BACKGROUND: Gray matter magnetic resonance imaging T2 hypointensity, a marker of iron deposition, is associated with clinical impairment and brain atrophy in cross-sectional studies of multiple sclerosis. Treatment with intramuscular interferon beta-1a limits brain atrophy in the second year of treatment. OBJECTIVE: To test whether T2 hypointensity predicts brain atrophy and whether interferon affects this relationship. DESIGN: Post hoc analysis. SETTING: A multicenter treatment trial conducted at tertiary care comprehensive multiple sclerosis centers. Patients Patients with multiple sclerosis who took part in a 2-year clinical trial in which they receivedintramuscular interferon beta-1a (30 mug/wk) or placebo. MAIN OUTCOME MEASURES: Deep gray matter T2 hypointensity, brain parenchymal fraction (BPF), and total T2, gadolinium-enhancing, and T1 lesion volumes. RESULTS: T2 hypointensity in various gray matter areas correlated with baseline BPF (r = 0.19-0.39; P = .001-.03). In placebo-treated patients (n = 68), baseline T2 hypointensity predicted the change in BPF in the first year and throughout 2 years (r = 0.26-0.42; P<.001-.03). T2 hypointensity was chosen in regression modeling as the best predictor of BPF change at the 1-year (R(2) = 0.23; P = .002) and 2-year (R(2) = 0.33; P<.001) time points after accounting for all magnetic resonance imaging variables. In the interferon group (n = 65), no relationship existed between baseline T2 hypointensity and BPF change. CONCLUSIONS: Gray matter T2 hypointensity predicts the progression of brain atrophy in placebo- but not interferon beta-1a-treated patients. This predictive effect is seen as early as the first year. We hypothesize that interferon beta may exert its effect on brain atrophy in part by reducing a cascade of events that involve iron deposition as a mediator of neurotoxicity or as a disease epiphenomenon.
RCT Entities:
BACKGROUND: Gray matter magnetic resonance imaging T2 hypointensity, a marker of iron deposition, is associated with clinical impairment and brain atrophy in cross-sectional studies of multiple sclerosis. Treatment with intramuscular interferon beta-1a limits brain atrophy in the second year of treatment. OBJECTIVE: To test whether T2 hypointensity predicts brain atrophy and whether interferon affects this relationship. DESIGN: Post hoc analysis. SETTING: A multicenter treatment trial conducted at tertiary care comprehensive multiple sclerosis centers. PatientsPatients with multiple sclerosis who took part in a 2-year clinical trial in which they received intramuscular interferon beta-1a (30 mug/wk) or placebo. MAIN OUTCOME MEASURES: Deep gray matter T2 hypointensity, brain parenchymal fraction (BPF), and total T2, gadolinium-enhancing, and T1 lesion volumes. RESULTS: T2 hypointensity in various gray matter areas correlated with baseline BPF (r = 0.19-0.39; P = .001-.03). In placebo-treated patients (n = 68), baseline T2 hypointensity predicted the change in BPF in the first year and throughout 2 years (r = 0.26-0.42; P<.001-.03). T2 hypointensity was chosen in regression modeling as the best predictor of BPF change at the 1-year (R(2) = 0.23; P = .002) and 2-year (R(2) = 0.33; P<.001) time points after accounting for all magnetic resonance imaging variables. In the interferon group (n = 65), no relationship existed between baseline T2 hypointensity and BPF change. CONCLUSIONS: Gray matter T2 hypointensity predicts the progression of brain atrophy in placebo- but not interferon beta-1a-treated patients. This predictive effect is seen as early as the first year. We hypothesize that interferon beta may exert its effect on brain atrophy in part by reducing a cascade of events that involve iron deposition as a mediator of neurotoxicity or as a disease epiphenomenon.
Authors: L D Jacobs; D L Cookfair; R A Rudick; R M Herndon; J R Richert; A M Salazar; J S Fischer; D E Goodkin; C V Granger; J H Simon Journal: Mult Scler Date: 1995-06 Impact factor: 6.312
Authors: Rohit Bakshi; Alan J Thompson; Maria A Rocca; Daniel Pelletier; Vincent Dousset; Frederik Barkhof; Matilde Inglese; Charles R G Guttmann; Mark A Horsfield; Massimo Filippi Journal: Lancet Neurol Date: 2008-07 Impact factor: 44.182
Authors: P Schmalbrock; R S Prakash; B Schirda; A Janssen; G K Yang; M Russell; M V Knopp; A Boster; J A Nicholas; M Racke; D Pitt Journal: AJNR Am J Neuroradiol Date: 2015-11-26 Impact factor: 3.825
Authors: Y Ge; J H Jensen; H Lu; J A Helpern; L Miles; M Inglese; J S Babb; J Herbert; R I Grossman Journal: AJNR Am J Neuroradiol Date: 2007-09-24 Impact factor: 3.825