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07-SEPTEMBER-2008 03:17:44 - Progressive multifocal leukoencephalopathy Progressive multifocal leukoencephalopathy Classification and external resources ICD-10 A81.2 ICD-9 046.3 DiseasesDB 10718 MedlinePlus 000674 eMedicine radio/573 MeSH D007968 Progressive multifocal leukoencephalopathy PML, also known as progressive multifocal leukoencephalitis, is a rare and usually fatal viral disease that is characterized by progressive damage -pathy or inflammation -itis of the white matter leuko- of the brain -encephalo- at multiple locations multifocal. It occurs almost exclusively in people with severe immune deficiency, e.g. transplant patients on immunosuppressive medications, or AIDS patients. Contents 1 Cause 2 Contributing causes 3 Disease process 4 Diagnosis 5 Treatment 6 See also 7 References 8 External links Cause The cause of PML is a type of polyomavirus called the JC virus JCV, after the initials of the patient in whom it was first discovered. The virus is widespread, with 86% of the general population presenting antibodies, but it usually remains latent, causing disease only when the immune system has been severely weakened. About 2-5% of AIDS patients develop PML. It is unclear why PML occurs more frequently in AIDS than in other immunosuppressive conditions; some research suggests that 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.1 See also recent announcement by Roche US Pharm regarding PML and CellCept http://www.fda.gov/cder/drug/early_comm/mycophenolate.htm Contributing causes There are case reports of PML being caused by pharmacological agents, although there is some speculation this could be due in part to the existing impaired immune response or 'drug combination therapies' rather than individual drugs. These include rituximab2, infliximab,3 natalizumab4, chemotherapy 5, corticosteroids 6, and various transplant drugs such as tacrolimus.7 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.8 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.9 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.10 One patient regained some cognitive function lost as a result of PML.11 See also Leukoencephalopathy Leukoencephalopathy with vanishing white matter toxic leukoencephalopathy References ^ Berger JR 2003. Progressive multifocal leukoencephalopathy in acquired immunodeficiency syndrome: explaining the high incidence and disproportionate frequency of the illness relative to other immunosuppressive conditions. J. Neurovirol. 9 Suppl 1: 38-41. doi:10.1080/13550280390195261 inactive 2008-06-25. PMID 12709870. ^ Off-Label Use of Rituxan Linked to Fatal Leukoencephalopathy. ^ Lavagna A, Bergallo M, Daperno M, et al 2007. Infliximab and the risk of latent viruses reactivation in active Crohn's disease. Inflamm. Bowel Dis. 13 7: 896-902. doi:10.1002/ibd.20131. PMID 17345605. ^ Potential risks of powerful MS drug are weighed - health - 02 March 2006 - New Scientist. Retrieved on 2008-01-28. ^ Connolly RM, Doherty CP, Beddy P, O'Byrne K 2007. Chemotherapy induced reversible posterior leukoencephalopathy syndrome. Lung Cancer 56 3: 459-63. doi:10.1016/j.lungcan.2007.01.012. PMID 17316891. ^ Viallard JF, Lazaro E, Ellie E, et al 2007. Improvement of progressive multifocal leukoencephalopathy after cidofovir therapy in a patient with a destructive polyarthritis. Infection 35 1: 33-6. doi:10.1007/s15010-006-5103-y. PMID 17297588. ^ Junna MR, Rabinstein AA 2007. Tacrolimus induced leukoencephalopathy presenting with status epilepticus and prolonged coma. J. Neurol. Neurosurg. Psychiatr. 78 12: 1410-1. doi:10.1136/jnnp.2007.121806. PMID 18024699. ^ 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 ^ Vendrely A, Bienvenu B, Gasnault J, Thiebault JB, Salmon D, Gray F April 2005. Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy. Acta Neuropathol. 109 4: 449-55. doi:10.1007/s00401-005-0983-y. PMID 15739098. ^ Aksamit AJ August 2001. Treatment of non-AIDS progressive multifocal leukoencephalopathy with cytosine arabinoside. J. Neurovirol. 7 4: 386-90. PMID 11517422. ^ Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D July 2005. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N. Engl. J. Med. 353 4: 375-81. doi:10.1056/NEJMoa051847. PMID 15947078. External links Overview at NIH Overview at Cleveland Clinic HIV-1 Associated Opportunistic Infections: PML at eMedicine MedlinePlus Encyclopedia Progressive multifocal leukoencephalopathy v d e Infectious diseases - Virus diseases A80-B34, 042-079 CNS Encephalitis/ meningitis DNA virus: Progressive multifocal leukoencephalopathy RNA virus: Subacute sclerosing panencephalitis - Lymphocytic choriomeningitis - Tick-borne meningoencephalitis unknown: Encephalitis lethargica Eye DNA virus: Cytomegalovirus retinitis Other RNA virus: Rabies - Myelitis: Poliomyelitis Post-polio syndrome - Tropical spastic paraparesis Skin and mucous membrane lesions DNA virus, Herpesviridae: Herpes simplex - Chickenpox - Herpes zoster - KSHV DNA virus, other: Poxviridae Smallpox, Monkeypox, Cowpox, Vaccinia, Molluscum contagiosum - exanthem Roseola, Fifth disease - HPV Wart RNA virus: exanthem Measles, Rubella - picornavirus Hand, foot and mouth disease, Foot-and-mouth disease Digestive system Hepatitis DNA virus: B RNA virus: A - D - C - E - G Gastroenteritis DNA virus: Adenovirus RNA virus: Rotavirus - Norovirus - Astrovirus - Coronavirus Respiratory system RNA virus, IV: Acute viral nasopharyngitis - Severe acute respiratory syndrome RNA virus, V: Influenza/Avian influenza - Human parainfluenza viruses - RSV - hMPV Other/varied: Infectious mononucleosis - Viral pneumonia Sexually transmitted DNA virus: HPV Genital warts, Cervical cancer RNA virus, retrovirus: HIV AIDS, AIDS dementia complex - Adult T-cell leukemia Oncovirus DNA virus: Hepatitis B - HPV - Kaposi's sarcoma-associated herpesvirus RNA virus: Hepatitis C - HTLV Systemic DNA virus: Cytomegalovirus RNA virus: Mumps - Bornholm disease - Coxsackie B Retrieved from http://en..org/wiki/Progressive_multifocal_leukoencephalopathy Categories: Neurological disorders | Mental disorders due to a general medical conditionHidden category: Pages with DOIs broken since 2008 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Français Bahasa Indonesia Italiano Nederlands 日本語 Polski This page was last modified on 6 August 2008, at 10:27
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