Progressive multifocal leukoencephalopathy (PML)

Progressive multifocal leukoencephalopathy (PML) is also known as progressive multifocal leukoencephalitis. It is a rare but usually fatal viral infection and inflammation of the white matter of the brain at multiple locations. The virus is believed to be the Jacob-Creutzfeldt (JC) papovavirus.

The JC virus (JVC) is widespread (most of us have it) but usually remains latent. It can cause disease, however, when the immune system has been severely compromised. PML nearly always occurs only in patients with severe immune deficiency, such as those with AIDS or receiving immunosuppressive medications for a transplant.

Recently, PML has been linked to Raptiva, a psoriasis drug that was recently recalled in the United States.

PML affects about two to five percent of AIDS patients. Research suggests that the reason its prevalence is relatively high in AIDS patients, even when compared with that of other immunosuppressive conditions, is that the effects of HIV on brain tissue, or maybe on JCV itself, make JCV likelier to become active in the brain and increase its damaging effects.

Signs and symptoms of PML include:

Headaches
Changes in mental status
Memory loss
Vision and speech difficulties
Limb weakness
Loss of strength

Loss of coordination
Partial paralysis
Seizures
Coma
Death

PML is classified as a demyelinating disease, in which a gradual loss of the myelin sheaths of nerve fibers leads to impaired transmission of nerve impulses, and to the symptoms listed. In some respects, PML is similar to multiple sclerosis, another demyelinating disease. But unlike MS, in which the myelin itself is attacked and can be replaced, the PML progresses much faster since it destroys the cells that produce the myelin. Most PML patients die within four months of onset.

Although certain pharmacological agents have been implicated in causing PML, it is thought that they do so due in part to the existing impaired immune response. And although “pharm combos” are currently more suspect than are individual drugs, drugs associated with PML include rituximab (Rituxan, MabThera), natalizumab (Tysabri), and interferon beta-1a (Avonex, Rebif, CinnoVex). In fact, in February 2005, the US Food and Drug Administration (FDA) issued an advisory notifying patients and health care providers that due to its potential relationship with PML, marketing of Tysabri, which was used to treat MS, had been suspended.

Diagnosis of PML can be determined by testing for JCV DNA in a brain biopsy specimen or in cerebrospinal fluid. MRI images of the brain may also divulge characteristic damage caused by the disease.

Although there is no known cure for PML, the disease sometimes slows or even discontinues its progress if the immune system improves. Some AIDS patients have been able to survive for several years when undergoing highly active antiretroviral therapy (HAART), but results tend to be slightly better when HAART is begun after the patient is diagnosed with PML.

Drugs and antiviral agents being studied for their effectiveness in treating PML include: