Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Herpes Zoster: HELP
Articles by Maria A. Nagel
Based on 37 articles published since 2009
(Why 37 articles?)
||||

Between 2009 and 2019, M. Nagel wrote the following 37 articles about Herpes Zoster.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Editorial commentary: varicella zoster virus infection: generally benign in kids, bad in grown-ups. 2014

Nagel, Maria / Gilden, Don. ·Department of Neurology. ·Clin Infect Dis · Pubmed #24700655.

ABSTRACT: -- No abstract --

2 Editorial Does herpes zoster ophthalmicus increase the risk of stroke? 2010

Nagel, Maria / Ortiz, Gustavo A. · ·Neurology · Pubmed #20200347.

ABSTRACT: -- No abstract --

3 Review Varicella zoster virus vasculopathy: The expanding clinical spectrum and pathogenesis. 2017

Nagel, Maria A / Jones, Dallas / Wyborny, Ann. ·Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: maria.nagel@ucdenver.edu. · Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: dallas.jones@ucdenver.edu. · Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: ann.wyborny@ucdenver.edu. ·J Neuroimmunol · Pubmed #28335992.

ABSTRACT: Varicella zoster virus (VZV) is a ubiquitous, human alphaherpesvirus that produces varicella on primary infection then becomes latent in ganglionic neurons along the entire neuraxis. In elderly and immunocompromised individuals, VZV reactivates and travels along nerve fibers peripherally resulting in zoster. However, VZV can also spread centrally and infect cerebral and extracranial arteries (VZV vasculopathy) to produce transient ischemic attacks, stroke, aneurysm, sinus thrombosis and giant cell arteritis, as well as granulomatous aortitis. The mechanisms of virus-induced pathological vascular remodeling are not fully elucidated; however, recent studies suggest that inflammation and dysregulation of programmed death ligand-1 play a significant role.

4 Review Varicella zoster virus triggers the immunopathology of giant cell arteritis. 2016

Gilden, Don / Nagel, Maria A. ·aDepartment of NeurologybDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA. ·Curr Opin Rheumatol · Pubmed #27224742.

ABSTRACT: PURPOSE OF REVIEW: Giant cell arteritis (GCA) is a severe form of vasculitis in the elderly. The recent discovery of varicella zoster virus (VZV) in the temporal arteries and adjacent skeletal muscle of patients with GCA, and the rationale and strategy for antiviral and corticosteroid treatment for GCA are reviewed. RECENT FINDINGS: The clinical features of GCA include excruciating headache/head pain, often with scalp tenderness, a nodular temporal arteries and decreased temporal artery pulsations. Jaw claudication, night sweats, fever, malaise, and a history of polymyalgia rheumatica (aching and stiffness of large muscles primarily in the shoulder girdle, upper back, and pelvis without objective signs of weakness) are common. ESR and CRP are usually elevated. Diagnosis is confirmed by temporal artery biopsy which reveals vessel wall damage and inflammation, with multinucleated giant cells and/or epithelioid macrophages. Skip lesions are common. Importantly, temporal artery biopsies are pathologically negative in many clinically suspect cases. This review highlights recent virological findings in temporal arteries from patients with pathologically verified GCA and in temporal arteries from patients who manifest clinical and laboratory features of GCA, but whose temporal artery biopsies (Bx) are pathologically negative for GCA (Bx-negative GCA). Virological analysis revealed that VZV is present in most GCA-positive and GCA-negative temporal artery biopsies, mostly in skip areas that correlate with adjacent GCA pathology. SUMMARY: The presence of VZV in Bx-positive and Bx-negative GCA temporal arteries indicates that VZV triggers the immunopathology of GCA. However, the presence of VZV in about 20% of temporal artery biopsies from non-GCA postmortem controls also suggests that VZV alone is not sufficient to produce disease. Treatment trials should be performed to determine if antiviral agents confer additional benefits to corticosteroids in both Bx-positive and Bx-negative GCA patients. These studies should also examine whether oral antiviral agents and corticosteroids are as effective as intravenous acyclovir and corticosteroids. Appropriate dosage and duration of treatment also remain to be determined.

5 Review Developments in Varicella Zoster Virus Vasculopathy. 2016

Nagel, Maria A / Gilden, Don. ·Department of Neurology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Box B182, Aurora, CO, 80045, USA. maria.nagel@ucdenver.edu. · Department of Neurology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Box B182, Aurora, CO, 80045, USA. don.gilden@ucdenver.edu. · Department of Immunology & Microbiology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Box B182, Aurora, CO, 80045, USA. don.gilden@ucdenver.edu. ·Curr Neurol Neurosci Rep · Pubmed #26750127.

