Page 62 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

38 David S. Younger

adults and immunocompromised individuals to produce shingles. An uncommon but serious
complication of virus reactivation is ischemic and hemorrhagic stroke. VZV vasculopathy
affects both immunocompetent and immunocompromised individuals typically presenting
with headache and mental status changes with or without focal neurological deficits and a
spectrum of vascular damage from vasculopathy to vasculitis with stroke [169, 170]. Both
large and small vessels can be involved and MRI shows multifocal ischemic lesions,
commonly at gray-white matter junctions. The diagnosis of VZV can be missed when
symptoms and signs occur months after zoster, or in the absence of a typical zoster rash.

Fourteen patients with VZV-related vasculopathy with detailed clinicopathologic data
have been described in the literature. One patient presented with headache, fever, mental
status change, focal neurological deficits, and focal narrowing of the ICA, anterior cerebral
artery (ACA) and MCA, with CSF antibodies to VZV, but without a rash [171]. VZV DNA
and VZV-specific antigen were found in three of five cerebral arteries examined with
histologically-confirmed CNS vasculitis involving the circle of Willis. Patient 1 of Eidelberg
and colleagues [172] who presented with headache and herpes zoster ophthalmicus (HZO)
rash was deemed to have CNS vasculitis based upon complete occlusion of the MCA and so
treated, however postmortem examination showed no evidence of vasculitis. Headache was
not mentioned in five other patients despite histologically-proven widespread small vessel
granulomatous angiitis associated with lymphoma in two patients [173] and basilar branch
vessel involvement of granulomatous angiitis in another [174]. One patient with contralateral
hemiplegia one month after HZO was found at postmortem examination to have endarteritis
of unilateral ACA, MCA and PCA [175] with VZV DNA from the involved vessels. One
patient with AIDS, unilateral weakness and garbled speech due to ischemic infarction in
association with lumbosacral zoster rash, was found to have CNS vasculitis of vessels of the
circle of Willis with VZV DNA without herpetic inclusions at postmortem examination.
Finally, neither headache nor supporting histopathology was present in seven other patients
with VZV-vasculopathy including five patients with HZO and contralateral hemiparesis
[176], and two patients with HZO and contralateral delayed hemiparesis [177].

Nagel and colleagues [178] analyzed virus-infected cerebral and temporal arteries from
three patients with VZV vasculopathy. Several characteristic were noted in all VZV-infected
arteries so studied including, disrupted internal elastic lamina, hyperplastic intima composed
of cells expressing a-smooth muscle actin and smooth muscle myosin heavy chain but not
endothelial cells expressing CD31, and 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 adventitia early in infection and
later in the media and intima supported the hypothesis that after reactivation from ganglia,
VZV spread transaxonally to the arterial adventitia followed by transmural spread of virus.
Stroke in VZV vasculopathy appears to result from changes in arterial caliber and
contractility produced in part by abnormal accumulation of smooth muscle cells and
myofibroblasts in thickened neointimal and disruption of the media [178]. Nagel and
colleagues [178] also studied the immune characteristics of virus-infected temporal artery
three days after onset of ischemic optic neuropathy, and after ten months of protracted CNS
disease in the MCA. In both early and later VZV vasculopathy, T-cells, activated
macrophages, and rare B-cells were found in adventitia and intima, whereas neutrophils and
VZV antigen were abundant along with a thickened intima associated with inflammatory cells

Complimentary Contributor Copy