To describe a patient with NMDAR-IgG and Septin-7-IgG autoimmunity post- HSE.

NMDAR-IgG has been reported with herpes simplex encephalitis (HSE). Recently, few cases with concurrent Septin-7-IgG have been identified.

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A 79-year-old male presented with acute expressive aphasia, altered mental status and seizures. Brain MRI revealed diffusion restriction, T2 hyperintensity and enhancement in the left temporal lobe and hippocampus. CSF showed 18 WBC(93% neutrophils), protein 144g/dL, HSV1 PCR+. Despite initiation of acyclovir, he continued to be encephalopathic. Repeat CSF on day 14 revealed persistent inflammation with 15 WBC(84% lymphocytes), protein 104g/dL, and HSV PCR+. He received 30 days of antiviral therapy and was discharged. Thirty-two days after presentation, he was readmitted for unresponsiveness, encephalopathy, and agitation. EEG revealed new generalized periodic pattern with triphasic morphology. Due to progressive neurological worsening, a 3rd CSF obtained and revealed persistent inflammation with 24 WBC(90% lymphocytes), protein 73g/dL, positive HSV PCR+, and testing for neural antibodies identified NMDAR-IgG, and Septin-7-IgG. He was treated with acyclovir for an additional 19 days, IV methylprednisolone, intravenous immunoglobulin, and rituximab. One-year from onset, he has residual amnesia, aphasia, and right facial droop with modest improvements in his cognition and mood. Follow-up MRI demonstrated gliosis and petechial hemorrhage in the left anterior temporal lobe.

While NMDAR-IgG has been frequently detected post-HSE, there are few reports of Septin-7-IgG. Septin-7 is expressed in the hippocampus, sperm, forebrain and NMDAR in the prefrontal cortex and hippocampus. Since the temporal lobe and hippocampus are commonly involved in HSE, inflammation induced breakdown of these structures may increase antigen presentation and trigger autoimmunity that cause persistent inflammation.

The red flags for post-HSE may include progressive neurological worsening, persistent inflammatory CSF and HSV PCR positivity. This case describes the presentation of a novel neuronal antibody, Septin-7-IgG, that can be associated with post-HSE autoimmunity.