N-methyl-d-aspartate receptor autoimmunity affects cognitive performance in herpes simplex encephalitis

Area of Science:

• Neuroimmunology
• Infectious Diseases
• Neurology

Background:

• Herpes simplex encephalitis (HSE) can lead to long-term neurological deficits.
• The role of autoimmune responses, specifically N-methyl-d-aspartate receptor (NMDAR) autoantibodies, in HSE is not fully understood.
• Investigating autoimmune complications is crucial for improving patient outcomes.

Purpose of the Study:

• To determine the prevalence and timing of N-methyl-d-aspartate receptor (NMDAR) autoantibody development in HSE patients.
• To assess the relationship between NMDAR autoantibodies and neurocognitive performance recovery.
• To explore potential therapeutic implications for HSE-associated autoimmunity.

Main Methods:

• Prospective observational study of 49 HSE patients.
• Collection of cerebrospinal fluid and serum samples at multiple time points (initial, 2-3 weeks, 3 months).
• Detection of anti-NMDAR IgG antibodies and comprehensive neurocognitive testing over 24 months.

Main Results:

• Anti-NMDAR IgG antibodies were found in 12 of 49 HSE patients, primarily developing after 3 months.
• Antibody development was significantly associated with impaired neurocognitive recovery.
• Patients with NMDAR autoantibodies showed a smaller increase in Mattis Dementia Rating Scale scores compared to antibody-negative patients.

Conclusions:

• Anti-NMDAR autoimmunity is a frequent complication of HSE, emerging within three months post-onset.
• Impaired neurocognitive recovery is linked to the development of NMDAR autoantibodies.
• These findings highlight the potential of immunotherapy for HSE-related central nervous system autoimmunity.