Vasculopathies caused by varicella zoster virus (VZV) represent a group of illness involving both small and large CNS arteries caused by a inflammatory process involving the media and the vascular endothelium, usually in immunocompromised individuals due the viral reactivation and spread thought the vessel wall. As consequence, It may cause ischaemic infarction, aneurysm, cerebral and subarachnoid haemorrhage, and arterial ectasia 3.
For a complementary discussion on CNS involvement, please refer on Varicella zoster virus encephalitis.
In children, VZV vasculopathy is responsable for ~ 30% of all arterial ischaemic strokes 2 and often occurs weeks to months after zoster or varicella. In adults, there is no accurate estimative, but it is definitely more common in immunocompromised individuals 3.
A variety of neurological symptoms could be present related to a stroke or transient ischaemic attacks.
VZV vasculopathy should be strongly suspected when after a recent history of varicella or zoster a patient presents a transient ischaemic attack or stroke corroborated by MRI abnormalities 3.
CSF: modest pleocytosis, predominantly mononuclear. Concentrations of protein are commonly increased and concentrations of glucose are normal 4. The presence of anti-VZV IgG antibody or VZV DNA usually confirm the diagnosis.
Varicela zoster is a an alpha herpesvirus found exclusively in humans 1. Primary VZV infection, which usually occurs in children, results in chickenpox (varicella) and, after the acute illness resolves, the virus remains latent in ganglionic neurons. In immunocompromised or elderly patients the VZV may reactivate.
Different theories try to explain how the virus achieve the intracranial vessels (such as haematogenous seeding or spreading via the sympathetic nervous system). The infection causes a inflammatory reaction and a functional damage to the vascular endothelium may resulting in thrombosis and promoting subendothelial proliferation of smooth muscle cells, fibroblasts, and collagen, leading to areas of stenosis and occlusion 1;3.
CT and MRI
Scans can show cortical and deep abnormalities involving both the grey and white matter, and grey-white matter junctions in special, mainly related to ischaemic lesions 3. VZV vasculopathy rarely can also affect the spinal-cord causing putative infarction.
Subarachnoid and intracerebral haemorrhage can also occur.
Contrast enhancement could be present in some lesions indicating breakdown of the blood–brain barrier.
Angiographic features (DSA/MRA/CTA)
About 70% of patients show vascular abnormalities on studies 4. The main feature is the presence of segmental arterial constrictions often followed by post stenotic dilatation, also creating a beading pattern. Occlusions could also be shown.
Complications of VZV vasculopathy include cerebral aneurysm and dissection.
It is important to note that a negative angiogram does not exclude the diagnosis, as the disease in small arteries is not detected as readily as in large arteries 3.
Treatment and prognosis
Patients are usually treated with intravenous aciclovir (category 3 of evidence).
- 1. Häusler MG, Ramaekers VT, Reul J et-al. Early and late onset manifestations of cerebral vasculitis related to varicella zoster. Neuropediatrics. 1998;29 (04): 202-7. doi:10.1055/s-2007-973561 - Pubmed citation
- 2. Askalan R, Laughlin S, Mayank S et-al. Chickenpox and stroke in childhood: a study of frequency and causation. Stroke. 2001;32 (6): 1257-62. Pubmed citation
- 3. Gilden D, Cohrs RJ, Mahalingam R et-al. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment. Lancet Neurol. 2009;8 (8): 731-40. doi:10.1016/S1474-4422(09)70134-6 - Free text at pubmed - Pubmed citation
- 4. Nagel MA, Cohrs RJ, Mahalingam R et-al. The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology. 2008;70 (11): 853-60. doi:10.1212/01.wnl.0000304747.38502.e8 - Free text at pubmed - Pubmed citation