Contactin-associated protein-like 2 (CASPR2) antibody generation in acute herpes simplex encephalitis: Case report and review of the literature

Introduction

Herpes simplex encephalitis (HSE) is the most common cause of sporadic viral encephalitis, and can lead to auto-antibody generation. HSE has mainly been reported in association with N-methyl-D-aspartate receptor (NMDAR) antibodies, but there have also been cases associated with contactin-associated protein-like 2 (CASPR2). This article aims to highlight the relevance of CASPR2 antibody generation in HSE.

Methods

This is a case presentation and literature review of HSE with CASPR2 antibody positivity.

Results

A 62-year-old male initially presented with fever, headache and confusion in September 2023. He then developed status epilepticus requiring intubation. MRI of the brain showed extensive bilateral mesiotemporal lobe abnormalities with an haemorrhagic component. Cerebrospinal fluid (CSF) analysis was positive for herpes simplex virus 1 DNA, and CSF and serum were also positive for CASPR2 antibodies. He was treated with intravenous aciclovir for 3 weeks and short course of high dose intravenous dexamethasone. The patient continued to deteriorate despite treatment and died from the complications of the disease. In this case, it was difficult to ascertain if the patient had symptoms of CASPR2 associated disease or if it was an epiphenomenon triggered by HSE.

Conclusion

A number of case reports have described HSE with CASPR2 positivity. Whereas our patient succumbed to the disease, other cases showed clinical response with aciclovir, corticosteroids and intravenous immunoglobulin. More research on this topic is warranted as there are no specific treatment guidelines due to the lack of robust clinical trial data.