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.
