Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)

Background:

- Progressive multifocal leukoencephalopathy (PML) is a severe viral infection of the brain. It is caused by JC virus. Many people have this virus in their bodies all their life, but it is usually kept in check by their immune system. If the immune system does not work right because of a disease or medication, the virus becomes active and can damage cells in the brain. Not much is known about PML or how it affects the immune system. Researchers want to study people with PML to better understand the natural history of the disease.

Objectives:

- To study the natural history of PML.

Eligibility:

- Individuals at least 2 years of age who have PML.

Design:

• Participants will be screened with a physical exam, medical history, and imaging studies.
• Participants will have several visits to the National Institutes of Health Clinical Center. There will be an initial visit, monthly visits for the next 6 months, a 12-month visit, and possible visits afterward.
• At the initial visit, participants will give blood, urine, and spinal fluid samples. They will also have neurological tests and imaging studies of the brain.
• For the next five visits, participants will give blood and urine samples. They will also have neurological tests and imaging studies of the brain.
• The 6-month and 12-month visits will repeat the tests from the initial visit.
• Other optional procedures include bone marrow samples and skin biopsies. Additional blood tests and imaging studies may be performed.
• Treatment will not be provided as part of this study.

The objective of this study is to examine the natural course of progressive multifocal leukoencephalopathy (PML). PML is a devastating, demyelinating neurological disease affecting the brain of patients with a compromised immune system. It is caused by reactivation of JC virus (JCV), a small DNA virus that infects the majority of the population without clinical significance. There are currently no treatments available for PML.

We plan to study patients with suspected or confirmed PML with different underlying conditions including patients on immune-modulatory therapies for multiple sclerosis (MS), rheumatologic diseases or other autoimmune diseases, as well as patients with HIV infection or other conditions leading to a compromised immune system. Patients will be seen at defined time points during their disease course and detailed assessments will be performed to collect clinical and imaging data. Blood and cerebrospinal fluid (CSF) will also be collected at these time points to evaluate the behavior and biology of the JCV and the patients immune responses to the infection. These tests will lead to a better understanding of the pathophysiology of PML and the course of this disease in different patient groups.

Specifically, this detailed characterization will be used to help identify:

1. Clinical and/or imaging features pathognomonic of PML that may aid in earlier diagnosis and intervention
2. Clinical imaging and/or laboratory features of the disease course that is predictive of clinical outcomes

This information will be integrated to develop a clinically relevant, disease-specific assessment scale of PML, which is currently not available. Such a scale would be a useful tool for the clinical management of patients (i.e., for development of standards of care), as well as for clinical trial design and interpretation.

The long-term objectives of this study are to improve the understanding of the disease course and underlying pathophysiology, to identify subgroups with different prognosis and/or susceptibility to interventions, and to help identify therapeutic targets and/or intervention strategies. Equally important, these efforts will allow development of a repository of cryopreserved biological samples that will be used for validation of candidate biomarkers in future studies; this data and biological bank will be made available to outside laboratories.