PML/JCV Flashcards
What is Progressive Multifocal Leukoencephalopathy (PML)?
An opportunistic infection of the CNS caused by the JC virus characterized by focal demyelination.
PML primarily occurs in immunocompromised individuals, especially those with HIV.
What virus causes Progressive Multifocal Leukoencephalopathy?
JC virus (JCV).
JCV is a human polyomavirus with a worldwide distribution.
What percentage of people exhibit serologic evidence of JCV exposure by their late teens or as adults?
20% to 70%.
This indicates widespread exposure to the virus.
How does primary JCV infection usually present?
Asymptomatically in childhood, leading to a chronic carrier state in most individuals.
What are common clinical manifestations of PML?
Focal neurological deficits with insidious onset and steady progression.
Specific deficits vary based on affected brain regions.
What brain regions can be affected by PML?
- Occipital lobes (hemianopsia)
- Frontal and parietal lobes (aphasia, hemiparesis, hemisensory deficits)
- Cerebellar peduncles and deep white matter (dysmetria, ataxia)
Spinal cord involvement is rare.
What is the typical time course of PML progression?
Clinical progression over several weeks.
What imaging technique is critical for diagnosing PML?
Magnetic resonance imaging (MRI).
What MRI findings are characteristic of PML?
Distinct white matter lesions that are hyperintense on T2-weighted and fluid-attenuated inversion recovery sequences, and hypointense on T1-weighted sequences.
What is the first step in confirming a PML diagnosis?
Testing cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) for JCV DNA.
What percentage of patients not on ART show positive JCV PCR results?
Approximately 70% to 90%.
What is the main treatment approach for PML?
Restoring the patient’s immune function through antiretroviral therapy (ART).
What is the prognosis for PML patients who start ART?
More than half experience a remission where disease progression stops.
What factors predict survival in PML patients?
- Peripheral blood CD4 count at presentation
- Plasma HIV RNA levels
- Presence of lesions in the brain stem
CD4 counts <100 cells/mm3 are associated with worse outcomes.
Is there a specific therapy for JCV infection or PML?
No specific therapy exists.
What treatments are not recommended for PML?
- Cytarabine
- Cidofovir
- Serotonergic 5HT2a receptor blockers
- Topotecan
These treatments have not demonstrated clinical benefit in controlled studies.
What is the relationship between ART and PML?
ART is crucial for reversing immunosuppression, which interferes with the host’s response to JCV.
True or False: PML can occur in patients treated with ART.
True.
What is the significance of contrast enhancement on imaging in PML?
It may predict better outcomes as it indicates an immune response to the virus.
What is the potential role of advanced neuroimaging techniques in PML diagnosis?
They may provide additional diagnostic information.
What is the prevalence of JCV DNA in CSF of patients with PML?
Virtually never detected in normal CSF samples.
What is the recommended action if JCV PCR is negative but suspicion of PML remains high?
Repeat CSF analysis.
What does a high CNS Penetration Effectiveness (CPE) score indicate?
The ability of ARV drugs to penetrate the CNS effectively.
What is the current understanding of the latency of JCV in the CNS?
It remains debated whether JCV is latent in the CNS or results from hematogenous dissemination.
What is the recommendation for treatment with serotonergic 5HT2a receptor blockers?
Not recommended (BIII)
What inhibitor was studied for JCV replication in a cell-culture study?
Topoisomerase inhibitor
What was the outcome of the small trial studying topotecan?
Suggested a salutary effect in some patients, but likely similar to natural course (BIII)
What is the recommendation for the use of topotecan?
Not recommended (BIII)
What antimalarial drug was studied for its anti-JCV activity?
Mefloquine
What was the outcome of the clinical trial for mefloquine?
Trial halted due to futility; not recommended (BIII)
What immunomodulatory agent showed initial promise but is not recommended?
Interferon-alpha (BIII)
What is the recommendation for interferon-beta treatment of HIV-associated PML?
Not recommended (BIII)
What treatment showed improvement or recovery in PML-related neurological dysfunction in non-HIV patients?
IL-2
What is the recommendation for treatment of PML with IL-2?
Not recommended (BIII)
What alternative therapy is under consideration for PML?
Recombinant IL-7 with VP-1 vaccination strategy
What type of therapy has been considered to enhance immune response to JCV?
Checkpoint inhibitor therapy
What is the recommendation for checkpoint inhibitors in HIV-related PML?
Not recommended (BIII)
What type of T cells have been used for PML treatment?
Autologous or allogeneic virus-specific T cells
What is the current recommendation for using disease-specific T cells for HIV-associated PML?
Cannot be recommended
When should ART be (re)started for patients with suspected PML?
As soon as possible (AII)
What should be done for patients already on treatment with plasma HIV viremia?
Adjust ART based on plasma virus susceptibility (AII)
What should treatment response be monitored with?
Clinical examination and brain MRI
How often should neuroimaging be obtained after ART initiation for stable or improved patients?
6 to 8 weeks (BIII)
What is PML-IRIS?
PML occurring within weeks to months after initiating ART with differing clinical features
What are the clinical features of PML-IRIS?
Lesions with contrast enhancement, edema, mass effect, rapid clinical course
What has been used empirically for PML-IRIS with reported benefit?
Corticosteroids
What is the proposed corticosteroid regimen for PML-IRIS?
3- to 5-day course of IV methylprednisolone followed by oral prednisone taper
What should be done during the corticosteroid taper?
Monitor clinical status carefully
What is the recommendation for maraviroc in treating PML-IRIS?
Not recommended (BIII)
What defines treatment failure in PML?
Continued clinical worsening after 3 months of ART initiation
What should be considered if PML worsens despite fully suppressive ART?
Consult an expert for unproven therapies (CIII)
What is the main preventive measure for recurrence of PML?
Effective ART regimen to suppress viremia and maintain CD4 counts (AII)
What should therapy during pregnancy consist of for PML?
Initiating or optimizing the ARV regimen
What is the main approach to treatment for PML?
Preserve immune function with effective ART
What should be done for patients not on ART diagnosed with PML?
ART should be (re)started immediately (AII)
What is not effective for preventing or treating JCV infections or PML?
Direct-acting antiviral therapy
What agents are not recommended for the treatment of PML?
- Cytarabine (AII) * Cidofovir (AII) * Interferon-alpha (BIII) * Interleukin-2 (BIII) * Topotecan (BIII) * Pembrolizumab (BIII)
What should guide the timing of follow-up assessments for PML?
Clinical progress (BIII)
When should repeat MRI be obtained after clinical worsening?
As soon as worsening is recognized (BIII)
