Anti-NMDAR Encephalitis Following Herpes Simplex Virus Encephalitis: 2 Cases From Portugal

Herpes simplex virus encephalitis (HSVE) usually presents as a monophasic disease. Symptomatic HSVE relapsing with seizures, encephalopathy, or involuntary movements associated with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis have been recently reported. We report 2 cases of adult post-HSVE anti-NMDAR encephalitis from Portugal. Two female patients aged 50 years and 30 years were diagnosed with herpes simplex virus type 2 and type 1 encephalitis, respectively. After the initial improvement with specific treatment and despite virologic negativization, both patients suffered clinical, electroencephalographic, and imaging deterioration. The autoimmune encephalitis hypothesis was confirmed with the demonstration of anti-NMDAR antibodies in both cerebrospinal fluid and serum. Both responded to human immunoglobulin and methylprednisolone, with progressive gain of autonomy along the follow-up period. Thymectomy for thymic hyperplasia diagnosed during follow-up was performed in 1 patient. Although being rare, post-HSVE anti-NMDAR encephalitis should be considered in all cases of symptomatic recrudescence after HSVE, since adequate immune-modulating treatment improves the outcome. The role of thyme hyperplasia in autoimmune encephalitis pathogenesis needs better understanding.