Progressive Multifocal Leukoencephalopathy

Progressive Multifocal Leukoencephalopathy

For general purposes

PML is a progressive disease of the brain caused by the infection with a virus named JC virus

JCV is a small and ubiquitous virus, which infects most of the people during their lifetime, without causing any symptoms. However, the virus may persist for life in cells of the urinary tract or other cell types and, in people with immune disorders, it may reactivate and cause PML.

This is a rare event, but it may occur in persons who are receiving immunosuppressive or immunomodulant drugs, such as transplanted persons, persons with multiple sclerosis treated with natalizumab, with untreated late stage HIV infection, hematological tumors or other immune dysfunctions.

When the virus attacks the brain cells, it produces lesions that cause loss of tissue and neurological deficits. The lesions, which are are initially small, tend to enlarge and merge over time leading to a progressively worsening neurological disease.

There is no specific cure for PML, because there are no drugs that target the virus. However, if the underlying immune dysfunction is resolved, then the immune system itself can regain the ability to control the infection and stop the progression of PML. This is the case of patients with PML that stop treatment with natalizumab or immunosuppressive drugs, or with HIV infection who start taking anti-HIV drugs.

Unfortunately, reversion of the immune dysfunction is not always feasible, and, in addition, the recovery of immunity takes a few weeks, during which the disease continues to progress. Therefore, it is important to recognize PML immediately after onset of initial symptoms, to act as soon as possible towards immune reconstitution.

There are diagnostic tools to recognise PML, primarily magnetic resonance imaging (MRI) of the brain, which enable identification and characterization of the lesions, and lumbar puncture, which leads in most of the cases to identificationa nd quantification of the virus in the cerebrospinal fluid.

Researchers are studying new approaches to the management and eventually the cure of PML, which include immune-based treatments aiming to enhance host immunity as fast as possible and contrast the spread of the virus. Although a few anecdotical cases have been reported of patients with PML who improved following administration of drugs such as interleukin-7 and a theraputic ‘vaccine’, the actual efficacy of such therapies requires evaluation of large number of cases in the context of structured clinical trials. Clinical trials in PML are currently planned but waiting to be initiated