Progressive Multifocal Leukoencephalopathy

An opportunistic viral infection of the central nervous system associated with conditions that impair cell-mediated immunity (e.g., ACQUIRED IMMUNODEFICIENCY SYNDROME and other IMMUNOLOGIC DEFICIENCY SYNDROMES; HEMATOLOGIC NEOPLASMS; IMMUNOSUPPRESSION; and COLLAGEN DISEASES). The causative organism is JC Polyomavirus (JC VIRUS) which primarily affects oligodendrocytes, resulting in multiple areas of demyelination. Clinical manifestations include DEMENTIA; ATAXIA; visual disturbances; and other focal neurologic deficits, generally progressing to a vegetative state within 6 months. (From Joynt, Clinical Neurology, 1996, Ch26, pp36-7)

Also Known As:

Networked: 864 relevant articles (54 outcomes, 54 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Acquired Immunodeficiency Syndrome (AIDS)
2.	Multiple Sclerosis
3.	Crohn Disease (Crohn's Disease)
4.	Infection
5.	Opportunistic Infections (Opportunistic Infection)

Experts

1.	Koralnik, Igor J: 22 articles (10/2015 - 12/2002)
2.	Gold, Ralf: 16 articles (07/2015 - 12/2008)
3.	Kieseier, Bernd C: 14 articles (07/2015 - 02/2007)
4.	Major, Eugene O: 14 articles (01/2015 - 11/2004)
5.	Berger, Joseph R: 12 articles (12/2015 - 07/2005)
6.	Cinque, Paola: 11 articles (12/2014 - 01/2003)
7.	Stüve, Olaf: 11 articles (09/2014 - 10/2006)
8.	Clifford, David B: 10 articles (12/2015 - 01/2003)
9.	Wattjes, Mike P: 10 articles (10/2015 - 10/2013)
10.	Hartung, Hans-Peter: 10 articles (07/2015 - 02/2007)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Progressive Multifocal Leukoencephalopathy:

