Varicella Zoster

Definition

Varicella zoster virus infection of the CNS can occur during the primary infection (varicella) or in the recrudescent disease (herpes zoster) and may result in cerebellitis, meningoencephalitis, encephalitis, vasculopathy and vasculitis.

Clinical Features

VZV Encephalitis

Rare form of encephalitis1–3
Chronic
Exclusively in immunocompromised with:
- Hodgkin's disease
- other cancers
- AIDS
May present:
- months after resolution of cutaneous zoster
- in absence of a preceding exanthem

VZV Cerebral Vasculitis

Rare cerebral vasculitis
May involve large arteries at base of brain as well as smaller branches
Typically follows resolution of cutaneous exanthem
Two major variants:
- overtly inflammatory and necrotizing angiitis:
  - often:
    - no major evidence of defective immunity 4
  - may result in:
    - fusiform aneurysmal dilatation
    - mural rupture
    - subarachnoid hemorrhage5
Sometimes both angiopathic and angiitic features:
- in patients seropositive for HIV-1

Gross Pathology

VZV Encephalitis

Location:
- anywhere along central neuraxis
- predilection for cerebral hemispheric white matter

Histopathology

VZV Encephalitis

Described by some as leukoencephalitis
Demyelination:
- multifocal
- centrifugally expanding
- coalescent foci
Variable axonal loss
Little inflammatory reaction
Often small infarcts:
- from VZV-mediated vascular injury
Nuclei of oligodendrocytes:
- on periphery of dymelinating lesions
- ground-glass transformation or homogeneous filling by basophilic material:
  - superficially similar to cytopathy induced by JC virus in progressive multifocal leukoencephalopathy but not conspicuously enlarged
Neighboring astrocytes (and sometimes neurons and ependymal cells) infected by VZV:
- contain well-demarcated Cowdry A-type intranuclear inclusions:
  - sort that typify herpes virus replication
Electron microscopy:
- herpes-type nucleocapsids:
  - average ≈ 100nm diameter
  - within nuclei of infected cells
  - differ slightly from herpes simplex-type virions because their core densities tend to be eccentrically positioned

VZV Cerebral Vasculitis

Noninflammatory ‘angiopathy’:
- striking fibrointimal proliferation
- thrombosis
- sometimes disruption of elastica and thinning of media without evident necrosis of mural elements6
Overtly inflammatory and necrotizing angiitis:
- multinucleated histiocytes within damaged vessel walls:
  - designated by some as granulomatous4,5

Diagnosis

VZV Encephalitis

Definitive identification of agent requires:
- immunocytochemical assay
- molecular hybridization studies, or
- culture

VZV Cerebral Vasculitis

Definitive diagnosis requires localization of VZV by:
- immunocytochemical assay
- ultrastructural study to elements of vessel wall:
  - typically:
    - smooth muscle cells in media, or
    - intimal (myo)fibroblasts

Differential Diagnosis

Select up to 2 differential diagnoses to compare with Varicella Zoster

VZV Encephalitis

Shares some clinical and histologic features with progressive multifocal leukoencephalopathy1–3

References

1 Horten B, Price RW, Jimenez D. Multifocal varicella-zoster virus leukoencephalitis temporally remote from herpes zoster. Ann Neurol. 1981;9:251–266.

2 Kleinschmidt-DeMasters BK, Amlie-Lefond C, Gilden DH. The patterns of varicella zoster virus encephalitis. Hum Pathol. 1996;27:927–938.

3 Weaver S, Rosenblum MK, DeAngelis LM. Herpes varicella zoster encephalitis in immunocompromised patients. Neurology. 1999;52:193–195.

4 Doyle PW, Gibson G, Dolman CL. Herpes zoster ophthalmicus with contralateral hemiplegia: identification of cause. Ann Neurol. 1983;14:84–85.

5 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.

6 Eidelberg D, Sotrel A, Horoupian DS, Neumann PE, Pumarola-Sune T, Price RW. Thrombotic cerebral vasculopathy associated with herpes zoster. Ann Neurol. 1986;19:7–14.

Last updated: 1 Jan 2007