title: The Effect of Fingolimod on Conversion of Acute Gadolinium-Enhancing Lesions to Chronic T1 Hypointensities in Multiple Sclerosis.
abstract: BACKGROUND
  Brain lesions converting to chronic T1 hypointensities ("chronic black holes" [CBH]), indicate severe tissue destruction (axonal loss and irreversible demyelination) in multiple sclerosis (MS). Two mechanisms by which fingolimod could limit MS lesion evolution include sequestration of lymphocytes in the periphery or direct neuroprotective effects. We investigated the effect of fingolimod on the evolution of acute gadolinium-enhancing (Gd+) brain lesions to CBH in patients with MS.
  
  
  METHODS
  This was a retrospective nonrandomized comparison of patients with Gd+ brain lesions at the time of starting oral fingolimod [.5 mg/day, n = 26, age (mean ± SD) 39.2 ± 10.6 years, Expanded Disability Status Scale (EDSS) score - median (range): 1.75 (0, 6.5)] to those on no therapy [n = 30, age 41.7 ± 9.3 years; EDSS 1.0 (0, 6)]. Each lesion was classified by whether it converted to a CBH in the year following treatment.
  
  
  RESULTS
  In the fingolimod group, 99 Gd+ baseline lesions (mean ± SD, range: 3.8 ± 5.1; 1, 21 per patient) were identified of which 25 (25%) evolved to CBH (1.0 ± 2.0; 0, 10 per patient). The untreated group had 62 baseline Gd+ lesions (2.1 ± 2.3; 1, 13), 26 (42%) of which evolved to CBH (.9 ± 1.4; 0, 7) (P = .063). Thirteen patients (50%) receiving fingolimod and 17 untreated patients (57%) developed CBH (P = .79).
  
  
  CONCLUSIONS
  This pilot study shows a trend of fingolimod on reducing the conversion rate from acute to chronic destructive MS lesions. Such an effect awaits verification in larger randomized prospective studies.
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School, Boston, MA.
authors.forename: Vinit V
authors.initials: VV
authors.lastname: Oommen
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School, Boston, MA.
authors.forename: Shahamat
authors.initials: S
authors.lastname: Tauhid
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School, Boston, MA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Healy
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School, Boston, MA.
authors.forename: Alicia S
authors.initials: AS
authors.lastname: Chua
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School, Boston, MA.
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Malik
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School, Boston, MA.
authors.forename: Camilo
authors.initials: C
authors.lastname: Diaz-Cruz
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School, Boston, MA.
authors.forename: Sheena L
authors.initials: SL
authors.lastname: Dupuy
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School, Boston, MA.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School, Boston, MA.
authors.forename: Tanuja
authors.initials: T
authors.lastname: Chitnis
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School, Boston, MA.|Department of Radiology, Brigham and Women's Hospital, Partners MS Center, Harvard Medical School, Boston, MA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Bakshi
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology* / Q000627:therapeutic use; D005682:Gadolinium; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D010865:Pilot Projects; D012189:Retrospective Studies; D016896:Treatment Outcome; D066127:White Matter / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology
chemical_list: D007166:Immunosuppressive Agents; D005682:Gadolinium; D000068876:Fingolimod Hydrochloride
keywords: Black holes; MRI; Multiple sclerosis; fingolimod; gadolinium-enhancing lesions