ABSTRACT: Varicella zoster virus (VZV) is a highly neurotropic human herpesvirus. Primary infection usually causes varicella (chicken pox), after which virus becomes latent in ganglionic neurons along the entire neuraxis. VZV reactivation results in zoster (shingles) which is frequently complicated by chronic pain (postherpetic neuralgia). VZV reactivation also causes meningoencephalitis, myelitis, ocular disorders, and vasculopathy, all of which can occur in the absence of rash. This review focuses on the association of VZV and stroke, and on the widening spectrum of disorders produced by VZV vasculopathy in immunocompetent and immunocompromised individuals, including recipients of varicella vaccine. Aside from ischemic stroke, VZV infection of cerebral arteries may lead to development of intracerebral aneurysms, with or without hemorrhage. Moreover, recent clinical-virological case reports and retrospective pathological-virological analyses of temporal arteries positive or negative for giant cell arteritis (GCA) indicate that extracranial VZV vasculopathy triggers the immunopathology of GCA. While many patients with GCA improve after corticosteroid treatment, prolonged corticosteroid use may potentiate VZV infection, leading to fatal vasculopathy in the brain and other organs.

6 Review The relationship between herpes zoster and stroke. 2015

Nagel, Maria A / Gilden, Don. ·Department of Neurology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Box B182, Aurora, CO, 80045, USA, maria.nagel@ucdenver.edu. ·Curr Neurol Neurosci Rep · Pubmed #25712420.

ABSTRACT: Varicella zoster virus (VZV) infects >95 % of the world population. Typically, varicella (chickenpox) results from primary infection. The virus then becomes latent in ganglionic neurons along the entire neuraxis. In immunocompromised individuals, VZV reactivates and causes herpes zoster (shingles), pain, and rash in 1-2 dermatomes. Multiple case reports showed a link between stroke and zoster, and recent studies have emerged which reveal that VZV infection of the cerebral arteries directly causes pathological vascular remodeling and stroke (VZV vasculopathy). In the past few years, several large epidemiological studies in Taiwan, Denmark, and the U.K. demonstrated that zoster is a risk factor for stroke and that antiviral therapy may reduce this risk. Herein, the history, clinical features, and putative mechanisms of VZV vasculopathy, as well as recent epidemiological studies demonstrating that zoster increases the risk of stroke, are discussed.

7 Review Varicella-zoster. 2014

Gilden, Don / Nagel, Maria A / Cohrs, Randall J. ·Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Microbiology, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: don.gilden@ucdenver.edu. · Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA. ·Handb Clin Neurol · Pubmed #25015490.

ABSTRACT: -- No abstract --

8 Review Neurological complications of varicella zoster virus reactivation. 2014

Nagel, Maria A / Gilden, Don. ·aDepartment of Neurology bDepartment of Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA. ·Curr Opin Neurol · Pubmed #24792344.

ABSTRACT: PURPOSE OF REVIEW: Varicella zoster virus (VZV) reactivation results in zoster, which may be complicated by postherpetic neuralgia, myelitis, meningoencephalitis, and VZV vasculopathy. This review highlights the clinical features, laboratory abnormalities, imaging changes, and optimal treatment of each of those conditions. Because all of these neurological disorders produced by VZV reactivation can occur in the absence of rash, the virological tests proving that VZV caused disease are discussed. RECENT FINDINGS: After primary infection, VZV becomes latent in ganglionic neurons along the entire neuraxis. With a decline in VZV-specific cell-mediated immunity, VZV reactivates from ganglia and travels anterograde to the skin to cause zoster, which is often complicated by postherpetic neuralgia. VZV can also travel retrograde to produce meningoencephalitis, myelitis, and stroke. When these complications occur without rash, VZV-induced disease can be diagnosed by detection of VZV DNA or anti-VZV antibody in cerebrospinal fluid and treated with intravenous acyclovir. SUMMARY: Awareness of the expanding spectrum of neurological complications caused by VZV reactivation with and without rash will improve diagnosis and treatment.

9 Review Varicella zoster virus vasculopathy: clinical features and pathogenesis. 2014

Nagel, Maria A. ·Department of Neurology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Mail Stop B182, Aurora, CO, 80045, USA, maria.nagel@ucdenver.edu. ·J Neurovirol · Pubmed #23918503.

