Update on Varicella Zoster Virus Vasculopathy

Abstract

Primary infection of humans with varicella zoster virus (VZV) causes varicella (chickenpox), after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. As VZV-specific cell-mediated immunity declines in elderly and immunocompromised individuals, VZV reactivates from one or more ganglia and typically causes herpes zoster (shingles). Zoster may also be complicated by VZV vasculopathy due to productive virus infection of cerebral arteries. In recent decades, the clinical spectrum of VZV vasculopathy has expanded to include not only transient ischemic attacks and ischemic and hemorrhagic stroke, but also multifocal VZV vasculopathy, with temporal artery infection mimicking giant cell arteritis, extracranial vasculopathy, aneurysm with and without subarachnoid hemorrhage, arterial dissection and dolichoectasia, ischemic cranial neuropathies, cerebral venous sinus thrombosis, spinal cord infarction and peripheral thrombotic disease.

Central Nervous System Vasculopathy In Varicella Zoster Virus Infection

“…Initially associated with TIA and stroke, predominantly ischemic, neurovascular involvement in VZV infection can manifest with aneurysmal dilatation of arteries that can result in subarachnoid hemorrhage, multifocal vasculitis, arterial dissection and dolicoectasia, ischemic cranial neuropathy, and as stated above, temporal arteriopathy resembling GCA, spinal cord infarction and even cerebral venous sinus thrombosis [22]. In adults, neurovascular involvement typically presents with focal neurological deficits related to the area of the CNS (Central Nervous System) involved, a few weeks after the onset of cutaneous varicella or herpes zoster [23], although in onethird of patients with virologically verified VZV vasculopathy, there may be no preceding rash [14].…”

Issues in the Treatment of Neurological Conditions Caused by Reactivation of Varicella Zoster Virus (VZV)

“…VZV vasculopathy is an important and increasingly recognized complication of VZV reactivation and is due to a productive viral infection of both large and small cerebral arteries [24]. An increasing disease spectrum of this condition now includes ischemic and hemorrhagic stroke, transient ischemic attacks, arterial dissection, temporal artery infection (see below), ischemic cranial neuropathies, cerebral venous thrombosis, peripheral thrombotic disease, and spinal cord infarction [24].…”

“…An increasing disease spectrum of this condition now includes ischemic and hemorrhagic stroke, transient ischemic attacks, arterial dissection, temporal artery infection (see below), ischemic cranial neuropathies, cerebral venous thrombosis, peripheral thrombotic disease, and spinal cord infarction [24]. It should be appreciated, however, that several of these complications are based on individual case reports, and zoster is not a frequent cause of these complications.…”

“…The clinical diagnosis may be difficult, especially when not temporally associated with the typical zosteriform rash, but the condition is usually characterized by magnetic resonance imaging and computed tomography features of cerebral ischemia or hemorrhage, which may affect both gray and white matter, evidence of narrowing and/or beading of cerebral arteries seen on angiography, and a pleocytosis with mononuclear cells detected in the cerebrospinal fluid (CSF) [25]. Typically, a patient with VZV vasculopathy may present with progressive cognitive decline and confusion, seizures, and focal neurological deficits [1], but the clinical presentation is protean [24]. Infected arteries contain Cowdry A inclusion bodies, multinucleated giant cells, herpes virions, and both VZV DNA and antigen [26].…”

“…Owing to the relatively small number of cases studied-there have not been large clinical trials-the current recommended treatment of VZV vasculopathy in immunocompetent individuals is 14 days of IV aciclovir and 5-7 days of oral corticosteroids (prednisone/prednisolone), though immunocompromised individuals or those relapsing with recurrent VZV vasculopathy may need a longer course of aciclovir and corticosteroids [24]. Consideration should also be given for long-term valaciclovir in the presence of recurrent VZV vasculopathy due to immunosuppressive or immunomodulatory drugs.…”