Rebound Syndrome in Patients With Multiple Sclerosis After Cessation of Fingolimod Treatment

The appropriate sequencing of agents with strong immune system effects has become increasingly important. Transitions require careful balance between safety and protection against relapse. The cases presented herein highlight that rebound events after ceasing fingolimod treatment may happen even wit...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:JAMA neurology Jg. 73; H. 7; S. 790 - 794
Hauptverfasser: Hatcher, Stacy Ellen, Waubant, Emmanuelle, Nourbakhsh, Bardia, Crabtree-Hartman, Elizabeth, Graves, Jennifer S
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.07.2016
Schlagworte:
ISSN:2168-6157
Online-Zugang:Weitere Angaben
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Abstract The appropriate sequencing of agents with strong immune system effects has become increasingly important. Transitions require careful balance between safety and protection against relapse. The cases presented herein highlight that rebound events after ceasing fingolimod treatment may happen even with short washout periods (4 weeks) and may perpetuate despite steroid treatment or the immediate use of fast-acting immune therapies, such as rituximab. To describe rebound syndrome in patients with multiple sclerosis (MS) after cessation of fingolimod treatment. Clinical and demographic data were extracted from electronic medical records from the University of California, San Francisco, Multiple Sclerosis Center from January 2014 to December 2015. Magnetic resonance images were reviewed by MS neurologists (J.S.G., E.W., B.N., and E.C.H.). Rebound syndrome was defined as new severe neurological symptoms after ceasing fingolimod treatment, with the development of multiple new or enhancing lesions exceeding baseline activity. We reviewed the PubMed database from January 2010 to December 2015 for similar cases of severe disease reactivation after ceasing fingolimod treatment using search terms fingolimod and either rebound or reactivation. Participants were included if they stopped receiving fingolimod between January 2014 and December 2015. Five patients were identified who experienced rebound after ceasing fingolimod treatment. Each patient received treatment with oral fingolimod for various durations. Occurrence of rebound after ceasing fingolimod treatment. The mean (SD) age of the 5 female patients presented in this case series was 35.2 (6.4) years. Of the 46 patients that stopped fingolimod treatment within the 2-year period, 5 (10.9%) experienced severe relapse 4 to 16 weeks after ceasing fingolimod treatment. Despite varying prior severity of relapsing-remitting course, all participants experienced unexpectedly severe clinical relapses accompanied by drastic increases in new or enhancing lesions seen on magnetic resonance imaging evidenced by a median (range) increase of 9 (0->30) new gadolinium-enhancing lesions and a median (range) of 9 (0->30) new T2 lesions. New lesion development persisted for 3 to 6 months despite treatment with corticosteroids (n = 3) and initiation of B-cell depleting therapy (n = 2). In addition, 11 patients were identified through literature review reported as having severe relapses consistent with a rebound syndrome and similar features to our 5 cases. These cases provide evidence for a fingolimod rebound syndrome at a clinically relevant frequency, highlighting the need to determine the best methods for sequencing or discontinuing MS therapies. A large prospective registry or population-based study would be helpful to confirm this rebound phenomenon and to determine contributing factors, including immune biomarkers, that increase risk for this syndrome.
AbstractList The appropriate sequencing of agents with strong immune system effects has become increasingly important. Transitions require careful balance between safety and protection against relapse. The cases presented herein highlight that rebound events after ceasing fingolimod treatment may happen even with short washout periods (4 weeks) and may perpetuate despite steroid treatment or the immediate use of fast-acting immune therapies, such as rituximab. To describe rebound syndrome in patients with multiple sclerosis (MS) after cessation of fingolimod treatment. Clinical and demographic data were extracted from electronic medical records from the University of California, San Francisco, Multiple Sclerosis Center from January 2014 to December 2015. Magnetic resonance images were reviewed by MS neurologists (J.S.G., E.W., B.N., and E.C.H.). Rebound syndrome was defined as new severe neurological symptoms after ceasing fingolimod treatment, with the development of multiple new or enhancing lesions exceeding baseline activity. We reviewed the PubMed database from January 2010 to December 2015 for similar cases of severe disease reactivation after ceasing fingolimod treatment using search terms fingolimod and either rebound or reactivation. Participants were included if they stopped receiving fingolimod between January 2014 and December 2015. Five patients were identified who experienced rebound after ceasing fingolimod treatment. Each patient received treatment with oral fingolimod for various durations. Occurrence of rebound after ceasing fingolimod treatment. The mean (SD) age of the 5 female patients presented in this case series was 35.2 (6.4) years. Of the 46 patients that stopped fingolimod treatment within the 2-year period, 5 (10.9%) experienced severe relapse 4 to 16 weeks after ceasing fingolimod treatment. Despite varying prior severity of relapsing-remitting course, all participants experienced unexpectedly severe clinical relapses accompanied by drastic increases in new or enhancing lesions seen on magnetic resonance imaging evidenced by a median (range) increase of 9 (0->30) new gadolinium-enhancing lesions and a median (range) of 9 (0->30) new T2 lesions. New lesion development persisted for 3 to 6 months despite treatment with corticosteroids (n = 3) and initiation of B-cell depleting therapy (n = 2). In addition, 11 patients were identified through literature review reported as having severe relapses consistent with a rebound syndrome and similar features to our 5 cases. These cases provide evidence for a fingolimod rebound syndrome at a clinically relevant frequency, highlighting the need to determine the best methods for sequencing or discontinuing MS therapies. A large prospective registry or population-based study would be helpful to confirm this rebound phenomenon and to determine contributing factors, including immune biomarkers, that increase risk for this syndrome.
IMPORTANCEThe appropriate sequencing of agents with strong immune system effects has become increasingly important. Transitions require careful balance between safety and protection against relapse. The cases presented herein highlight that rebound events after ceasing fingolimod treatment may happen even with short washout periods (4 weeks) and may perpetuate despite steroid treatment or the immediate use of fast-acting immune therapies, such as rituximab.OBJECTIVETo describe rebound syndrome in patients with multiple sclerosis (MS) after cessation of fingolimod treatment.DESIGN, SETTING, AND PARTICIPANTSClinical and demographic data were extracted from electronic medical records from the University of California, San Francisco, Multiple Sclerosis Center from January 2014 to December 2015. Magnetic resonance images were reviewed by MS neurologists (J.S.G., E.W., B.N., and E.C.H.). Rebound syndrome was defined as new severe neurological symptoms after ceasing fingolimod treatment, with the development of multiple new or enhancing lesions exceeding baseline activity. We reviewed the PubMed database from January 2010 to December 2015 for similar cases of severe disease reactivation after ceasing fingolimod treatment using search terms fingolimod and either rebound or reactivation. Participants were included if they stopped receiving fingolimod between January 2014 and December 2015. Five patients were identified who experienced rebound after ceasing fingolimod treatment.EXPOSURESEach patient received treatment with oral fingolimod for various durations.MAIN OUTCOMES AND MEASURESOccurrence of rebound after ceasing fingolimod treatment.RESULTSThe mean (SD) age of the 5 female patients presented in this case series was 35.2 (6.4) years. Of the 46 patients that stopped fingolimod treatment within the 2-year period, 5 (10.9%) experienced severe relapse 4 to 16 weeks after ceasing fingolimod treatment. Despite varying prior severity of relapsing-remitting course, all participants experienced unexpectedly severe clinical relapses accompanied by drastic increases in new or enhancing lesions seen on magnetic resonance imaging evidenced by a median (range) increase of 9 (0->30) new gadolinium-enhancing lesions and a median (range) of 9 (0->30) new T2 lesions. New lesion development persisted for 3 to 6 months despite treatment with corticosteroids (n = 3) and initiation of B-cell depleting therapy (n = 2). In addition, 11 patients were identified through literature review reported as having severe relapses consistent with a rebound syndrome and similar features to our 5 cases.CONCLUSIONS AND RELEVANCEThese cases provide evidence for a fingolimod rebound syndrome at a clinically relevant frequency, highlighting the need to determine the best methods for sequencing or discontinuing MS therapies. A large prospective registry or population-based study would be helpful to confirm this rebound phenomenon and to determine contributing factors, including immune biomarkers, that increase risk for this syndrome.