1.	natalizumab (Tysabri)FDA Link 04/01/2011 - "Natalizumab was shown to be highly efficacious in the treatment of MS. However, the risk of progressive multifocal leukoencephalopathy was confirmed and defined better. " 09/01/2010 - "Natalizumab is a therapy which, although associated with a 1 : 1000 risk for progressive multifocal leukoencephalopathy (PML), has been shown to be well tolerated in the adult population and may lead to disease remission in adults with highly active disease. " 11/01/2013 - "The intravenous DMT natalizumab (Tysabri; dosed monthly) provides high therapeutic efficacy and good compliance but is considered a second-line intervention because of the associated increased risk for progressive multifocal leukoencephalopathy. " 01/01/2012 - "While having shown high therapeutic efficacy, treatment by natalizumab has been linked to progressive multifocal leukoencephalopathy (PML) as a serious adverse effect. " 03/01/2012 - "This review first analyzes the experience from the early stages of the disease-modifying therapies, then, expanding on the concept of early treatment for improved outcomes, it focuses on natalizumab and its major complication, progressive multifocal leukoencephalopathy. "
2.	Mefloquine (Lariam)FDA LinkGeneric 01/15/2013 - "Although progressive multifocal leukoencephalopathy (PML) cases showing responses to mefloquine therapy have been reported, the efficacy of mefloquine for PML remains unclear. " 04/01/2011 - "Mefloquine, an antimalarial medication with efficacy against JC virus, was used to treat progressive multifocal leukoencephalopathy. " 08/01/2013 - "A study of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes." 10/01/2012 - "Pharmacokinetic considerations in the repositioning of mefloquine for treatment of progressive multifocal leukoencephalopathy." 08/01/2012 - "Favourable outcome of progressive multifocal leukoencephalopathy with mefloquine treatment in combination with antiretroviral therapy in an HIV-infected patient."
3.	cidofovir (Vistide)FDA Link 06/01/2003 - "There is growing evidence suggesting cidofovir's effectiveness against progressive multifocal leukoencephalopathy (PML) caused by a reactivation of JC-virus. " 09/06/2002 - "To assess the safety, tolerability and effect of cidofovir for HIV-1 associated progressive multifocal leukoencephalopathy. " 06/01/2001 - "Use of cidofovir in progressive multifocal leukoencephalopathy." 05/01/2001 - "The effects of cidofovir on progressive multifocal leukoencephalopathy: an MRI case study." 01/01/2001 - "We describe the first reported human immunodeficiency virus (HIV)-seronegative patient treated with cidofovir for progressive multifocal leukoencephalopathy (PML). "
4.	AntibodiesIBA 06/01/2013 - "A second-generation ELISA (STRATIFY JCV™ DxSelect™) for detection of JC virus antibodies in human serum and plasma to support progressive multifocal leukoencephalopathy risk stratification." 06/01/1997 - "Detection of CSF-specific oligoclonal antibodies to recombinant JC virus VP1 in patients with progressive multifocal leukoencephalopathy." 04/01/1973 - "Prevalence of antibodies in human sera against JC virus, an isolate from a case of progressive multifocal leukoencephalopathy." 09/23/2015 - "Broadly neutralizing human monoclonal JC polyomavirus VP1-specific antibodies as candidate therapeutics for progressive multifocal leukoencephalopathy." 09/01/2010 - "A study was undertaken to establish an enzyme-linked immunosorbent assay (ELISA) to detect JC virus (JCV)-specific antibodies in multiple sclerosis (MS) patients, and to evaluate its potential utility for identifying patients at higher or lower risk (ie, risk stratification) of developing progressive multifocal leukoencephalopathy (PML). "
5.	N-acetyltalosaminuronic acid (NAT)IBA 01/01/2013 - "While pivotal and postmarketing studies have showed considerable and sustained efficacy of NAT in RRMS, the increasing incidence of therapy-associated progressive multifocal leukoencephalopathy (PML), a brain infection caused by the John Cunningham virus (JCV), is a risk associated with long-term therapy. " 01/01/2014 - "Therapeutic efficacy has to be weighed against the risk of developing potentially fatal progressive multifocal leukoencephalopathy (PML), an opportunistic infection by JC-virus (JCV) with an incidence of 3.4/1000 (95% CI 3.08-3.74) in Nat treated MS patients. " 07/01/2015 - "Progressive multifocal leukoencephalopathy (PML) is the most feared complication when natalizumab (NAT) is used in the treatment of relapsing multiple sclerosis (MS). " 01/01/2014 - "Little is known about seizures in natalizumab-associated progressive multifocal leukoencephalopathy (NAT-PML). "
6.	nitazoxanide (NTZ)FDA Link 03/01/2014 - "Despite evidence to support its use as first-line therapy, risk of NTZ-associated progressive multifocal leukoencephalopathy (PML) has largely contributed to it being relegated to a second-line position. " 11/01/2007 - "In February 2005, the production of NTZ was suspended by Producer Firms on account of the occurrence of two serious adverse events: two patients who had been taking NTZ manifested a progressive multifocal leukoencephalopathy; the patients showed progressive neurologic deterioration, initially believed to be a worsening of the pre-existing condition of MS. In March 2006, the Advisory Panel of the Food and Drug Administration voted unanimously in favor of the return of NTZ on the market with the majority of the panel also recommending that NTZ be considered the first choice of treatment in MS. NTZ should only be administered to patients who are not taking other medicines for MS and only in highly specialized centers. " 01/01/2015 - "This review provides an update on the efficacy of an inhibition of relapses, adverse effects including progressive multifocal leukoencephalopathy, treatment after NTZ discontinuation, and body weight based treatment. " 01/01/2015 - "A correlation between CD62LCD4+ T cells low expression and progressive multifocal leukoencephalopathy (PML) development has been suggested in multiple sclerosis (MS) patients treated with NTZ. " 11/01/2007 - "We must conclude that 1) in remittent MS, between one attack and another (successive re-infection of bordetella pertussis) there are no CICs that can precipitate into the central nervous system, and thus the treatment with NTZ is useless and superfluous; 2) in chronic-progressive MS, the final result of the treatment with NTZ will be that of transforming MS into lateral amyotrophic sclerosis or progressive multifocal leukoencephalopathy; 3) in progressive MS, however, NTZ can be of considerable use in the first 2 months of antibiotic treatment to prevent the formation of new patches or the re-activation of previous ones. "
7.	Risperidone (Risperdal Consta)FDA LinkGeneric 10/01/2008 - "These data indicate that risperidone does not inhibit JCV(Mad1) attachment, internalisation, and replication in PHFG cells, and 5HT(2A)R blockers may not be effective in treating progressive multifocal leukoencephalopathy (PML)." 05/01/2007 - "Progressive multifocal leukoencephalopathy in a haploidentical stem cell transplant recipient: a clinical, neuroradiological and virological response after treatment with risperidone." 06/01/2007 - "Treatment schedules for 5-HT2A blocking in progressive multifocal leukoencephalopathy using risperidone or ziprasidone." 05/01/2007 - "Risperidone-induced reduction in JC viruria as a surrogate marker for efficacy against progressive multifocal leukoencephalopathy and hemorrhagic cystitis."
8.	DNA (Deoxyribonucleic Acid)IBA 01/15/2004 - "MRI study of the brain suggested a diagnosis of progressive multifocal leukoencephalopathy (PML), which was confirmed by JC virus DNA detection on CSF by polymerase chain reaction (PCR). " 12/16/2000 - "In recent years there has been a notable increase in the number of patients diagnosed as having progressive multifocal leukoencephalopathy due to the possibility of carrying out studies to detect the DNA of the JC virus by polymerase chain reaction techniques. " 06/01/1996 - "DNA amplification in glial cells of progressive multifocal leukoencephalopathy: an image analysis study." 01/15/2015 - "By applying 454 sequencing on NCCR DNA amplified from body fluid samples (urine, plasma, and cerebrospinal fluid [CSF]) from 19 progressive multifocal leukoencephalopathy (PML) patients, we attempted to reveal the composition of the JC polyomavirus population (the quasispecies, i.e., the whole of the consensus population and minor viral variants) contained in different body compartments and to better understand intrapatient viral dissemination. " 01/01/2014 - "Quantitative PCR testing for JC virus (JCV) DNA in the cerebrospinal fluid (CSF) is one of the diagnostic standards for progressive multifocal leukoencephalopathy (PML). "
9.	rituximab (Mabthera)FDA Link 07/01/2010 - "Results of small studies have suggested that rituximab is usually well tolerated but that adverse events (such as severe mucocutaneous reactions, fatal infusion reactions, progressive multifocal leukoencephalopathy, and bowel perforation) can occur. " 03/01/2015 - "A concern for developing progressive multifocal leukoencephalopathy (PML), which is caused by John Cunningham virus (JCV), has been suggested particularly in patients treated long term with rituximab. " 11/01/2014 - "Both progressive multifocal leukoencephalopathy (PML) and posterior reversible encephalopathy syndrome (PRES) have been reported as complications of rituximab therapy. " 01/01/2014 - "The rare but fatal progressive multifocal leukoencephalopathy linked to the use of rituximab has to be noted. " 06/01/2013 - "Progressive multifocal leukoencephalopathy in an HIV-negative patient following treatment with rituximab."
10.	Cytarabine (Cytosar-U)FDA LinkGeneric 01/01/1990 - "Progressive multifocal leukoencephalopathy-remission with cytarabine." 08/01/1980 - "We report an instance of progressive multifocal leukoencephalopathy in which cytarabine administration was successful as demonstrated by clinical course and follow-up computerized tomography studies. " 08/01/2001 - "Convection-enhanced intraparenchymal delivery (CEID) of cytosine arabinoside (AraC) for the treatment of HIV-related progressive multifocal leukoencephalopathy (PML)." 03/01/1999 - "We describe the clinical and virological outcome of human immunodeficiency virus-infected patients with progressive multifocal leukoencephalopathy (PML) treated with cytarabine. " 11/01/1996 - "ACTG 243 closed early after finding that treatment with cytarabine in persons with progressive multifocal leukoencephalopathy (PML) offers no benefit and no statistical difference was found in survival rates. "

