In an interview with MIMS Doctor, Dr Kay-Cheong Teo, Specialist in Neurology, and Dr Anthony Tam, Specialist in Infectious Disease, both from the University of Hong Kong, discussed the intricate herpes zoster (HZ)–stroke relationship. They also highlighted how recombinant zoster vaccine (RZV), with its high efficacy and favourable safety profile, can play a significant role in preventing HZ, mitigating varicella zoster virus (VZV)–related sequelae such as debilitating post-herpetic neuralgia (PHN), and potentially reducing stroke risk, as demonstrated by recent cohort studies.
The reciprocal HZ-stroke relationship
Large nationwide population-based studies and meta-analyses found that comÂpared with matched controls, patients with a prior cardiovascular (CV) event (including stroke) are at significantly greater risk of HZ and/or HZ hospitalization, especially within 1 year after the index event. Reciprocally, the risk of stroke is significantly increased after HZ, with prior RZV vaccination asÂsociated with a >40 percent decreased risk. [J Dematol 2018;45:1312-1318; PLoS ONE 2020;15:e0228409; J NeuÂrovirol 2023;29:449-459; Clin Infect Dis 2023;76:e1335-e1340]
Several pathophysiological mechaÂnisms may explain the increased risk of stroke after HZ. Among them, systemic inflammation during HZ can cause endoÂthelial injury, promote arterial thrombosis, and increase hypercoagulability; acute pain and distress associated with HZ may trigÂger adverse emotional responses, resulting in increased sympathetic activity, elevated blood pressure, and immune dysregulation; and direct viral replication within arteries can also lead to vessel inflammation and stroke, a condition referred to as VZV vasculopathy. [J Stroke Cerebrovasc Dis 2017;26:1807-1816; J Am Coll Cardiol 2017;70:295-296]
VZV vasculopathy
“In our centre, most patients who develÂop a stroke after HZ do not have VZV vasÂculopathy [as in our Case report]. However, a history of HZ is often overlooked. Hence, a positive HZ history in a stroke patient should raise suspicion of VZV vasculopathy, for which further investigation and manageÂment are warranted,” Teo noted. “The risk of VZV vasculopathy is highest following HZ ophthalmicus, likely due to the anatomical proximity to intracranial arteries.” [Viruses 2025;17:1591]
Imaging may reveal multifocal intra-arterial stenoses with multiple infarcts, parÂticularly involving the white matter or gray–white matter junctions. (Figure 1) Small vessel VZV vasculopathy can also occur, resulting in lacunar infarcts over deep strucÂtures of the brain. Cerebrospinal fluid (CSF) virological analysis remains the cornerstone of diagnosis, where anti-VZV immunoglobÂulin G antibody testing is essential, as VZV DNA is often undetectable by polymerase chain reaction (PCR). Once diagnosed, paÂtients are typically treated with 14 days of intravenous (IV) acyclovir, along with a 5-day course of oral prednisolone at 1 mg/kg/day. [Neurology 2008;70:853-860; Viruses 2025;17:1591]
“VZV vasculopathy is underdiagnosed due to the often-long interval between zoster infection and stroke [average, 4.1 months], as well as the practical challenges of obtaining and testing CSF. Furthermore, about 40 perÂcent of patients with VZV vasculopathy do not have the characteristic rash,” noted Teo.
Vaccination to reduce HZ burden
“While disease severity may be reduced with timely antiviral and other supportive treatments, such as corticosteroids, the proÂtective effect of vaccination is more consisÂtent and compelling, making HZ prevention a more cost-effective and sustainable strateÂgy,” stated Tam. [J Neurovirol 2023;29:449-459; Viruses 2025;17:1591]
RZV’s safety and efficacy
RZV’s safety, efficacy and durability were confirmed in the ZOE-50 and ZOE- 70 pivotal phase III trials and their long-term follow-up study (ZOE-LTFU). Vaccine efficaÂcy (VE) was 97.2 and 91.3 percent against HZ, and 91.2 and 88.8 percent against PHN, in adults aged ≥50 and ≥70 years, respecÂtively, over 3–4 years of follow-up. In the 11th year post-vaccination, VE was sustained at 82.0 percent in those vaccinated at ≥50 years of age, with no serious adverse events reported. [N Engl J Med 2016;372:2087-2096; N Engl J Med 2016;375:1019-1032; eClinicalMedicine 2025;83:103241]
The favourable benefit–risk profile of RZV is reaffirmed by pooled data from real-world studies. [Hum Vacc Immunother 2023;19:2263979]
Guideline recommendations
The US Centers for Disease Control and Prevention (CDC) recommend two doses of RZV for all adults aged ≥50 years and those aged 19–49 years with immunocomproÂmizing conditions. The WHO recommends two doses of RZV administered ≥2 months apart to prevent HZ in older adults and those with chronic conditions. [www.cdc.gov/ vaccines/hcp/imz-schedules/downloads/ adult/adult-combined-schedule.pdf; www.who.int/news-room/fact-sheets/detail/shinÂgles-(herpes-zoster)]
In Hong Kong, RZV is approved for prevention of HZ and PHN in adults aged ≥50 years and those aged ≥18 years at inÂcreased risk of HZ. The Hong Kong Medical Association echoes the US CDC’s recomÂmendations in its Adult Immunization Public Education Campaign. [Shingrix Hong Kong Prescribing Information, v HK102021; www. adultvax.thkma.org/%E7%96%AB%E8% 8B%97%E5%BB%BA%E8%AD%B0]
The above editorial is for medical education purpose
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