Varicella Zoster Virus Encephalitis in Denmark From 2015 to 2019—A Nationwide Prospective Cohort Study
Open accessAbstract
Background: Knowledge of the epidemiology and clinical characteristics of varicella zoster virus (VZV) encephalitis remains limited. Methods: Nationwide prospective cohort study of adults treated for microbiologically confirmed VZV encephalitis at Danish departments of infectious diseases from 2015 to 2019. Modified Poisson regression analysis was used to compute adjusted relative risks (RRs) of unfavorable outcome. Results: We identified 92 adults (49% female) with VZV encephalitis, yielding an incidence of 5.3/1 000 000 per year (95% CI, 4.2–6.6). Median age was 75 years (IQR, 67–83) and immunocompromising conditions were frequent (39%). Predominant symptoms were confusion (76%), headache (56%), nausea (45%), gait disturbance (42%), and personality changes (41%). Cranial imaging showed cerebral vasculitis (including infarction and hemorrhage) in 14 (16%) patients and encephalitic abnormalities in 11 (13%) with predilection for the brainstem and deep brain structures. Intravenous acyclovir treatment was initiated a median (IQR) of 13.4 hours (5.2–46.3) since admission, while cranial imaging and lumbar puncture were performed after 6.3 hours (2.5–31.0) and 18.5 hours (4.9–42.0). In-hospital, 1-month, and 3-month mortalities were 4%, 9%, and 11%, respectively. Unfavorable outcome (Glasgow Outcome Score of 1–4) was found in 69% at discharge, with age (adjusted RR [aRR], 1.02; 95% CI, 1.01–1.03), vasculitis (aRR, 1.38; 95% CI, 1.02–1.86), and Glasgow Coma Scale (GCS) <15 (aRR, 1.32; 95% CI, 1.01–1.73) identified as independent risk factors. Conclusions: VZV encephalitis occurs primarily in elderly or immunocompromised patients with a higher incidence than previously estimated. The diagnosis is often delayed; risk factors for unfavorable outcome are age, cerebral vasculitis, and GCS <15.
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Studies assessing prognosis using hard endpoints in the post-acyclovir era showed neurological impairment in 20-60% of VZV patients upon hospital discharge, 55% after one month, 51% after three months, and 71% after one year after the acute episode.
“Studies assessing prognosis using hard endpoints in the post-acyclovir era showed neurological impairment in 20–60% of patients upon hospital discharge [62–64], 55% after one month, 51% after three months and 71% after one year [62, 65] after the acute episode.”
From Cognitive decline following acute viral infections: literature review and projections for post-COVID-19 (2022) · cites this paper as [62]
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Cites
A Modified Poisson Regression Approach to Prospective Studies with Binary Data
Zou, G. (2004) · American Journal of Epidemiology · doi:10.1093/aje/kwh090 · Cited by 9,767 · see citing works
Granerod, J., Ambrose, H. E., Davies, N. W., Clewley, J. P., Walsh, A. L., Morgan, D., Cunningham, R., Zuckerman, M., Mutton, K. J., Solomon, T., et al. (2010) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(10)70222-x · Cited by 1,358 · see citing works
Venkatesan, A., Tunkel, A. R., Bloch, K. C., Lauring, A. S., Sejvar, J. J., Bitnun, A., Stahl, J. ‐., Mailles, A., DREBOT, M. A., Rupprecht, C. E., et al. (2013) · Clinical Infectious Diseases · doi:10.1093/cid/cit458 · Cited by 1,223 · see citing works
Neurologic Complications of the Reactivation of Varicella–Zoster Virus
Gilden, D. H., Kleinschmidt-DeMasters, B. K., LaGuardia, J. J., Mahalingam, R., & Cohrs, R. J. (2000) · New England Journal of Medicine · doi:10.1056/nejm200003023420906 · Cited by 851 · see citing works
Gilden, D., Cohrs, R. J., Mahalingam, R., & Nagel, M. A. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70134-6 · Cited by 613 · see citing works
Teasdale, G. M., Pettigrew, L. E. L., Wilson, L., Murray, G. D., & Jennett, B. (1998) · Journal of Neurotrauma · doi:10.1089/neu.1998.15.587 · Cited by 553 · see citing works