Therapies and Procedures

1.	Highly Active Antiretroviral Therapy (HAART) 02/01/2007 - "Visual loss secondary to acquired immunodeficiency virus-related progressive multifocal leukoencephalopathy demonstrating clinical improvement with highly active antiretroviral therapy." 01/01/2003 - "The effect of highly active antiretroviral therapy-induced immune reconstitution on development and outcome of progressive multifocal leukoencephalopathy: study of 43 cases with review of the literature." 04/01/2011 - "Progressive multifocal leukoencephalopathy (PML) has been traditionally associated to severe immunosuppression and described mainly in highly active antiretroviral therapy (HAART)-naïve patients with a low lymphocyte CD4+ count. " 04/01/2011 - "Progressive multifocal leukoencephalopathy in an HIV patient receiving successful long-term HAART." 06/01/2010 - "Use of diffusion-weighted imaging to evaluate the initial response of progressive multifocal leukoencephalopathy to highly active antiretroviral therapy: early experience."
2.	Therapeutics 08/01/2001 - "The design of a comparative treatment trial to evaluate the efficacy of therapeutics for progressive multifocal leukoencephalopathy (PML) is outlined. " 08/01/2001 - "Designs for clinical trials to test the efficacy of therapeutics in progressive multifocal leukoencephalopathy." 09/23/2015 - "Broadly neutralizing human monoclonal JC polyomavirus VP1-specific antibodies as candidate therapeutics for progressive multifocal leukoencephalopathy." 01/01/2014 - "Multiple sclerosis (MS) therapeutics entered a new era after the development of anti-JC virus (anti-JCV) antibody assay that assesses the risk of development of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab. "
3.	Aftercare (After-Treatment) 09/01/2011 - "Hidden in plain view: emergence of progressive multifocal leukoencephalopathy after treatment of CNS toxoplasmosis." 01/01/2009 - "New cases of progressive multifocal leukoencephalopathy after treatment with natalizumab." 07/01/2007 - "Recently, JC-polyomavirus (JCV) was studied after 3 cases of progressive multifocal leukoencephalopathy (PML) were found after treatment with natalizumab. " 11/08/2005 - "Sustained recovery of progressive multifocal leukoencephalopathy after treatment with IL-2." 05/01/2007 - "Progressive multifocal leukoencephalopathy in a haploidentical stem cell transplant recipient: a clinical, neuroradiological and virological response after treatment with risperidone."
4.	Peripheral Blood Stem Cell Transplantation (Peripheral Stem Cell Transplantation) 02/15/2002 - "We report the first 2 cases of progressive multifocal leukoencephalopathy caused by JC papovavirus after autologous peripheral blood stem cell transplantation and a case each of cytomegalovirus retinitis and pneumonitis. " 01/01/2014 - "Significant improvement following combination treatment with mefloquine and mirtazapine in a patient with progressive multifocal leukoencephalopathy after allogeneic peripheral blood stem cell transplantation."
5.	Radiotherapy 07/13/2006 - "Remission of AIDS-associated progressive multifocal leukoencephalopathy with combined cidofovir and radiotherapy: a case report."