By: Giuseppe Reale, MD. Catholic University of the Sacred Heart – Rome.
Varicella Zoster Virus (VZV) is a well-known herpesvirus causing chickenpox in children and shingles in older adults. Accumulating evidence suggest that more than 95% of adults worldwide are infected with VZV, and approximately 30% will develop shingles in their lifetime, with even higher proportions in over-85. In fact, VZV reactivation is linked to several factors, including immuno-depression and ageing1.
After the first infection, VZV enters an inactive period in cranial nerves, dorsal roots and autonomic ganglia along the entire neuraxis; when reactivated, VZV usually travels back along sensory fibers and causes the typical shingles’ rash and pain2. However, sometimes VSV might reach, along autonomic fibers, arterial walls, causing damage and inflammation. This so-called VZV vasculopahty might result in ischemic stroke, aneurysms, subarachnoid and intraparenchimal hemorrhage, with radiological and laboratory features similar to other vasculitides3.
Several studies have pointed out that, in the first three months after shingles, there is an increased risk of stroke4. Although ophthalmic-distribution shingles are associated to high rates of stroke, VZV vasculopathy has been described even in absence of typical shingles symptoms, suggesting a subtle VZV reactivation5. In fact, detection of anti-VZV IgG antibody in cerebrospinal fluid confirms the diagnosis, while clinical and radiological findings are less sensitive5. Thus, the real burden of VZV-related strokes might be underestimated.
Here comes a very interesting preliminary study presented at the 2020 International Stroke Conference by Yang et al6. The authors analyzed the 4 years stroke incidence in a group of one million people aged over 65 who had received the Zoster Vaccine Live between 2008 and 2014. Compared with a matched group of people who had not received the vaccine, the incidence of overall stroke was 16% lower in the vaccine group (18% for ischemic stroke, 12% for hemorrhagic stroke). These results are very encouraging, considering that new adjuvanted, non-live vaccine (available since 2017) seems to be even stronger than the previous one7. Moreover, in a 2019 study, Yang et al. found that shingles vaccination was not effective in reducing the risk of stroke when administered after the first shingles episode8.
Further studies will shed light on this burning topic. However, Centre for Disease Control already recommends shingles vaccination to all people over-50 to prevent complications such as post-herpetic neuralgia. If the connection with stroke will be confirmed, shingles vaccination will become a feasible, low-cost stroke primary prevention strategy.
- Yawn BP, Saddier P, Wollan PC, St Sauver JL, Kurland MJ, Sy LS. A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clin Proc. 2007;82:1341–1349.
- Cohen JI. Clinical practice: herpes zoster. N Engl J Med. 2013;369:255–263
- Gilden D, Cohrs RJ, Mahalingam R, Nagel MA. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment.. Lancet Neurol. 2009;8:731-740
- Lian Y, Zhu Y, Tang F, Yang B, Duan R. Herpes zoster and the risk of ischemic and hemorrhagic stroke: A systematic review and meta-analysis. PLoS ONE. 2017;12: e0171182
- Nagel MA, Cohrs RJ, Mahalingam R, Wellish MC, Forghani B, Schiller A, et al. The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology. 2008;70:853–860
- Yang Q, Chang A, Tong X, Merritt R. Abstract TP493: Herpes Zoster Vaccine Live And Risk For Stroke Among Medicare Beneficiaries: Population Based Matched Cohort Study. Stroke. 2020;51:ATP493
- Shafran SD. Prevention of Shingles: Better Protection and Better Value With Recombinant Vaccine. Ann Intern Med. 2019;170:416-417
- Yang Q, George MG, Chang A, Merritt R, Hong Y. Effect of herpes zoster vaccination and antiviral treatment on risk of ischemic stroke among older adults. Presented at: 2019 International Stroke Conference. February 6-8, 2019; Honolulu, HI. Abstract 39