ABSTRACT: Varicella zoster virus (VZV) vasculopathy is caused by productive virus infection of cerebral arteries, leading to inflammation, pathological vascular remodeling, and ischemic or hemorrhagic stroke. VZV vasculopathy occurs in immunocompetent and immunocompromised individuals and involves both large and small vessels. MRI abnormalities include more deep-seated than superficial lesions, particularly at gray-white matter junctions, and lesions may enhance. Diagnosis is challenging, since stroke can occur months after zoster rash and in the absence of rash or CSF pleocytosis. The best virological test for diagnosis is detection of anti-VZV IgG antibody in the CSF. Pathological studies of VZV-infected arteries from patients with VZV vasculopathy reveal that the arterial adventitia is the initial site of infection, after which virus spreads transmuraly towards the lumen. Histological and immunohistochemical studies of VZV-infected arteries show a thickened intima, disrupted internal elastic lamina, and loss of smooth muscle cells, that likely contribute to weakening of the vessel wall and occlusion. Early in disease, VZV-infected arteries contain CD4+ and CD8+ T cells, macrophages, and rare B cells, in addition to abundant neutrophils in early disease. Importantly, perivascular inflammatory cells underlie the areas of thickened intima, raising the possibility that soluble factors secreted by these cells contribute to arterial remodeling. This review discusses the clinical features of VZV vasculopathy and potential mechanisms of VZV-induced cerebrovascular remodeling and stroke.

10 Review The variegate neurological manifestations of varicella zoster virus infection. 2013

Gilden, Don / Nagel, Maria A / Cohrs, Randall J / Mahalingam, Ravi. ·Department of Neurology and Microbiology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Box B182, Aurora, CO 80045, USA. don.gilden@ucdenver.edu ·Curr Neurol Neurosci Rep · Pubmed #23884722.

ABSTRACT: Varicella zoster virus (VZV) is an exclusively human neurotropic alphaherpesvirus. Primary infection causes varicella (chickenpox), after which the virus becomes latent in ganglionic neurons along the entire neuraxis. With advancing age or immunosuppression, cell-mediated immunity to VZV declines, and the virus reactivates to cause zoster (shingles), dermatomal distribution, pain, and rash. Zoster is often followed by chronic pain (postherpetic neuralgia), cranial nerve palsies, zoster paresis, vasculopathy, meningoencephalitis, and multiple ocular disorders. This review covers clinical, laboratory, and pathological features of neurological complications of VZV reactivation, including diagnostic testing to verify active VZV infection in the nervous system. Additional perspectives are provided by discussions of VZV latency, animal models to study varicella pathogenesis and immunity, and of the value of vaccination of elderly individuals to boost cell-mediated immunity to VZV and prevent VZV reactivation.

11 Review Review: The neurobiology of varicella zoster virus infection. 2011

Gilden, D / Mahalingam, R / Nagel, M A / Pugazhenthi, S / Cohrs, R J. ·Department of Neurology, University of Colorado School of Medicine, USA. don.gilden@ucdenver.edu ·Neuropathol Appl Neurobiol · Pubmed #21342215.

ABSTRACT: Varicella zoster virus (VZV) is a neurotropic herpesvirus that infects nearly all humans. Primary infection usually causes chickenpox (varicella), after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. Although VZV cannot be isolated from human ganglia, nucleic acid hybridization and, later, polymerase chain reaction proved that VZV is latent in ganglia. Declining VZV-specific host immunity decades after primary infection allows virus to reactivate spontaneously, resulting in shingles (zoster) characterized by pain and rash restricted to one to three dermatomes. Multiple other serious neurological and ocular disorders also result from VZV reactivation. This review summarizes the current state of knowledge of the clinical and pathological complications of neurological and ocular disease produced by VZV reactivation, molecular aspects of VZV latency, VZV virology and VZV-specific immunity, the role of apoptosis in VZV-induced cell death and the development of an animal model provided by simian varicella virus infection of monkeys.

12 Review Neurological disease produced by varicella zoster virus reactivation without rash. 2010

Gilden, Don / Cohrs, Randall J / Mahalingam, Ravi / Nagel, Maria A. ·Departments of Neurology, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA. don.gilden@ucdenver.edu ·Curr Top Microbiol Immunol · Pubmed #20186614.