Infectious Encephalitis in France in 2007: A National Prospective Study
Mailles, A., & Stahl, J. ‐. (2009) · Clinical Infectious Diseases · doi:10.1086/648419 · Cited by 431 · see citing works
Tyler, K. L. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1708714 · Cited by 282 · see citing works
The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy
Nagel, M. A., Forghani, B., Mahalingam, R., Wellish, M., Cohrs, R. J., Russman, A., Katzan, I., Lin, R., Gardner, C. J., & Gilden, D. (2007) · Neurology · doi:10.1212/01.wnl.0000258549.13334.16 · Cited by 251 · see citing works
Kamei, S. (2005) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2004.049676 · Cited by 237 · see citing works
Koskiniemi, M., Rantalaiho, T., Piiparinen, H., von Bonsdorff, C., Färkkilä, M., Järvinen, A., Kinnunen, E., Koskiniemi, S., Mannonen, L., Muttilainen, M., et al. (2001) · Journal of NeuroVirology · doi:10.1080/135502801753170255 · Cited by 222 · see citing works
Grahn, A., & Studahl, M. (2015) · Journal of Infection · doi:10.1016/j.jinf.2015.06.004 · Cited by 221 · see citing works
Acute encephalitis in immunocompetent adults
Venkatesan, A., Michael, B. D., Probasco, J. C., Geocadin, R. G., & Solomon, T. (2019) · The Lancet · doi:10.1016/s0140-6736(18)32526-1 · Cited by 191 · see citing works
Varicella-zoster virus CNS disease—Viral load, clinical manifestations and sequels
Persson, A., Bergström, T. B., Lindh, M., Namvar, L., & Studahl, M. (2009) · Journal of Clinical Virology · doi:10.1016/j.jcv.2009.07.014 · Cited by 168 · see citing works
Mailles, A., De Broucker, T., Costanzo, P., Martinez-Almoyna, L., Vaillant, V., Stahl, J.-P., & on behalf of the Steering Committee and Investigators Group (2012) · Clinical Infectious Diseases · doi:10.1093/cid/cis226 · Cited by 161 · see citing works
Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections
Ogunjimi, B., Zhang, S., Sørensen, K. B., Skipper, K. A., Carter-Timofte, M. E., Kerner, G., Luecke, S., Prabakaran, T., Cai, Y., Meester, J., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92280 · Cited by 152 · see citing works
Self-citationDoes the Extended Glasgow Outcome Scale Add Value to the Conventional Glasgow Outcome Scale?
Weir, J., Steyerberg, E. W., Butcher, I., Lü, J., Lingsma, H. F., McHugh, G. S., Roozenbeek, B., Maas, A. I. R., & Murray, G. D. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2011.2137 · Cited by 148 · see citing works
New Estimates of Incidence of Encephalitis in England
Granerød, J., Cousens, S. N., Davies, N. W. S., Crowcroft, N. S., & Thomas, S. L. (2013) · Emerging infectious diseases · doi:10.3201/eid1909.130064 · Cited by 126 · see citing works
de Broucker, T., Mailles, A., Chabrier, S., Morand, P., & Stahl, J. ‐. (2011) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2011.03705.x · Cited by 102 · see citing works
Britton, P. N., Eastwood, K., Paterson, B., Dürrheim, D. N., Dale, R. C., Cheng, A. C., Kenedi, C. A., Brew, B. J., Burrow, J., Nagree, Y., et al. (2015) · Internal Medicine Journal · doi:10.1111/imj.12749 · Cited by 101 · see citing works
Wood, M., Shukla, S., Fiddian, A. P., & Crooks, R. J. (1998) · The Journal of Infectious Diseases · doi:10.1086/514271 · Cited by 85 · see citing works
Bodilsen, J., Storgaard, M., Larsen, L., Wiese, L., Helweg‐Larsen, J., Lebech, A., Brandt, C., Østergaard, C., & Nielsen, H. (2018) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2018.01.016 · Cited by 74 · see citing works
Self-citationNeuroimaging in encephalitis: analysis of imaging findings and interobserver agreement
Granerød, J., Davies, N. W. S., Mukonoweshuro, W., Mehta, A., Das, K., Lim, M. J., Solomon, T., Biswas, S., Rosella, L. C., Brown, D., et al. (2016) · Clinical Radiology · doi:10.1016/j.crad.2016.03.015 · Cited by 70 · see citing works
Varicella-zoster virus CNS vasculitis and RNA polymerase III gene mutation in identical twins
