Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal viral disease characterized by progressive damage (-pathy) or inflammation of the white matter (leuko-) of the brain (-encephalo-) at multiple locations (multifocal). It is caused by the JC virus, which is normally present and kept under control by the immune system. The JC virus is harmless except in cases of weakened immune systems. In general, PML has a mortality rate of 30–50% in the first few months, and those who survive can be left with varying degrees of neurological disabilities. PML occurs almost exclusively in patients with severe immune deficiency, most commonly among patients with acquired immune deficiency syndrome (AIDS), but people on chronic immunosuppressive medications including chemotherapy are also at increased risk of PML, such as patients with transplants, Hodgkin's lymphoma, multiple sclerosis, psoriasis, rheumatoid arthritis, and other autoimmune diseases. Signs and symptoms Symptoms can develop over several weeks to months, and they depend on location of damage in the brain and the degree of damage. The most prominent symptoms are "clumsiness, progressive weakness, and visual, speech, and sometimes personality changes". The lesions affecting the parietal and occipital lobes of the brain can lead to a phenomenon known as alien hand syndrome. Cause JC virus infection The cause of PML is a type of polyomavirus called the JC virus (JCV), after the initials of the person (John Cunningham) from whose tissue the virus was first successfully cultured. Publications indicate 39 to 58% of the general population are seropositive for antibodies to JCV, indicating current or previous infection with the virus. Other publications put the percentage at 70 to 90% of the general population. JCV causes persistent asymptomatic infection in about one-third of the adult population, based on viral shedding into the urine from the site of asymptomatic infection in the kidney. The virus causes disease only when the immune system has been severely weakened. Immunosuppression PML is most common in people with HIV1 infection; prior to the advent of effective antiretroviral therapy, as many as 5% of people with AIDS eventually developed PML. Why PML occurs more frequently in people with AIDS than in other immunosuppressive conditions is unclear; some research suggests the effects of HIV on brain tissue, or on JCV itself, make JCV more likely to become active in the brain and increase its damaging inflammatory effects. PML can still occur in people on immunosuppressive therapy, such