(508) Vasculopathy and Demyelinating Complications of Varicella in an Immunocompromised Patient

Introduction: Sporadic reports of association of the varicella zoster virus (VZV) with reversible cerebral vasoconstrictive syndrome (RCVS) and multiple sclerosis (MS) in the general population are available. We present the first report of VZV meningoencephalitis resulting in new onset RCVS in a patient with connective tissue disease (CTD) undergoing lung transplant (LT) evaluation.

Description: A 42-year-old woman with CTD overlap syndrome–related interstitial lung disease treated with mycophenolate, hydroxychloroquine, and prednisone was undergoing LT evaluation in January 2023. She presented in April 2023 for new onset severe headache, seizure, altered mental status, gaze deviation, and urinary incontinence. Cerebrospinal fluid (CSF) analysis showed elevated protein, lymphocytic pleocytosis, high HSV1 IgG, high VZV IgG, and low VZV IgM. Viral PCR in blood was negative. MRA of the head demonstrated beaded appearance of M1 and M2 branches, suggesting RCVS. Cerebral angiogram was negative for vasculitis prompting treatment with intravenous acyclovir for 14 days. Follow-up MRI in May 2023 demonstrated leptomeningeal enhancement; the patient was readmitted for lower extremity weakness. Inpatient imaging demonstrated multifocal abnormal areas of nodular leptomeningeal enhancement involving cauda equina roots, and new linear tract of left frontal white matter abnormality. Repeat CSF analysis demonstrated elevated protein, lymphocytic pleocytosis, high HSV ½ IgG, high VZV IgG, high VZV IgM, and oligoclonal bands. The patient was treated with intravenous valacyclovir for 3 weeks for recurrent VZV meningoencephalitis. She is now following with neurology for motor deficits due to the possibility of MS and RCVS. Of note, she had received the Shingrex vaccine in January 2023 as pre-LT requirement.

Discussion: VZV can result in demyelination by direct lysis of oligodendrocytes, stimulating host immune response and molecular mimicry of the virus with myelin proteins. Vasculopathy appears to be caused by transaxonal spread from afferent fibers of the trigeminal and other ganglia to the arterial adventitia, with the ensuing transmural propagation of the virus. Pre-existing CTD and immunosuppression medications may have increased risk in our patient.