Immune Checkpoint Inhibitors, Progressive Multifocal Leukoencephalopathy
Conditions
Brief summary
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.
Interventions
DRUGImmune Checkpoint Inhibitors
Immune Checkpoint Inhibitors for PML treatment
Sponsors
Peking Union Medical College Hospital
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Rankin Scale (mRS) Score at 1 Year | 1 year (±3 months) after onset | 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) |
| Neuroimaging Findings at 1 Year | 1 year (±3 months) after onset | 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) |
| Neuroimaging Findings at 1 Year (±3 months) | 1 year (±3 months) after onset | 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) |
| Cerebrospinal Fluid (CSF) Viral Nucleic Acid Detection at 1 Year | 1 year (±3 months) after onset | 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) |
| Cerebrospinal Fluid (CSF) Viral Nucleic Acid Detection at 1 Year (±3 months) | 1 year (±3 months) after onset | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Residual Neurological Symptoms at 1 Month and During Follow-up | At 1 month after onset, and every 3 months within 1 year | 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) |
| Modified Rankin Scale (mRS) Score Trends at 1 Month and Every 3 Months Within 1 Year | At 1 month after onset, 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. |
Countries
China
Contacts
CONTACTSiyuan Fan
Outcome results
None listed