Varicella-zoster virus vasculopathy

David Goldemund M.D.
Updated on 21/02/2024, published on 20/02/2024
  • varicella-zoster virus (VZV) is a neurotropic herpesvirus responsible for two distinct clinical conditions: varicella (primary infection) and herpes zoster (reactivation)
  • while the cutaneous manifestation is a well-known aspect of VZV infection, the virus also harbors the potential for serious neurovascular complications (after either primary infection or viral reactivation)
  • CNS complications of VZV infection:
    • encephalitis
    • aseptic meningitis
    • myelitis
    • acute cerebellar ataxia
    • Reye’s syndrome
    • Ramsay-Hunt syndrome
    • stroke
  • stroke due to VZV vasculitis is, however, rare
    • VZV vasculitis involves inflammation of the blood vessels triggered by the virus, affecting both large and small vessels
    • affected arterial walls show thickening, reduced elasticity, and arterial occlusion
    • vasculopathy is more common in immunocompromised individuals
    • stroke due to vasculitis may occur without apparent herpes zoster, leading to underdiagnosis
    • VZV vasculopathy is also called VZV vasculitis, or post-varicella arteriopathy


  • the exact mechanism of VZV-induced vasculitis is complex and involves direct viral invasion of the arterial wall, followed by an inflammatory response (Gilden, 1996)
    • VZV targets endothelial cells, smooth muscle cells, and perivascular nerves, leading to vessel wall damage, thrombosis, and ischemia
    • the immune response to the virus further exacerbates vascular injury through inflammatory mediators
    • transient protein S deficiency and high APL antibody titers have also been described in association with varicella infection
  • ⇒  segmental stenoses develop

Clinical presentation

  • recent varicella or herpes zoster (most commonly in the ophthalmic region) in a younger stroke patient without traditional risk factors should raise suspicion of possible VZV-related vasculitis  Ohthalmic herpes zoster
  • neurological deficits may develop within days to months after infection
  • symptoms depend on the affected vessels and brain regions – focal deficit may be accompanied by headache, seizures, or altered mental status
    • some patients may initially present with symptoms and signs of encephalitis followed by a focal deficit
  • intracranial hemorrhage and SAH have also been described   [Jain, 2003]

Diagnostic evaluation

Parenchymal and vascular imaging

  • parenchymal imaging
    • detects nonspecific ischemic lesion(s) (ideally FLAIR, DWI and GRE); rarely, the spinal cord is affected
    • often multifocal and/or bilateral strokes
    • contrast enhancement may be present (a sign of breakdown of the blood-brain barrier)
    • vessel-wall imaging (T1C+ BB) may show enhancement in larger arteries  Demonstration of ICA vasculitis using post-contrast high resolution MRI (HRMRI) (Obuses, 2014)
  • vascular imaging (CTA/MRA, DSA)
    • angiography may show features suggestive of vasculitis (typically segmental constrictions often followed by poststenotic dilatation)
    • complications may lead to aneurysm formation or dissection
    • MRA and CTA have low sensitivity if small vessels are affected

Antibodies detection

  • elevated titers of VZV antibodies (IgM, IgG)
    • confirmation of either intrathecal production of anti-VZV antibodies or the presence of VZV DNA in CSF is required
  • IgM antibodies indicate recent or acute infection, positive IgG antibodies indicate past infection or immunity to VZV
  • negative results of antibody testing and PCR in the CSF exclude the diagnosis of VZV vasculopathy

CSF analysis

  • pleocytosis + elevated protein
  • glucose concentration is normal
  • PCR (gold standard)
    • PCR detects VZV DNA in various samples, including blood, cerebrospinal fluid (CSF), and vesicular fluid
    • PCR is generally the most sensitive and specific method for CNS infection, especially during the first two weeks and in immunocompromised hosts
    • a negative finding does not rule out infection entirely (especially beyond 2 weeks)
  • elevated titers of anti-VZV antibodies (IgM, IgG)
    • intrathecal antibodies and a reduced serum/CSF ratio suggest the diagnosis
    • detectable since the second week after infection


  • if VZV infection is suspected, start antiviral treatment (acyclovir IV 10 mg/kg every 8 hours)  [Gilden, 2004]
    • antivirals reduce the risk of stroke due to VZV vasculitis [Nagel, 2017]
    • if anti-VZV IgG antibody or VZV DNA in CSF confirms the diagnosis, continue for 14-21 days
    • the patient should be monitored clinically, perform repeated MRI or CSF analysis in case of poor response or worsening
  • corticosteroids (DEXONA 8 mg every 8 hours or PREDNISONE 1mk/kg for 5 days) may be added to reduce inflammation, particularly in severe vasculitis
  • start antiplatelet therapy (DAPT may be considered, but there is no hard data on risk-benefit)+ treat vascular risk factors
  • prognosis depends on the timeliness of treatment and extent of vascular involvement; early therapeutic intervention can significantly improve outcomes

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Varicella zoster virus vasculopathy