Varicella Zoster Virus Ischemic Optic Neuropathy and Subclinical Temporal Artery Involvement

Salazar, Richard; Russman, Andrew; Nagel, Maria A.; Cohrs, Randall J.; Mahalingam, Ravi; Schmid, Daniela; Kleinschmidt‐DeMasters, Bette K.; VanEgmond, Eve M.; Gilden, Don

doi:10.1001/archneurol.2011.64

Cited by 54 publications

(48 citation statements)

References 10 publications

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“…1,7 The presence of neutrophils in early VZV vasculopathy is supported by their abundance in vesicular fluid of zoster patients 13 and in CSF throughout the protracted course of VZV vasculopathy, meningoencephalitis, encephalomyelitis, myelitis, and inflammatory brainstem disease. 9,[14][15][16][17] Although mechanisms of vascular remodeling triggered by VZV are unknown, neutrophils may play a role.…”

Section: Figure 3 T-cell Subsets In Varicella-zoster Virus (Vzv) Vascmentioning

confidence: 98%

“…3 In atherosclerosis, activated macrophages, in addition to other cells, secrete platelet-derived growth factor-BB and insulin-like growth factor-I, which promote VSMC migration 4 ; interleukin-1B also promotes VSMC proliferation. 5,6 We hypothesize that 1) after reactivation from trigeminal ganglia, virus spreads transaxonally to infect the adventitia, followed by transmural migration to the media 1,7 ; 2) inflammatory cells are recruited to virus-infected sites; and 3) inflammatory cells secrete factors that contribute to vessel wall changes seen in VZV vasculopathy. Characterization of immune cells involved in VZV vasculopathy could elucidate mechanisms of VZV-induced vascular remodeling and identify potential targets for therapy.…”

mentioning

confidence: 99%

“…Temporal and middle cerebral arteries from 2 subjects with VZV vasculopathy were studied; pathologic and virologic analyses of these arteries have been described. 1,[7][8][9] The VZV-infected temporal artery was obtained 3 days after ischemic optic neuropathy (early VZV vasculopathy) in an 80-year-old man who developed left ophthalmic-distribution zoster 4 weeks earlier 7 ; the temporal artery did not exhibit pathologic changes of giant-cell arteritis, but did contain VZV antigen and CSF contained anti-VZV immunoglobulin G and M consistent with the diagnosis of VZV vasculopathy. The patient improved after antiviral treatment.…”

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confidence: 99%

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Varicella-zoster virus vasculopathy

et al. 2013

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Objective: Pathologic changes in varicella-zoster virus (VZV)-infected arteries include inflammation, thickened intima, and paucity of smooth muscle cells. Since no criteria have been established for early vs late VZV vasculopathy, we examined inflammatory cells and their distribution in 6 normal arteries, and 2 VZV-infected arteries 3 days after onset of disease (early) and 10 months after protracted neurologic disease (late).Methods: VZV-infected temporal artery obtained 3 days after onset of ischemic optic neuropathy from an 80-year-old man, VZV-infected middle cerebral artery (MCA) obtained 10 months after protracted disease from a 73-year-old man, and 5 MCAs and 1 temporal artery from normal subjects, age 22-60 years, were examined histologically and immunohistochemically using antibodies against VZV and inflammatory cell subsets. Results:In both early and late VZV vasculopathy, T cells, activated macrophages, and rare B cells were found in adventitia and intima. In adventitia of early VZV vasculopathy, neutrophils and VZV antigen were abundant and a thickened intima was associated with inflammatory cells in vaso vasorum vessels. In media of late VZV vasculopathy, viral antigen, but not leukocytes, was found. VZV was not seen in inflammatory cells. Inflammatory cells were absent in control arteries. In varicella-zoster virus (VZV) vasculopathy, virus-infected regions are associated with a thickened intima composed of myofibroblasts, a paucity of smooth muscle cells in media, and disruption of internal elastic lamina.1 Similar morphologic changes have been found in other vascular diseases, such as pulmonary arterial hypertension (PAH) and atherosclerosis, 2 in which inflammation has emerged as a pathogenic component. For example, in PAH, inflammatory cells surrounding pulmonary artery lesions secrete CX3CL1, which induces vascular smooth muscle cell (VSMC) proliferation.3 In atherosclerosis, activated macrophages, in addition to other cells, secrete platelet-derived growth factor-BB and insulin-like growth factor-I, which promote VSMC migration 4 ; interleukin-1B also promotes VSMC proliferation. 5,6 We hypothesize that 1) after reactivation from trigeminal ganglia, virus spreads transaxonally to infect the adventitia, followed by transmural migration to the media 1,7 ; 2) inflammatory cells are recruited to virus-infected sites; and 3) inflammatory cells secrete factors that contribute to vessel wall changes seen in VZV vasculopathy. Characterization of immune cells involved in VZV vasculopathy could elucidate mechanisms of VZV-induced vascular remodeling and identify potential targets for therapy.

