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

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.

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.

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).

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.