ABSTRACT: Reactivation of varicella zoster virus (VZV) from latently infected human ganglia usually produces herpes zoster (shingles), characterized by dermatomal distribution pain and rash. Zoster is often followed by chronic pain (postherpetic neuralgia or PHN) as well as meningitis or meningoencephalitis, cerebellitis, isolated cranial nerve palsies that produce ophthalmoplegia or the Ramsay Hunt syndrome, multiple cranial nerve palsies (polyneuritis cranialis), vasculopathy, myelopathy, and various inflammatory disorders of the eye. Importantly, VZV reactivation can produce chronic radicular pain without rash (zoster sine herpete), as well as all the neurological disorders listed above without rash. The protean neurological and ocular disorders produced by VZV in the absence of rash are a challenge to the practicing clinician. The presentation of these conditions varies from acute to subacute to chronic. Virological confirmation requires the demonstration of amplifiable VZV DNA in cerebrospinal fluid (CSF) or in blood mononuclear cells, or the presence of anti-VZV IgG antibody in CSF or of anti-VZV IgM antibody in CSF or serum.

13 Article Varicella zoster virus productively infects human peripheral blood mononuclear cells to modulate expression of immunoinhibitory proteins and blocking PD-L1 enhances virus-specific CD8+ T cell effector function. 2019

Jones, Dallas / Como, Christina N / Jing, Lichen / Blackmon, Anna / Neff, Charles Preston / Krueger, Owen / Bubak, Andrew N / Palmer, Brent E / Koelle, David M / Nagel, Maria A. ·Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, United States of America. · Department of Medicine, University of Washington, Seattle, Washington, United States of America. · Department of Medicine, Division of Allergy and Clinical Immunology, University of Colorado School of Medicine, Aurora, Colorado, United States of America. · Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America. · Department of Global Health, University of Washington, Seattle, Washington, United States of America. · Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, United States of America. · Benaroya Research Institute, Seattle, Washington, United States of America. · Department of Ophthalmology, University of Colorado School of Medicine, Aurora, Colorado, United States of America. ·PLoS Pathog · Pubmed #30870532.

ABSTRACT: Varicella zoster virus (VZV) is a lymphotropic alpha-herpesvirinae subfamily member that produces varicella on primary infection and causes zoster, vascular disease and vision loss upon reactivation from latency. VZV-infected peripheral blood mononuclear cells (PBMCs) disseminate virus to distal organs to produce clinical disease. To assess immune evasion strategies elicited by VZV that may contribute to dissemination of infection, human PBMCs and VZV-specific CD8+ T cells (V-CD8+) were mock- or VZV-infected and analyzed for immunoinhibitory protein PD-1, PD-L1, PD-L2, CTLA-4, LAG-3 and TIM-3 expression using flow cytometry. All VZV-infected PBMCs (monocytes, NK, NKT, B cells, CD4+ and CD8+ T cells) and V-CD8+ showed significant elevations in PD-L1 expression compared to uninfected cells. VZV induced PD-L2 expression in B cells and V-CD8+. Only VZV-infected CD8+ T cells, NKT cells and V-CD8+ upregulated PD-1 expression, the immunoinhibitory receptor for PD-L1/PD-L2. VZV induced CTLA-4 expression only in V-CD8+ and no significant changes in LAG-3 or TIM-3 expression were observed in V-CD8+ or PBMC T cells. To test whether PD-L1, PD-L2 or CTLA-4 regulates V-CD8+ effector function, autologous PBMCs were VZV-infected and co-cultured with V-CD8+ cells in the presence of blocking antibodies against PD-L1, PD-L2 or CTLA-4; ELISAs revealed significant elevations in IFNγ only upon blocking of PD-L1. Together, these results identified additional immune cells that are permissive to VZV infection (monocytes, B cells and NKT cells); along with a novel mechanism for inhibiting CD8+ T cell effector function through induction of PD-L1 expression.

14 Article Burning mouth syndrome associated with varicella zoster virus. 2016

Nagel, Maria A / Gilden, Don. ·Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA. ·BMJ Case Rep · Pubmed #27382016.

ABSTRACT: We present two cases of burning mouth syndrome (BMS)-of 8-month duration in a 61-year-old woman and of 2-year duration in a 63-year-old woman-both associated with increased levels of antivaricella zoster virus (VZV) IgM antibodies in serum and with pain that improved with antiviral treatment. Combined with our previous finding of BMS due to herpes simplex virus type 1 (HSV-1) infection, we recommend evaluation of patients with BMS not only for VZV or HSV-1 DNA in the saliva, but also for serum anti-VZV and anti-HSV-1 IgM antibodies. Both infections are treatable with oral antiviral agents.

