Spinal cord atrophy as a primary outcome measure in phase II trials of progressive multiple sclerosis

Mult Scler. 2018 Jun;24(7):932-941. doi: 10.1177/1352458517709954. Epub 2017 May 18.


Objectives: To measure the development of spinal cord (SC) atrophy over 1 year in patients with progressive multiple sclerosis (PMS) and determine the sample sizes required to demonstrate a reduction in spinal cord cross-sectional area (SC-CSA) as an outcome measure in clinical trials.

Methods: In total, 44 PMS patients (26 primary progressive multiple sclerosis (PPMS), 18 secondary progressive multiple sclerosis (SPMS)) and 29 healthy controls (HCs) were studied at baseline and 12 months. SC-CSA was measured using the three-dimensional (3D) fast field echo sequences acquired at 3T and the active surface model. Multiple linear regressions were used to investigate changes in imaging measurements.

Results: PPMS patients had shorter disease duration, lower Expanded Disability Status Scale (EDSS) and larger SC-CSA than SPMS patients. All patients together showed a significantly greater decrease in percentage SC-CSA change than HCs, which was driven by the PPMS. All patients deteriorated over 1 year, but no association was found between percentage SC-CSA change and clinical changes. The sample size per arm required to detect a 50% treatment effect over 1 year, at 80% power, was 57 for PPMS and 546 for SPMS.

Conclusion: SC-CSA may become an outcome measure in trials of PPMS patients, when they are at an early stage of the disease, have moderate disability and modest SC atrophy.

Keywords: Multiple sclerosis; atrophy; magnetic resonance imaging; progressive; spinal cord.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atrophy / diagnostic imaging
  • Atrophy / pathology
  • Brain / pathology
  • Clinical Trials, Phase II as Topic*
  • Disease Progression
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnostic imaging
  • Multiple Sclerosis / pathology*
  • Outcome Assessment, Health Care*
  • Research Design
  • Retrospective Studies
  • Spinal Cord / diagnostic imaging
  • Spinal Cord / pathology*