Progressive Multifocal Leukoencephalopathy

Introduction

Characteristics of Disease:

Progressive Multifocal Leukoencephalopathy is a rare and usually fatal disease that infects and kills oligodendrocytes in the white matter of the brain. Oligodendrocytes are a part of the central nervous system and are responsible for manufacturing the myelin that encloses and insulates some of the never cells. (micro text book p 697) Since PML affects the nerves that send/receive information from various body parts and organs the symptoms vary. According to right diagnosis.com some of these symptoms include:

Mental deterioration

Vision loss

Speech disturbances

Ataxia

Paralysis

Coma

Seizures

Muscle weakness

Hemiparesis

Facial weakness

Dyshasis

Memory failure

Cognition failure

Most people are exposed to the JC polyoma virus by the age of 15, but most healthy individuals build up immunity to the virus. (Bauman et al. 696) When the immune system becomes compromised then the virus can attack the body. The disease is usually seen in patients who are receiving chronic corticosteroid or immunosuppressive therapy such as organ transplants, cancer, and AIDS patients. The JVC virus is thought to be reactivated in those individuals who have autoimmune disorders such as systemic lupus erythematosis, rheumatoid arthritis, and multiple sclerosis and are also undergoing biological treatment. PML is commonly seen in HIV-1/AIDS patients. (NINDS Progressive Multifoca ...)

History

PML was an infrequent disease until the AIDS pandemic in 1981. It was first discovered in 1958, and until 1984 only about 230 cases had been identified. A majority, 95%, of these cases had a condition which predisposed them to PML. About 5 cases were reported as being associated with AIDS. People with lymphoproliferative (a B-cell disorder) disorders made up the majority, 66%, of the reported cases. In the late 1980's the number of PML cases increased significantly. Before the antiretroviral therapies were given to HIV patients, PML was only seen in 5% of the cases. After the introduction of the therapy the amount of PML cases increased 4-fold between 1979-1989. It was found that 87% of the PML cases in 1993, in the US, had the underlying disease AIDS. (Berger)

Current Status

There are diagnostics tests that can be performed to a confirm Multifocal Leukoencephalopathy diagnosis. Multiple diffuse asymmetrical lesions can usually be seen in the subcortical hemispheric white matter and cerebellar peduncles by an MRI. Other signs that may show on an MRI are lesions in the grey matter, reactive gliosis and large, multinucleated astrocytes in the affected area. (Gudesblatt) Image 1 shows a MRI scan with lesions in the periventricular and subcortical white matter. Image 2 is from a brain biopsy sample with enlarged, bizarre eosinphilic astrocytes were abundant. (Cole et. al.)

Figure 1

"MRI findings are well-demarcated, asymmetric lesions in periventricular and subcortical white matter. The lesions are characteristically hyperintense on FLAIR/T2-weighted images, hypointense on T1-weighted images, and non-enhancing with gadolinium and do not create mass effect.4 JCV DNA can often be isolated from CSF by PCR." (Cole et. al.)

Figure 2."Brain biopsy sample showing central oligodendrocyte with viral inclusion bodies giving a smudged appearance to nucleus. At other foci, enlarged, bizarre eosinophilic astrocytes were abundant. Confirmation of JC virus infection involved additional immunohistochemical analysis (hematoxylin and eosin stain, original magnification ×1000)." (Cole et. al.)

A spinal tap maybe performed to test the spinal fluid to test for the existence of JCV DNA and can be used to confirm diagnosis of the disease. Blood and urine test may also be performed for detection of JCV; however, the existence of PML is minor even with serial measures. Blood tests have shown to be only fifty percent effective in the diagnosis of PML in AIDS patients. Polyconal antibody test, Enzyme linked immunosorbent assays (ELISA) have been used for diagnosis of PML, but due to some patients having low or undetectable JVC in the CSF, they have not always been effective diagnostics tools. A MRI along with symptoms have proven to be the best tool for diagnosing the disease .A brain biopsy may also be performed, but due to the risks involved, are rare or performed during an autopsy after a patient has died. (Gudesblatt,)

To date the only effective treatments are dangerous and would be highly toxic, although it has been found that discontinuing certain monoclonal antibody therapies can slow the progression of the disease. It has also been shown that removal of the therapeutic agents, those that put patients at risk can be beneficial to those patients