Varicella zoster virus vasculopathy Analysis of virus-infected arteries

Department of Neurology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Box B182, Aurora, CO 80045, USA.
Neurology (Impact Factor: 8.3). 07/2011; 77(4):364-70. DOI: 10.1212/WNL.0b013e3182267bfa
Source: PubMed

ABSTRACT Varicella zoster virus (VZV) is an under-recognized yet treatable cause of stroke. No animal model exists for stroke caused by VZV infection of cerebral arteries. Thus, we analyzed cerebral and temporal arteries from 3 patients with VZV vasculopathy to identify features that will help in diagnosis and lead to a better understanding of VZV-induced vascular remodeling.
Normal and VZV-infected cerebral and temporal arteries were examined histologically and by immunohistochemistry using antibodies directed against VZV, endothelium, and smooth muscle actin and myosin.
All VZV-infected arteries contained 1) a disrupted internal elastic lamina; 2) a hyperplastic intima composed of cells expressing α-smooth muscle actin (α-SMA) and smooth muscle myosin heavy chain (SM-myosin) but not endothelial cells expressing CD31; and 3) decreased medial smooth muscle cells. The location of VZV antigen, degree of neointimal thickening, and disruption of the media were related to the duration of disease.
The presence of VZV primarily in the adventitia early in infection and in the media and intima later supports the notion that after reactivation from ganglia, VZV spreads transaxonally to the arterial adventitia followed by transmural spread of virus. Disruption of the internal elastic lamina, progressive intimal thickening with cells expressing α-SMA and SM-MHC, and decreased smooth muscle cells in the media are characteristic features of VZV vasculopathy. Stroke in VZV vasculopathy may result from changes in arterial caliber and contractility produced in part by abnormal accumulation of smooth muscle cells and myofibroblasts in thickened neointima and disruption of the media.

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    • "Zoster is also associated with several central nervous system (CNS) diseases of a range of severity and complexity, with some neurological disease resulting from VZV-induced vasculopathies of cranial arteries and stroke (Gilden et al. 2009, 2011; Steiner et al. 2007). Neurological disease is not only caused directly by virus replication but can result from indirect causes such as stroke (Mareedu et al. 2011; Nagel et al. 2011) or by uncontrolled innate and adaptive immune responses to the virus infections that are capable of causing significant collateral damage to normal tissue function, even after active virus clearance in the host (Gilden et al. 2011; Nagel et al. 2011). Pain associated with zoster reaches rates as high as 90% (see recent reviews including Argoff 2011, Gilden et al. 2011, Johnson et al. 2010, Philip and Thakur 2011, and Pickering and Leplege 2011). "
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