progressive multifocal leukoencephalopathy


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Related to progressive multifocal leukoencephalopathy: subacute sclerosing panencephalitis

Progressive Multifocal Leukoencephalopathy

 

Definition

Progressive multifocal leukoencephalopathy (PML) is a rapidly progressive neuromuscular disease caused by opportunistic infection of brain cells (oligodendrocytes and astrocytes) by the JC virus (JCV).

Description

PML is an opportunistic infection associated with AIDS and certain cancers. It occurs in people with inadequate immune response and carries a poor prognosis. The incidence of PML, once quite rare, is rising as the numbers of people living with persistently compromised immune systems rises. An estimated 2-7% of people with HIV disease will develop PML. The infection also occurs among people undergoing long-term chemotherapy for cancer. PML is not considered a contagious disease. According to the Centers for Disease Control definition of AIDS, PML in the presence of HIV infection is sufficient to form a diagnosis of AIDS.

Causes and symptoms

Although at least 80% of the adults in the United States have been exposed to JC virus (as evidenced by the presence of antibodies to this virus), very few will develop PML. Little is certain about what causes JCV to produce active disease, but the virus persists in the kidneys of otherwise healthy people without making them ill. Recent evidence suggests that after prolonged compromise of the immune system, the virus changes into a form that can reach brain tissue and cause disease. In PML, the JCV infects and kills the cells (oligodendrocytes) that produce myelin, which is needed to form the sheath that surrounds and protects nerves.
About 45% of people with PML experience vision problems, most often a blindness affecting half of the visual field of each eye. Mental impairment affects about 38% of people with PML. Eventually, about 75% experience extreme weakness. Other symptoms include lack of coordination, paralysis on one side of the body (hemiparesis), and problems in speaking or using language.

Diagnosis

Diagnosis is difficult, but usually relies on a neurologist and radiologist assessing the white matter of the brain on a computed tomography scan or a magnetic resonance imaging (MRI). Tests of the cerebrospinal fluid can help distinguish between PML and other diseases, such as multiple sclerosis and acute hemorrhagic leukoencephalopathy. The rapid clinical progression in immunocompromised patients is another distinguishing factor.

Treatment

Currently, there is no known cure for PML, although it sometimes responds to treatment in patients with AIDS who are taking anti-HIV drugs (such as AZT, alpha-interferon, and peptide T). Although several agents have shown some potential in the last few years, such as the highly toxic cancer drug cytarabine, none are safe enough or sufficiently effective to be approved for PML.

Prognosis

PML is usually a very aggressive disease. The time between the onset of symptoms and death can be as little as one to six months. However, some patients infected with HIV have improved without receiving treatment specifically for PML.

Resources

Periodicals

Royal III, Walter. "Update on Progressive MultifocalLeukoencephalopathy." The Hopkins HIV Report 9 (March 1997).

Key terms

Multifocal — Having many focal points. In progressive multifocal leukoencephalopathy, it means that damage caused by the disease occurs at multiple sites.
Opportunistic infection — A illness caused by infecting organisms that would not be able to produce disease in a person with a healthy immune system, but are able to take advantage of an impaired immune response.

pro·gress·ive mul·ti·fo·cal leu·ko·en·ceph·a·lop·a·thy (PML),

a rare, afebrile, fatal disease caused by the human polyomavirus JC; clinically characterized by progressive, widespread neurologic deficits, including impairment of higher cortical functions, visual problems, hemiparesis, and cerebellar dysfunction; pathologically consists of multiple disseminated areas of demyelination surrounded by markedly altered neuroglia; typically occurs in patients with disturbed immune systems (for example, those with AIDS, leukemia, lymphoma, or those receiving immunosuppressive therapy).

progressive multifocal leukoencephalopathy

A demyelinising CNS lesion, caused by a human papovavirus, usually JC virus (rarely also BK virus), which affects ±4% of AIDS patients.
 
Clinical
Dementia, spastic paralysis, blindness, opportunistic infections; PML occurs in immunocompromised hosts—e.g., with leukaemia or AIDS.

Management
Cytarabine; antiretrovirals are very ineffective.

progressive multifocal leukoencephalopathy

Neurology A demyelinizing CNS lesion, caused by a human papovavirus, usually JC virus, rarely also BK virus, affecting ±4% of AIDS Pts Clinical Dementia, spastic paralysis, blindness, opportunistic infections; PML occurs in immunocompromised hosts–eg, with leukemia, AIDS Management Cytarabine, antiretrovirals are useless

pro·gres·sive mul·ti·fo·cal leu·ko·en·ceph·a·lop·a·thy

(PML) (prŏ-gres'iv mŭl'tē-fō'kăl lū'kō-en-sef'ă-lop'ă-thē)
A rare, subacute, afebrile disease characterized by areas of demyelinization surrounded by markedly altered neuroglia, including inclusion bodies in glial cells; it occurs usually in people with AIDS, leukemia, lymphoma, or other debilitating diseases, or in those who have been receiving immunosuppressive treatment. Caused by JC virus, a human polyoma virus.
References in periodicals archive ?
The report reviews key players involved Progressive Multifocal Leukoencephalopathy therapeutics and enlists all their major and minor projects
Detection of JC virus by anti-VP1 immunohistochemistry in brains with progressive multifocal leukoencephalopathy.
Progressive multifocal leukoencephalopathy and retroviral encephalitis in acquired immunodeficiency syndrome.
2000) and the treatment of progressive multifocal leukoencephalopathy caused by the JC virus (Segarra-Newnham & Vodolo, 2001).
As with most HIV-associated comorbidities, minimizing viral replication and immune suppression remains the most effective approach to reducing the debilitating and often fatal effects of progressive multifocal leukoencephalopathy.
Progressive multifocal leukoencephalopathy revisited: Has the disease outgrown its name?
JC virus granule cell neuronopathy: a novel clinical syndrome distinct from progressive multifocal leukoencephalopathy.
Both patients had been on natalizumab monotherapy for more than 1 year at the time that progressive multifocal leukoencephalopathy (PML) was diagnosed, although one had been treated in the past with azathioprine and [beta]-interferons, according to the FDA.
The good and evil of HAART in HIV-related progressive multifocal leukoencephalopathy.
Clinical vigilance for early signs of progressive multifocal leukoencephalopathy is a cornerstone of the mandatory risk minimization plan that will be in place for natalizumab's return to the market for treating patients with relapsing forms of multiple sclerosis.
A number of diseases--including HIV encephalitis, progressive multifocal leukoencephalopathy (PML), toxoplasmosis, lymphoma, and cryptococcal infection--have clinical presentations ranging from subtle personality and mental status changes and difficulty with concentration, depression, and memory loss to profound confusion that progresses to dementia.
due to an increased risk of an opportunistic viral infection, progressive multifocal leukoencephalopathy (PML), TYSABRI is generally recommended for people living with relapsing forms of MS whose disease is not responding to, or who are unable to tolerate, an alternative therapy regardless of JCV status.

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