PMID- 31044147
OWN - NLM
STAT- MEDLINE
DCOM- 20200924
LR  - 20200924
IS  - 2332-7812 (Print)
IS  - 2332-7812 (Electronic)
IS  - 2332-7812 (Linking)
VI  - 6
IP  - 3
DP  - 2019 May
TI  - Three cases of non-carryover fingolimod-PML: Is the risk in Japan increased?
PG  - e559
LID - 10.1212/NXI.0000000000000559 [doi]
LID - e559
AB  - OBJECTIVE: To report the course of 3 recent Japanese and European cases of 
      fingolimod-associated progressive multifocal leukoencephalopathy (PML) and to 
      analyze its risk factors and increased incidence in Japan. METHODS: Case series 
      and literature review. RESULTS: Fingolimod-associated PML may cause both 
      supratentorial and infratentorial lesions and a pronounced disability. Diagnosis 
      can be challenging because PML lesions (especially infratentorial) can be 
      initially misdiagnosed as extensive MS lesions. Immune reconstitution 
      inflammatory syndrome (IRIS) develops a few weeks after fingolimod 
      discontinuation and is usually mild. Age factor and therapy duration seem to be 
      relevant because most reported patients were older than 45 years and were treated 
      with fingolimod for more than 3 years. Combined IgG/IgM deficiency has been 
      identified as a possible further predisposing condition in 1 case. Another 
      patient developed an endogenous fungal skin infection, as a sign of generally 
      compromised cellular immune response, shortly before PML. None of the reported 
      patients had lymphocyte counts below 200/mul. Two of the 3 reported and 4 of the 
      21 (19%) registered fingolimod-PML cases occurred in Japan (estimated risk of 
      0.652 per 1,000 compared with 0.083 per 1.000 worldwide). CONCLUSIONS: The risk 
      of PML under fingolimod is low, but there are no reliable predictors. Despite a 
      mild IRIS phase, it causes profound disability. Patients older than 45 years, 
      especially with known comorbid immunodeficiencies or manifestation of other 
      opportunistic infections, should be monitored more closely. Increased 
      surveillance and identification of further risk factors are urgently needed in 
      Japan.
FAU - Nakahara, Jin
AU  - Nakahara J
AD  - Department of Neurology (J.N., K. Kufukihara), Keio University School of 
      Medicine, Tokyo; Department of Neurology (L.T., R.S., R.G., I.A.), St. Josef 
      Hospital, Ruhr University Bochum, Bochum, Germany; Department of Gastroenterology 
      and Neurology (K. Kume, T.T., M.K., K.D.), Kagawa University Faculty of Medicine, 
      Japan; and Department of Neurology (I.A.), Sechenov First Moscow State Medical 
      University, Moscow, Russia.
FAU - Tomaske, Laura
AU  - Tomaske L
AD  - Department of Neurology (J.N., K. Kufukihara), Keio University School of 
      Medicine, Tokyo; Department of Neurology (L.T., R.S., R.G., I.A.), St. Josef 
      Hospital, Ruhr University Bochum, Bochum, Germany; Department of Gastroenterology 
      and Neurology (K. Kume, T.T., M.K., K.D.), Kagawa University Faculty of Medicine, 
      Japan; and Department of Neurology (I.A.), Sechenov First Moscow State Medical 
      University, Moscow, Russia.
FAU - Kume, Kodai
AU  - Kume K
AD  - Department of Neurology (J.N., K. Kufukihara), Keio University School of 
      Medicine, Tokyo; Department of Neurology (L.T., R.S., R.G., I.A.), St. Josef 
      Hospital, Ruhr University Bochum, Bochum, Germany; Department of Gastroenterology 
      and Neurology (K. Kume, T.T., M.K., K.D.), Kagawa University Faculty of Medicine, 
      Japan; and Department of Neurology (I.A.), Sechenov First Moscow State Medical 
      University, Moscow, Russia.
FAU - Takata, Tadayuki
AU  - Takata T
AD  - Department of Neurology (J.N., K. Kufukihara), Keio University School of 
      Medicine, Tokyo; Department of Neurology (L.T., R.S., R.G., I.A.), St. Josef 
      Hospital, Ruhr University Bochum, Bochum, Germany; Department of Gastroenterology 
      and Neurology (K. Kume, T.T., M.K., K.D.), Kagawa University Faculty of Medicine, 
      Japan; and Department of Neurology (I.A.), Sechenov First Moscow State Medical 
      University, Moscow, Russia.
