{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T01:59:28Z","timestamp":1793325568079,"version":"4.5.0"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,30]],"date-time":"2023-07-30T00:00:00Z","timestamp":1690675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Varicella\u2013Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of latency in different ganglionic neurons, it reactivates to produce herpes zoster (shingles). The focus of this review is on the wide spectrum of the possible neurological manifestations of VZV reactivation. While the most frequent reactivation syndrome is herpes zoster, this may be followed by the serious and painful post-herpetic neuralgia (PHN) and by many other neurological conditions. Prominent among these conditions is a VZV vasculopathy, but the role of VZV in causing giant cell arteritis (GCA) is currently controversial. VZV reactivation can also cause segmental motor weakness, myelitis, cranial nerve syndromes, Guillain\u2013Barre syndrome, meningoencephalitis, and zoster sine herpete, where a neurological syndrome occurs in the absence of the zoster rash. The field is complicated by the relatively few cases of neurological complications described and by the issue of causation when a neurological condition is not manifest at the same time as the zoster rash.<\/jats:p>","DOI":"10.3390\/v15081663","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T01:28:46Z","timestamp":1690766926000},"page":"1663","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["The Spectrum of Neurological Manifestations of Varicella\u2013Zoster Virus Reactivation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8420-8583","authenticated-orcid":false,"given":"Peter G. E.","family":"Kennedy","sequence":"first","affiliation":[{"name":"School of Psychology and Neuroscience, College of Medical, Veterinary & Life Sciences, Garscube Campus, University of Glasgow, Glasgow G61 1QH, Scotland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kennedy, P.G.E., and Gershon, A.A. (2018). Clinical features of Varicella-Zoster virus infection of the nervous system. Viruses, 10.","DOI":"10.3390\/v10110609"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4658","DOI":"10.1073\/pnas.95.8.4658","article-title":"Latent varicella\u2013zoster virus is located predominantly in neurons in human trigeminal ganglia","volume":"95","author":"Kennedy","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15016","DOI":"10.1038\/nrdp.2015.16","article-title":"Varicella zoster virus infection","volume":"1","author":"Gershon","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1099\/vir.0.000128","article-title":"A comparison of herpes simplex virus type 1 andvaricella-zoster virus latency and reactivation","volume":"96","author":"Kennedy","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1128\/jvi.70.5.2789-2796.1996","article-title":"Varicella-zoster virus (VZV) transcription during latency in human ganglia: Detection of transcripts to genes 21, 29, 62, and 63 in a cDNA library enriched for VZV RNA","volume":"70","author":"Cohrs","year":"1996","journal-title":"J. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11893","DOI":"10.1128\/JVI.74.24.11893-11898.2000","article-title":"Varicella-Zoster Virus Gene Expression in Latently Infected and Explanted Human Ganglia","volume":"74","author":"Kennedy","year":"2000","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6660","DOI":"10.1128\/JVI.77.12.6660-6665.2003","article-title":"Varicella-Zoster Virus Gene 66 Transcription and Translation in Latently Infected Human Ganglia","volume":"77","author":"Cohrs","year":"2003","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/s41467-018-03569-2","article-title":"A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene 61","volume":"9","author":"Depledge","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6324","DOI":"10.1038\/s41467-020-20031-4","article-title":"Varicella-zoster virus VLT-ORF63 fusion transcript induces broad viral gene expression during reactivation from neuronal latency","volume":"11","author":"Ouwendijk","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kennedy, P.G.E., Mogensen, T.H., and Cohrs, R.J. (2021). Recent Issues in Varicella-Zoster Virus Latency. Viruses, 13.","DOI":"10.3390\/v13102018"},{"key":"ref_11","first-page":"482","article-title":"Determinants of neurological syndromes caused by varicella zoster virus (VZV)","volume":"26","author":"Kennedy","year":"2020","journal-title":"J. Neuro Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1007\/s10875-015-0145-5","article-title":"Long-term follow-up of STAT5B deficiency inthree argentinian patients: Clinical and immunological features","volume":"35","author":"Bezrodnik","year":"2015","journal-title":"J. Clin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e500","DOI":"10.1212\/NXI.0000000000000500","article-title":"Varicella-zoster virus CNS vasculitis and RNA polymerase III gene mutation in identical twins","volume":"5","author":"Hansen","year":"2018","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_14","first-page":"9","article-title":"The Nature of Herpes Zoster: A Long-Term Study and a New Hypothesis","volume":"58","year":"1965","journal-title":"Proc. R. Soc. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1097\/00005792-198209000-00003","article-title":"Population-based study of herpes zoster and its sequelae","volume":"61","author":"Ragozzino","year":"1982","journal-title":"Medicine (Baltimore)"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1136\/bmj.39206.571042.AE","article-title":"Herpes zoster","volume":"334","author":"Wareham","year":"2007","journal-title":"Brit. Med. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1093\/cid\/ciy953","article-title":"The Epidemiology of Herpes Zoster in the United States During the Era of Varicella and Herpes Zoster Vaccines: Changing Patterns among Older Adults","volume":"69","author":"Harpaz","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3949\/ccjm.74.7.489","article-title":"The protean neurologic manifestations of varicella-zoster virus","volume":"74","author":"Nagel","year":"2007","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_19","unstructured":"Kennedy, P.G.E., and Johnson, R.T. (1987). Infections of the Nervous System, Butterworths."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1212\/01.WNL.0000148484.19070.4D","article-title":"VZV vasculopathy and postherpetic neuralgia: Progress and perspective on antiviral therapy","volume":"64","author":"Gilden","year":"2005","journal-title":"Neurology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kennedy, P.G.E., Montague, P., Scott, F., Grinfeld, E., Ashrafi, G.H., Breuer, J., and Rowan, E.G. (2013). Varicella-zoster viruses associated with postherpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line. PLoS ONE., 8.","DOI":"10.1371\/journal.pone.0051570"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1056\/NEJMoa051016","article-title":"A Vaccine to Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults","volume":"352","author":"Oxman","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1056\/NEJMoa1603800","article-title":"Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older","volume":"375","author":"Cunningham","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s11908-014-0407-z","article-title":"Update on Varicella Zoster Virus Vasculopathy","volume":"16","author":"Nagel","year":"2014","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s13311-016-0430-x","article-title":"Issues in the Treatment of Neurological Conditions Caused by Reactivation of Varicella Zoster Virus (VZV)","volume":"13","author":"Kennedy","year":"2016","journal-title":"Neurotherapeutics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1212\/01.wnl.0000258549.13334.16","article-title":"The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy","volume":"68","author":"Nagel","year":"2007","journal-title":"Neurology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1212\/WNL.0000000000001409","article-title":"Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis","volume":"84","author":"Gilden","year":"2015","journal-title":"Neurology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1001\/jamaneurol.2015.2101","article-title":"Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis","volume":"72","author":"Nagel","year":"2015","journal-title":"JAMA Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/ana.410440323","article-title":"Search for varicella zoster virus in giant cell arteritis","volume":"44","author":"Nordborg","year":"1998","journal-title":"Ann. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0022-510X(03)00167-9","article-title":"Absence of detection of varicella-zoster virus DNA in temporal artery biopsies obtained from patients with giant cell arteritis","volume":"215","author":"Kennedy","year":"2003","journal-title":"J. Neurol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ajo.2017.12.017","article-title":"Identification of Herpes Zoster-Associated Temporal Arteritis Among Cases of Giant Cell Arteritis","volume":"187","author":"Buckingham","year":"2018","journal-title":"Am. J. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.yexmp.2015.12.007","article-title":"VZV, temporal arteritis, and clinical practice: False positive immunohistochemical detection due to antibody cross-reactivity","volume":"100","author":"Pisapia","year":"2016","journal-title":"Exp. Mol. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1212\/WNL.0000000000001459","article-title":"Varicella-zoster virus claims yet another painful scalp\u2014Giant cell arteritis","volume":"84","author":"Kennedy","year":"2015","journal-title":"Neurology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1080\/01658107.2019.1604763","article-title":"Varicella Zoster Virus in Giant Cell Arteritis: A Review of Current Medical Literature","volume":"43","author":"Ostrowski","year":"2019","journal-title":"Neuroophthalmology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/B978-0-444-53488-0.00012-2","article-title":"Varicella-zoster","volume":"123","author":"Gilden","year":"2014","journal-title":"Handb. Clin. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1002\/ana.410350505","article-title":"Zoster sine herpete, a clinical variant","volume":"35","author":"Gilden","year":"1994","journal-title":"Ann. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1212\/WNL.0b013e31820a0d5d","article-title":"Zoster sine herpete: It would be rash to ignore it","volume":"76","author":"Kennedy","year":"2011","journal-title":"Neurology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s10096-018-3199-5","article-title":"Guillain-Barr\u00e9 syndrome following varicella-zoster virus infection","volume":"37","author":"Islam","year":"2018","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/ana.410090308","article-title":"Multifocal varicella-zoster virus leukoencephalitis temporally remote from herpes zoster","volume":"9","author":"Horten","year":"1981","journal-title":"Ann. Neurol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/8\/1663\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:22:43Z","timestamp":1760127763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/8\/1663"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,30]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["v15081663"],"URL":"https:\/\/doi.org\/10.3390\/v15081663","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,30]]}}}