PMID- 29725611
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220318
IS  - 2332-7812 (Print)
IS  - 2332-7812 (Electronic)
IS  - 2332-7812 (Linking)
VI  - 5
IP  - 1
DP  - 2018 Jan
TI  - Fingolimod-associated PML with mild IRIS in MS: A clinicopathologic study.
PG  - e415
LID - 10.1212/NXI.0000000000000415 [doi]
LID - e415
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/muL). 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.
FAU - Nishiyama, Shuhei
AU  - Nishiyama S
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
FAU - Misu, Tatsuro
AU  - Misu T
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
FAU - Shishido-Hara, Yukiko
AU  - Shishido-Hara Y
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
FAU - Nakamichi, Kazuo
AU  - Nakamichi K
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
FAU - Saijo, Masayuki
AU  - Saijo M
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
FAU - Takai, Yoshiki
AU  - Takai Y
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
FAU - Takei, Kentarou
AU  - Takei K
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
FAU - Yamamoto, Naoki
AU  - Yamamoto N
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
FAU - Kuroda, Hiroshi
AU  - Kuroda H
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
FAU - Saito, Ryuta
AU  - Saito R
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
FAU - Watanabe, Mika
AU  - Watanabe M
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
FAU - Tominaga, Teiji
AU  - Tominaga T
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
FAU - Nakashima, Ichiro
AU  - Nakashima I
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
FAU - Fujihara, Kazuo
AU  - Fujihara K
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
FAU - Aoki, Masashi
AU  - Aoki M
AD  - Department of Neurology (S.N., T.M., Y.T., K.T., N.Y., H.K., M.A.), Department of 
      Multiple Sclerosis Therapeutics (T.M.), Department of Neurosurgery (R.S., T.T.), 
      and Department of Pathology (M.W.), Tohoku University Graduate School of 
      Medicine, Sendai; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical 
      University; Department of Virology 1 (K.N., M.S.), Laboratory of Neurovirology, 
      National Institute of Infectious Diseases; Department of Neurology (I.N.), Tohoku 
      Medical and Pharmaceutical University, Sendai; and Department of Multiple 
      Sclerosis Therapeutics (K.F.), Fukushima Medical University School of Medicine 
      and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research 
      Institute for Neuroscience, Japan.
LA  - eng
PT  - Journal Article
DEP - 20171110
PL  - United States
TA  - Neurol Neuroimmunol Neuroinflamm
JT  - Neurology(R) neuroimmunology & neuroinflammation
JID - 101636388
PMC - PMC5930970
EDAT- 2018/05/05 06:00
MHDA- 2018/05/05 06:01
PMCR- 2017/11/10
CRDT- 2018/05/05 06:00
PHST- 2017/07/25 00:00 [received]
PHST- 2017/09/26 00:00 [accepted]
PHST- 2018/05/05 06:00 [entrez]
PHST- 2018/05/05 06:00 [pubmed]
PHST- 2018/05/05 06:01 [medline]
PHST- 2017/11/10 00:00 [pmc-release]
AID - NEURIMMINFL2017014282 [pii]
AID - 10.1212/NXI.0000000000000415 [doi]
PST - epublish
SO  - Neurol Neuroimmunol Neuroinflamm. 2017 Nov 10;5(1):e415. doi: 
      10.1212/NXI.0000000000000415. eCollection 2018 Jan.