Treatment of Progressive Multifocal Leukoencephalopathy With Mirtazapine. 2016

Yvan Jamilloux, and Sébastien Kerever, and Tristan Ferry, and Christiane Broussolle, and Jérôme Honnorat, and Pascal Sève
Department of Internal Medicine, Hopital de la Croix-Rousse, Hospices Civils de Lyon, Université Claude Bernard-Lyon 1, 103 Grande rue de la Croix-Rousse, 69004, Lyon, France. yvanjamilloux@hotmail.com.

OBJECTIVE Progressive multifocal leukoencephalopathy (PML) is a rare, JC-virus-mediated, demyelinating disease with a high mortality rate. As no recommended treatment exists, mirtazapine, a potential blocker of virus entry into cells, has been empirically used. METHODS We analysed existing data on mirtazapine's efficacy to treat PML by systematically reviewing the literature since 2005, when it was first used. RESULTS Searches in PubMed, EBSCO, SCOPUS and Google Scholar between January 2005 and December 2015, identified five cohort studies and 74 case reports. No statistically significant effect of mirtazapine on PML outcome was observed in the cohort studies. From studying the case reports, mortality rate for PML was associated with the underlying circumstances, such as an older age, the use of an immunosuppressant, or PML occurring in patients with a haematological malignancy or a transplant. CONCLUSIONS Except for natalizumab-associated PML, we did not highlight any potential benefit of mirtazapine on disease outcomes. Further interventional studies are needed to confirm that 5-HT2AR inhibition is relevant to treat PML.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D007577 JC Virus A species of POLYOMAVIRUS, originally isolated from the brain of a patient with progressive multifocal leukoencephalopathy. The patient's initials J.C. gave the virus its name. Infection is not accompanied by any apparent illness but serious demyelinating disease can appear later, probably following reactivation of latent virus. Human Polyomavirus JC,JC polyomavirus,Polyomavirus, JC,John Cunningham Virus,Polyomavirus hominis 2,Polyomavirus JC, Human,Virus, John Cunningham
D007968 Leukoencephalopathy, Progressive Multifocal 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) Encephalitis, JC Polyomavirus,Progressive Multifocal Leukoencephalopathy,JC Polyomavirus Encephalopathy,Encephalopathies, JC Polyomavirus,Encephalopathy, JC Polyomavirus,JC Polyomavirus Encephalitis,Leukoencephalopathies, Progressive Multifocal,Multifocal Leukoencephalopathies, Progressive,Multifocal Leukoencephalopathy, Progressive,Progressive Multifocal Leukoencephalopathies
D008803 Mianserin A tetracyclic compound with antidepressant effects. It may cause drowsiness and hematological problems. Its mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors. Lerivon,Mianserin Hydrochloride,Mianserin Monohydrochloride,Org GB 94,Tolvon,Hydrochloride, Mianserin,Monohydrochloride, Mianserin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000069442 Natalizumab A humanized monoclonal immunoglobulin G4 antibody to human INTEGRIN ALPHA4 that binds to the alpha4 subunit of INTEGRIN ALPHA4BETA1 and integrin alpha4beta7. It is used as an IMMUNOLOGIC FACTOR in the treatment of RELAPSING-REMITTING MULTIPLE SCLEROSIS and CROHN'S DISEASE. Antegren,Tysabri
D000078785 Mirtazapine A piperazinoazepine tetracyclic compound that enhances the release of NOREPINEPHRINE and SEROTONIN through blockage of presynaptic ALPHA-2 ADRENERGIC RECEPTORS. It also blocks both 5-HT2 and 5-HT3 serotonin receptors and is a potent HISTAMINE H1 RECEPTOR antagonist. It is used for the treatment of depression, and may also be useful for the treatment of anxiety disorders. (N-Methyl-11C)mirtazapine,(S)-Mirtazapine,6-Azamianserin,Esmirtazapine,Norset,ORG 3770,ORG-3770,Org 50081,Remergil,Remeron,Rexer,Zispin,6 Azamianserin,ORG3770

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