Viral Infections of the Central Nervous System: Diagnosis and Clinical Outcome

Central Nervous System (CNS) infections are caused by bacteria, viruses, fungi, helminths, with several clinical aspects. Studies in the literature generally focus on a single patient type, and no experiences have been reported in which immunosuppressed and immunocompetent adult and pediatric patients were simultaneously examined. Our study will include all possible patient types (immunocompetent adults, immunocompetent pediatric patients, and subjects immunosuppressed by co-softness), to try to more precisely define the clinical and population characteristics of patients who have had an episode of CNS viral infection. These indications may be useful in the future to more specifically guide diagnostic investigations on patients considered at risk.

Study Overview

• Status: Active, not recruiting
• Conditions: Infection; CNS Infection; Virus Disease

Detailed Description

The objectives are: 1) to verify whether the different categories of patients present a different distribution of etiological agents (Citomegalovirus, Herpes Simplex Virus 1, Herpes Simplex Virus 2, Human Herpesvirus 6, Varicella Zoster Virus, Epstein-Barr Virus, Enterovirus) for CNS infection; 2) to verify whether the course and clinical manifestations of the disease can be associated with the identified etiological agent and the type of patient; 3) to describe the results of instrumental tests (EEC and/or MRI and/or CT) in patients who tested positive for a neurotropic virus responsible for the infection.

• Study Type: Observational
• Enrollment (Estimated): 4000

Contacts and Locations

Study Locations

• Italy
  • Bologna
    • Bologna, Bologna, Italy, 40138
      • IRCCS Azienda Ospedaliero-Universitaria di Bologna

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study will include cases from various centers in the Bologna metropolitan area, involving adult and pediatric patients, including newborns, whose CSF was analyzed at the Microbiology Unit of the IRCCS AOUBO, Policlinico di Sant'Orsola, between January 1, 2014, and December 31, 2024.

Description

Inclusion Criteria:

• Patients whose CSF was analyzed for HSV-1, HSV-2, VZV, EV, EBV, CMV and HHV-6 between 01/01/2014 and 31/12/2024.
• Obtaining informed consent.

Exclusion Criteria:

- None

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
immunocompetent adults
immunocompetent pediatric
adult and paediatric immunosuppressed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positivity to different etiological agents (CMV, HSV-1, HSV-2, HHV-6, VZV, EBV, EV) by patient type (pediatric, adult, immunocompetent, immunocompromised)	For the primary objective, all required molecular investigations of LCRs collected from patients with suspected viral meningitis will be selected from the management software used at the Virology Laboratory between January 1, 2014, and December 31, 2024. Infectious episodes will be identified in relation to the positivity of the viral etiological agent, considering the result (positive or negative) obtained at the time of diagnosis, without having the need to re-examine the sample. An infectious episode is defined as a hospital admission event with a clinical picture of presumed meningitis of viral origin and consequent microbiological confirmation. Therefore, in case of multiple molecular investigations on the same patient during a single hospitalization, it will be considered as the only infectious event. On the other hand, in the event of multiple hospitalizations per single patient with suspected viral meningitis, they will be considered as different infectious episodes.	at enrolment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical course of the patient with episode of viral meningitis, taking into account the type of patient (pediatric, adult, immunocompetent, immunocompromised) and the pathogen	For secondary objectives, only positive cases of viral etiological agent will be considered and, by accessing the data recorded in the patient's medical record, information regarding symptoms, the outcome of the instrumental examination performed, and the course of the individual hospital stay will be retrieved. Post-discharge, only neurological sequelae will be considered at follow-up at > 6 months, during the follow-up visit with the infectious disease physician.	at enrolment
Distribution of instrumental outcomes of EEC, MRI, CT (normal or non-normal), in the patient with infectious episode, taking into account the patient type (pediatric, adult, immunocompetent, immunocompromised) and the pathogen detected.	For secondary objectives, only positive cases of viral etiological agent will be considered and, by accessing the data recorded in the patient's medical record, information regarding symptoms, the outcome of the instrumental examination performed, and the course of the individual hospital stay will be retrieved. Post-discharge, only neurological sequelae will be considered at follow-up at > 6 months, during the follow-up visit with the infectious disease physician.	at enrolment

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Liliana Gabrielli, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna; Study Chair: Giulio Virgili, MD, AUSL di Bologna

Publications and helpful links

General Publications

• Jakobsen A, Skov MT, Larsen L, Trier Petersen P, Brandt C, Wiese L, Hansen BR, Luttichau HR, Tetens MM, Helweg-Larsen J, Storgaard M, Nielsen H, Bodilsen J. Herpes Simplex Virus 2 Meningitis in Adults: A Prospective, Nationwide, Population-Based Cohort Study. Clin Infect Dis. 2022 Sep 14;75(5):753-760. doi: 10.1093/cid/ciab1071.
• Handley G, Pankow S, Bard JD, Yee R, Nigo M, Hasbun R. Distinguishing cytomegalovirus meningoencephalitis from other viral central nervous system infections. J Clin Virol. 2021 Sep;142:104936. doi: 10.1016/j.jcv.2021.104936. Epub 2021 Jul 25.
• Aiba Y, Ohshiba S, Horiguchi S, Morioka I, Miyashita K, Kiyota I, Endo G, Takada H, Iwata H. Peripheral hemodynamics evaluated by acceleration plethysmography in workers exposed to lead. Ind Health. 1999 Jan;37(1):3-8. doi: 10.2486/indhealth.37.3.
• Lane B, Marks MP, Steinberg GK. Interventional neuroradiology--a new approach to difficult vascular lesions of the brain. West J Med. 1993 Jan;158(1):68-9. No abstract available.
• Mazziotti MV, Strasberg SM, Langer JC. Intestinal rotation abnormalities without volvulus: the role of laparoscopy. J Am Coll Surg. 1997 Aug;185(2):172-6. doi: 10.1016/s1072-7515(97)00058-6.

Helpful Links

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Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Actual): December 1, 2025
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: December 10, 2025
• First Submitted That Met QC Criteria: January 13, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Virus Diseases; Central Nervous System Infections
• Other Study ID Numbers: LCR-VIR

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