Virus vasculopathy and stroke: an under-recognized cause and treatment target

Abstract

While arteriosclerotic disease and hypertension, with or without diabetes, are the most common causes of stroke, viruses may also produce transient ischemic attacks and stroke. The three most-well studied viruses in this respect are varicella zoster virus (VZV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV), all of which are potentially treatable with antiviral agents. Productive VZV infection in cerebral arteries after reactivation (zoster) or primary infection (varicella) has been documented as a cause of ischemic and hemorrhagic stroke, aneurysms with subarachnoid and intracerebral hemorrhage, arterial ectasia and as a co-factor in cerebral arterial dissection. CMV has been suggested to play a role in the pathogenesis of arteriosclerotic plaques in cerebral arteries. HIV patients have a small but definite increased incidence of stroke which may be due to either HIV infection or opportunistic VZV infection in these immunocompromised individuals. Importantly, many described cases of vasculopathy in HIV-infected patients were not studied for the presence of anti-VZV IgG antibody in CSF, a sensitive indicator of VZV vasculopathy. Unlike the well-documented role of VZV in vasculopathy, evidence for a causal link between HIV or CMV and stroke remains indirect and awaits further studies demonstrating productive HIV and CMV infection of cerebral arteries in stroke patients. Nonetheless, all three viruses have been implicated in stroke and should be considered in clinical diagnoses.

Fig. 1. MRI scan of a patient with VZV multifocal vasculopathy

Proton-density brain MRI scan shows multiple areas of infarction in both hemispheres, particularly involving white matter. Arrows point to gray-white matter junction lesions. Reproduced from Gilden et al. [29] with permission from the Journal of NeuroVirology.

Fig. 2. Cerebral angiogram from a patient with VZV vasculopathy

Cerebral angiogram shows focal areas of stenosis (white arrows) and poststenotic dilatation (black arrows) involving the right posterior cerebral artery. Reproduced from Russman et al. [30] with permission from the American Medical Association.

Fig. 3. Pathological and virological findings in the arteries of patients who died from VZV vasculopathy

(A) A cerebral artery with multinucleated giant cells (arrow). (B) Multiple herpesvirions within a cerebral artery. (C) VZV DNA in the posterior cerebral artery (lane 3) and basilar artery (lane 5). (D) VZV antigen (red) in the media of a cerebral artery. Reproduced from Gilden et al. [42] with permission from the Lancet Neurology.