Page 159 - The Vasculitides Volumes 2

Central Nervous System Vasculitis Due to Infection 135

Viral Pathogens

Herpes Viruses

Herpes viruses are a large family of enveloped DNA viruses. Nine distinct agents affect
humans, and all result in lifelong latent infection.

Varicella Zoster Virus
Varicella zoster virus (VZV) is the principal agent associated with blood vessel disease. It

is the only virus documented to replicate in human arteries, and is a recognized risk factor for
ischemic stroke in children, and stroke and TIA in adults under age 40 [45, 46]. It is latent in
cranial nerve, dorsal root, and autonomic nervous system ganglia. VZV but when re-
activated, spreads to arteries of the brain and spinal cord to produce a large and small vessel
vasculopathy. Cerebral blood vessels show multinucleated giant cells, Cowdry type A
inclusion bodies with viral particles, and detectable VZV antigens and DNA, consistent with
direct infection. In one series of 30 patients [7], 50% had both large and small vessel
involvement; 37% showed small artery involvement and 13% manifested large artery
invasion [47]. Clinical sequela includes infarction, aneurysm, hemorrhage, and ICA
dissection [48]. Recently, VZV vasculopathy was recognized as an etiologic agent in patients
presenting with giant cell arteritis (GCA) in spite of non-informative temporal artery biopsy
[49]. Vascular involvement can be unifocal or multifocal. Both immunocompetent and
immunocompromised hosts are affected, although more commonly it is the
immunocompromised patient. Infarctions can be superficial or deep. Gray-white matter
junction lesions are suggestive. With regard to primary infection, there are unusual cases of
cerebral infarction or hemorrhage in children. With regard to reactivated infection,
vasculopathy can occur up to 6 months after a zoster outbreak. Herpes zoster ophthalmicus
(HZO) can be followed weeks later by delayed contralateral hemiparesis, with segmental
carotid siphon arteritis, typically in immunocompetent individuals [50].

Small vessel involvement may lead to central retinal or posterior ciliary artery
involvement, with monocular vision loss. Neuroimaging in these VZV cases is typically
abnormal. CSF is often abnormal with an increase in WBC and RBC, raised CSF protein
content and present oligoclonal bands. The CSF VZV IgG antibody should be measured
along with a sample for PCR analysis however the former is more likely to be informative in
true cases. CNS VZV vasculopathy often presents with headache and progressive neurologic
deficits without a history of zoster rash; rarely is VZV associated with spinal cord infarction
[51]. Treatment involves antiviral therapy with IV acyclovir however oral valacyclovir can be
employed to extend the length of treatment in more profoundly affected or refractory cases
due to concomitant HIV-infection.

Cytomegalovirus
Cytomegalovirus (CMV) replicates in leukocytes and vascular endothelial cells during

primary infection with single patient reports of CMV associated with vasculitis [52]. Venous
involvement can be found in addition to occlusive arteritis [53]. Affected individuals are
usually HIV-positive or an immunocompromised host. Diagnosis involves serological studies,
PCR, culture, and histopathological tissue analysis for the causative organism. Therapy

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