TY - JOUR
T1 - Fingolimod-associated PML with mild IRIS in MS
AU - Nishiyama, Shuhei
AU - Misu, Tatsuro
AU - Shishido-Hara, Yukiko
AU - Nakamichi, Kazuo
AU - Saijo, Masayuki
AU - Takai, Yoshiki
AU - Takei, Kentarou
AU - Yamamoto, Naoki
AU - Kuroda, Hiroshi
AU - Saito, Ryuta
AU - Watanabe, Mika
AU - Tominaga, Teiji
AU - Nakashima, Ichiro
AU - Fujihara, Kazuo
AU - Aoki, Masashi
N1 - Funding Information:
Shuhei Nishiyama has received Grants-in-Aid for Scientific Research. Tatsuro Misu has received Grants-in-Aid for Scientific Research; has received speaker honoraria from Bayer Schering Pharma, Biogen Idec Japan, and Mitsubishi Tanabe Pharma Corporation; and has received research support from Mitsubishi Tanabe Pharma, Chugai Pharma, The Chemo-Sero-Therapeutic Research Institute, Takeda Pharmaceutical, Asahi Kasei Medical Co., and Cosmic Corporation. Yukiko Shishido-Hara has received Grants-in-Aid for Scientific Research and is on the editorial board for Pathology International. Kazuo Nakamichi has received Grants-in-Aid for Scientific Research. Masayuki Saijo has received Grants-in-Aid for Scientific Research; is Editor-in-Chief for Japanese Journal of Infectious Diseases; and received research support from Japan Agency for Medical Research and Development. Yoshiki Takai has received Grants-in-Aid for Scientific Research. Kentarou Takei and Nao-ki Yamamoto report no disclosures. Hiroshi Kuroda, Ryuta Saito, Mika Watanabe, and Teiji Tominaga have received Grants-in-Aid for Scientific Research. Ichiro Nakashima has received Grants-in-Aid for Scientific Research; has received funding for travel; received speaker honoraria from Tanabe Mitsubishi Pharma Corporation; has received research funding from LSI Medience Corporation; and is an editorial board for Multiple Sclerosis International. Kazuo Fujihara has received Grants-in-Aid for Scientific Research; serves on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, Merck Serono, Alexion Pharmaceuticals, MedImmune, and Medical Review; has received funding for travel and speaker honoraria from Bayer Schering Pharma, Biogen Idec, Eisai Inc., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited, Asahi Kasei Medical Co., Daiichi Sankyo, and Nihon Pharmaceutical; serves as an editorial board member of Clinical and Experimental Neuroimmunology (2009 till present) and an advisory board member of Sri Lanka Journal of Neurology; and has received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Medical, The Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical, Mitsubishi Tanabe Pharma, Teijin Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, and Genzyme Japan. Masashi Aoki has received Grants-in-Aid for Scientific Research. Go to Neurology.org/nn for full disclosure forms.
Funding Information:
This work was partly supported by JSPS KAKENHI (Grant Number 26461286, 17K09768, 26293205, 15K09332, and 17H04192), the Research Committee of Prion Disease and Slow Virus Infection Research on Policy Planning and Evaluation for Rare and Intractable Diseases and a Grant-in-Aid for Scientific Research (Neuroimmunological Diseases) from the Ministry of Health, Labor, and Welfare of Japan, and the Research Committee of Molecular Pathogenesis and Therapies for Prion Disease and Slow Virus Infection, the Practical Research Project for Rare/ Intractable Disease from Japan Agency for Medical Research and Development, AMED.
Publisher Copyright:
Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Objective: To clarify the clinical, neuropathologic, and virologic characteristics of progressive multifocal leukoencephalopathy (PML) and its immune reconstitution inflammatory syndrome (IRIS) in a patient with fingolimod-treated MS. Methods: A case study. Results: A 34-year-old patient with MS using fingolimod for 4 years had a gradual progression of right hemiparesis and aphasia with a new subcortical white matter lesion in the precentral gyrus by initial MRI. Blood tests were normal, except for lymphopenia (160 cells/L). One month after the cessation of fingolimod, brain MRI depicted a diffusely exacerbated hyperintensity on fluid-attenuated inversion recovery and diffusion-weighed imaging in the white matter with punctate gadolinium enhancement, suggesting PML-IRIS. A very low level of JC virus (JCV)-DNA (15 copies/mL) was detected in the CSF as judged by quantitative PCR. Brain tissues were biopsied from the left frontal lesion, which showed some small demyelinated foci with predominant loss of myelin-associated glycoprotein with infiltrations of lymphocytes and macrophages, but clear viral inclusion was not observed with hematoxylin-eosin staining. JCV-DNA was uniquely detectable in an active inflammatory demyelinating lesion by in situ hybridization, possibly suggesting an early phase of PML. DNA extracted from the brain sample was positive for JCV-DNA (151 copies/cell). It took 3 months to normalize the blood lymphocyte count. The patient was treated with 1 g of IV methylprednisolone for 3 days and a weekly oral dose (375 mg) of mefloquine, and her symptoms gradually improved. Conclusion: Low CSF JCV-DNA and unfound viral inclusions initially made her diagnosis difficult. The clinical course of fingolimod-associated PML may be associated with mild immune reconstitution.
AB - Objective: To clarify the clinical, neuropathologic, and virologic characteristics of progressive multifocal leukoencephalopathy (PML) and its immune reconstitution inflammatory syndrome (IRIS) in a patient with fingolimod-treated MS. Methods: A case study. Results: A 34-year-old patient with MS using fingolimod for 4 years had a gradual progression of right hemiparesis and aphasia with a new subcortical white matter lesion in the precentral gyrus by initial MRI. Blood tests were normal, except for lymphopenia (160 cells/L). One month after the cessation of fingolimod, brain MRI depicted a diffusely exacerbated hyperintensity on fluid-attenuated inversion recovery and diffusion-weighed imaging in the white matter with punctate gadolinium enhancement, suggesting PML-IRIS. A very low level of JC virus (JCV)-DNA (15 copies/mL) was detected in the CSF as judged by quantitative PCR. Brain tissues were biopsied from the left frontal lesion, which showed some small demyelinated foci with predominant loss of myelin-associated glycoprotein with infiltrations of lymphocytes and macrophages, but clear viral inclusion was not observed with hematoxylin-eosin staining. JCV-DNA was uniquely detectable in an active inflammatory demyelinating lesion by in situ hybridization, possibly suggesting an early phase of PML. DNA extracted from the brain sample was positive for JCV-DNA (151 copies/cell). It took 3 months to normalize the blood lymphocyte count. The patient was treated with 1 g of IV methylprednisolone for 3 days and a weekly oral dose (375 mg) of mefloquine, and her symptoms gradually improved. Conclusion: Low CSF JCV-DNA and unfound viral inclusions initially made her diagnosis difficult. The clinical course of fingolimod-associated PML may be associated with mild immune reconstitution.
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U2 - 10.1212/NXI.0000000000000415
DO - 10.1212/NXI.0000000000000415
M3 - Article
AN - SCOPUS:85044261163
VL - 5
JO - Neurology: Neuroimmunology and NeuroInflammation
JF - Neurology: Neuroimmunology and NeuroInflammation
SN - 2332-7812
IS - 1
M1 - e415
ER -