Carter-Timofte, M. E., Hansen, A. F., Mardahl, M., et al. (2018) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000000500 · Cited by 68 · see citing works
Ramos-Estébanez, C., Lizárraga, K. J., & Merenda, A. (2013) · Antiviral Therapy · doi:10.3851/imp2683 · Cited by 67 · see citing works
Jørgensen, L. K., Dalgaard, L. S., Østergaard, L. J., Nørgaard, M., & Mogensen, T. H. (2016) · Journal of Infection · doi:10.1016/j.jinf.2016.09.004 · Cited by 55 · see citing works
Self-citationHeininger, U., Braun‐Fahrländer, C., Desgrandchamps, D., et al. (2001) · The Pediatric Infectious Disease Journal · doi:10.1097/00006454-200108000-00011 · Cited by 48 · see citing works
Varicella zoster virus immunity: A primer
Duncan, C. J. A., & Hambleton, S. (2015) · Journal of Infection · doi:10.1016/j.jinf.2015.04.015 · Cited by 46 · see citing works
Subcortical type cognitive impairment in herpes zoster encephalitis
Hokkanen, L., Launes, J., Poutiainen, E. T., Valanne, L. K., Salonen, O. L. M., Sirén, J., & Iivanainen, M. V. (1997) · Journal of Neurology · doi:10.1007/s004150050078 · Cited by 39 · see citing works
Grahn, A., Nilsson, S., Nordlund, A., Linden, T. K. A., & Studahl, M. (2013) · Journal of Neurology · doi:10.1007/s00415-013-7057-1 · Cited by 38 · see citing works
Child, N., Croxson, M. C., Rahnama, F., & Anderson, N. E. (2012) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2012.03.010 · Cited by 17 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Britton PN, Eastwood K, Paterson B, et al. Consensus guidelines for the investigation and management of encephalitis in adults and children in Australia and New Zealand. Intern Med J 2015; 45:563-576.
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Damiano, R. F., Guedes, B. F., de Rocca, C. C., de Pádua Serafim, A., Castro, L. H. M., Munhoz, C. D., Nitrini, R., Filho, G. B., Miguel, E. C., Lucchetti, G., et al. (2022) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-021-01286-4 · Cited by 98 · see citing works
Bodilsen, J., Larsen, L., Brandt, C. T., Wiese, L., Hansen, B. R., Andersen, C. Ø., Lüttichau, H. R., Helweg-Larsen, J., Storgaard, M., & Nielsen, H. (2021) · Clinical Epidemiology · doi:10.2147/clep.s326461 · Cited by 33 · see citing works
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- Authors
- Herlin, L. K., Hansen, K. S., Bodilsen, J., Larsen, L., Brandt, C., Andersen, C. Ø., Hansen, B. R., Lüttichau, H. R., Helweg-Larsen, J., Wiese, L., Storgaard, M., Nielsen, H., & Mogensen, T. H.
- Affiliations
- Aarhus University Hospital (DK)
- Aalborg University Hospital (DK)
- University of Southern Denmark (DK)
- Nordsjællands Hospital (DK)
- Hvidovre Hospital (DK)
- Herlev Hospital (DK)
- Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark
- Roskilde Sygehus (DK)
- Aarhus University (DK)
- Corresponding author
- Herlin, Laura Krogh
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-02-27
- Volume
- 72
- Issue
- 7
- Pages
- 1192-1199
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- OpenAlex
- W3008855890
- Cited by
- 96
- References
- 31
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 25 · 2023: 17 · 2022: 14 · 2021: 9 · 2020: 4
- FWCI
- 7.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, other-oa)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion, other-oa)
- Funders
- Lundbeckfonden (R268‐406 2016‐3927, 4004-00047B)
- H. Lundbeck A/S
- Topics
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- varicella-zoster virus encephalitis, varicella-zoster virus reactivation, incidence, immunocompromised adults, cerebral vasculitis, brainstem involvement, Glasgow Outcome Scale, mortality, risk factors, elderly patients, Denmark
- MeSH terms
- Acyclovir, Adult, Aged, Denmark, Female, Herpes Zoster, Humans, Male, Prospective Studies, Herpesvirus 3, Human, Encephalitis, Varicella Zoster
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