Determinants of survival in progressive multifocal leukoencephalopathy

Marzocchetti, Angela; Tompkins, Troy; Clifford, David B.; Gandhi, Rajesh T.; Kesari, Santosh; Berger, Joseph R.; Simpson, David M.; Prosperi, Mattia; Luca, Andrea De; Koralnik, Igor J.

doi:10.1212/wnl.0b013e3181c0d4a1

Cited by 155 publications

(108 citation statements)

References 21 publications

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“…Interestingly, the development of IRIS has no impact in the outcome of PML as observed in a recent study 23 .…”

mentioning

confidence: 63%

Progressive multifocal leukoencephalopathy: new concepts

Lima

2013

Arq. Neuro-Psiquiatr.

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Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the CNS caused by reactivation of JC virus (JCV). Primary infection occurs in childhood and it is asymptomatic in most patients. Thereafter, the virus remains latent in the kidney, bone marrow and lymphoid organs, but, in a setting of cellular immunosuppression, the virus reactivates, spreads to the central nervous system (CNS), leading to infection of oligodendrocytes and demyelination 1 . Most often, PML presents with motor deficits, visual disturbances and cognitive impairment, in a subacute evolution. On MRI, lesions are hyperintense on T2-weighted and Fluid attenuated inversion recovery (FLAIR) sequences and located predominantely in the subcortical white matter of the cerebral hemispheres and cerebellar peduncles 2 . Originally, PML was observed in patients with advanced HIV infection, lymphoproliferative disorders and transplant recipients. However, the widespread use of HIV antiretroviral drugs and new selective immunomodulatory and immunosuppressive medications, such as Rituximab and Natalizumab, had recently modified the epidemiology, clinical presentation and prognosis of PML 3 . Herein, we discuss the new concepts on PML, emphasizing the recent modification in the epidemiology, the impact of new immunomodulatory treatments in the disease, PML-IRIS, new treatment strategies and other JCV related CNS diseases. EpidemiologyFrom the 1958 to 1980`s, PML was observed mostly in patients being treated with corticosteroids and other immunosuppressive drugs, as well as individuals with hematological malignancies. A review of the literature in 1984 revealed only 230 cases, most of them associated with hematological diseases 4 . The emergence of AIDS changed the PML ABStrACt Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the CNS caused by reactivation of JC virus (JCV) in a setting of cellular immunosuppression. Originally, PML was observed in patients with advanced HIV infection, lymphoproliferative disorders and transplant recipients. However, the widespread use of HIV antiretroviral drugs and the new selective immunomodulatory and immunosuppressive medications, such as Rituximab and Natalizumab, has recently modified the epidemiology, clinical presentation and prognosis of PML. Herein, we discuss the new concepts on PML, emphasizing the recent modification in the epidemiology; the impact of new immunomodulatory treatments in the disease, PML-IRIS (Immune reconstitution inflammatory síndrome), new treatment strategies and other JCV related CNS diseases.Keywords: leukoencephalopathy, natalizumab, JC virus. rESUMO A leucoencefalopatia multifocal progressiva (LMP) é uma doença desmielinizante do sistema nervoso central (SNC) causada pela reativação do vírus JC (JCV) em um ambiente de imunossupressão celular. Originalmente, LMP foi descrita em pacientes com infecção avançada pelo HIV, doenças linfoproliferativas e transplantados. No entanto, a utilização generalizada de anti-retrovirais para a infecç...

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“…Interestingly, the development of IRIS has no impact in the outcome of PML as observed in a recent study 23 .…”

mentioning

confidence: 63%

Progressive multifocal leukoencephalopathy: new concepts

Lima

2013

Arq. Neuro-Psiquiatr.

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“…Untreated group consisted with 11 patients with PML (6 HIV-positive and 5 HIV-negative patients) who were not receiving any treatment except cART, matched for CD4 count and HIV viral load. The 1-year survival rate was 62% in patients treated with 5HT2A receptor blockers versus 45% untreated patients, but no significant difference was observed (p=0.45) [54].…”

Section: New Anti-viral Drugs Against Jc Virus Mirtazapinementioning

confidence: 81%

A New Therapeutic Option for Progressive Multifocal Leukoencephalopathy after Allogeneic Hematopoietic Cell Transplantation

Yoshida¹,

Masaie²,

Hino³

et al. 2017

J Clin Infect Dis Pract

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Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of central nervous system caused by human polyoma virus, JC virus, which can occur in the patients with severe immune compromised condition. PML is a rare disease, seen in hematologic malignancies, organ transplantation, and HIV infected patients. PML is often fatal, because of the lack of effective anti-viral drug for JC virus. Clinical observations of survival improvement in HIV-positive patients after the introduction of combination antiretroviral therapy (cART) could suggest the importance of restoration of immune response.In the setting of PML after allogeneic hematopoietic cell transplantation (HCT), it is very difficult to reduce or stop immunosuppressants to restore immune response, because of graft versus host disease (GVHD) and so on. Therefore, new anti-viral drugs against JC virus should be needed. Recently, mirtazapine (antagonists of 5-HT 2 serotonergic receptor) and mefloquine (anti-malarial drug), have been shown to have anti-viral activities against JC virus even in the clinical setting as well as in vitro experiments. Several case reports using each drug have been found in recent years. A controlled study for PML patients treated with or without mirtazapine has shown superior survival rate at 1-year in the patients treated with mirtazapine, although statistical significance was not observed. Concomitant usage of both mirtazapine and mefloquine could be expected to induce more effective anti-viral activities, because the mechanism of each drug to inhibit JC virus proliferation is independent. Indeed, some case reports have shown the efficacies of these drugs for the treatment of the patients with PML including after allogenic HCT patients.Controlled study should be required to identify the efficacies of the combinational treatment of both mirtazapine and mefloquine for the treatment of PML patients after allogenic HCT.

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“…13 Also there was not shown clinical confirmation with mirtazapine. 15 In our patient, mefloquine and mirtazapine were not given for the supportive therapy of PML.…”

mentioning

confidence: 75%