Observational Cohort Study of Chronic Viral Infection in the Central Nervous System

Central Nervous System Chronic Viral Infections: A Cohort Study

This research team intends to conduct a real-world cohort study of chronic CNS viral infections represented by PML, to evaluate whether administration of immune checkpoint inhibitors improves long-term outcomes in this patient population.Patients with prior follow-up will be enrolled into a retrospective/prospective ambidirectional cohort, and newly diagnosed patients will be enrolled into a prospective cohort.

Study Overview

• Status: Recruiting
• Conditions: Progressive Multifocal Leukoencephalopathy; Immune Checkpoint Inhibitors
• Intervention / Treatment: Drug: Immune Checkpoint Inhibitors

• Study Type: Observational
• Enrollment (Estimated): 66

Contacts and Locations

• Study Contact: Name: Siyuan Fan; Phone Number: +86 13426341726; Email: siyuanfan@outlook.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Siyuan Fan; Phone Number: 13426341726; Email: siyuanfan@outlook.com

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 subjects are patients with chronic viral infections of the central nervous system (CNS), predominantly Progressive Multifocal Leukoencephalopathy (PML).Patients are enrolled consecutively through the neurology encephalitis outpatient department, emergency department, inpatient department, and neurology consultation services.

Description

Inclusion Criteria:

1. Age > 14 years old.
2. Confirmed diagnosis of chronic viral infection of the central nervous system (CNS).
3. Signed informed consent. The diagnosis of Progressive Multifocal Leukoencephalopathy (PML) shall meet one of the following criteria:(1) Neuropathological diagnosis: Pathological examination of brain tissue shows demyelination, bizarre astrocytes, and enlarged oligodendroglial nuclei; immunohistochemical detection of JC virus (JCV) antigen.(2) Clinical + imaging + cerebrospinal fluid (CSF) diagnosis: Clinical manifestations of progressive neurological dysfunction; neuroimaging shows single or multiple asymmetric white matter lesions with large volume, mostly involving the U-fibers, and rare mass effect; detection of JC virus DNA in cerebrospinal fluid. Specific reference shall be made to the 2013 American Academy of Neurology (AAN) diagnostic criteria.

For the diagnosis of other chronic viral infections of the central nervous system, the clinical manifestations shall be consistent with the characteristics of the relevant diseases, and the relevant viral DNA shall be detected in the cerebrospinal fluid.

The diagnosis of all cases must be independently confirmed by two physicians from the Encephalitis Professional Group, Department of Neurology, Peking Union Medical College Hospital, with consistent diagnostic results, to be included in the study. For cases with inconsistent diagnoses, the two physicians shall conduct consultations to reach a consensus. Patients with unreached diagnostic consensus shall not be included in the study.

Exclusion Criteria:

1. Presence of lumbar puncture contraindications, making it impossible to collect cerebrospinal fluid.
2. The attending physician and the researcher consider that the detection of virus in cerebrospinal fluid cannot explain the patient's clinical manifestations.
3. Inability to complete 1-year follow-up.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ambidirectional cohort; an ambidirectional cohort for patients with existing follow-up data	Drug: Immune Checkpoint Inhibitors; Immune Checkpoint Inhibitors for PML treatment
prospective cohort; a prospective cohort for newly diagnosed patients.	Drug: Immune Checkpoint Inhibitors; Immune Checkpoint Inhibitors for PML treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS) Score at 1 Year	Assessment of functional disability and neurological recovery using the Modified Rankin Scale at 1 year (±3 months) after onset. Measurement Tool: Modified Rankin Scale (mRS) Unit of Measure: Scale score (0-6; 0 = no symptoms, 6 = death, the higher the worse)	1 year (±3 months) after onset
Neuroimaging Findings at 1 Year	Description: Evaluation of brain structural changes, including the location, extent, and resolution of white matter lesions, using neuroimaging at 1 year (±3 months) after onset. Measurement Tool: Brain Magnetic Resonance Imaging (MRI) Unit of Measure: Qualitative radiological description (e.g., lesion resolution, progression, stability)	1 year (±3 months) after onset
Neuroimaging Findings at 1 Year (±3 months)	Description: Evaluation of brain structural changes, including the location, extent, and resolution of white matter lesions, using neuroimaging at 1 year (±3 months) after onset. Measurement Tool: Brain Magnetic Resonance Imaging (MRI) Unit of Measure: quantitative measurement (e.g., lesion volume in cm³)	1 year (±3 months) after onset
Cerebrospinal Fluid (CSF) Viral Nucleic Acid Detection at 1 Year	Description: Detection of viral nucleic acid (including JC virus and other relevant neurotropic viruses) in cerebrospinal fluid to assess viral clearance or persistence at 1 year (±3 months) after onset. Measurement Tool: Real-time Quantitative Polymerase Chain Reaction (qPCR) Unit of Measure: Qualitative (positive/negative)	1 year (±3 months) after onset
Cerebrospinal Fluid (CSF) Viral Nucleic Acid Detection at 1 Year (±3 months)	Description: Detection of viral nucleic acid (including JC virus and other relevant neurotropic viruses) in cerebrospinal fluid to assess viral clearance or persistence at 1 year (±3 months) after onset. Measurement Tool: Real-time Quantitative Polymerase Chain Reaction (qPCR) Unit of Measure: viral load (copies/mL)	1 year (±3 months) after onset

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Residual Neurological Symptoms at 1 Month and During Follow-up	Documentation of residual neurological symptoms (e.g., motor weakness, sensory disturbance, cognitive impairment) at 1 month after onset, and every 3 months thereafter within 1 year, to assess longitudinal recovery trends. Measurement Way: telephone or outpatient visit conducted by experienced neurologist Unit of Measure: Categorical description of symptoms (newly occurred/presence/absence)	At 1 month after onset, and every 3 months within 1 year
Modified Rankin Scale (mRS) Score Trends at 1 Month and Every 3 Months Within 1 Year	Description: Serial assessment of functional disability using the Modified Rankin Scale at 1 month after onset, and every 3 months thereafter within 1 year, to evaluate longitudinal changes in neurological function. Measurement Tool: Modified Rankin Scale (mRS) obtained by telephone or outpatient visit. Unit of Measure: Scale score (0-6, 0 = no symptoms, 6 = death) at each follow-up time point.	At 1 month after onset, and every 3 months within 1 year

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2023
• Primary Completion (Estimated): October 25, 2030
• Study Completion (Estimated): October 25, 2030

Study Registration Dates

• First Submitted: March 24, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infectious Encephalitis; Neuroinflammatory Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Virus Diseases; Demyelinating Diseases; DNA Virus Infections; Slow Virus Diseases; Leukoencephalopathies; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Polyomavirus Infections; Encephalitis; Leukoencephalopathy, Progressive Multifocal; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Immune Checkpoint Inhibitors
• Other Study ID Numbers: K23C353

Plan for Individual participant data (IPD)

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