Differential Impact of Multiple Sclerosis on Cortical and Deep Gray Matter Structures in African Americans and Caucasian Americans

Al‐Kawaz, Mais; Monohan, Elizabeth; Morris, Eric D.; Perumal, Jai; Nealon, Nancy; Vartanian, Timothy; Gauthier, Susan A.

doi:10.1111/jon.12393

Cited by 18 publications

(15 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The increase in outer retinal layer thicknesses in African Americans likely relates to the marked predilection for MMP noted, and is relevant as MMP has been shown to be a potential marker of disability in multiple sclerosis. In general, our study findings are collectively consistent with a more inflammatory disease course, as well as more profound neurodegeneration, in African Americans and are in accordance with prior suggestions that multiple sclerosis may have a more ominous disease course in the African American population (Kaufman et al, 2003;Cree et al, 2004;Naismith et al, 2006;Weinstock-Guttman et al, 2010;Howard et al, 2012;Kimbrough et al, 2015;Seraji-Bozorgzad et al, 2016;Al-Kawaz et al, 2017). Based on our exploratory statistical analyses, our study findings suggest that, at least in part, the accelerated rates of MRI derived brain substructure atrophy observed in African Americans as compared to Caucasian Americans are independent of overt T 2 lesion accumulation.…”

Section: Discussionsupporting

confidence: 92%

“…Despite its potential clinical relevance, there are few longitudinal studies definitively characterizing neurodegeneration according to race. It has been shown cross-sectionally that African Americans with multiple sclerosis have greater reductions in whole brain volumes, greater aberrations in MTR measures, and higher T 2 and T 1 lesion volumes as compared to Caucasian Americans (Weinstock-Guttman et al, 2010;Al-Kawaz et al, 2017). However, there is a paucity of longitudinal studies examining MRI volumetrics in African American patients, and the regional or brain substructure atrophy that may be of greater clinical relevance than whole brain atrophy (Bermel and Bakshi, 2006;Horakova et al, 2012;Minagar et al, 2013) has remained largely unexplored with respect to the impact of race.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Brain and retinal atrophy in African-Americans versus Caucasian-Americans with multiple sclerosis: a longitudinal study

Caldito

Saidha

Sotirchos

et al. 2018

Brain

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Brain and retinal atrophy in African-Americans versus Caucasian-Americans with multiple sclerosis: a longitudinal study

Caldito

Saidha

Sotirchos

et al. 2018

Brain

View full text Add to dashboard Cite

show abstract

“…The most commonly-assessed aspect of brain atrophy is whole brain volume, due to the availability of numerous highly reliable and sensitive methods for its measurement [ 1 , 4 ]. Analysis of regional brain volume also has important implications related to clinical impairment, disease progression, and therapeutic monitoring [ 5 , 6 ]. Gray matter (GM) tissue loss is of particular importance because of its functional relevance.…”

Section: Introductionmentioning

confidence: 99%

Whole brain and deep gray matter atrophy detection over 5 years with 3T MRI in multiple sclerosis using a variety of automated segmentation pipelines