15 Article SUNCT headaches after ipsilateral ophthalmic-distribution zoster. 2016

Nagel, Maria A / Burns, Ted M / Gilden, Don. ·Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA. · Department of Neurology, University of Virginia, Charlottesville, VA, USA. · Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: don.gilden@ucdenver.edu. ·J Neurol Sci · Pubmed #27288808.

ABSTRACT: Nine days after left ophthalmic-distribution zoster, a 47-year-old man developed SUNCT headaches (short-lasting unilateral neuralgiform headache with conjunctival injection and tearing). In contrast to two prior cases of SUNCT that developed after varicella zoster virus (VZV) meningoencephalitis without rash, this case describes an association of SUNCT with overt zoster, thus adding to the spectrum of headache and facial pain syndromes caused by VZV reactivation.

16 Article Blinded search for varicella zoster virus in giant cell arteritis (GCA)-positive and GCA-negative temporal arteries. 2016

Gilden, Don / White, Teresa / Khmeleva, Nelly / Katz, Bradley J / Nagel, Maria A. ·Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: don.gilden@ucdenver.edu. · Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA. · Department of Ophthalmology and Visual Sciences, University of Utah Health Sciences Center, Salt Lake City, UT, USA; Department of Neurology, University of Utah Health Sciences Center, Salt Lake City, UT, USA. ·J Neurol Sci · Pubmed #27084233.

ABSTRACT: Recent analysis of archived temporal arteries (TAs) acquired from 13 pathology laboratories in the US, Canada, Iceland, France, Germany and Israel from patients with pathologically-verified giant cell arteritis (GCA-positive) and TAs from patients with clinical features and laboratory abnormalities of GCA but whose TAs were pathologically negative (GCA-negative) revealed VZV antigen in most TAs from both groups. Despite formalin-fixation, VZV DNA was also found in many VZV-antigen positive sections that were scraped, subjected to DNA extraction, and examined by PCR with VZV-specific primers. Importantly, in past studies, the pathological diagnosis (GCA-positive or -negative) was known to the neurovirology laboratory. Herein, GCA-positive and GCA-negative TAs were provided by an outside institution and examined by 4 investigators blinded to the pathological diagnoses. VZV antigen was found in 3/3 GCA-positive TAs and in 4/6 GCA-negative TAs, and VZV DNA in 1/3 VZV antigen-positive, GCA-positive TAs and in 3/4 VZV antigen-positive, GCA-negative TAs. VZV DNA was also detected in one GCA-negative, VZV-antigen negative TA. Overall, the detection of VZV antigen in 78% of GCA-positive and GCA-negative TAs is consistent with previous reports on the prevalence of VZV antigen in patients with clinically suspect GCA.

17 Article Varicella Zoster Virus Infection in Granulomatous Arteritis of the Aorta. 2016

Gilden, Don / White, Teresa / Boyer, Philip J / Galetta, Kristin M / Hedley-Whyte, E Tessa / Frank, Meredith / Holmes, Dawn / Nagel, Maria A. ·Department of Neurology Department Immunology and Microbiology, University of Colorado School of Medicine, Aurora. · Department of Neurology. · Department of Pathology, East Carolina University, Greenville, North Carolina. · Department of Neurology, Brigham and Women's Hospital Department of Neurology. · Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston. · Office of the Medical Examiner, Department of Environmental Health, Denver, Colorado. ·J Infect Dis · Pubmed #27037084.

ABSTRACT: Granulomatous arteritis characterizes the pathology of giant cell arteritis, granulomatous aortitis, and intracerebral varicella zoster virus (VZV) vasculopathy. Because intracerebral VZV vasculopathy and giant cell arteritis are strongly associated with productive VZV infection in cerebral and temporal arteries, respectively, we evaluated human aortas for VZV antigen and VZV DNA. Using 3 different anti-VZV antibodies, we identified VZV antigen in 11 of 11 aortas with pathologically verified granulomatous arteritis, in 1 of 1 cases of nongranulomatous arteritis, and in 5 of 18 control aortas (28%) obtained at autopsy. The presence of VZV antigen in granulomatous aortitis was highly significant (P = .0001) as compared to control aortas, in which VZV antigen was never associated with pathology, indicating subclinical reactivation. VZV DNA was found in most aortas containing VZV antigen. The frequent clinical, radiological, and pathological aortic involvement in patients with giant cell arteritis correlates with the significant detection of VZV in granulomatous aortitis.

