Specific clinical and radiological characteristics of anti-NMDA receptor autoimmune encephalitis following herpes encephalitis

Abstract

Background: Herpes simplex virus encephalitis (HSE) frequently triggers secondary anti-N-methyl-D-aspartate receptor encephalitis (NMDARE), but markers predicting the occurrence of this entity (HSE-NMDARE) are lacking.

Methods: We conducted a retrospective description of patients with HSE-NMDARE diagnosed between July 2014 and August 2022 and compared them to both patients with regular forms of HSE and NMDARE.

Results: Among the 375 patients with NMDARE, 13 HSE-NMDARE were included. The median age was 19 years (0.5-73), 4/13 (31%) were children < 4 years old, and 7/13 (54%) were male. The median time between HSE and NMDARE onset was 30 days (21-46). During NMDARE, symptoms differed from HSE, including increased behavioral changes (92% vs 23%, p = 0.008), movements disorders (62% vs 0%, p = 0.013), and dysautonomia (54% vs 0%, p = 0.041). Compared to 21 patients with regular HSE, patients with HSE-NMDARE more often achieved severity-associated criteria on initial MRIs, with extensive lesions (11/11, 100% vs 10/21, 48%, p = 0.005) and bilateral diffusion-weighted imaging sequence abnormalities (9/10, 90% vs 6/21, 29%, p = 0.002). Compared to 198 patients with regular NMDARE, patients with HSE-NMDARE were more frequently males (7/13, 54% vs 43/198, 22%; p = 0.015) and children < 4 (4/13, 31% vs 14/198, 7%; p = 0.016), with a worse 12-month mRS (2[1-6] vs 1[0-6], p = 0.023).

Conclusions: Herein, patients with HSE-NMDARE have a poorer long-term prognosis than patients with regular NMDARE. We report a greater rate of severity-associated criteria on initial MRIs for HSE-NMDARE compared to regular HSE, which may help identify patients with higher risk of HSE-NMDARE.

Keywords: N-methyl-d-aspartate receptor; Antibody-mediated encephalitis; Infectious encephalitis; Post-infectious.

Fig. 1

Study flowchart. Diagram of patients’ inclusion. Abbreviations: HSE herpetic encephalitis, NMDARE anti-N-methyl-d-aspartate receptor encephalitis, MRI magnetic resonance imaging

Fig. 2

Variation of symptoms between HSE onset and NMDARE post-HSE, (%, n = 13). Comparison of symptoms at HSE onset and during NMDARE post-HSE in the HSE-NMDARE cohort, frequencies are represented as percentages. For the same 13 patients, HSE symptoms are represented on the negative axis in blue, NMDARE symptoms on the positive axis in orange. Speech and memory impairment were only assessed for patients aged ≥ 4 years (n = 9). P values < 0.05 are indicated with *. Abbreviations: HSE herpetic encephalitis, NMDARE anti-N-methyl-d-aspartate receptor encephalitis

Fig. 3

Temporal and thalamic patterns on longitudinal MRIs of patients with HSE-NMDARE. T2-Fluid-attenuated inversion recovery sequences are shown for patients 8 and 13. For each patient, the temporal pattern is shown on the left (a), and the thalamic on the right with yellow arrows (b). Longitudinal MRIs are shown at HSE diagnosis (first line), NMDARE diagnosis (second line), and follow-up (third line). Abbreviations: HSE herpetic encephalitis, NMDARE anti-N-methyl-d-aspartate receptor encephalitis

Fig. 4

Topography of thalamic lesions in patients with HSE-NMDARE. The characteristics of thalamic lesions are shown for 4 patients at NMDARE diagnosis, according to their age. On the left (a), T2 sequence shows median/anterior thalamic lesions in patients 3 and 11, who were children < 4 years old. On the right (b), FLAIR sequence shows hyperintensity in the pulvinar region in adult patients 5 and 9. Abbreviations: FLAIR T2-fluid-attenuated inversion recovery, NMDARE anti-N-methyl-d-aspartate receptor encephalitis