Progressive multifocal leukoencephalopathy


Progressive multifocal leukoencephalopathy

Description, Causes and Risk Factors:

Abbreviation: PML

Progressive multifocal leukoencephalopathy is a fatal demyelinating disease of the central nervous system [CNS] that predominantly affects immunocompromized individuals. The etiologic agent, JC virus, is a widespread polyomavirus with a very specific target, the myelin-producing oligodendrocytes of the brain. During periods of immune suppression, the virus can be reactivated from lymphoid tissues and kidney, causing targeted myelin destruction and corresponding neurological deficits. The incidence of PML has increased in recent years, due in large part to the advent of AIDS and the growing number of immunodeficient individuals. Furthermore, previous serological studies have shown that greater than 80% of the human population has antibodies to JC virus in circulation. When combined, these statistics highlight an increasing need to establish effective treatment regimens for infected individuals as well as strategies to identify those at risk for developing PML.

The pathology of PML is caused by the cytolytic destruction of oligodendrocytes, resulting in lesions that appear initially in a sparse, asymmetric distribution. With disease progression, the foci of demyelination or plaques can enlarge to a few centimeters across and coalesce, making them visible in the brain upon gross anatomical examination. The periphery of the lesions contains astrocytes and oligodendrocytes that may be infected with JC virus, but have not yet undergone lysis. The morphology of these cells is characteristic of this disease with nuclei 2 ± 3-fold larger than normal, and often containing inclusion bodies. Electron microscopy of the intranuclear inclusions reveals a dense array of JC virus virion particles, arranged in a crystalline lattice. Other pathologic features of this disease include bizarre, enlarged astrocytes and mononuclear cell infiltration. Macrophages swollen with lipids can often be found in the lesioned areas, evidence of myelin degradation. However, recruitment of other cells involved in inflammation is rarely observed.

Two human cases of probable progressive multifocal leukoencephalopathy infection were identified in 2010 and 2011 in NS presenting as acute polyneuropathies with cognitive changes. CSF showed an inflammatory reaction with lymphocytic pleocytosis and elevated protein. Electromyography and nerve conduction studies demonstrated acute polyneuropathy in both, with prominent demyelination in one. Microbiologic investigations including culture, PCR for HSV, and enteroviruses were negative. Serology for typical arboviruses were negative. Serum IgM and PRNT (plaque reduction neutralization test) for JCV was positive. Both cases were treated with intravenous immunoglobulin with improvement, but deficits from the polyneuropathy persisted. Literature review indicated that JCV infection is often limited to a mild febrile illness which can progress to an encephalitis and/or meningitis. No reports of demyelinating polyneuropathy as a result of JCV were previously identified.

Symptoms:

Symptoms may include:

    Headaches.

  • Loss of coordination, clumsiness.

  • Loss of language ability (aphasia).

  • Memory loss.

  • Vision problems.

  • Weakness of the legs and arms that gets worse.

Diagnosis:

Differential diagnosis should consider other primary as well as opportunistic infections of CNS, other demyelinating diseases (such as multiple sclerosis), vascular lesions (e.g. ischemic stroke, HIV vasculopathy), tumors (e.g. lymphoma) and HIV encephalopathy with secondary changes in white matter.

Neuroimaging studies have been useful in determining the location and extent of the demyelinated plaques. Computerized tomography (CT) and magnetic resonance imaging (MRI) scans are the most frequently used methods of visualization. The lesions are typically non-contrast enhancing and periventricular in nature, most often located at the gray-white matter junction. Although the lesions can occur anywhere in the subcortical white matter, they appear most frequently in the parietooccipital or frontal lobes. In comparison with CT scans, MRI is the more sensitive; often revealing PML pathology where CT scans appeared normal. The extent of lesioning is also demonstrated more clearly by MRI because it is capable of detecting lesions located in the cerebellum, which is of particular interest since there has been a recent rise in reports of PML lesions located in the posterior fossa.

Other tests:

    Brain biopsy (rare).

  • Cerebrospinal fluid test for the JC virus.

Treatment:

At present, there is no specific, satisfactory treatment for PML. However, anti-HIV drugs seem to be useful in controlling PML. Since the introduction of triple combination therapy, there have been a few published reports of individual patients being given combination antiretroviral therapy when diagnosed with PML. Symptoms have improved, and in some patients, brain scans have shown improved results. For the treatment to be "highly active," though, all drugs should be new to the patient.

NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.

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