PT  - JOURNAL ARTICLE
AU  - Hemond, Christopher C.
AU  - Healy, Brian C.
AU  - Tauhid, Shahamat
AU  - Mazzola, Maria A.
AU  - Quintana, Francisco J.
AU  - Gandhi, Roopali
AU  - Weiner, Howard L.
AU  - Bakshi, Rohit
TI  - MRI phenotypes in MS
AID  - 10.1212/NXI.0000000000000530
DP  - 2019 Mar 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e530
VI  - 6
IP  - 2
4099  - http://nn.neurology.org/content/6/2/e530.short
4100  - http://nn.neurology.org/content/6/2/e530.full
SO  - Neurol Neuroimmunol Neuroinflamm2019 Mar 01; 6
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