Case Presentation: A 55-year-old female with history of hypertension, fibromyalgia, systemic lupus erythematosus, radiculopathy, anxiety disorder, and childhood varicella presented to an outside hospital for new onset altered mental status. She was diagnosed with acute non-hemorrhagic stroke of the right occipital lobe and anterior right frontal lobe without known cause or findings suggestive of vasculitis on CT imaging. She was discharged to rehabilitation facility and twelve days later she presented again altered with episodes of word finding difficulty and staring spells. Upon arrival, vital signs were stable and physical exam was unremarkable except for a slight left facial droop. There was no rash. Admission labs were unremarkable except for imaging. CT revealed new hyperdense caudate nuclei suggestive of petechial microhemorrhage. MRI of the brain with and without contrast revealed subacute infarcts within the bilateral carotid nuclei and adjacent white matter of the corona radiata. Lumbar puncture was performed based on new imaging findings, and CSF was found positive for Varicella Zoster Virus through nuclei acid amplification. Based on clinical presentation, abnormal lumbar puncture, imaging, and recommendations from neurology and infectious disease, the patient was started on IV acyclovir for one week and transitioned to two weeks of oral valacyclovir. Her condition improved dramatically, and she was transferred to an outside hospital while awaiting placement.
Discussion: Varicella Zoster Virus (VZV) vasculopathy is a disease that primarily affects the elderly and immunocompromised. In contrast to the typical reactivation that occurs along peripheral nerve fibers to skin, as seen in zoster (shingles), VZV vasculopathy occurs when latent reactivation of the virus has central involvement of cerebral and extracranial arteries. This can present as transient ischemic attack, stroke, aneurysm, sinus thrombosis, giant cell arteritis, and granulomatous aortitis. The exact frequency of stroke secondary to VZV vasculopathy is unknown, but studies have suggested that adults with VZV reactivation with associated zoster rash have up to a 31% increase in stroke in the following year. However, VZV vasculopathy has also been reported to occur on rare occasions without history of rash, making diagnosis difficult. Here, we report a case of VZV vasculopathy with associated subacute stroke in a patient who presented with new onset altered mental status. This patient’s diagnosis was complicated not only due to the absence of a recent zoster rash and history of zoster, but also by her recent stroke which raised clinical suspicion for recurrent stroke. CT showed new findings compared to recent stroke, which ultimately led to further workup of CSF, the primary means of diagnosing VZV vasculopathy. Even if PCR – amplifiable VZV DNA is not detected in CSF, the presence of antibodies against VZV can indicate central nervous system infection and support the diagnosis. Timely diagnosis of VZV vasculopathy is crucial as this treatable cause of stroke is often missed, especially in those who have no history of zoster rash. Additionally, severe cases can be fatal and require prompt IV acyclovir for a minimum of two weeks.
Conclusions: Here, we emphasize the importance of neuroimaging and CSF studies in patients with a history of childhood varicella despite having no history of zoster rash and to pursue thorough workup even when recurrent stroke seems like the likely diagnosis.