Author Hatcher, Stacy Ellen
Waubant, Emmanuelle
Graves, Jennifer S
Crabtree-Hartman, Elizabeth
Nourbakhsh, Bardia
Author_xml – sequence: 1
  givenname: Stacy Ellen
  surname: Hatcher
  fullname: Hatcher, Stacy Ellen
  organization: Department of Neurology, University of California, San Francisco
– sequence: 2
  givenname: Emmanuelle
  surname: Waubant
  fullname: Waubant, Emmanuelle
  organization: Department of Neurology, University of California, San Francisco
– sequence: 3
  givenname: Bardia
  surname: Nourbakhsh
  fullname: Nourbakhsh, Bardia
  organization: Department of Neurology, University of California, San Francisco
– sequence: 4
  givenname: Elizabeth
  surname: Crabtree-Hartman
  fullname: Crabtree-Hartman, Elizabeth
  organization: Department of Neurology, University of California, San Francisco
– sequence: 5
  givenname: Jennifer S
  surname: Graves
  fullname: Graves, Jennifer S
  organization: Department of Neurology, University of California, San Francisco
BackLink https://www.ncbi.nlm.nih.gov/pubmed/27135594$$D View this record in MEDLINE/PubMed
BookMark eNo1kMFLwzAchYMobs79ByI5eulM0qRJjmM4FRTFTbwIJW1_0Yw0mU172H9vwfku7_Lx8XgX6DTEAAhdUbKghNDbnWlNgKGLfsEILRZEseIETRktVFZQISdontKOjFGE8JyfowmTNBdC8yn6fIMqDqHBm0NoutgCdgG_mt5B6BP-cP03fh587_Ye8Kb20MXkEl7aHjq8gpRGMgYcLV678BW9a2ODtx2Yvh0Fl-jMGp9gfuwZel_fbVcP2dPL_eNq-ZQZTkSf2ZzXoJtKUFnpcbEARQmXWjbaMmKJtUpxqOvG2FpXhVGUVsKKnHJQ2hSazdDNn3ffxZ8BUl-2LtXg_fhLHFJJFcmlFlKyEb0-okPVQlPuO9ea7lD-P8J-AaAVZsY
CitedBy_id crossref_primary_10_1007_s40120_021_00320_w
crossref_primary_10_3390_ijms20235985
crossref_primary_10_1177_1352458518763095
crossref_primary_10_1212_NXI_0000000000000377
crossref_primary_10_1055_a_2496_5294
crossref_primary_10_3390_children6060073
crossref_primary_10_1016_j_neurol_2023_03_028
crossref_primary_10_1212_NXI_0000000000001183
crossref_primary_10_1177_1352458520937644
crossref_primary_10_3389_fimmu_2019_01564
crossref_primary_10_1016_j_msard_2022_103805
crossref_primary_10_1080_17425255_2022_2138330
crossref_primary_10_1177_1756286419846818
crossref_primary_10_1177_1352458520929628
crossref_primary_10_1007_s00415_021_10556_z
crossref_primary_10_1007_s40278_017_33427_6
crossref_primary_10_1111_cen3_12477
crossref_primary_10_1016_j_jns_2020_117156
crossref_primary_10_1177_13524585251342727
crossref_primary_10_3389_fneur_2018_00782
crossref_primary_10_1016_j_jns_2018_06_001
crossref_primary_10_1136_jnnp_2022_329607
crossref_primary_10_3390_cells10113177
crossref_primary_10_1080_14737175_2025_2508777
crossref_primary_10_1007_s00415_025_13283_x
crossref_primary_10_1017_cjn_2018_17
crossref_primary_10_1007_s11910_023_01306_x
crossref_primary_10_3389_fimmu_2023_1115120
crossref_primary_10_1155_2018_5190794
crossref_primary_10_3389_fimmu_2018_02669
crossref_primary_10_1016_j_msard_2018_08_006
crossref_primary_10_1111_cns_12992
crossref_primary_10_2147_DDDT_S240861
crossref_primary_10_1016_j_msard_2017_05_003
crossref_primary_10_1016_j_msard_2018_02_031
crossref_primary_10_1093_brain_awae409
crossref_primary_10_1016_S1634_7072_24_49343_4
crossref_primary_10_1186_s12883_024_03793_y
crossref_primary_10_1111_ane_12882
crossref_primary_10_3390_cells11132058
crossref_primary_10_1007_s00415_019_09272_6
crossref_primary_10_1080_14656566_2017_1372747
crossref_primary_10_1111_ene_13536
crossref_primary_10_3389_fneur_2022_824926
crossref_primary_10_1177_1352458517741191
crossref_primary_10_3390_biomedicines8070227
crossref_primary_10_1007_s00415_022_11341_2
crossref_primary_10_1016_j_msard_2022_104157
crossref_primary_10_1212_WNL_0000000000201029
crossref_primary_10_1136_jnnp_2022_330104
crossref_primary_10_1002_jcph_945
crossref_primary_10_1016_j_msard_2020_102727
