Varicella Zoster Virus encephalitis in Denmark from 2015 to 2019- A nationwide prospective cohort study

Laura Krogh Herlin, Kristoffer Skaalum Hansen, Jacob Bodilsen, Lykke Larsen, Christian Brandt, Christian Østergaard Andersen, Birgitte Rønde Hansen, Hans Rudolf von Lüttichau, Jannik Helweg Larsen, Lothar Wiese, Merete Storgaard, Henrik Ib Nielsen, Trine Hyrup Mogensen, Dasgib

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Abstract

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.

Original languageEnglish
JournalClinical Infectious Diseases
Volume72
Issue number7
Pages (from-to)1192-1199
ISSN1058-4838
DOIs
Publication statusPublished - 8. Apr 2021

Keywords

  • encephalitis
  • varicella zoster virus
  • vasculitis
  • viral encephalitis

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