Antibodies against unknown neuronal antigens following herpes simplex virus encephalitis: A report of three patients

Abstract

Herpes simplex virus encephalitis (HSVE) is common form of viral encephalitis, but mortality remains high. Antibodies against synaptic receptors have been implicated in the development of antibody-associated autoimmune encephalitis after an HSVE-related neurological relapse. Both known and unknown antibodies against neuronal antigens have been detected following HSVE. However, details regarding the characteristics of patients with HSVE who have unknown antibodies, including the true nature of the antibodies, remain unknown. Until the pathophysiology of unknown autoantibodies is determined, neurologists can benefit from understanding the clinical features of individuals with unknown antibodies.

Here, we describe the cases of three patients with unknown neuronal antibodies in CSF following HSVE.

A previously reported patient showed a progressive clinical course, along with prominently expanding white matter lesions. The second patient showed neurological relapse, and the third patient achieved a monophasic clinical course. MRI in the three patients revealed white matter lesion progression in the tentorium. CSF samples from all patients showed surface antigen reactivity upon immunohistochemical evaluation using a rat hippocampus and a live neuronal assay using rat hippocampal primary cultured cells. Cell-based assays revealed that the CSF did not contain neuronal surface antibodies (A-NSAs), such as anti-NMDA receptor antibodies. The samples also tested negative for aquaporin-4 antibodies and myelin-oligodendrocyte glycoproteins. Antibodies against unknown NSAs were detected in all three patients.

HSVE can be associated with A-NSAs, and its clinical course varies. One possible sign of the presence of A-NSAs in patients with HSVE is the detection of atypical white matter lesions on cranial MRI.