crossref_primary_10_1177_17562864211006499
crossref_primary_10_1186_s12883_021_02058_2
crossref_primary_10_1016_j_msard_2018_09_017
crossref_primary_10_1016_j_neurol_2019_08_008
crossref_primary_10_1155_2016_1034912
crossref_primary_10_1212_NXI_0000000000000719
crossref_primary_10_1007_s00415_019_09450_6
crossref_primary_10_1177_13524585211049986
crossref_primary_10_1016_j_ejmech_2025_117508
crossref_primary_10_1016_j_msard_2023_105134
crossref_primary_10_1212_WNL_0000000000004354
crossref_primary_10_1177_17562864231162153
crossref_primary_10_3389_fmed_2025_1593933
crossref_primary_10_1007_s40120_022_00339_7
crossref_primary_10_1016_j_msard_2021_102981
crossref_primary_10_1016_j_msard_2021_103278
crossref_primary_10_1016_j_msard_2023_104564
crossref_primary_10_1177_13524585221111677
crossref_primary_10_1016_j_ncl_2018_09_007
crossref_primary_10_1007_s40120_024_00654_1
crossref_primary_10_1007_s40265_023_01942_0
crossref_primary_10_1007_s11940_024_00814_6
crossref_primary_10_1016_j_msard_2018_11_034
crossref_primary_10_1002_acn3_410
crossref_primary_10_1007_s00415_019_09424_8
crossref_primary_10_1007_s11055_018_0619_z
crossref_primary_10_1212_CON_0000000000000738
crossref_primary_10_1111_ane_12864
crossref_primary_10_1177_1352458517751049
crossref_primary_10_1007_s40265_017_0814_1
crossref_primary_10_1177_1756286420936166
crossref_primary_10_1016_j_msard_2023_105100
crossref_primary_10_1177_13524585231200719
crossref_primary_10_1016_j_intimp_2023_111192
crossref_primary_10_1016_j_msard_2020_101938
crossref_primary_10_1016_j_msard_2021_103329
crossref_primary_10_1016_j_pharmthera_2017_11_001
crossref_primary_10_1016_j_jns_2017_07_014
crossref_primary_10_1038_s41582_019_0170_8
crossref_primary_10_1177_17562864221150312
crossref_primary_10_1007_s40266_019_00741_1
crossref_primary_10_36290_neu_2017_095
crossref_primary_10_1007_s00415_021_10956_1
crossref_primary_10_1016_j_nerep_2023_100175
crossref_primary_10_1016_j_msard_2019_101883
crossref_primary_10_1111_cen3_12397
crossref_primary_10_1007_s13311_017_0568_1
crossref_primary_10_1007_s40120_019_00160_9
crossref_primary_10_1016_j_msard_2019_101483
crossref_primary_10_1080_14740338_2024_2448826
crossref_primary_10_1007_s00415_021_10658_8
crossref_primary_10_1136_jnnp_2022_328797
crossref_primary_10_36290_neu_2016_064
crossref_primary_10_1177_1352458517731913
crossref_primary_10_1097_NRL_0000000000000154
crossref_primary_10_1016_j_msard_2020_101927
crossref_primary_10_1212_NXI_0000000000200110
crossref_primary_10_1212_NXI_0000000000200231
crossref_primary_10_1007_s15202_018_1900_2
crossref_primary_10_1177_1352458516682858
crossref_primary_10_1007_s40278_016_17554_2
crossref_primary_10_1016_j_jneuroim_2021_577599
crossref_primary_10_1111_cen3_12441
crossref_primary_10_1177_2055217318759692
crossref_primary_10_1002_acn3_52017
crossref_primary_10_1212_NXI_0000000000000874
crossref_primary_10_1002_advs_202300738
crossref_primary_10_7759_cureus_84587
crossref_primary_10_1177_13524585211005657
crossref_primary_10_1080_14737175_2023_2208347
crossref_primary_10_1016_j_neurol_2022_11_003
crossref_primary_10_1177_1756286419837809
crossref_primary_10_2217_nmt_2021_0005
crossref_primary_10_1016_j_msard_2020_102529
crossref_primary_10_1111_ene_13694
crossref_primary_10_7224_1537_2073_2023_050
crossref_primary_10_3389_fimmu_2018_01560
crossref_primary_10_1177_17562864241239117
crossref_primary_10_1080_14656566_2020_1774554
crossref_primary_10_1007_s00415_017_8594_9
crossref_primary_10_1177_2055217317730096
crossref_primary_10_1007_s11910_024_01355_w
crossref_primary_10_1111_ene_70282
crossref_primary_10_1038_s41586_021_03227_6
crossref_primary_10_1007_s00415_021_10708_1
