Cerebral Microbleeds in Multiple Sclerosis Evaluated on Susceptibility-weighted Images and Quantitative Susceptibility Maps: A Case-Control Study.
Purpose To assess cerebral microbleed (CMB) prevalence in patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS) and associations with clinical outcomes. Materials and Methods CMBs are associated with aging and neurodegenerative disorders. The prevalence of CMBs has not previously been well established. In this study, 445 patients with MS (266 with relapsing-remitting MS, 138 with secondary progressive MS, and 41 with primary progressive MS), 45 patients with CIS, 51 patients with other neurological diseases, and 177 healthy control subjects (HCs) underwent 3-T magnetic resonance (MR) imaging and clinical examinations. A subset of 168 patients with MS and 50 HCs underwent neuropsychological testing. Number of CMBs was assessed on susceptibility-weighted minimum intensity projections by using the Microbleed Anatomic Rating Scale; volume was calculated by using quantitative susceptibility maps. Differences between groups were analyzed with the χ2test, Fisher exact test, Student t test, and analysis of variance; associations of CMBs with clinical and other MR imaging outcomes were explored with correlation and regression analyses. Because CMB frequency increases with age, prevalence was investigated in participants at least 50 years of age and younger than 50 years. Results Significantly more patients with MS than HCs had CMBs (19.8% vs 7.4%, respectively; P = .01) in the group at least 50 years old. A trend toward greater presence of CMBs was found in patients with MS (P = .016) and patients with CIS who were younger than 50 years (P = .039) compared with HCs. In regression analysis adjusted for age, hypertension, and normalized brain volume, increased number of CMBs was significantly associated with increased physical disability in the MS population (R2= 0.23, P < .0001). In correlation analysis, increased number of CMBs was significantly associated with deteriorated auditory and verbal learning and memory (P = .006) and visual information processing speed trends (P = .049) in patients with MS. Conclusion Monitoring CMBs may be relevant in patients with MS and CIS at higher risk for developing cognitive and physical disability.©RSNA, 2016 Online supplemental material is available for this article.
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
Robert
R
Zivadinov
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
Deepa P
DP
Ramasamy
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
Ralph R H
RR
Benedict
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
Paul
P
Polak
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
Jesper
J
Hagemeier
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
Christopher
C
Magnano
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
Michael G
MG
Dwyer
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
Niels
http://orcid.org/0000-0002-7792-0433
N
Bergsland
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
Nicola
N
Bertolino
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
Bianca
B
Weinstock-Guttman
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
Channa
C
Kolb
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
David
D
Hojnacki
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
David
D
Utriainen
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
E Mark
EM
Haacke
From the Buffalo Neuroimaging Analysis Ctr, Dept of Neurology (R.Z., D.P.R., P.P., J.H., C.M., M.G.D., N. Bergsland, N. Bertolino, F.S.), MR Imaging Clinical and Translational Research Ctr (R.Z., C.M., F.S.), and Jacobs Multiple Sclerosis Ctr, Dept of Neurology (R.R.H.B., B.W.G., C.K., D.H.), Jacobs School of Medicine and Biomedical Sciences, Univ at Buffalo, The State Univ of New York, 100 High St, Buffalo, NY 14203; GE Healthcare, Waukesha, Wis (C.M.); Magnetic Resonance Laboratory, IRCCS Don Gnocchi Foundation, Milan, Italy (N. Bergsland); Magnetic Resonance Innovations, Detroit, Mich (D.U.); Dept of Radiology, Wayne State Univ, Detroit, Mich (E.M.H.); School of Biomedical Engineering, McMaster Univ, Hamilton, Ontario, Canada (E.M.H.); and Shanghai Key Laboratory of Magnetic Resonance, East China Normal Univ, Shanghai, China (E.M.H.).
Ferdinand
F
Schweser
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000473:pathology; D004185:Disability Evaluation; D006233:Persons with Disabilities; D004198:Disease Susceptibility; D006801:Humans; D007859:Learning Disabilities / Q000209:etiology / Q000473:pathology; D018810:Magnetic Resonance Angiography; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications* / Q000473:pathology; D009483:Neuropsychological Tests; D011446:Prospective Studies; D055815:Young Adult