TY - JOUR
T1 - Brain and retinal atrophy in African-Americans versus Caucasian-Americans with multiple sclerosis
T2 - A longitudinal study
AU - Caldito, Natalia Gonzalez
AU - Saidha, Shiv
AU - Sotirchos, Elias S.
AU - Dewey, Blake E.
AU - Cowley, Norah J.
AU - Glaister, Jeffrey
AU - Fitzgerald, Kathryn C.
AU - Al-Louzi, Omar
AU - Nguyen, James
AU - Rothman, Alissa
AU - Ogbuokiri, Esther
AU - Fioravante, Nicholas
AU - Feldman, Sydney
AU - Kwakyi, Ohemaa
AU - Risher, Hunter
AU - Kimbrough, Dorlan
AU - Frohman, Teresa C.
AU - Frohman, Elliot
AU - Balcer, Laura
AU - Crainiceanu, Ciprian
AU - Van Zijl, Peter C.M.
AU - Mowry, Ellen M.
AU - Reich, Daniel S.
AU - Oh, Jiwon
AU - Pham, Dzung L.
AU - Prince, Jerry
AU - Calabresi, Peter A.
N1 - Funding Information:
This study was funded by the NIH/NINDS [R01NS082347 (to P.A.C.), National MS Society [RG-1606-08768 (to S.S.), TR-3760-A-3 (to P.A.C.) and RG-4212-A-4 (to L.J.B. subcontracted to P.A.C.), RG-1507-05243 (to D.P.)], Race to Erase MS (to S.S.), Intramural Research Program (to D.S.R.), and Walters Foundation (to E.M.F., P.A.C., and L.J.B).
Funding Information:
S.S. has received consulting fees from Medical Logix for the development of CME programs in neurology and has served on scientific advisory boards for Biogen-Idec, Genzyme, Genentech Corporation, EMD Serono and Novartis. He is the PI of investigator-initiated studies funded by Genentech Corporation and Biogen Idec, and received support from the Race to Erase MS foundation. He has received equity compensation for consulting from JuneBrain LLC, a retinal imaging device developer. He is also the site investigator of a trial sponsored by MedDay Pharmaceuticals. T.F. has received speaker and consulting fees from Acorda, Genzyme, and Novartis. E.F. has received speaker and consulting fees from Genzyme, Acorda, Novartis, and TEVA. L.B. has received consulting fees from Biogen. J.O. has received personal honoraria for consulting from Biogen-Idec, EMD-Serono, Novartis, Sanofi-Genzyme, and Roche. She is a PI on research grants to St. Michael’s Hospital from Biogen-Idec. E.M.
Publisher Copyright:
© The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - On average, African Americans with multiple sclerosis demonstrate higher inflammatory disease activity, faster disability accumulation, greater visual dysfunction, more pronounced brain tissue damage and higher lesion volume loads compared to Caucasian Americans with multiple sclerosis. Neurodegeneration is an important component of multiple sclerosis, which in part accounts for the clinical heterogeneity of the disease. Brain atrophy appears to be widespread, although it is becoming increasingly recognized that regional substructure atrophy may be of greater clinical relevance. Patient race (within the limitations of self-identified ancestry) is regarded as an important contributing factor. However, there is a paucity of studies examining differences in neurodegeneration and brain substructure volumes over time in African Americans relative to Caucasian American patients. Optical coherence tomography is a non-invasive and reliable tool for measuring structural retinal changes. Recent studies support its utility for tracking neurodegeneration and disease progression in vivo in multiple sclerosis. Relative to Caucasian Americans, African American patients have been found to have greater retinal structural injury in the inner retinal layers. Increased thickness of the inner nuclear layer and the presence of microcystoid macular pathology at baseline predict clinical and radiological inflammatory activity, although whether race plays a role in these changes has not been investigated. Similarly, assessment of outer retinal changes according to race in multiple sclerosis remains incompletely characterized. Twenty-two African Americans and 60 matched Caucasian Americans with multiple sclerosis were evaluated with brain MRI, and 116 African Americans and 116 matched Caucasian Americans with multiple sclerosis were monitored with optical coherence tomography over a mean duration of 4.5 years. Mixed-effects linear regression models were used in statistical analyses. Grey matter (-0.9%/year versus -0.5%: P =0.02), white matter (-0.7%/year versus -0.3%: P =0.04) and nuclear thalamic (-1.5%/year versus -0.7%/year: P =0.02) atrophy rates were approximately twice as fast in African Americans. African Americans also exhibited higher proportions of microcystoid macular pathology (12.1% versus 0.9%, P =0.001). Retinal nerve fibre layer (-1.1% versus -0.8%: P =0.02) and ganglion cell+ inner plexiform layer (-0.7%/year versus -0.4%/year: P =0.01) atrophy rates were faster in African versus Caucasian Americans. African Americans on average exhibited more rapid neurodegeneration than Caucasian Americans and had significantly faster brain and retinal tissue loss. These results corroborate the more rapid clinical progression reported to occur, in general, in African Americans with multiple sclerosis and support the need for future studies involving African Americans in order to identify individual differences in treatment responses in multiple sclerosis.
