Progressive multifocal leukoencephalopathy

] natalizumabcite web |url=http://www.newscientist.com/channel/health/dn8796.html |title=Potential risks of powerful MS drug are weighed - health - 02 March 2006 - New Scientist |accessdate=2008-01-28 |format= |work=] , chemotherapy cite journal |author=Connolly RM, Doherty CP, Beddy P, O'Byrne K |title=Chemotherapy induced reversible posterior leukoencephalopathy syndrome |journal=Lung Cancer |volume=56 |issue=3 |pages=459–63 |year=2007 |pmid=17316891 |doi=10.1016/j.lungcan.2007.01.012 |url=http://linkinghub.elsevier.com/retrieve/pii/S0169-5002(07)00050-5] , corticosteroids cite journal |author=Viallard JF, Lazaro E, Ellie E, "et al" |title=Improvement of progressive multifocal leukoencephalopathy after cidofovir therapy in a patient with a destructive polyarthritis |journal=Infection |volume=35 |issue=1 |pages=33–6 |year=2007 |pmid=17297588 |doi=10.1007/s15010-006-5103-y] , and various transplant drugs such as tacrolimus.cite journal |author=Junna MR, Rabinstein AA |title=Tacrolimus induced leukoencephalopathy presenting with status epilepticus and prolonged coma |journal=J. Neurol. Neurosurg. Psychiatr. |volume=78 |issue=12 |pages=1410–1 |year=2007 |pmid=18024699 |doi=10.1136/jnnp.2007.121806 |url=http://jnnp.bmj.com/cgi/pmidlookup?view=long&pmid=18024699]

Disease process

PML is a demyelinating disease, in which the myelin sheath covering the axons of nerve cells is gradually destroyed, impairing the transmission of nerve impulses. It affects the white matter, which is mostly composed of axons from the outermost parts of the brain (cortex). Symptoms include weakness or paralysis, vision loss, impaired speech, and cognitive deterioration. PML is similar to another demyelinating disease, multiple sclerosis, but since it destroys the cells that produce myelin (unlike MS, in which myelin itself is attacked but can be replaced), it progresses much more quickly. Most patients die within four months of onset.PML destroys oligodendrocytes and produces intranuclear inclusions.

Diagnosis

PML is diagnosed by testing for JC virus DNA in cerebrospinal fluid or in a brain biopsy specimen. Characteristic evidence of the damage caused by PML in the brain can also be detected on MRI images.

Treatment

There is no known cure. In some cases, the disease slows or stops if the patient's immune system improves; some AIDS patients with PML have been able to survive for several years, with the advent of highly active antiretroviral therapy (HAART).

AIDS patients who start HAART after being diagnosed with PML tend to have a slightly longer survival time than patients who were already on HAART and then develop PML. [Wyen, C., Hoffmann, C., Schmeisser, N., Wohrmann, A., Qurishi, N., Rockstroh, J., Esser, S., Rieke, A., Ross, B., Lorenzen, T., Schmitz, K., Stenzel, W., Salzberger, B. and Fatkenheuer, G. (2004) Progressive multifocal leukencephalopathy in patients on highly active antiretroviral therapy: survival and risk factors of death. "Journal of Acquired Immune Deficiency Syndrome" 37, 1263-1268. PMID 15385733] A rare complication of effective HAART is immune reconstitution inflammatory syndrome (IRIS), in which increased immune system activity actually increases the damage caused by the infection; though IRIS is often manageable with other types of infections, it is extremely dangerous if it occurs in PML. [cite journal |author=Vendrely A, Bienvenu B, Gasnault J, Thiebault JB, Salmon D, Gray F |title=Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy |journal=Acta Neuropathol. |volume=109 |issue=4 |pages=449–55 |year=2005 |month=April |pmid=15739098 |doi=10.1007/s00401-005-0983-y |url=]

Other antiviral agents that have been studied as possible treatments for PML include cidofovir and interleukin-2, but this research is still preliminary.

Cytarabine (also known as ARA-C), a chemotherapy drug used to treat certain cancers, has been prescribed on an experimental basis for a small number of non-AIDS PML patients. It is reported to have stabilized the neurological condition of a minority of these patients. [cite journal |author=Aksamit AJ |title=Treatment of non-AIDS progressive multifocal leukoencephalopathy with cytosine arabinoside |journal=J. Neurovirol. |volume=7 |issue=4 |pages=386–90 |year=2001 |month=August |pmid=11517422 |doi= |url=] One patient regained some cognitive function lost as a result of PML. [cite journal |author=Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D |title=Progressive multifocal leukoencephalopathy in a patient treated with natalizumab |journal=N. Engl. J. Med. |volume=353 |issue=4 |pages=375–81 |year=2005 |month=July |pmid=15947078 |doi=10.1056/NEJMoa051847 |url=]

See also

* Leukoencephalopathy
* Leukoencephalopathy with vanishing white matter
* toxic leukoencephalopathy

References

External links

* [http://www.ninds.nih.gov/disorders/pml/pml.htm Overview] at NIH
* [http://www.clevelandclinic.org/health/health-info/docs/1300/1322.asp?index=6101 Overview] at Cleveland Clinic
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