crossref_primary_10_1007_s40261_019_00804_6
crossref_primary_10_1016_j_msard_2018_07_001
crossref_primary_10_1016_j_neurot_2025_e00582
crossref_primary_10_1016_j_msard_2024_105757
crossref_primary_10_1016_j_msard_2019_101517
crossref_primary_10_1016_j_msard_2022_104066
crossref_primary_10_3390_cells9020482
crossref_primary_10_1111_cen3_12470
crossref_primary_10_1016_j_msard_2022_103812
crossref_primary_10_1007_s40263_022_00965_7
crossref_primary_10_1155_2019_7151685
crossref_primary_10_3390_jcm11206033
crossref_primary_10_1177_17562864241300047
crossref_primary_10_1111_cen3_12504
crossref_primary_10_1002_jmv_26279
crossref_primary_10_1016_j_mycmed_2024_101529
crossref_primary_10_1007_s13311_021_01106_6
crossref_primary_10_1186_s41983_021_00386_1
crossref_primary_10_1212_NXI_0000000000000508
crossref_primary_10_1038_nrneurol_2016_192
crossref_primary_10_1007_s10072_025_08098_7
crossref_primary_10_1016_j_msard_2021_103072
ContentType Journal Article
DBID CGR
CUY
CVF
ECM
EIF
NPM
7U8
7X8
C1K
JXQ
DOI 10.1001/jamaneurol.2016.0826
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
TOXLINE
MEDLINE - Academic
Environmental Sciences and Pollution Management
Toxline
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
TOXLINE
MEDLINE - Academic
Environmental Sciences and Pollution Management
DatabaseTitleList MEDLINE
TOXLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: 7X8
  name: MEDLINE - Academic
  url: https://search.proquest.com/medline
  sourceTypes: Aggregation Database
DeliveryMethod no_fulltext_linktorsrc
Discipline Medicine
EISSN 2168-6157
EndPage 794
ExternalDocumentID 27135594
Genre Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural
GroupedDBID 0R~
4.4
53G
AAGZG
ABIVO
ABJNI
ACDNT
ACGFS
ACPRK
ADBBV
ADHGD
AENEX
AFRAH
AHMBA
ALMA_UNASSIGNED_HOLDINGS
AMJDE
ANMPU
BRYMA
C45
CGR
CUY
CVF
EBD
EBS
ECM
EIF
EJD
EMOBN
EX3
H13
NPM
OB2
OBH
OHH
OVD
PQQKQ
RAJ
SV3
TEORI
WOW
7U8
7X8
C1K
JXQ
ID FETCH-LOGICAL-a405t-f34ce9db517b96155e8104797d9f20f0ff884eccdafc9b6a811b5f5314e89a692
IEDL.DBID 7X8
ISICitedReferencesCount 165
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000379420500010&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
IngestDate Thu Jul 10 22:43:09 EDT 2025
Thu Apr 03 07:08:30 EDT 2025
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 7
Language English
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-a405t-f34ce9db517b96155e8104797d9f20f0ff884eccdafc9b6a811b5f5314e89a692
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
OpenAccessLink https://jamanetwork.com/journals/jamaneurology/articlepdf/2516773/noi160024.pdf
PMID 27135594
PQID 1803795772
PQPubID 23479
PageCount 5
ParticipantIDs proquest_miscellaneous_1803795772
pubmed_primary_27135594
PublicationCentury 2000
PublicationDate 2016-07-01
PublicationDateYYYYMMDD 2016-07-01
PublicationDate_xml – month: 07
  year: 2016
  text: 2016-07-01
  day: 01
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle JAMA neurology
PublicationTitleAlternate JAMA Neurol
PublicationYear 2016
References 27669336 - JAMA Neurol. 2016 Nov 1;73(11):1375
27669463 - JAMA Neurol. 2016 Nov 1;73(11):1375-1376
27669526 - JAMA Neurol. 2016 Nov 1;73(11):1376
27136400 - JAMA Neurol. 2016 Jul 1;73(7):775-6
References_xml – reference: 27669463 - JAMA Neurol. 2016 Nov 1;73(11):1375-1376
– reference: 27136400 - JAMA Neurol. 2016 Jul 1;73(7):775-6
– reference: 27669526 - JAMA Neurol. 2016 Nov 1;73(11):1376
– reference: 27669336 - JAMA Neurol. 2016 Nov 1;73(11):1375
SSID ssj0000800434
Score 2.567908
Snippet The appropriate sequencing of agents with strong immune system effects has become increasingly important. Transitions require careful balance between safety...