et al. 2018

View full text Add to dashboard Cite

BackgroundCerebral atrophy is common in multiple sclerosis (MS) and selectively involves gray matter (GM). Several fully automated methods are available to measure whole brain and regional deep GM (DGM) atrophy from MRI.ObjectiveTo assess the sensitivity of fully automated MRI segmentation pipelines in detecting brain atrophy in patients with relapsing-remitting (RR) MS and normal controls (NC) over five years.MethodsConsistent 3D T1-weighted sequences were performed on a 3T GE unit in 16 mildly disabled patients with RRMS and 16 age-matched NC at baseline and five years. All patients received disease-modifying immunotherapy on-study. Images were applied to two pipelines to assess whole brain atrophy [brain parenchymal fraction (BPF) from SPM12; percentage brain volume change (PBVC) from SIENA] and two other pipelines (FSL-FIRST; FreeSurfer) to assess DGM atrophy (thalamus, caudate, globus pallidus, putamen). MRI change was compared by two sample t-tests. Expanded Disability Status Scale (EDSS) and timed 25-foot walk (T25FW) change was compared by repeated measures proportional odds models.ResultsUsing FreeSurfer, the MS group had a ~10-fold acceleration in on-study volume loss than NC in the caudate (mean decrease 0.51 vs. 0.05 ml, p = 0.022). In contrast, caudate atrophy was not detected by FSL-FIRST (mean decrease 0.21 vs. 0.12 ml, p = 0.53). None of the other pipelines showed any difference in volume loss between groups, for whole brain or regional DGM atrophy (all p>0.38). The MS group showed on-study stability on EDSS (p = 0.47) but slight worsening of T25FW (p = 0.054).ConclusionsIn this real-world cohort of mildly disabled treated patients with RRMS, we identified ongoing atrophy of the caudate nucleus over five years, despite the lack of any significant whole brain atrophy, compared to healthy controls. The detectability of caudate atrophy was dependent on the MRI segmentation pipeline employed. These findings underscore the increased sensitivity gained when assessing DGM atrophy in monitoring MS.

show abstract

“…1,2 Paraclinical measures of CNS inflammation (T2 lesion accumulation and lesion volume) may be pronounced, 3,4 whereas atrophy metrics, including brain and retinal degeneration, appear accelerated among BALAwMS compared with CAwMS. 5–7 Ethno-ancestry is clearly an important consideration in MS. Unfortunately, the paradox of ethno-ancestry being simultaneously relevant in MS yet underrepresented in both clinical and translational investigation is apparent both in clinical trials and observational research.…”

mentioning

confidence: 99%

Black African and Latino/a identity correlates with increased plasmablasts in MS

Telesford

Kaunzner

Perumal

et al. 2020

Neurol Neuroimmunol Neuroinflamm

Self Cite

View full text Add to dashboard Cite

ObjectiveTo determine the influence of self-reported Black African and Latin American identity on peripheral blood antibody-secreting cell (ASC) frequency in the context of relapsing-remitting MS.MethodsIn this cross-sectional study, we recruited 74 subjects with relapsing-remitting MS and 24 age-, and self-reported ethno-ancestral identity-matched healthy donors (HDs) to provide peripheral blood study samples. Subjects with MS were either off therapy at the time of study draw or on monthly natalizumab therapy infusions. Using flow cytometry, we assessed peripheral blood mononuclear cells for antibody-secreting B-cell subsets.ResultsWhen stratified by self-reported ethno-ancestry, we identified significantly elevated frequencies of circulating plasmablasts among individuals with MS identifying as Black African or Latin American relative to those of Caucasian ancestry. Ethno-ancestry–specific differences in ASC frequency were observed only among individuals with MS. By contrast, this differential was not observed among HDs. ASCs linked with poorer MS prognosis and active disease, including IgM+- and class-switched CD138+ subsets, were among those significantly increased.ConclusionThe enhanced peripheral blood plasmablast signature revealed among Black African or Latin American subjects with MS points to distinct underlying mechanisms associated with MS immunopathogenesis. This dysregulation may contribute to the disease disparity experienced by patient populations of Black African or Latin American ethno-ancestry.

show abstract

Differential Impact of Multiple Sclerosis on Cortical and Deep Gray Matter Structures in African Americans and Caucasian Americans

Abstract: AAwMS and CAwMS patients differ with regard to global and regional cortical thickness and thalamic volume. This diverging pattern of gray matter volumetrics among otherwise matched patients suggests that racial-specific disease differences may exist.

Cited by 18 publications

References 34 publications

Brain and retinal atrophy in African-Americans versus Caucasian-Americans with multiple sclerosis: a longitudinal study

Brain and retinal atrophy in African-Americans versus Caucasian-Americans with multiple sclerosis: a longitudinal study

Whole brain and deep gray matter atrophy detection over 5 years with 3T MRI in multiple sclerosis using a variety of automated segmentation pipelines

Black African and Latino/a identity correlates with increased plasmablasts in MS

Contact Info

Product

Resources

About