18 Article Risk of Stroke and Myocardial Infarction After Herpes Zoster in Older Adults in a US Community Population. 2016

Yawn, Barbara P / Wollan, Peter C / Nagel, Maria A / Gilden, Don. ·Department of Research, Olmsted Medical Center, Rochester, MN. Electronic address: byawn47@gmail.com. · Department of Research, Olmsted Medical Center, Rochester, MN. · Department of Neurology, Univerity of Colorado School of Medicine, Aurora, CO. · Department of Neurology, Univerity of Colorado School of Medicine, Aurora, CO; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO. ·Mayo Clin Proc · Pubmed #26704438.

ABSTRACT: OBJECTIVE: To assess the risk of stroke and myocardial infarction (MI) after herpes zoster in a US community population of older adults. PATIENTS AND METHODS: We performed a community cohort study (January 1, 1986, to October 1, 2011) comparing the risk of stroke and MI in 4862 adult residents of Olmsted County, Minnesota, 50 years and older with and without herpes zoster and 19,433 sex- and age-matched individuals with no history of herpes zoster. Odds ratios are presented for MI and stroke at 3, 6, 12, and 36 months after index herpes zoster plus hazard ratios for long-term risk (up to 28.6 years). RESULTS: Individuals with herpes zoster had more risk or confounding factors for MI and stroke, suggesting that they had worse health status overall. When controlling for the multiple risk factors, those with herpes zoster were at increased risk for stroke at 3 months after herpes zoster compared with those without a history of herpes zoster (odds ratio, 1.53; 95% CI, 1.10-2.33; P=.04). The association between herpes zoster and MI at 3 months was not robust across analytic methods. Herpes zoster was not associated with an increased risk of stroke or MI at any point beyond 3 months. CONCLUSIONS: Herpes zoster was associated with only a short-term increased risk of stroke, which may be preventable with the prevention of herpes zoster.

19 Article Differential regulation of matrix metalloproteinases in varicella zoster virus-infected human brain vascular adventitial fibroblasts. 2015

Nagel, Maria A / Choe, Alexander / Rempel, April / Wyborny, Ann / Stenmark, Kurt / Gilden, Don. ·Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: maria.nagel@ucdenver.edu. · Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA. · Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA. · Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA. ·J Neurol Sci · Pubmed #26443282.

ABSTRACT: Upon reactivation, varicella zoster virus (VZV) spreads transaxonally, infects cerebral arteries and causes ischemic or hemorrhagic stroke, as well as aneurysms. The mechanism(s) of VZV-induced aneurysm formation is unknown. However, matrix metalloproteinases (MMPs), which digest extracellular structural proteins in the artery wall, play a role in cerebral and aortic artery aneurysm formation and rupture. Here, we examined the effect of VZV infection on expression of MMP-1, -2, -3, and -9 in primary human brain vascular adventitial fibroblasts (BRAFS). At 6 days post-infection, VZV- and mock-infected BRAFs were analyzed for mRNA levels of MMP-1, -2, -3 and -9 by RT-PCR and for corresponding total intra- and extracellular protein levels by multiplex ELISA. The activity of MMP-1 was also measured in a substrate cleavage assay. Compared to mock-infected BRAFs, MMP-1, MMP-3 and MMP-9 transcripts, cell lysate protein and conditioned supernatant protein were all increased in VZV-infected BRAFs, whereas MMP-2 transcripts, cell lysate protein and conditioned supernatant protein were decreased. MMP-1 from the conditioned supernatant of VZV-infected BRAFs showed increased cleavage activity on an MMP-1-specific substrate compared to mock-infected BRAFs. Differential regulation of MMPs in VZV-infected BRAFs may contribute to aneurysm formation in VZV vasculopathy.

