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Review
, 70 (11), 853-60

The Varicella Zoster Virus Vasculopathies: Clinical, CSF, Imaging, and Virologic Features

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Review

The Varicella Zoster Virus Vasculopathies: Clinical, CSF, Imaging, and Virologic Features

M A Nagel et al. Neurology.

Abstract

Background: Varicella zoster virus (VZV) vasculopathy produces stroke secondary to viral infection of cerebral arteries. Not all patients have rash before cerebral ischemia or stroke. Furthermore, other vasculitides produce similar clinical features and comparable imaging, angiographic, and CSF abnormalities.

Methods: We review our 23 published cases and 7 unpublished cases of VZV vasculopathy. All CSFs were tested for VZV DNA by PCR and anti-VZV IgG antibody and were positive for either or both.

Results: Among 30 patients, rash occurred in 19 (63%), CSF pleocytosis in 20 (67%), and imaging abnormalities in 29 (97%). Angiography in 23 patients revealed abnormalities in 16 (70%). Large and small arteries were involved in 15 (50%), small arteries in 11 (37%), and large arteries in only 4 (13%) of 30 patients. Average time from rash to neurologic symptoms and signs was 4.1 months, and from neurologic symptoms and signs to CSF virologic analysis was 4.2 months. CSF of 9 (30%) patients contained VZV DNA while 28 (93%) had anti-VZV IgG antibody in CSF; in each of these patients, reduced serum/CSF ratio of VZV IgG confirmed intrathecal synthesis.

Conclusions: Rash or CSF pleocytosis is not required to diagnose varicella zoster virus (VZV) vasculopathy, whereas MRI/CT abnormalities are seen in almost all patients. Most patients had mixed large and small artery involvement. Detection of anti-VZV IgG antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection of VZV DNA (p < 0.001). Determination of optimal antiviral treatment and benefit of concurrent steroid therapy awaits studies with larger case numbers.

Conflict of interest statement

Disclosure: The authors report no conflicts of interest.

Figures

Figure 1
Figure 1. Characteristic angiographic, imaging, and pathologic abnormalities in varicella zoster virus (VZV) vasculopathy
(A) Three-dimensional time-of-flight magnetic resonance angiography of the Circle of Willis shows marked narrowing of the left anterior cerebral artery (short arrow) and occlusion of the right anterior cerebral artery (long arrow). (B) Brain MRI scan shows multiple areas of infarction in both hemispheres, primarily involving white matter and gray-white matter junctions (arrows). (C) Diffusion-weighted MRI in a patient with small vessel VZV vasculopathy. Top figure shows two ischemic lesions in the posterior thalamus and one in the hypothalamus; in addition, a small ischemic lesion is seen in the posterior limb of the internal capsule (white arrow); 1 week later, the patient became hemiplegic. Although the ischemic thalamic and hypothalamic lesions had resolved, a new MRI (bottom figure) showed a discrete infarct in the area of the posterior limb of the internal capsule. (D) Macroscopic changes in brain from a patient who died of chronic VZV vasculopathy; arrows indicate ovoid areas of ischemia/demyelination of varying size, primarily at gray-white matter junctions. (A) Reprinted from Gilden DH, Lipton HL, Wolf JS, et al. Two patients with unusual forms of varicella zoster virus vasculopathy. N Engl J Med 2002;347:1500–1503. Reprinted with permission from Massachusetts Medical Society. Copyright 2002. All rights reserved. (B) Reprinted from Gilden DH, Mahalingam R, Cohrs RJ, Kleinschmidt-DeMasters BK, Forghani B. The protean manifestations of varicella-zoster virus vasculopathy. J Neurovirol 2002;8:75–79. Reprinted with permission from Journal of Neurovirology. (D) Reprinted from Nagel MA, Gilden DH. Protean neurologic manifestations of varicella zoster virus infection. Cleve Clin J Med 2007;74: 489–504. Reprinted with permission from the Cleveland Clinic Journal of Medicine.
Figure 2
Figure 2. Artery of a patient who died of varicella zoster virus (VZV) vasculopathy and immunohistochemical analysis of cerebral artery from a patient with VZV vasculopathy
(A) Artery of a patient who died of VZV vasculopathy reveals a multinucleated giant cell (arrow) with abundant histiocytes and lymphocytes. (B) Same artery as in A; avidin-biotin-peroxidase staining shows VZV-specific antigen within Cowdry A inclusion bodies in the cytoplasm of histiocytes (arrows). (C) Same artery as in A; electron microscopy shows herpes virus particles. (D) Immunohistochemical analysis of cerebral artery from a patient with VZV vasculopathy; VZV antigen (red staining) was detected using rabbit antiserum directed against the VZV open reading frame 63 protein (magnification ×86). (A, B) Reprinted from Fukumoto S, Kinjo M, Hokamura K, Tanaka K. Subarachnoid hemorrhage and granulomatous angiitis of the basilar artery: demonstration of the varicella-zoster virus in the basilar artery lesions. Stroke 1986;17:1024 –1028. Reprinted with permission from Lippincott Williams & Wilkins. (C) Reprinted from Gilden DH. Shingles and postherpetic neuralgia: an unmet need? Consultant 2005;45:S13–19. Reprinted with permission from Cliggott Publishing, CMP Healthcare Media LLC. (D) Reprinted from Gilden DH, Mahalingam R, Cohrs RJ, Kleinschmidt-DeMasters BK, Forghani B. The protean manifestations of varicella-zoster virus vasculopathy. J Neurovirol 2002;8:75–79. Reprinted with permission from Journal of Neurovirology.

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