Multiple sclerosis lesion formation and early evolution revisited: A weekly high-resolution magnetic resonance imaging study

Mult Scler. 2016 May;22(6):761-9. doi: 10.1177/1352458515600247. Epub 2015 Sep 11.


Background: Several magnetic resonance imaging (MRI) studies investigated the evolution of multiple sclerosis (MS) lesions to understand the pathophysiological mechanisms leading to blood-brain barrier breakdown and lesion formation. Only a few assessed the early natural history of MS lesions using short-interval longitudinal MRI.

Objective: The purpose of this study was to characterize MS lesion occurrence and early evolution on high-resolution MRI acquired at weekly intervals.

Methods: Active lesions were characterized on 3D fluid attenuation inversion recovery (FLAIR) and gadolinium-enhanced 3D T1-weighted MRI performed weekly (seven weeks) on five untreated patients with relapsing-remitting MS (RRMS).

Results: Active lesions (n=212) were detected in all patients. All showed contrast-enhancement on at least one time-point. Most new lesions (83.5%) were visible on FLAIR and post-contrast T1-weighted images at first detection; 11.2% showed activity on FLAIR images, one or more weeks before the appearance of contrast-enhancement; 12.5% enhanced before being apparent on FLAIR.

Conclusion: Blood brain barrier disruption is a constant step in the natural history of active MS lesions, but does not always constitute the initial event. These findings are consistent with the existence of a subpopulation of lesions with an 'inside-out' genesis, where neurodegenerative processes might precede microglial activation, and a subsequent adaptive immune response.

Keywords: Magnetic resonance imaging; T2 lesions; multiple sclerosis; relapsing–remitting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Disease Progression*
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging*