Case Presentation: A 39-year-old female with a history of primary sclerosing cholangitis status post-liver transplant in 1986 on cyclosporine, ankylosing spondylitis, Monoclonal gammopathies with undetermined significance, and migraines presents with progressive headaches, fevers (up to 101 F), and neck stiffness over the past 2 weeks. She was found to have photophobia, meningismus, and a positive Kernig’s sign upon admission; labs revealed leukocytosis 27,000 with lymphocytes. Meningitis was suspected and the patient was started on broad-spectrum antibiotics and acyclovir. Lumbar puncture showed opening pressure mildly elevated 15mm H2O, pleocytosis with 214 cells/mm3 (91% lymphocyte), 49 mg/dL protein and 75 mg/dL glucose, elevated IgG index 21. Confirmation was provided by positive HSV type 2 PCR positivity. MRI for persistent headaches despite treatment revealed subtle leptomeningeal enhancement. It was found that she had aseptic Herplex simplex virus(HSV) meningitis. Her migraine headaches could have previously confounded prior episodes, she was given the diagnosis of Mollaret’s syndrome by Infectious disease, Neurology, and Transplant medicine despite recurrence and was aggressively managed with IV antivirals for 5 days then transitioned to lifelong HSV prophylaxis with valacyclovir due to severity of hospitalization and leptomeningeal involvement. She improved and did not have any repeat episodes while on prophylaxis.

Discussion: Mollaret’s meningitis, aseptic meningitis characterized by recurring episodes of severe headache, meningismus, and fever (1,2,3), was first reported by Mollaret in 1944 (1). In 1962, Bruyn et al. (4) outlined the criteria for a diagnosis of Mollaret meningitis as follows: (2) Recurring episodes presenting with severe headache, meningismus, and a fever; (3) pleocytosis in the CSF composed of endothelial cells, neutrophils, and lymphocytes; (4) the development of episodes after symptom-free periods of weeks to months; and (5) the absence of a detectable etiological agent. Despite such a guideline, this diagnosis has been quite elusive. Our patient had aseptic meningitis, fevers, and headaches, all of which had recurred and worsened at intervals of two weeks to two years, with remission of all symptoms within two weeks without any sequelae. Typically, Mollaret’s is relapsing and remitting HSV infection, where a non-immunocompromised person would take courses of acyclovir whenever they had an episode of aseptic meningitis. In her case, she had one significant episode and due to past history of liver transplant on cyclosporine, she was recommended to proactively have lifelong HSV prophylaxis due to immunosuppressed status rather than the usual protocol to reactively treat each episode as it recurs.

Conclusions: The precise etiology and optimal treatment protocol of Mollaret’s syndrome remain unclear and at times tailored to the clinical picture. In our case, it is proposed that the patient already had a stimulated immune system as delineated by her preexisting autoimmune conditions and this could cause a quick reactivation of latent HSV. She had completed a year of Valacyclovir during her transplant period as part of her regimen for HSV and VZV prophylaxis, and the appearance of HSV at this time had a pathophysiological mechanism related to immune activation rather than autoimmunity. Mollaret’s meningitis is under-recognized, and improved recognition of this entity may limit unwarranted antibiotic use and shorten or eliminate unnecessary hospital admission.

IMAGE 1: Summary of Mollaret’s meningitis

IMAGE 2: Bruyn’s diagnostic criteria for Mollaret’s meningitis