AB - On average, African Americans with multiple sclerosis demonstrate higher inflammatory disease activity, faster disability accumulation, greater visual dysfunction, more pronounced brain tissue damage and higher lesion volume loads compared to Caucasian Americans with multiple sclerosis. Neurodegeneration is an important component of multiple sclerosis, which in part accounts for the clinical heterogeneity of the disease. Brain atrophy appears to be widespread, although it is becoming increasingly recognized that regional substructure atrophy may be of greater clinical relevance. Patient race (within the limitations of self-identified ancestry) is regarded as an important contributing factor. However, there is a paucity of studies examining differences in neurodegeneration and brain substructure volumes over time in African Americans relative to Caucasian American patients. Optical coherence tomography is a non-invasive and reliable tool for measuring structural retinal changes. Recent studies support its utility for tracking neurodegeneration and disease progression in vivo in multiple sclerosis. Relative to Caucasian Americans, African American patients have been found to have greater retinal structural injury in the inner retinal layers. Increased thickness of the inner nuclear layer and the presence of microcystoid macular pathology at baseline predict clinical and radiological inflammatory activity, although whether race plays a role in these changes has not been investigated. Similarly, assessment of outer retinal changes according to race in multiple sclerosis remains incompletely characterized. Twenty-two African Americans and 60 matched Caucasian Americans with multiple sclerosis were evaluated with brain MRI, and 116 African Americans and 116 matched Caucasian Americans with multiple sclerosis were monitored with optical coherence tomography over a mean duration of 4.5 years. Mixed-effects linear regression models were used in statistical analyses. Grey matter (-0.9%/year versus -0.5%: P =0.02), white matter (-0.7%/year versus -0.3%: P =0.04) and nuclear thalamic (-1.5%/year versus -0.7%/year: P =0.02) atrophy rates were approximately twice as fast in African Americans. African Americans also exhibited higher proportions of microcystoid macular pathology (12.1% versus 0.9%, P =0.001). Retinal nerve fibre layer (-1.1% versus -0.8%: P =0.02) and ganglion cell+ inner plexiform layer (-0.7%/year versus -0.4%/year: P =0.01) atrophy rates were faster in African versus Caucasian Americans. African Americans on average exhibited more rapid neurodegeneration than Caucasian Americans and had significantly faster brain and retinal tissue loss. These results corroborate the more rapid clinical progression reported to occur, in general, in African Americans with multiple sclerosis and support the need for future studies involving African Americans in order to identify individual differences in treatment responses in multiple sclerosis.
KW - African American
KW - magnetic resonance imaging (MRI)
KW - multiple sclerosis
KW - optical coherence tomography (OCT)
KW - race
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U2 - 10.1093/brain/awy245
DO - 10.1093/brain/awy245
M3 - Article
C2 - 30312381
AN - SCOPUS:85055619692
SN - 0006-8950
VL - 141
SP - 3115
EP - 3129
JO - Brain
JF - Brain
IS - 11
ER -