Successful treatment of non-HIV progressive multifocal leukoencephalopathy: case report and literature review

Hamaguchi, Mai; Suzuki, Keisuke; Uzuka, Takeo; Matsuda, Hirotsugu; Shishido‐Hara, Yukiko; Arai, Satoko; Nakamura, Toshiki; Kikuchi, Shigeru; Nakamichi, Kazuo; Saijo, Masayuki; Hirata, Koichi

doi:10.1007/s00415-019-09629-x

Cited by 16 publications

(25 citation statements)

References 38 publications

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“…In an autopsy case of NTZ‐associated PML‐IRIS, a pathological investigation revealed only CD8 + T cell parenchymal infiltration without CD4 + T cells 17 . In contrast, in this and other biopsy cases, 10,18–20 both CD4 + and CD8 + T cells, B cells, and plasma cells were observed. Thus, the inflammatory cell profiles were analyzed in detail.…”

Section: Pathological Findingscontrasting

confidence: 54%

Pathology for severe inflammatory PML with PD1/PD‐L1 expression of favorable prognosis: What's a prognostic factor for PML‐IRIS?

et al. 2023

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A 72‐year‐old woman with dermatomyositis (DM) developed neurological manifestation, and magnetic resonance imaging (MRI) revealed multiple T2/fluid‐attenuated inversion recovery (FLAIR)‐hyperintense lesions predominantly in the deep white matter of the cerebral hemisphere. Punctate or linear contrast enhancement was observed surrounding the T1‐hypointense area. Multiple T2/FLAIR‐hyperintense lesions were aligned along with the corona radiata. Malignant lymphoma was first suspected, and a brain biopsy was performed. Pathological investigation suggested the provisional diagnosis of “suspicious of malignant lymphoma.” Owing to emergent clinical conditions, high‐dose methotrexate (MTX) therapy was conducted, and then T2/FLAIR‐hyperintense lesions were dramatically reduced. However, the diagnosis of malignant lymphoma was concerning since multiplex PCR demonstrated clonal restriction of the Ig H gene for B cells and TCR beta genes for T cells. Histopathology revealed the infiltration of both CD4+ and CD8+ T cells, and the CD4+/CD8+ ratio was 4.0. Moreover, prominent plasma cells were observed, in addition to CD20+ B cells. Atypical cells with enlarged nuclei were present, and they were not hematopoietic but found as glial cells. JC virus (JCV) infection was verified with both immunohistochemistry and in situ hybridization; the final diagnosis was progressive multifocal leukoencephalopathy (PML). The patient was treated with mefloquine and discharged. This case is informative in understanding the host anti‐viral response. Variable inflammatory cells were observed, including CD4+ and CD8+ T cells, plasma cells, and a small amount of perivascular CD20+ B cells. PD‐1 and PD‐L1 expression was observed in lymphoid cells and macrophages, respectively. PML with inflammatory reactions was thought fatal, and autopsy cases of PML with immune reconstitution inflammatory syndrome (IRIS) demonstrated excessive infiltration of only CD8+ T cells. However, this case revealed infiltration of variable inflammatory cells, and a favorable prognosis would be expected under PD‐1/PD‐L1 immune‐checkpoint regulation.

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Section: Pathological Findingscontrasting

confidence: 54%

Pathology for severe inflammatory PML with PD1/PD‐L1 expression of favorable prognosis: What's a prognostic factor for PML‐IRIS?

et al. 2023

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“…In vitro studies suggest that mefloquine not only has an anti-JCV property by inhibiting viral DNA replication but also sufficiently penetrates the blood brain barrier [2]. Moreover, these in vitro studies are supported by several case reports of PML successfully treated with mefloquine [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]37]. In PubMed, at least 21 case reports published in English were available, and these cases even included treatment without additional immune reconstitution therapy [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]37] (Table 3).…”

Section: Discussionmentioning

confidence: 78%

“…Moreover, these in vitro studies are supported by several case reports of PML successfully treated with mefloquine [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]37]. In PubMed, at least 21 case reports published in English were available, and these cases even included treatment without additional immune reconstitution therapy [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]37] (Table 3). Some clinical studies failed to show the clinical efficacy of mefloquine [23], but some points must be considered.…”

Section: Discussionmentioning

confidence: 87%

Progressive multifocal leukoencephalopathy successfully treated with mefloquine and literature review

et al. 2021

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Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection due to reactivation of John Cunningham virus (JCV). The diagnosis depends on evidence from clinical, imaging, and virologic studies. When the cerebrospinal fluid shows a negative polymerase chain reaction result, brain biopsy is required to confirm the diagnosis. PML has no standard treatment except for immune reconstitution. The anti-JCV effect of mefloquine, however, is supported by some studies, and if brain biopsy is difficult, a mefloquine trial can be considered. We describe a case of possible PML successfully treated with mefloquine.

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“…Mirtazapine, used in this case, is an antidepressive drug and was also reported to be used empirically in some other non-HIV PML patients [5]. JC virus entry in astroglial cells in vitro is mediated in part through the 5HTA2 receptors.…”

Section: Discussionmentioning

confidence: 85%

JC virus-induced progressive multifocal leukoencephalopathy in a presumably healthy patient

et al. 2022

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Background JC virus (JCV) is common among healthy individuals and remains latent but may be reactivated under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy (PML). Here, we present a rare case of PML caused by JC virus infection in a previously healthy and immunocompetent patient. Case presentation A 67-year-old female without any disease history was admitted after presenting with rapidly progressive dementia. The preoperative diagnosis was progressive multifocal leukoencephalopathy, and corticosteroid treatment did not improve the symptoms. Brain lesions were surgically sampled, and JCV infection was confirmed by high-throughput DNA gene detection. This patient received a combined treatment of mirtazapine, mefloquine, and traditional Chinese herbs, and had stabilization of the disease on followed-up. Conclusions Although it is a rare, this case demonstrates that JC virus infection within the brain occurs in apparently healthy people. This case may increase our understanding of virus infection when facing the coronavirus epidemic in recent years, considering that similar medications were used. Graphical Abstract

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Successful treatment of non-HIV progressive multifocal leukoencephalopathy: case report and literature review

Cited by 16 publications

References 38 publications

Pathology for severe inflammatory PML with PD1/PD‐L1 expression of favorable prognosis: What's a prognostic factor for PML‐IRIS?

Pathology for severe inflammatory PML with PD1/PD‐L1 expression of favorable prognosis: What's a prognostic factor for PML‐IRIS?

Progressive multifocal leukoencephalopathy successfully treated with mefloquine and literature review

JC virus-induced progressive multifocal leukoencephalopathy in a presumably healthy patient

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