Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment

Abstract

Vasculopathies caused by varicella zoster virus (VZV) are indicative of a productive virus infection in cerebral arteries after either reactivation of VZV (shingles) or primary infection (chickenpox). VZV vasculopathy can cause ischaemic infarction of the brain and spinal cord, as well as aneurysm, subarachnoid and cerebral haemorrhage, carotid dissection, and, rarely, peripheral arterial disease. VZV vasculopathy in immunocompetent or immunocompromised individuals can be unifocal or multifocal with deep-seated and superficial infarctions. Lesions at the grey-white matter junction on brain imaging are a clue to diagnosis. Involvement of both large and small arteries is more common than that of either alone. Most patients have a mononuclear cerebrospinal fluid pleocytosis, often with red blood cells. Cerebrospinal fluid pleocytosis and rash are absent in about a third of cases. Anti-VZV IgG antibody in the cerebrospinal fluid is found more frequently than VZV DNA. In recent years, the number of recognised VZV vasculopathies has grown, and accurate diagnosis is important for the effective treatment of these disorders.

Influenza‐like illness as a trigger for ischemic stroke

“…The increase in odds may also be due to general effects of infection, such as fever and dehydration. We do not hypothesize that influenza plays a direct role in the risk of stroke by, for example, infiltrating blood vessels, as other viruses, such as varicella zoster virus, may do 35. While this study suggests an association, further studies are needed to explore a potential causal connection between ILI and stroke.…”

Multifocal strokes in a 56-year-old man with HIV infection

“…Expert opinion recommends a 14-day course in immunocompetent patients, and a longer course in immunocompromised patients, particularly if they have persistent neurologic symptoms, where expert opinion recommends oral valacyclovir treatment for one to two additional months. 4 Because the onset of symptoms of VZV vasculopathy in many patients is remote from the episode of VZV infection, the host inflammatory response may in part be responsible for the injury that occurs to the blood vessels. For this reason, some experts have recommended the addition of corticosteroid treatment to control inflammation of vessel walls.…”

“…This choice is recommended by most experts, at the dose typically used for the treatment of encephalitis due to herpes simplex virus (10-15 mg/kg every 8 h, assuming normal renal function). 4 Oral use of valacyclovir has not been fully studied in this setting, and to our knowledge its use as primary therapy has not been reported in the literature. Evidence for the addition of corticosteroids for treatment of this condition is in the form of case reports and expert opinion.…”

“…A positive PCR result from an unroofed vesicle will establish the diagnosis of VZV; however, detection of VZV from a sample of cerebrospinal fluid provides strong evidence in support of CNS involvement. 4 Positive results of VZV blood serology will not confirm CNS involvement; an isolated elevated IgG titer would be compatible with the patient's remote history of chickenpox. Biopsy of the cerebral artery wall has not been established as a gold standard for the diagnosis of VZV CNS vasculopathy and would expose the patient to unnecessary operative risk.…”

Varicella zoster virus infection

“…Indeed, stroke following zoster ophthalmicus is of high clinical importance 83,84 . VZV that reactivates in the trigeminal nerve can travel via the ophthalmic sensory nerves to the face and via afferent sensory fibres to the internal carotid artery and its intracranial branches 85,86 . Thereafter, the virus establishes infection in the arterial wall, which leads to inflammation, arterial weakening, aneurysm formation, occlusion and stroke 87 .…”