Post-Herpetic Anti-NMDAR Encephalitis in Denmark: Current Status and Future Challenges

Area of Science:

• Neuroscience
• Immunology
• Infectious Diseases

Background:

• Herpes simplex virus 1 encephalitis (HSE) is a known trigger for N-methyl-D-aspartate receptor encephalitis (NMDARE).
• The incidence and diagnostic patterns of post-HSE NMDARE in Denmark remain largely unknown.
• Understanding this association is crucial for improving diagnosis and patient outcomes.

Purpose of the Study:

• To determine the incidence of post-HSE NMDARE in Denmark.
• To compare clinical characteristics of Danish post-HSE NMDARE patients with existing literature.
• To assess the diagnostic rate of NMDARE in HSE patients in Denmark.

Main Methods:

• Literature review of 80 post-HSE NMDARE cases globally.
• Retrospective analysis of Danish national autoimmune encephalitis and regional infectious encephalitis databases (2009-2021).
• Comparison of clinical phenotypes and diagnostic criteria (Graus criteria) between literature and Danish cohorts.

Main Results:

• Nine post-HSE NMDARE patients identified in Denmark; none were children.
• Literature cases predominantly affected children (66%) with distinct symptoms.
• In Denmark, 36% of HSE patients met NMDARE criteria, but only 17% of those with available CSF tested positive for NMDARE antibodies; overall diagnosis rate was low (7% in one region).

Conclusions:

• Adult post-HSE NMDARE appears underdiagnosed in Denmark, with a low incidence of 0.17 per million/year in one region.
• The lack of identified pediatric post-HSE NMDARE cases in Denmark is concerning and warrants further investigation.
• Improved diagnostic strategies for NMDARE in HSE patients are needed.