FAU - Kamada, Masaki
AU  - Kamada M
AD  - Department of Neurology (J.N., K. Kufukihara), Keio University School of 
      Medicine, Tokyo; Department of Neurology (L.T., R.S., R.G., I.A.), St. Josef 
      Hospital, Ruhr University Bochum, Bochum, Germany; Department of Gastroenterology 
      and Neurology (K. Kume, T.T., M.K., K.D.), Kagawa University Faculty of Medicine, 
      Japan; and Department of Neurology (I.A.), Sechenov First Moscow State Medical 
      University, Moscow, Russia.
FAU - Deguchi, Kazushi
AU  - Deguchi K
AD  - Department of Neurology (J.N., K. Kufukihara), Keio University School of 
      Medicine, Tokyo; Department of Neurology (L.T., R.S., R.G., I.A.), St. Josef 
      Hospital, Ruhr University Bochum, Bochum, Germany; Department of Gastroenterology 
      and Neurology (K. Kume, T.T., M.K., K.D.), Kagawa University Faculty of Medicine, 
      Japan; and Department of Neurology (I.A.), Sechenov First Moscow State Medical 
      University, Moscow, Russia.
FAU - Kufukihara, Kenji
AU  - Kufukihara K
AD  - Department of Neurology (J.N., K. Kufukihara), Keio University School of 
      Medicine, Tokyo; Department of Neurology (L.T., R.S., R.G., I.A.), St. Josef 
      Hospital, Ruhr University Bochum, Bochum, Germany; Department of Gastroenterology 
      and Neurology (K. Kume, T.T., M.K., K.D.), Kagawa University Faculty of Medicine, 
      Japan; and Department of Neurology (I.A.), Sechenov First Moscow State Medical 
      University, Moscow, Russia.
FAU - Schneider, Ruth
AU  - Schneider R
AD  - Department of Neurology (J.N., K. Kufukihara), Keio University School of 
      Medicine, Tokyo; Department of Neurology (L.T., R.S., R.G., I.A.), St. Josef 
      Hospital, Ruhr University Bochum, Bochum, Germany; Department of Gastroenterology 
      and Neurology (K. Kume, T.T., M.K., K.D.), Kagawa University Faculty of Medicine, 
      Japan; and Department of Neurology (I.A.), Sechenov First Moscow State Medical 
      University, Moscow, Russia.
FAU - Gold, Ralf
AU  - Gold R
AD  - Department of Neurology (J.N., K. Kufukihara), Keio University School of 
      Medicine, Tokyo; Department of Neurology (L.T., R.S., R.G., I.A.), St. Josef 
      Hospital, Ruhr University Bochum, Bochum, Germany; Department of Gastroenterology 
      and Neurology (K. Kume, T.T., M.K., K.D.), Kagawa University Faculty of Medicine, 
      Japan; and Department of Neurology (I.A.), Sechenov First Moscow State Medical 
      University, Moscow, Russia.
FAU - Ayzenberg, Ilya
AU  - Ayzenberg I
AD  - Department of Neurology (J.N., K. Kufukihara), Keio University School of 
      Medicine, Tokyo; Department of Neurology (L.T., R.S., R.G., I.A.), St. Josef 
      Hospital, Ruhr University Bochum, Bochum, Germany; Department of Gastroenterology 
      and Neurology (K. Kume, T.T., M.K., K.D.), Kagawa University Faculty of Medicine, 
      Japan; and Department of Neurology (I.A.), Sechenov First Moscow State Medical 
      University, Moscow, Russia.
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20190410
PL  - United States
TA  - Neurol Neuroimmunol Neuroinflamm
JT  - Neurology(R) neuroimmunology & neuroinflammation
JID - 101636388
RN  - 0 (Immunosuppressive Agents)
RN  - G926EC510T (Fingolimod Hydrochloride)
SB  - IM
MH  - Europe
MH  - Female
MH  - Fingolimod Hydrochloride/*adverse effects
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/*chemically induced
MH  - Immunosuppressive Agents/*adverse effects
MH  - Japan
MH  - Leukoencephalopathy, Progressive Multifocal/*chemically induced
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*drug therapy
PMC - PMC6467684
EDAT- 2019/05/03 06:00
MHDA- 2019/05/03 06:01
PMCR- 2019/04/10
CRDT- 2019/05/03 06:00
PHST- 2018/10/10 00:00 [received]
PHST- 2019/02/19 00:00 [accepted]
PHST- 2019/05/03 06:00 [entrez]
PHST- 2019/05/03 06:00 [pubmed]
PHST- 2019/05/03 06:01 [medline]
PHST- 2019/04/10 00:00 [pmc-release]
AID - NEURIMMINFL2018018838 [pii]
AID - 10.1212/NXI.0000000000000559 [doi]
PST - epublish
SO  - Neurol Neuroimmunol Neuroinflamm. 2019 Apr 10;6(3):e559. doi: 
      10.1212/NXI.0000000000000559. eCollection 2019 May.