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|LETTER TO EDITOR
|Year : 2016 | Volume
| Issue : 7 | Page : 118-120
Varicella-zoster virus vasculopathy in a 75-year-old immunocompetent man
Artemios K Artemiadis, Evgenia Karantoni, George Nikolaou, Aspasia Terentiou
Department of Neurology, 417 Army Share Fund Hospital, Athens, Greece
|Date of Web Publication||3-Mar-2016|
Artemios K Artemiadis
Department of Neurology, 417 Army Share Fund Hospital, Athens
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Artemiadis AK, Karantoni E, Nikolaou G, Terentiou A. Varicella-zoster virus vasculopathy in a 75-year-old immunocompetent man. Neurol India 2016;64, Suppl S1:118-20
|How to cite this URL:|
Artemiadis AK, Karantoni E, Nikolaou G, Terentiou A. Varicella-zoster virus vasculopathy in a 75-year-old immunocompetent man. Neurol India [serial online] 2016 [cited 2020 Jul 7];64, Suppl S1:118-20. Available from: http://www.neurologyindia.com/text.asp?2016/64/7/118/178054
Varicella-zoster virus (VZV) is a neurotropic herpesvirus that causes chickenpox. The virus remains dormant within the trigeminal and dorsal root ganglia across the neuraxis., It is reactivated when cell-mediated immunity is compromised, presenting with a characteristic dermatomal vesicular eruption (zoster or shingles).  Late-onset central nervous system (CNS) complications include postherpetic neuralgia, retinal necrosis, cerebellitis, encephalomyelitis, cranial nerve palsies, and vasculopathy, even in the absence of the herpetic rash (zoster sine herpete). , The clinical manifestations of VZV CNS vasculopathy are either unifocal or multifocal, and include ischemic infarction(s), aneurysm formation, cerebral and subarachnoid hemorrhage, and cerebral arterial dissection. 
When corroborating evidence exists, vascular studies (conventional angiography and magnetic resonance angiography) and cerebrospinal fluid (CSF) tests are recommended. CSF abnormalities consist of a modest pleocytosis (<100 cells), mainly of mononuclear type; increased CSF protein, with normal glucose; and presence of oligoclonal bands (oligoclonal immunoglobulin G (IgG) directed against VZV). Polymerase chain reaction (PCR) for VZV DNA is highly specific for VZV infection (detectable until 14-50 days from the onset), but negative results cannot rule out the diagnosis, except in the case of concomitant negative anti-VZV IgG antibodies. 
A 75-year-old man presented with a 4-day history of 38.5°C fever, progressive gait difficulty, and right facial palsy. Examination revealed right Bell's palsy, urinary retention (wetting also mentioned), and incomplete Brown-Séquard syndrome. A right sided lower limb weakness (Medical Research Council [MRC] grade 2 out of 5), Babinski's reflex present on the right side, hyperactive deep tendon reflexes in the right lower limb, absence of superficial abdominal reflexes on the right side, and a left sided hypoalgesia below the twelfth thoracic dermatome were observed. A left sided unilateral sensorineural hearing loss was also noted. Rest of the neurological examination and his personal and family history were unremarkable. Age was the sole risk factor for the occurrence of a cerebrovascular disease.
Spinal magnetic resonance imaging (MRI) revealed two sites of occurrence of the lesions, one on the right at the level of T7 vertebrae (T8-T9 spinal cord levels and a second on the left at the level of C7-T1 vertebrae junction (T1-T2 myelotome). Both lesions had an increased signal on T2-weighted images and showed gadolinium induced enhancement on T1-weighted images [Figure 1]a and b. The initial brain MRI showed T1-gadolinium enhanced lesions in both internal auditory meati [Figure 1]c.
|Figure 1: Sagittal T1-weighted spinal cord (a and b) and coronal T1-weighted brain (c) images show gadolinium-enhanced lesions in the cervical and thoracic spinal cord and in both internal auditory meati (white arrows)|
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The initial CSF analysis disclosed a lymphocytic pleocytosis, 255 cells/μL, 20 erythrocytes/μL, protein content of 314 mg/dL, and a glucose level of 81 mg/dL. CSF cytological examination revealed the presence of mature lymphocytes, with no evidence of cancer cells, bacteria or fungi. CSF immunophenotyping revealed CD4+ and CD8+ lymphocytes (52% in total) and increased NK (natural killer; CD56+) lymphocytes (35%). The CSF culture was negative. PCR for VZV DNA in the CSF was positive. On day 88, PCR for VZV DNA was negative, and the IgG index for anti-VZV antibodies in the CSF was increased (32.6).
