In:
Neurology - Neuroimmunology Neuroinflammation, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 2 ( 2019-03), p. e530-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2332-7812
DOI:
10.1212/NXI.0000000000000530
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2019
detail.hit.zdb_id:
2767740-0