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Section: Figure 3 T-cell Subsets In Varicella-zoster Virus (Vzv) Vascmentioning

confidence: 98%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Varicella-zoster virus vasculopathy

et al. 2013

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“…Virologic verification was provided by detection of VZV antigen in adventitia of clinically asymptomatic and pathologically GCA-negative temporal artery ipsilateral to vision loss and anti-VZV IgG antibody in CSF with reduced serum/CSF ratios indicating intrathecal synthesis of anti-VZV IgG antibody. Recently, VZV ION was confirmed by presence of VZV antigen in ipsilateral clinically asymptomatic GCA-negative temporal artery 1 ; the latter patient had ophthalmic-distribution zoster weeks earlier, unlike our patient without history of zoster. Overall, our case expands the spectrum of disease produced by VZV without rash to ION, reveals ipsilateral GCA-negative temporal artery VZV infection useful in diagnosis, and confirms early VZV infection of adventitia in VZV vasculopathy, providing additional evidence that extracranial arteries become infected transaxonally after VZV reactivates from ganglia.…”

mentioning

confidence: 42%

VZV ischemic optic neuropathy and subclinical temporal artery infection without rash

Nagel

Russman²,

Feit³

et al. 2013

Neurology

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A 75-year-old woman developed periorbital pain and blurred vision OS. Visual acuity (VA) was 20/40 OD, 20/400 OS with mild left relative afferent pupillary defect (APD). Left optic nerve was swollen and hyperemic with peripapillary flame hemorrhages (figure, A). Erythrocyte sedimentation rate (ESR) was 124 mm/h. She was treated with IV methylprednisolone, 250 mg every 6 h. On day 3, headache and vision improved. ESR was 98 mm/h and C-reactive protein was 1.40 mg/L. Rheumatoid factor, antinuclear antibodies, and antineutrophil cytoplasmic antibodies titers were negative. On day 4, left temporal artery biopsy revealed thickened intima and intact internal elastic lamina (figure, B) but no medial necrosis characteristic of giant cell arteritis (GCA). Sections of the temporal artery were deparaffinized and incubated with 10% normal sheep serum (NSS) in phosphate-buffered saline (PBS) for 1 hour at room temperature, rinsed 3 times in PBS, and incubated overnight at 4°C with polyclonal antibodies raised against the varicella-zoster virus (VZV) open reading frame 63 protein (1:1,000 dilution) or with normal rabbit serum (1:1,000 dilution). The next day, sections were washed 3 times in PBS, incubated with a 1:300 dilution of biotinylated goat antirabbit immunoglobulin G (IgG) in PBS containing 5% NSS, washed 3 times in PBS, incubated for 1 hour at room temperature with alkaline phosphatase-conjugated streptavidin (1:100 dilution), and washed 3 times with PBS. The color reaction was developed for 5-30 minutes with fresh fuchsin substrate system. Levamisole was added to the color reaction to block endogenous phosphatase. Uninfected and VZV-infected human fibroblast lung cells were used as controls (not shown). Steroids were changed to oral prednisone 60 mg daily. On day 7, brain MRI with gadolinium was negative. On day 9, pain and vision worsened. On day 11, orbital CT and head CT angiography were negative. On day 15, VA was 20/400 OS with relative left APD. On day 17, OS became blind without direct pupillary light reaction; fundus was obscured by vitreous hemorrhage. CSF contained 8 leukocytes/mm 3 , protein 72 mg/L, and glucose 54 mg/L. CSF cultures for bacteria, fungi, acid-fast bacilli, and cytology were negative. Because asymptomatic temporal artery biopsy was GCA-negative, VZV ischemic optic neuropathy (ION) was considered, and she was treated with IV acyclovir, 10 mg/kg every 8 hours for 7 days. On day 31, CSF contained anti-VZV IgG but not anti-herpes simplex virus IgG antibody, and serum-to-CSF ratio of anti-VZV IgG was reduced (14) compared to ratios for total IgG (121) and albumin (81). Immunohistochemistry and pathology revealed VZV antigen and neutrophils in the original left temporal artery specimen (figure, C). On day 31, she was treated with oral valacyclovir, 1 gram TID for 6 weeks; prednisone was reduced to 20 mg daily and tapered 5 mg/week. Six weeks later, pain resolved, and VA improved to finger counting. Left optic nerve was pale with clear margins and resolution of hemorrhage.Discussion. We present a...

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“…Given the similar clinical and pathological features seen in VZV vasculopathy and giant cell arteritis (GCA), it has been postulated that there may be a role of VZV in the pathogenesis of GCA [15][16][17][18]. The study by Gilden et al [19] has shown the presence of VZV antigen in 74% patients of temporal artery biopsy-proven GCA versus 8% in normal temporal arteries (p<0.0001), while Nagel et al [20] found the proportions to be 64% and 22% respectively (p<0.001).…”

Section: Vzv Vasculopathy and Giant Cell Arteritismentioning

confidence: 99%

Central Nervous System Vasculopathy In Varicella Zoster Virus Infection

Mehta¹,

Desai²,

Mirtchev³

2017

J Neuroinfect Dis

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Varicella zoster virus is an exclusively human double-stranded DNA virus that is the causative factor for two ubiquitous conditions: varicella in children and zoster in adults. Both conditions are associated with neurological complications. Centripetal trans-axonal spread via cranial nerve ganglia appears to afford entry into the central nervous system. There is increasing evidence of varicella zoster virus playing a role in the development of giant cell arteritis. First associated with transient ischemic attacks and ischemic strokes, vasculopathy secondary to varicella zoster virus infections has now been associated with aneurysms that may or may not lead to subarachnoid hemorrhage, multifocal vasculitis, arterial dissection, dolicoectasia, cortical venous sinus thrombosis, ischemic cranial neuropathies and spinal cord infarction. Prior knowledge of the myriad clinical manifestations helps in early diagnosis and treatment of the complications.

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Varicella Zoster Virus Ischemic Optic Neuropathy and Subclinical Temporal Artery Involvement

Cited by 54 publications

References 10 publications

Varicella-zoster virus vasculopathy

Varicella-zoster virus vasculopathy

VZV ischemic optic neuropathy and subclinical temporal artery infection without rash

Central Nervous System Vasculopathy In Varicella Zoster Virus Infection

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