20 Article Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis. 2015

Nagel, Maria A / White, Teresa / Khmeleva, Nelly / Rempel, April / Boyer, Philip J / Bennett, Jeffrey L / Haller, Andrea / Lear-Kaul, Kelly / Kandasmy, Balasurbramaniyam / Amato, Malena / Wood, Edward / Durairaj, Vikram / Fogt, Franz / Tamhankar, Madhura A / Grossniklaus, Hans E / Poppiti, Robert J / Bockelman, Brian / Keyvani, Kathy / Pollak, Lea / Mendlovic, Sonia / Fowkes, Mary / Eberhart, Charles G / Buttmann, Mathias / Toyka, Klaus V / Meyer-ter-Vehn, Tobias / Petursdottir, Vigdis / Gilden, Don. ·Department of Neurology, University of Colorado School of Medicine, Aurora. · Department of Pathology, University of Colorado School of Medicine, Aurora. · Department of Neurology, University of Colorado School of Medicine, Aurora3Department of Ophthalmology, University of Colorado School of Medicine, Aurora. · Fort Wayne Neurological Center, Fort Wayne, Indiana. · Arapahoe County Coroner's Office, Centennial, Colorado. · Texas Oculoplastic Consultants, Austin. · Texas Oculoplastic Consultants, Austin7University of Texas Southwestern-Austin Transitional Year Program, Austin. · Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia. · Scheie Eye Institute, University of Pennsylvania, Philadelphia. · Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia. · A. M. Rywlin Department of Pathology, Mount Sinai Medical Center and Florida International University, Miami. · Institute of Neuropathology, University of Duisburg-Essen, Essen, Germany. · Department of Neurology, Assaf Harofeh Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. · Pathological Institute, Assaf Harofeh Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. · Department of Pathology, Icahn School of Medicine, Mount Sinai Health System, New York, New York. · Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Neurology, University of Würzburg, Würzburg, Germany. · Department of Ophthalmology, University of Würzburg, Würzburg, Germany. · Landspitali University Hospital, Reykjavik, Iceland. · Department of Neurology, University of Colorado School of Medicine, Aurora20Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora. ·JAMA Neurol · Pubmed #26349037.

ABSTRACT: IMPORTANCE: Giant cell arteritis (GCA) is the most common systemic vasculitis in elderly individuals. Diagnosis is confirmed by temporal artery (TA) biopsy, although biopsy results are often negative. Despite the use of corticosteroids, disease may progress. Identification of causal agents will improve outcomes. Biopsy-positive GCA is associated with TA infection by varicella-zoster virus (VZV). OBJECTIVE: To analyze VZV infection in TAs of patients with clinically suspected GCA whose TAs were histopathologically negative and in normal TAs removed post mortem from age-matched individuals. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study for VZV antigen was performed from January 2013 to March 2015 using archived, deidentified, formalin-fixed, paraffin-embedded GCA-negative, GCA-positive, and normal TAs (50 sections/TA) collected during the past 30 years. Regions adjacent to those containing VZV were examined by hematoxylin-eosin staining. Immunohistochemistry identified inflammatory cells and cell types around nerve bundles containing VZV. A combination of 17 tertiary referral centers and private practices worldwide contributed archived TAs from individuals older than 50 years. MAIN OUTCOMES AND MEASURES: Presence and distribution of VZV antigen in TAs and histopathological changes in sections adjacent to those containing VZV were confirmed by 2 independent readers. RESULTS: Varicella-zoster virus antigen was found in 45 of 70 GCA-negative TAs (64%), compared with 11 of 49 normal TAs (22%) (relative risk [RR] = 2.86; 95% CI, 1.75-5.31; P < .001). Extension of our earlier study revealed VZV antigen in 68 of 93 GCA-positive TAs (73%), compared with 11 of 49 normal TAs (22%) (RR = 3.26; 95% CI, 2.03-5.98; P < .001). Compared with normal TAs, VZV antigen was more likely to be present in the adventitia of both GCA-negative TAs (RR = 2.43; 95% CI, 1.82-3.41; P < .001) and GCA-positive TAs (RR = 2.03; 95% CI, 1.52-2.86; P < .001). Varicella-zoster virus antigen was frequently found in perineurial cells expressing claudin-1 around nerve bundles. Of 45 GCA-negative participants whose TAs contained VZV antigen, 1 had histopathological features characteristic of GCA, and 16 (36%) showed adventitial inflammation adjacent to viral antigen; no inflammation was seen in normal TAs. CONCLUSIONS AND RELEVANCE: In patients with clinically suspected GCA, prevalence of VZV in their TAs is similar independent of whether biopsy results are negative or positive pathologically. Antiviral treatment may confer additional benefit to patients with biopsy-negative GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.

21 Article Varicella Zoster Virus in Ischemic Optic Neuropathy. 2015

Golas, Liliya / Bennett, Jeffrey L / White, Teresa M / Skarf, Barry / Lesser, Robert / Nagel, Maria A / Gilden, Don. ·Department of Ophthalmology, University of Colorado School of Medicine, Aurora, Colorado. · Department of Ophthalmology, University of Colorado School of Medicine, Aurora, Colorado; Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado. Electronic address: Jeffrey.bennett@ucdenver.edu. · Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado. · Department of Neurology, Henry Ford Hospital, Detroit, Michigan. · Department of Ophthalmology and Neurology, Yale University School of Medicine, New Haven, Connecticut. · Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado. ·Ophthalmology · Pubmed #26050536.

