Herpes simplex virus encephalitis is a trigger of brain autoimmunity

Area of Science:

• Neurology
• Immunology
• Infectious Diseases

Background:

• Relapsing neurological conditions can occur after herpes simplex encephalitis (HSE).
• The role of autoimmune responses, particularly N-methyl-D-aspartate receptor (NMDAR) antibodies, in post-HSE relapses is not fully understood.

Purpose of the Study:

• To investigate the potential link between HSE and the development of NMDAR antibodies.
• To determine the frequency and timing of autoantibody onset following HSE.
• To evaluate the efficacy of immunotherapy in patients with relapsing post-HSE and NMDAR antibodies.

Main Methods:

• Prospective diagnosis and monitoring of 5 patients with relapsing HSE.
• Retrospective analysis of 34 HSE patients for neuronal surface autoantibodies.
• Serological and cerebrospinal fluid analysis for NMDAR antibodies and other autoantibodies.
• Assessment of patient outcomes following immunotherapy or spontaneous recovery.

Main Results:

• NMDAR antibodies were identified in 5 prospectively diagnosed patients with relapsing HSE, appearing 1-4 weeks after the initial infection.
• Three of these patients showed improvement after immunotherapy, one improved spontaneously, and one began to improve.
• Retrospective analysis revealed additional NMDAR antibody-positive cases and an increasing frequency of autoantibodies over time in HSE patients.
• The onset of NMDAR antibodies preceded neurological relapses in HSE patients.

Conclusions:

• Herpes simplex encephalitis serves as a trigger for the production of NMDAR antibodies.
• Brain autoimmunity, including NMDAR antibody encephalitis, can manifest as a relapsing condition post-HSE.
• Immunotherapy may be a beneficial treatment strategy for relapsing post-HSE associated with NMDAR antibodies.