RT Journal Article
SR Electronic
T1 MRI phenotypes in MS
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e530
DO 10.1212/NXI.0000000000000530
VO 6
IS 2
A1 Hemond, Christopher C.
A1 Healy, Brian C.
A1 Tauhid, Shahamat
A1 Mazzola, Maria A.
A1 Quintana, Francisco J.
A1 Gandhi, Roopali
A1 Weiner, Howard L.
A1 Bakshi, Rohit
YR 2019
UL http://nn.neurology.org/content/6/2/e530.abstract
AB 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.BPF=brain parenchymal fraction; Cq=cycle quantification; EDSS=Expanded Disability Status Scale; miRNA=microRNA; SP=secondary progressive; T2LV=T2-hyperintense lesion volume