Varicella‐zoster virus reactivation is frequently detected in HIV‐infected individuals presenting with stroke.

Infections are an underappreciated cause of stroke, particularly in young and immunocompromised individuals. Varicella‐zoster virus (VZV) reactivation, particularly ophthalmic zoster, has been linked to increased risk of stroke but diagnosing VZV‐associated cerebral vasculopathy is challenging as neither a recent zoster rash, nor detectable levels of VZV DNA are universally present at stroke presentation. Detection of VZV IgG in cerebrospinal fluid (CSF‐VZVG) presents a promising alternative, but requires evaluation of individual blood‐CSF dynamics, particularly in the setting of chronic inflammatory states such as HIV infection. Consequently, its use has not been broadly adopted as simple diagnostic algorithms are not available. In this study looking at young adults presenting with acute stroke, we used an algorithm that includes testing for both VZV nucleic acids and CSF‐VZVG which was corrected for blood‐CSF barrier dynamics and poly‐specific immune activation. We found that 13 of 35 (37%), including 7 with a positive CSF VZV PCR, young HIV‐infected adults presenting with stroke, 3 of 34 (9%) young HIV‐uninfected adults presenting with stroke, and 1 of 18 (6%) HIV‐infected nonstroke controls demonstrated evidence of central nervous system reactivation of VZV. Highlights: Current nucleic acid detection‐based methods are inadequate as a standalone test for detecting clinically relevant episodes of central nervous system varicella‐zoster virus reactivation (CVR).A diagnostic algorithm which includes the calculation of intrathecally produced varicella‐zoster virus (VZV) IgG concentration aids the detection of CVR in young patients with stroke.CVR was more common in HIV‐infected (37%) stroke patients than in HIV‐uninfected (9%) cases.In the absence of CVR, HIV‐positive status is associated with significantly lower levels of VZV‐specific IgG production in CSF.In contrast, intrathecally produced VZV IgG levels were significantly higher in HIV‐positive patients with evidence of recent CVR. [ABSTRACT FROM AUTHOR]