Progressive multifocal

Adelman B, Sandrock A, Panzara MA (2005) Natalizumab and progressive multifocal leukoen-cephalopathy. N Engl J Med 353 432-433... 

Progressive multifocal leukoencephalopathy (PML) is historically a rare demyelinating disease that is usually associated with disorders of the reticuloendothelial system, neoplasias and immunosuppressive therapy [1, 2]. However, it has become more important in clinical medicine because it is frequently seen as an opportunistic secondary infection in immunocompromised persons with AIDS. PML is characterized by focal lesions that are noninflammatory and caused by infection of oligodendrocytes with the JC papovavirus. 

NRPE N-retinylidene phosphatidylethanolamine PML progressive multifocal leukoencephalopathy... 

Progressive multifocal leukoencephalopathy Salmonella septicemia, recurrent Toxoplasmosis of brain Wasting syndrome due to HIV... 

Natalizumab was approved by the U.S. FDA for the treatment of MS in November 2004, and is being evaluated in Phase 3 clinical trials for IBD and CD.105 Based on Phase 3 clinical trials in MS patients, natalizumab appeared to be safe, since an increased rate of infection was not observed after 1 year of treatment.106 The safety of combined treatment with immunosuppressants, other than short courses of corticosteroids, was not evaluated and was not recommended because of the potential for an increased risk of infections. Flowever, barely three months after its approval, natalizumab was voluntarily withdrawn from the MS market by its manufacturer and all ongoing clinical trials were suspended due to the occurrence of a rare neurological disease, progressive multifocal leukoencephalopathy (PML), in 3 out of approximately 3,000 patients enrolled in clinical trials (2 in MS and 1 in CD).107 108 109... 

Van Assche, G. et al., Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn s disease, N. Engl. J. Med., 353, 2005. 

Extrapuhnonary cryptococcosis including meningitis Disseminated non-tuberculous mycobacteria infection Progressive multifocal leukoencephalopathy (PML)... 

Cidofovir is approved for the treatment and prophylaxis of CMV retinitis in AIDS patients. It has also been used in the treatment of acyclovir-resistant (viral thymidine kinase-dehcient) HSV infections, polyomavirus-associated progressive multifocal leukoencephalopathy, condylomata acuminata (anogenital warts), and mollus-cum contagiosum. 

Natalizumab has shown significant efficacy for a subset of patients with moderate to severe Crohn s disease. Unfortunately, in initial clinical trials of patients with Crohn s disease and multiple sclerosis, 3 of 3100 patients treated with natalizumab developed progressive multifocal leukoencephalopathy due to reactivation of a human... 

Other potential uses of cidofovir that are currently under investigation include treatment of the polyomavirus-associated progressive multifocal leukoencephalopathy syndrome in patients with AIDS, postexposure prophylaxis against smallpox, and topical treatment of molluscum contagiosum. Topical cidofovir is not currently available in a standardized preparation. 

Langer-Gould, A., S.W. Atlas, A.J. Green, A.W. Bollen, and D. Pelletier. 2005. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. 

Natalizumab (Tysabri), an anti-a4 integrin monoclonal antibody approved for the treatment of multiple sclerosis, was recently withdrawn from the market temporarily due to cases of progressive multifocal leukoencephalopathy, a demyelinating disease of the central nervous system associated with immunosuppression [32], These cases highlight our incomplete understanding of the immune system and the translation of preclinical results to humans. 

MYCOPHENOLATE NATALIZUMAB T risk of infections including progressive multifocal leuko-encephalopathy, a potentially fatal virus infection of the brain Due to additive immunosuppressant effects. Natalizumab inhibits migration of leukocytes into the CNS Avoid co-administration... 

Case Study 2 Intraventricular Administration of Cytosine Arahinoside for the Treatment of JC Virus Infection in Patients with Progressive Multifocal Leuko encephalopathy... 

This approach has been explored in attempts to treat progressive multifocal leukoencephalopathy/ a rapidly fatal disease caused by the JC virus and characterized by regions of central nervous system demyelination and markedly altered neuroglia. The virus is known to be sensitive in vitro to the action of cytosine arabi-noside (ARA-C) concentrations of 40 M (10 pg/mL) or more (12). Because the agent crosses the blood-brain barrier slowly Hall et al. (13) designed a study to test whether intraventricular/intrathecal administration of ARA-C could successfully treat JC virus in humans. ARA-C was administered as a bolus into the cerebrospinal fluid (CSF) space at the initial rate of 50 mg every 7 days. This ARA-C regimen was found to be... 

Hall CD, Dafni U, Simpson D, Clifford D, Wetherill PE, Cohen B, McArthur J, Hollander H, Yainnoutsos C, Major E, Millar L, Timpone J. Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. N Engl J Med 1998 338 1345-51. 

While inflammation is associated negatively with vasculitis and autoimmune disease, it is also necessary to protect normal cells from viral and bacterial infection. Many of the therapies that act positively as immunosuppressants have an initial inflammatory response. While lENp is an effective therapy in the inflammatory phases of MS, the initial response to each injection is an increase in inflammatory cytokines, IL-2 and lENy (Elliott et al., 2001). Conversely, natalizumab a therapy that show ed great potential in phase EE trials for aggressive MS by blocking activated lymphocyte trafficking into the CNS was withdrawn because of deaths due to progressive multifocal leukoencephalopathy. 

Kleinsclrmidt-DeMasters BK, Tyler KL (2005) Progressive multifocal leuko-encephalopathy complicating treatment with natali-zumab and interferon beta-la for multiple sclerosis. N Engl J Med 353 369-374. 

Nelson PK, Masters LT, Zagzag D, Kelly PJ (1999) Angiographic abnormalities in progressive multifocal leukoencephalopathy An explanation based on neuropathologic findings. Am J Neuroradiol 20 487 94. 

Among 18 patients with chronic lymphocytic leukemia, one with a long-lasting lymphocytopenia died 3 months after treatment, owing to progressive multifocal leuko-encephalopathy papovavirus was isolated from the cerebrospinal fluid (12). 

Progressive multifocal leukoencephalopathy is sometimes associated with Wegener s granulomatosis, but one case occurred in a patient who was taking low-dose cyclophosphamide, with subsequent significant improvement on withdrawal of the drug (SEDA-19, 347). 

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