Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Jul 2025)

Detection of Varicella Zoster Virus Reactivation in Cerebrospinal Fluid in Ischemic Stroke or Transient Ischemic Attack

  • Wenyang Li,
  • Peter Sguigna,
  • Chintan Rupareliya,
  • Suriya Subramanian,
  • Hisham Salahuddin,
  • Khalil S. Husari,
  • William Moore,
  • Mark Johnson,
  • Alejandro Magadan,
  • Charles Grose,
  • Ank E. Nijhawan,
  • Ty Shang

DOI
https://doi.org/10.1161/jaha.124.039489
Journal volume & issue
Vol. 14, no. 13

Abstract

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Background Epidemiological data suggest that the risk of ischemic stroke increases after varicella‐zoster virus (VZV) reactivation. The frequency of VZV reactivation in acute ischemic stroke (AIS) is unknown. The risk of recurrent stroke and the antiviral treatment effect, particularly in patients with HIV infection, have yet to be defined. Here, we investigate the proportion of VZV reactivation in the cerebrospinal fluid (CSF) of patients who presented with AIS or transient ischemic attack and underwent VZV testing, along with relevant follow‐up information. Methods We retrospectively reviewed medical records of patients who presented with AIS or transient ischemic attack and underwent VZV polymerase chain reaction and anti‐VZV IgG testing in CSF during their workup from January 1, 2014, to December 31, 2021. VZV reactivation was confirmed by a positive VZV polymerase chain reaction result or increased intrathecal anti‐VZV IgG synthesis in CSF. The cause of AIS and transient ischemic attack was classified using the SSS‐TOAST (Stop Stroke Study‐Trial of ORG 10172 in Acute Stroke Treatment) criteria. The occurrence of recurrent ischemic stroke during follow‐up was compared between patients who received antiviral treatment and those who did not, as well as between patients with and without HIV. Results Among the 177 patients included, VZV reactivation in CSF was found in 23.2%. VZV reactivation was more common in strokes involving intracranial arteries compared with those that did not (28% versus 3%, P=0.01). Seven (17%) patients with VZV reactivation had recurrent ischemic stroke within 1 year from positive test results. There was no significant difference in recurrent ischemic stroke between patients who received short‐term antiviral therapy and those who did not (14.8% versus 21%, P=0.593). Patients with AIS and HIV had a significantly higher risk of VZV reactivation (57% versus 20%, P=0.002) and recurrent ischemic stroke despite antiviral treatment (42.8% versus 5.0%, P=0.02) compared with patients without HIV. Conclusions Among individuals who underwent VZV testing in CSF, VZV reactivation was present in 1 of 5 patients with AIS/transient ischemic attack. Patients with HIV were at particularly high risk of VZV reactivation and recurrent ischemic stroke.

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