs, and socioeconomic status data. The study authors noted that it is unclear whether the findings from the study, which featured data from California, can be extrapolated to other diverse populations. In contrast, the study was strengthened by a search strategy to identify cases, long study period that improved precision, and decreased possibility of underdetection.

Among those identified with anti-NMDAR encephalitis, ovarian teratomas were found in 21 female patients and a mediastinal teratoma in 1 Black male patient. Ovarian teratomas were more frequent in Black female patients compared with other racial/ethnic groups, accounting for two-thirds of Black patients with anti-NMDAR encephalitis. Most of the patients (61.4%; n = 43) had no identifiable trigger of their condition, particularly those younger than 13 years (n = 12; 81.3%) compared with other age groups (≥13-40 years [n = 26]: 59.1%; >40 years [n = 4]: 40.0%; P = .012).

REFERENCE
1. Alsalek S, Schwarzmann KB, Budhathoki S, Hernandez-Lopez V, Smith JB, Li BH. Racial and ethnic disparities in the incidence of anti-NMDA receptor encephalitis. Neurology, Neuroimmunol, Neuroinflamm. 2024;11(4). doi:10.1212/NXI.0000000000200255