The Effect of Fingolimod on Conversion of Acute Gadolinium-Enhancing Lesions to Chronic T1 Hypointensities in Multiple Sclerosis

J Neuroimaging. 2016 Mar-Apr;26(2):184-7. doi: 10.1111/jon.12307. Epub 2015 Oct 8.

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).

Conclusion: 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.

Keywords: Black holes; MRI; Multiple sclerosis; fingolimod; gadolinium-enhancing lesions.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / pathology
  • Female
  • Fingolimod Hydrochloride / pharmacology*
  • Fingolimod Hydrochloride / therapeutic use
  • Gadolinium
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / therapeutic use
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnostic imaging*
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / pathology
  • Pilot Projects
  • Retrospective Studies
  • Treatment Outcome
  • White Matter / diagnostic imaging
  • White Matter / drug effects*
  • White Matter / pathology

Substances

  • Immunosuppressive Agents
  • Gadolinium
  • Fingolimod Hydrochloride