ABSTRACT: -- No abstract --

22 Article Disseminated VZV infection and asymptomatic VZV vasculopathy after steroid abuse. 2015

Nagel, Maria A / Lenggenhager, Daniela / White, Teresa / Khmeleva, Nelly / Heintzman, Anna / Boyer, Philip J / Gilden, Don. ·Department of Neurology, University of Colorado School of Medicine, Aurora, CO, United States. Electronic address: maria.nagel@ucdenver.edu. · Institute of Pathology, Kantonsspital, St. Gallen, Switzerland. Electronic address: Daniela.lenggenhager@usz.ch. · Department of Neurology, University of Colorado School of Medicine, Aurora, CO, United States. Electronic address: Teresa.m.white@ucdenver.edu. · Department of Neurology, University of Colorado School of Medicine, Aurora, CO, United States. Electronic address: nelly.khmeleva@ucdenver.edu. · Department of Neurology, University of Colorado School of Medicine, Aurora, CO, United States. Electronic address: anna.heintzman@gmail.com. · Department of Pathology, University of Colorado School of Medicine, Aurora, CO, United States. Electronic address: Philip.boyer@ucdenver.edu. · Department of Neurology, University of Colorado School of Medicine, Aurora, CO, United States; Department of Microbiology and Immunology, University of Colorado School of Medicine, Aurora, CO, United States. Electronic address: don.gilden@ucdenver.edu. ·J Clin Virol · Pubmed #25866342.

ABSTRACT: A 60-year-old man who abused corticosteroids developed thoracic-distribution zoster. Varicella zoster virus (VZV) DNA was found in non-healing skin 3 months later. He died suddenly 2 months later. Skin was ulcerated and necrotic. VZV was widespread in organs and arteries, particularly coronary arteries and aorta, with VZV vasculopathy in the posterior cerebral artery.

23 Article Rapid development of 9 cerebral aneurysms in varicella-zoster virus vasculopathy. 2014

Liberman, Ava L / Nagel, Maria A / Hurley, Michael C / Caprio, Frances Z / Bernstein, Richard A / Gilden, Don. ·From the McGaw Medical Center of Northwestern University (A.L.L., M.C.H., F.Z.C., R.A.B.), Chicago, IL · and the University of Colorado School of Medicine (M.A.N., D.G.), Aurora. ·Neurology · Pubmed #24827494.

ABSTRACT: -- No abstract --

24 Article Vaccine strain varicella-zoster virus-induced central nervous system vasculopathy as the presenting feature of DOCK8 deficiency. 2014

Sabry, Angela / Hauk, Pia J / Jing, Huie / Su, Helen C / Stence, Nicholas V / Mirsky, David M / Nagel, Maria A / Abbott, Jordan K / Dragone, Leonard L / Armstrong-Wells, Jennifer / Curtis, Donna J / Cohrs, Randall / Schmid, D Scott / Gilden, Don / Gelfand, Erwin W. ·Department of Pediatrics, Divisions of Allergy/Immunology and Cell Biology, National Jewish Health, Denver, CO 80206. · NIAID, National Institutes of Health, Bethesda, MD 20892. · University of Colorado School of Medicine, Aurora, CO 80045. · Children's Hospital Colorado, Aurora, CO 80045. · National Center for Immunizations and Respiratory Diseases, Division of Viral Diseases, Herpesvirus Team Centers for Disease Control and Prevention, Atlanta, GA 30333. ·J Allergy Clin Immunol · Pubmed #24418481.

ABSTRACT: -- No abstract --

25 Article Varicella-zoster virus trigeminal ganglioneuritis without rash. 2014

Birlea, Marius / Nagel, Maria A / Khmeleva, Nelly / Choe, Alex / Kleinschmidt-Demasters, Bette / Hevner, Robert / Boyer, Philip / Lear-Kaul, Kelly C / Bos, Nathan / Wellish, Mary / Cohrs, Randall J / Gilden, Don. ·From the University of Colorado School of Medicine (M.B., M.A.N., N.K., A.C., B.K.-D., P.B., N.B., M.W., R.J.C., D.G.), Aurora · the University of Washington School of Medicine (R.H.), Seattle · and the Seattle, Washington and Arapahoe County Coroner's Office (K.C.L-K.), WA. ·Neurology · Pubmed #24285619.

ABSTRACT: -- No abstract --

Next