A Case Report of Herpes Virus Encephalitis during Natalizumab Treatment for Relapsing Remitting Multiple Sclerosis

Background: Natalizumab is approved for the treatment of patients with relapsing remitting multiple sclerosis (RRMS) who have had an inadequate response to, or are unable to tolerate, an alternate disease modifying therapy (DMT). Natalizumab inhibits migration of lymphocytes into the central nervous system (CNS), which potentially impairs immune surveillance for CNS infections. Natalizumab-associated reactivation of JC virus causing progressive multifocal leukoencephalopathy (PML) is well documented. However, natalizumab treatment for MS is less clearly linked to increased risk of other viral infections. A recent case series by Fine et al (2013) reported 20 natalizumab-treated MS patients who developed CNS herpes simplex virus (HSV) infections. The potential role of prior immunosuppressant (IS) exposure in enhancing the risk of CNS HSV infection could not be determined.

Objectives: To describe a non-fatal case of herpes simplex virus encephalitis (HSE) in a patient with fulminant MS treated with natalizumab without prior IS or DMT exposure.

Methods: Case report

Results: A 38 year-old man with fulminant MS was treated with natalizumab as initial therapy. He developed acute encephalitis after four monthly infusions of natalizumab. Brain MRI showed a new hemorrhagic left temporal lesion with associated focal edema. HSV type 1 DNA was detected in cerebrospinal fluid (CSF) by PCR. He responded well to six weeks of IV acyclovir therapy followed by 30 days of oral treatment, aside from continued neuropsychiatric symptoms, including severe anterograde amnesia and impaired executive function. Repeat CSF studies after completion of six weeks of IV antiviral therapy showed no detectable HSV DNA.

Conclusions: Our case and the previously reported cases suggest that there is increased risk of CNS HSV infection with natalizumab therapy, even without prior IS exposure. Previous cases demonstrated apparent good response with early detection and appropriate treatment with antiviral agents. In addition to monitoring for PML, clinicians caring for patients treated with natalizumab should remain vigilant for other CNS infections.