Abstract
Varicella zoster virus (VZV) infects >95 % of the world population. Typically, varicella (chickenpox) results from primary infection. The virus then becomes latent in ganglionic neurons along the entire neuraxis. In immunocompromised individuals, VZV reactivates and causes herpes zoster (shingles), pain, and rash in 1–2 dermatomes. Multiple case reports showed a link between stroke and zoster, and recent studies have emerged which reveal that VZV infection of the cerebral arteries directly causes pathological vascular remodeling and stroke (VZV vasculopathy). In the past few years, several large epidemiological studies in Taiwan, Denmark, and the U.K. demonstrated that zoster is a risk factor for stroke and that antiviral therapy may reduce this risk. Herein, the history, clinical features, and putative mechanisms of VZV vasculopathy, as well as recent epidemiological studies demonstrating that zoster increases the risk of stroke, are discussed.
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References
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Baudouin E, Lantué joul P. Les troublecas moteurs dans le zona. Gazette des Hopitaux. 1919.
Gordon IR, Tucker JF. Lesions of the central nervous sytem in herpes zoster. J Neurol Neurosurg Psychiatry. 1945;8:40–66.
Hughes WN. Herpes zoster of the right trigeminal nerve with left hemiplegia. Neurology. 1951;1:167–9.
Cope S, Jones AT. Hemiplegia complicating ophthalmic zoster. Lancet. 1954;267:898–9.
Nagel MA, Cohrs RJ, Mahalingam R, et al. The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology. 2008;70:853–60.
Nagel MA, Forghani B, Mahalingam R, et al. The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy. Neurology. 2007;68:1069–73.
Cravioto H, Feigin I. Noninfectious granulomatous angiitis with a predilection for the nervous system. Neurology. 1959;9:599–609.
Rosenblum WI, Hadfield MG. Granulomatous angiitis of the nervous system in cases of herpes zoster and lymphosarcoma. Neurology. 1972;22:348–54.
Gilbert GJ. Herpes zoster ophthalmicus and delayed contralateral hemiparesis. Relationship of the syndrome to central nervous system granulomatous angiitis. JAMA. 1974;229:302–4.
Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 5–1995. A 73-year-old man with focal brain lesions and peripheral-nerve disease. N Engl J Med. 1995;332:452–9.
Gilden DH, Kleinschmidt-DeMasters BK, Wellish M, et al. Varicella zoster virus, a cause of waxing and waning vasculitis: the New England Journal of Medicine case 5–1995 revisited. Neurology. 1996;47:1441–6. This article was the first to demonstrate VZV DNA, antigen and herpesvirus particles, as well as Cowdry A inclusions and giant cells, in the cerebral arteries of a patient who died of VZV vasculopathy.
Nagel MA, Traktinskiy I, Azarkh Y, et al. Varicella zoster virus vasculopathy: analysis of virus-infected arteries. Neurology. 2011;77:364–70. Nagel et al. examined cerebral and temporal arteries from 3 patients with VZV vasculopathy and characterized changes in the intima, media and internal elastic lamina associated with infection.
Nagel MA, Traktinskiy I, Stenmark KR, et al. Varicella-zoster virus vasculopathy: immune characteristics of virus-infected arteries. Neurology. 2013;80:62–8.
Dal Canto AJ, Swanson PE, O’Guin AK, et al. IFN-gamma action in the media of the great elastic arteries, a novel immunoprivileged site. J Clin Invest. 2001;107:15–22.
Frid MG, Brunetti JA, Burke DL, et al. Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage. Am J Pathol. 2006;168:659–69.
Stenmark KR, Yeager ME, El Kasmi KC, et al. The adventitia: essential regulator of vascular wall structure and function. Annu Rev Physiol. 2013;75:23–47.
Kang JH, Ho JD, Chen YH, et al. Increased risk of stroke after a herpes zoster attack: a population-based follow-up study. Stroke. 2009;40:3443–8.
Lin HC, Chien CW, Ho JD. Herpes zoster ophthalmicus and the risk of stroke: a population-based follow-up study. Neurology. 2010;74:792–7.
Sreenivasan N, Basit S, Wohlfahrt J, et al. The short- and long-term risk of stroke after herpes zoster—a nationwide population-based cohort study. PLoS One. 2013;8:e69156.
Breuer J, Pacou M, Gauthier A, Brown MM. Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study in the UK. Neurology. 2014;82:206–12.
Langan SM, Minassian C, Smeeth L, Thomas SL. Risk of stroke following herpes zoster: a self-controlled case-series study. Clin Infect Dis. 2014;58:1497–503. Langan et al. studied 6584 individuals with zoster and stroke using a self-controlled case series method and showed that there was an increased stroke rate within 6 months following zoster and that antiviral therapy may reduce this risk.
Acknowledgment
The study was supported by grants from the National Institutes of Health (AG032958 and AG006127 to Dr. Gilden and NS06070 to Dr. Nagel). We thank Marina Hoffman for editorial review and Cathy Allen for manuscript preparation.
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Conflict of Interest
Maria A. Nagel has received the following grant: NIH/NIA PPG, Molecular Pathogenesis of VZV Infection.
Don Gilden has received the following grants: NIH/NIA PPG, Molecular Pathogenesis of VZV Infection and NIH/NINDS R01, Neurobiology of VZV.
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Nagel, M.A., Gilden, D. The Relationship Between Herpes Zoster and Stroke. Curr Neurol Neurosci Rep 15, 16 (2015). https://doi.org/10.1007/s11910-015-0534-4
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DOI: https://doi.org/10.1007/s11910-015-0534-4