Negative to normal or unremarkable tests included the following: Serum B12 and folic acid; thyroid function tests; ferritin; blood, urinary, bronchial, and feces culture tests; CSF tests for tuberculosis; quantiferon-TB gold test (interferon-g release assay for tuberculosis); PCR for HSV (herpes simplex virus) 1, HSV2, CMV (cytomegalovirus), EBV (Epstein-Barr virus), and RNA enteroviruses in the CSF; antibodies against Leptospira and Brucella More Details; anti-CMV IgM (IgG anti-CMV antibodies were positive); anti-EBV IgM (IgG anti-EBV for viral capsid antigen were positive); antibodies to HSV1, HSV2, and HIV (human immunodeficiency virus, 1 and 2); serum protein electrophoresis; levels of antibody isotypes (using nephelometry); serum angiotensin-converting enzyme; complement component 3 and 4; kappa and lambda chains; rheumatoid factor (slightly increased); autoantibodies (ANA, anti-TPO, anti-TG, anti-dsDNA, anti-ENA, anti-RNP, anti-Sm, anti-Ro, anti-La, anti-pANCA, anti-cANCA, anti-tTG, endomysial antibodies); cancer biomarkers; abdominal ultrasonography; full-body computed tomography scan; gastroscopy; and colonoscopy.
He was diagnosed as having a CNS complication of VZV infection and was initially treated (starting before diagnosis) with intravenous acyclovir (750 mg tid) for 14 days. After 7 days of fever remission, intravenous methylprednisolone (1 g once a day) was administered, leading to marked improvement of his right lower limb muscle weakness (MRC grade 4 out of 5). Eighty-eight days after his discharge, he was readmitted owing to dystonic-like movements in his left lower limb. MRI of the brain revealed a high signal intensity both in T1- and T2-weighted images at the right basal ganglia indicative of a late subacute (>7 days) right basal ganglia hemorrhage [Figure 2]. He was subsequently treated with oral valacyclovir (1 g tid) for 20 days and oral methylprednisolone (16 mg tid) for 5 days, followed by complete cessation of symptoms. Later MRI workups revealed marked resolution of the lesions. The patient continues on a scheduled rehabilitation program.
|Figure 2: Axial T2-weighted brain image shows a high signal intensity lesion at the right basal ganglia. T1-weighted images (not shown) also showed the high signal intensity lesion, which was indicative of late subacute hemorrhage|
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To our knowledge, this is the first case of VZV vasculopathy of the CNS presenting with spinal lesions and basal ganglia hemorrhage. Vasculopathy was diagnosed on the basis of the basal ganglia hemorrhage and the marked clinical improvement after steroid treatment. There is now accumulating evidence implicating VZV vasculopathy, and not direct nervous damage, as the main pathogenetic mechanism for all the VZV-related CNS complications (especially encephalomyelitis).  VZV vasculopathy results from direct infection of large and small arteries. The route of infection is through small afferent fibers of both trigeminal and cervical root ganglia, innervating arteries of the CNS.  VZV vasculopathy characteristically produces ovoid well-demarcated ischemic and rarely hemorrhagic lesions, especially in the gray-white matter junction, characterized by the triad of vasculitis, necrosis, and demyelination in biopsy samples.  In 50% of clinical cases, both large and small artery involvement is observed.  VZV, so far, appears to be the only herpes virus causing CNS vasculopathy and stroke-like manifestations. 
In general, clinicians should hold a high index of suspicion for this entity, as it could be a risk factor for stroke and a reversible cause of dementia in cases of encephalopathy. Future studies need to address further the association between VZV vasculopathy and stroke.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]