Mirtazapine treatment ceased the progression of progressive multifocal leukoencephalopathy associated with systemic sarcoidosis

Abstract

Progressive multifocal leukoencephalopathy occurs almost exclusively in immunosuppressed individuals. Mirtazapine, a 5-hydroxytryptamine-2A antagonist, has been used empirically against progressive multifocal leukoencephalopathy. A 60-year-old man who was diagnosed with sarcoidosis at 20 years-of-age and had not taken immunosuppressive therapies developed dysarthria, left hemiparesis and dressing apraxia. Cranial fluid-attenuated inversion-recovery magnetic resonance imaging showed hyperintense areas in the right frontal and temporoparietal white matter. The initial diagnosis was neurosarcoidosis, based on non-caseating granuloma in a lymph node biopsy. Immunosuppressive therapy was initiated; however, this aggravated his neurological symptoms. Immunohistochemistry of the brain biopsy showed John Cunningham virus infected large ballooned oligodendrocytes, leading to a diagnosis of progressive multifocal leukoencephalopathy. Treatment with mirtazapine improved the neurological symptoms, and the magnetic resonance imaging abnormality did not progress. We stress the diagnostic difficulties of distinguishing progressive multifocal leukoencephalopathy from neurosarcoidosis, and suggest that mirtazapine treatment is effective against progressive multifocal leukoencephalopathy associated with sarcoidosis.

JC Virus-Associated Progressive Multifocal Leukoencephalopathy with Transverse Myelitis Successfully Treated Using Mirtazapine

“…Mirtazapine is thought to prevent viral entry into glial cells by antagonizing 5-HT2AR [1]. There is a small body of evidence suggesting that mirtazapine may be an effective treatment for PML -particularly PML associated with natalizumab [2][3][4][5].…”

“…Due to the rarity of the disease, PML treatment is guided by very limited evidence and involves immune reconstitution and direct antiviral therapy [1]. Mirtazapine, a serotonergic 5-hydroxytriptamine 2A receptor (5-HT2AR) antagonist, has been proposed as a potential treatment for PML, with benefit described in a few case reports [2][3][4][5].…”

Progressive Multifocal Leukoencephalopathy in a Chemotherapy-Naive Patient With Chronic Lymphocytic Leukemia: A Case Report

“…We opted to start the patient on immunoglobulin, given the hypogammaglobulinemia she presented, and mirtazapine, a 5HT2A receptor antagonist. According to in vitro studies, the infection of glial cells by the JC virus is mediated by the 5HT-2A receptors, and its antagonist might impede its entry into CNS cells and, thus, it's spread [ 15 ]. Given the rapid progress of our patient’s symptoms, poor performance status, and poor prognosis, it was decided that no specific treatment for leukemia or PML would be started after a hematology and neurology consultation since the risk and adverse effects of the therapy did not outweigh the benefit.…”

Characteristics of Progressive Multifocal Leukoencephalopathy Associated With Sarcoidosis Without Therapeutic Immune Suppression

“…Sarcoidosis associated with a PML-like disease was described in 1955, although in this report, 1 of the defining histopathologic features of the disease (enlarged oligodendrocyte nuclei) was not described. In the intervening 7 decades, the occurrence of PML associated with systemic sarcoidosis (S-PML) in the absence of therapeutic immune suppression has been described in 37 patients . Recent research for possible PML treatment includes infusion of interleukin (IL) 2 and IL-7, checkpoint inhibitors, polyoma virus-specific T-cell therapy (PyVST), and infliximab, the last of which was used for patients with sarcoidosis specifically .…”