Akinetic Mutism Caused by HIV-associated Progressive Multifocal Leukoencephalopathy was Successfully Treated with Mefloquine: A Serial Multimodal MRI Study

Naito, Kasane; Ueno, Hiroki; Sekine, Mayu; Kanemitsu, Munekazu; Ohshita, Tomohiko; Nakamura, Takeshi; Yamawaki, Takemori; Matsumoto, Masayasu

doi:10.2169/internalmedicine.51.6253

Cited by 17 publications

(18 citation statements)

References 23 publications

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“…There are only very few case reports of mefloquine therapy in HIV-negative and HIV-positive patients with PML. These reports show positive results after the administration of mefloquine in PML [33,34,35]. The antimalarial agent mefloquine was tested in a small clinical trial (phase I and II) with some non-HIV patients, but mostly HIV-positive patients.…”

Section: Discussionmentioning

confidence: 99%

Progressive Multifocal Leukoencephalopathy in Patients with a Hematological Malignancy: Review of Therapeutic Options

Kalisch¹,

Wilhelm²,

Erbguth

et al. 2014

Chemotherapy

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In the context of 2 patients with hematological malignancy who developed progressive multifocal leukoencephalopathy (PML), we review the current therapeutic options for this serious complication. Both patients had lymphoma and had been pretreated with the antibody rituximab. Diagnosis of PML was obtained upon the detection of the JC virus. The outcome was fatal in both cases. So far, no standard therapeutic approach for JC virus infection has been established in HIV-negative patients with hematological malignancies and the outcome is usually fatal. Serotonin receptor antagonists might have a beneficial effect by blocking the virus from entering the cells. Although hopes for the efficacy of mefloquine were disappointed by the results of 1 study, several case reports describe improvements in neurological impairment when this drug is administered. Taking the desperate situation of this patient group into consideration, the combination of mirtazapine and mefloquine might be worthy of an attempt.

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Section: Discussionmentioning

confidence: 99%

Progressive Multifocal Leukoencephalopathy in Patients with a Hematological Malignancy: Review of Therapeutic Options

Kalisch¹,

Wilhelm²,

Erbguth

et al. 2014

Chemotherapy

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“…Because there is no known specific antiviral agent against JCV, we treated PML in the two HIV-negative patients with mefloquine based on case reports describing the efficacy of mefloquine for PML [16][17][18][19][20]. However, during mefloquine therapy, clinical and radiological progression was observed, and JCV DNA in the CSF was increased in both patients.…”

Section: Discussionmentioning

confidence: 99%

“…Since then, there have been at least 5 reported cases of PML in which mefloquine was effective [16][17][18][19][20]. In contrast, a recent mefloquine trial of 24 patients with PML (21 HIV-positive and 3 HIV-negative) reported failure in reducing JCV DNA levels in the CSF [21], although it is pending publication.…”

Section: Introductionmentioning

confidence: 99%

Failure of mefloquine therapy in progressive multifocal leukoencephalopathy: Report of two Japanese patients without human immunodeficiency virus infection

Kobayashi¹,

Akaza²,

Numasawa³

et al. 2013

Journal of the Neurological Sciences

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“…As same in mirtazapine, several case reports have shown a favorable outcome in HIV-positive and HIV-negative patients with PML [56][57][58][59][60], even in the setting of allogeneic HCT (Table 1) Each drug has independent mechanisms to inhibit the proliferation of JC virus. Mirtazapine inhibits the entry of JC virus into glial cells via serotonergic receptor [15].…”

Section: Mefloquinementioning

confidence: 99%

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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Akinetic Mutism Caused by HIV-associated Progressive Multifocal Leukoencephalopathy was Successfully Treated with Mefloquine: A Serial Multimodal MRI Study

Cited by 17 publications

References 23 publications

Progressive Multifocal Leukoencephalopathy in Patients with a Hematological Malignancy: Review of Therapeutic Options

Progressive Multifocal Leukoencephalopathy in Patients with a Hematological Malignancy: Review of Therapeutic Options

Failure of mefloquine therapy in progressive multifocal leukoencephalopathy: Report of two Japanese patients without human immunodeficiency virus infection

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

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