IMPORTANCEThe appropriate sequencing of agents with strong immune system effects has become increasingly important. Transitions require careful balance between...
SourceID proquest
pubmed
SourceType Aggregation Database
Index Database
StartPage 790
SubjectTerms Adult
Female
Fingolimod Hydrochloride - adverse effects
Humans
Immunosuppressive Agents - adverse effects
Longitudinal Studies
Magnetic Resonance Imaging
Middle Aged
Multiple Sclerosis - diagnostic imaging
Multiple Sclerosis - drug therapy
Multiple Sclerosis, Relapsing-Remitting - chemically induced
Multiple Sclerosis, Relapsing-Remitting - diagnostic imaging
PubMed - statistics & numerical data
Recurrence
Title Rebound Syndrome in Patients With Multiple Sclerosis After Cessation of Fingolimod Treatment
URI https://www.ncbi.nlm.nih.gov/pubmed/27135594
https://www.proquest.com/docview/1803795772
Volume 73
WOSCitedRecordID wos000379420500010&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText
inHoldings 1
isFullTextHit
isPrint
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8NAEF7Uinjx_agvVvC62iSbZPckpVi8tBRasQehZB-DAUmqqf5-Z5NtPQmCl9yyhPlmdz52Jt9HyI1SBqzihmnJU8aRUDOlQ8uSTIQa61tkkqw2m0iHQzGdypG_cKv8WOXyTKwPalNqd0d-F4hOlMoYyeD9_J051yjXXfUWGuukFSGVcVmdTsXqjsWxIR7x1R9zjdhQLRTpug5BcosFMPmdW9Y1pr_736_bIzueXdJukw77ZM0WB2Rr4Pvnh-QFo-l8lOjYCxXQvKCjRlq1os_54pUO_IQhHeMKWELzinadjzjtObMUByMtgfax4pVviLOhk-Wo-hF56j9Meo_M-yuwDGnagkHEtZVGxUGqpOtPWuGEG2RqJIQd6AAIwRFik4GWCtELAhUDblpuhcwSGR6TjaIs7CmhOozDTCO7yCLFIdBCAODiAEkM0kSmTa6XcZth_rqmBOJQflazn8i1yUkT_Nm8EdqYhc4_MJb87A9vn5Nth2gzSXtBWoC7116STf21yKuPqzox8DkcDb4BMBbHVA
linkProvider ProQuest
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Rebound+Syndrome+in+Patients+With+Multiple+Sclerosis+After+Cessation+of+Fingolimod+Treatment&rft.jtitle=JAMA+neurology&rft.au=Hatcher%2C+Stacy+Ellen&rft.au=Waubant%2C+Emmanuelle&rft.au=Nourbakhsh%2C+Bardia&rft.au=Crabtree-Hartman%2C+Elizabeth&rft.date=2016-07-01&rft.eissn=2168-6157&rft.volume=73&rft.issue=7&rft.spage=790&rft_id=info:doi/10.1001%2Fjamaneurol.2016.0826&rft_id=info%3Apmid%2F27135594&rft_id=info%3Apmid%2F27135594&rft.externalDocID=27135594