MRI phenotypes in MS: Longitudinal changes and miRNA signatures

Neurol Neuroimmunol Neuroinflamm. 2019 Feb 14;6(2):e530. doi: 10.1212/NXI.0000000000000530. eCollection 2019 Mar.


Objective: To classify and immunologically characterize persons with MS based on brain lesions and atrophy and their associated microRNA profiles.

Methods: Cerebral T2-hyperintense lesion volume (T2LV) and brain parenchymal fraction (BPF) were quantified and used to define MRI phenotypes as follows: type I: low T2LV, low atrophy; type II: high T2LV, low atrophy; type III: low T2LV, high atrophy; type IV: high T2LV, high atrophy, in a large cross-sectional cohort (n = 1,088) and a subset with 5-year lngitudinal follow-up (n = 153). Serum miRNAs were assessed on a third MS cohort with 2-year MRI phenotype stability (n = 98).

Results: One-third of the patients had lesion-atrophy dissociation (types II or III) in both the cross-sectional and longitudinal cohorts. At 5 years, all phenotypes had progressive atrophy (p < 0.001), disproportionally in type II (BPF -2.28%). Only type IV worsened in physical disability. Types I and II showed a 5-year MRI phenotype conversion rate of 33% and 46%, whereas III and IV had >90% stability. Type II switched primarily to IV (91%); type I switched primarily to II (47%) or III (37%). Baseline higher age (p = 0.006) and lower BPF (p < 0.001) predicted 5-year phenotype conversion. Each MRI phenotype demonstrated an miRNA signature whose underlying biology implicates blood-brain barrier pathology: hsa.miR.22.3p, hsa.miR.361.5p, and hsa.miR.345.5p were the most valid differentiators of MRI phenotypes.

Conclusions: MRI-defined MS phenotypes show high conversion rates characterized by the continuation of either predominant neurodegeneration or inflammation and support the partial independence of these 2 measures. MicroRNA signatures of these phenotypes suggest a role for blood-brain barrier integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atrophy / pathology
  • Brain / pathology*
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging / methods
  • Male
  • MicroRNAs / blood
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multiple Sclerosis / pathology*
  • Retrospective Studies


  • MIRN22 microRNA, human
  • MIRN345 microRNA, human
  • MIRN361 microRNA, human
  • MicroRNAs