Clinical Features and Outcomes of VZV CNS Infections

Clinical Features, Risk Factors, and Functional Outcomes of Varicella Zoster Virus Central Nervous System Infections: A BUHASDER Multicenter Retrospective Cohort Study

The goal of this observational study is to learn about the clinical characteristics, risk factors, and long-term outcomes of varicella zoster virus (VZV)-related central nervous system (CNS) infections in adults. The main questions it aims to answer are:

What are the risk factors associated with VZV meningitis and encephalitis? Which clinical and laboratory findings are associated with complications and poor functional outcomes? Researchers will collect retrospective data from participating centers across the country, including demographic, clinical, laboratory, imaging, and treatment variables. Participants diagnosed with VZV-related central nervous system infections will be followed through medical records, and outcomes such as complications, functional status, and mortality will be evaluated.

Study Overview

• Status: Active, not recruiting
• Conditions: Varicella Zoster; Varicella Meningitis; Varicella Encephalitis; Varicella Neurological

Detailed Description

Varicella zoster virus (VZV) is a well-established cause of central nervous system infections, including meningitis and encephalitis, which may lead to significant morbidity and mortality. These infections can occur with or without the typical dermatomal rash and may present with a wide spectrum of neurological findings. With increasing life expectancy and the widespread use of immunosuppressive and immunomodulatory therapies, the incidence of VZV reactivation and related complications is expected to rise.

Despite advances in molecular diagnostic methods, which have improved the timely and accurate detection of VZV in cerebrospinal fluid, large-scale multicenter data on VZV-related central nervous system infections remain limited, particularly at the national level.

This multicenter retrospective cohort study aims to evaluate the clinical features, risk factors, and functional outcomes of adult patients diagnosed with VZV meningitis and encephalitis. Data will be collected from participating centers using a standardized dataset, including demographic characteristics, clinical presentation, comorbidities, laboratory findings, cerebrospinal fluid analysis, imaging results, treatment details, and follow-up outcomes.

The study will compare patients with and without complications to identify factors associated with adverse outcomes. Complications assessed during follow-up (minimum 1 month, up to 12 months) will include neurological sequelae such as epilepsy, cognitive impairment, cranial nerve deficits, and functional disability measured by the Modified Rankin Scale. Mortality and intensive care unit requirements will also be evaluated.

Statistical analyses will be performed to determine associations between clinical variables and outcomes. Categorical variables will be compared using chi-square or Fisher's exact tests, and continuous variables will be analyzed according to their distribution. Logistic regression models will be used to identify independent predictors of complications. A p-value of <0.05 will be considered statistically significant.

The study will be conducted under the coordination of the Association of Infectious Diseases and Clinical Microbiology Specialists (BUHASDER).

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Kocaeli
    • İzmit, Kocaeli, Turkey (Türkiye), 41380
      • Kocaeli University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (≥18 years) diagnosed with varicella zoster virus (VZV)-related central nervous system infections, including meningitis and encephalitis, identified from participating centers. Patients are included based on molecular confirmation of VZV in cerebrospinal fluid and availability of clinical follow-up data.

Description

Inclusion Criteria:

Age ≥18 years Molecular confirmation of VZV (PCR-Polymerase Chain Reaction) in CSF fluid Diagnosis of meningitis or encephalitis

Exclusion Criteria:

Missing key clinical data Inadequate follow-up

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients with Complications; Adult patients diagnosed with varicella zoster virus (VZV)-related central nervous system infections who developed complications during follow-up. Complications include neurological sequelae such as epilepsy, cognitive impairment, cranial nerve deficits, functional disability, or mortality.
Patients without Complications; Adult patients diagnosed with varicella zoster virus (VZV)-related central nervous system infections who did not develop complications during the follow-up period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Complications	Presence of complications in patients with varicella zoster virus (VZV)-related central nervous system infections, including neurological sequelae such as epilepsy, cognitive impairment, cranial nerve deficits, functional disability, or death.	Up to 12 months after diagnosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Outcome (Modified Rankin Scale)	Functional status assessed using the Modified Rankin Scale (mRS) in patients with VZV CNS infections.	Up to 12 months after diagnosis
Neurological Sequelae	Development of long-term neurological complications such as epilepsy, cognitive impairment, or motor deficits.	Up to 12 months after diagnosis
Intensive Care Unit (ICU) Requirement	Requirement for ICU admission during the course of illness.	Up to 1 month after diagnosis
Mortality	All-cause mortality related to VZV central nervous system infection.	Up to 1 month after diagnosis

Collaborators and Investigators

• Sponsor: Kocaeli University
• Investigators: Principal Investigator: Özlem Güler, MD, Kocaeli University, Kocaeli, Turkey

Publications and helpful links

General Publications

• Tyrberg T, Hagberg L, Nilsson S, Grahn A. Incidence and Risk Factors for Varicella-Zoster Virus-Associated Central Nervous System Infections: A Nationwide Swedish Retrospective Case-Control Study. J Med Virol. 2025 Feb;97(2):e70166. doi: 10.1002/jmv.70166.

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2026
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 7, 2026

Study Registration Dates

• First Submitted: April 17, 2026
• First Submitted That Met QC Criteria: April 23, 2026
• First Posted (Actual): April 28, 2026

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Varicella Zoster Virus Infection; Encephalitis, Varicella Zoster
• Additional Relevant MeSH Terms: Infectious Encephalitis; Neuroinflammatory Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Encephalitis; Varicella Zoster Virus Infection; Encephalitis, Varicella Zoster
• Other Study ID Numbers: GOKAEK-2026/06/41 2026/190

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No