Herpes simplex encephalitis as a potential cause of anti-N-methyl-D- aspartate receptor antibody encephalitis: Report of 2 cases

IMPORTANCE: Encephalitis mediated by anti-N-methyl-D-aspartate (NMDA) receptor antibodies and herpes simplex (HS) encephalitis are seemingly separate causes of encephalopathy in adults and children. Herpes simplex encephalitis is infectious, and anti-NMDA receptor antibody encephalitis is autoimmune in origin. Both can cause seizures and encephalopathy, although the latter can also cause psychiatric symptoms and movement disorders. Owing to the rarity of these 2 diseases, patients with co-occurrence are important because they alert clinicians to possible links between 2 seemingly separate processes. OBSERVATIONS: In a case series of 2 patients observed at our center, we describe an infant and an adult who had confirmed HS encephalitis and then developed confirmed anti-NMDA receptor antibody encephalitis. Polymerase chain reaction testing for HS virus was performed. Testing for NMDA receptor antibodies was performed by Associated Regional and University Pathologists Laboratory in Salt Lake City, Utah. CONCLUSIONS AND RELEVANCE: We conclude that atypical cases of HS or other viral encephalitides should be investigated for concomitance of an autoimmune encephalitis. We suspect that the pathophysiologic mechanisms by which HS virus infects neurons produce a higher likelihood of contracting anti-NMDA receptor antibody encephalitis.