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

Kobayashi, Zen; Akaza, Miho; Numasawa, Yoshiyuki; Ishihara, Shoichiro; Tomimitsu, Hiroyuki; Nakamichi, Kazuo; Saijo, Masayuki; Morio, Tomohiro; Shimizu, Norio; Sanjo, Nobuo; Sato, Shuzo; Mizusawa, Hidehiro

doi:10.1016/j.jns.2012.11.004

Cited by 19 publications

(13 citation statements)

References 27 publications

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“…HIV infection, hematopoietic malignancies, collagen diseases and renal failure are major underlying causes of PML, whereas the etiology is unknown in a subset of patients (8,9). However, in recent years, several cases of PML in patients with ICL in the absence of other underlying diseases have been reported (6,10). While a study by Gheuens et al revealed that 13% of non-HIV PML cases also had ICL (8), another study suggested that ICL is underdiagnosed as the cause of PML (9).…”

Section: Discussionmentioning

confidence: 99%

Progressive Multifocal Leukoencephalopathy Localized in the Cerebellum and Brainstem Associated with Idiopathic CD4<sup>+</sup> T Lymphocytopenia

et al. 2016

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Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that favors the cerebrum and typically occurs in immunosuppressed patients. We herein report the case of a 66-year-old man with PML, idiopathic CD4 + T lymphocytopenia (ICL), and chronic renal failure. Cranial magnetic resonance imaging (MRI) showed a crescent-shaped lesion in the left cerebellum, brainstem, and middle cerebellar peduncle. Although the patient did not present with HIV infection, collagen diseases, or tumors, JC virus DNA was detected in the cerebrospinal fluid. Clinicians should consider PML and ICL in the differential diagnosis if the patient develops progressive ataxia and a crescent-shaped cerebellar lesion on MRI.

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Section: Discussionmentioning

confidence: 99%

Progressive Multifocal Leukoencephalopathy Localized in the Cerebellum and Brainstem Associated with Idiopathic CD4<sup>+</sup> T Lymphocytopenia

et al. 2016

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“…Taken together, the weekly administration of 250 mg of mefloquine as a maintenance dose may be insufficient for suppressing the activity of JC viruses in the brain in cases of PML, particularly rituximab-associated cases derived from NHL, and a weekly dose of 500 mg or higher may therefore be suitable for treating PML in patients with a severe condition. Although several cases of PML in which mefloquine was shown to be effective have been reported (5-9), recent reports have indicated a failure to reduce the JCV DNA titer in the CSF (19)(20)(21). At present, the differences in the backgrounds of PML patients between responders and nonresponders to mefloquine have not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

Rituximab-associated Progressive Multifocal Leukoencephalopathy Derived from Non-Hodgkin Lymphoma: Neuropathological Findings and Results of Mefloquine Treatment

et al. 2015

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A 66-year-old man with non-Hodgkin lymphoma (NHL) developed progressive multifocal leukoencephalopathy (PML) after undergoing chemotherapy including rituximab. Although the administration of mefloquine at a dose of 500 mg weekly temporarily led to a dramatic decrease in the copy number of JC Virus DNA in the cerebrospinal fluid, the patient's symptoms gradually worsened. The CD4 + T count remained continuously low, at least until approximately five months after the last cycle of chemotherapy. A postmortem examination performed 10 months after the onset of PML disclosed a severe condition associated with rituximab-treated PML originating from NHL and a high mefloquine concentration in the brain. The accumulation of further data regarding mefloquine treatment in PML cases may help to elucidate the optimal dosage and time window for effectively treating PML.

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“…This study was, due to failing positive results, prematurely terminated [36]. Despite these disappointing results, further use of mefloquine only or in combination with mirtazapine, in non-HIV patients, has produced varying results [37,38,39]. A loading dose of 250 mg for 3 consecutive days and a maintenance dose of 250 mg/week for up to 6 months was used [40,41].…”

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

Cited by 19 publications

References 27 publications

Progressive Multifocal Leukoencephalopathy Localized in the Cerebellum and Brainstem Associated with Idiopathic CD4<sup>+</sup> T Lymphocytopenia

Progressive Multifocal Leukoencephalopathy Localized in the Cerebellum and Brainstem Associated with Idiopathic CD4<sup>+</sup> T Lymphocytopenia

Rituximab-associated Progressive Multifocal Leukoencephalopathy Derived from Non-Hodgkin Lymphoma: Neuropathological Findings and Results of Mefloquine Treatment

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

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