Disability-Specific Atlases of Gray Matter Loss in Relapsing-Remitting Multiple Sclerosis

Overview

Journal JAMA Neurol

Publisher American Medical Association

Date 2016 Jun 14

PMID 27294295

Citations 16

Authors

Allan MacKenzie-Graham

Florian Kurth

Yuichiro Itoh

He-Jing Wang

Michael J Montag

Robert Elashoff

Rhonda R Voskuhl

Affiliations

Soon will be listed here.

Abstract

Importance: Multiple sclerosis (MS) is characterized by progressive gray matter (GM) atrophy that strongly correlates with clinical disability. However, whether localized GM atrophy correlates with specific disabilities in patients with MS remains unknown.

Objective: To understand the association between localized GM atrophy and clinical disability in a biology-driven analysis of MS.

Design, Setting, And Participants: In this cross-sectional study, magnetic resonance images were acquired from 133 women with relapsing-remitting MS and analyzed using voxel-based morphometry and volumetry. A regression analysis was used to determine whether voxelwise GM atrophy was associated with specific clinical deficits. Data were collected from June 28, 2007, to January 9, 2014.

Main Outcomes And Measures: Voxelwise correlation of GM change with clinical outcome measures (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores).

Results: Among the 133 female patients (mean [SD] age, 37.4 [7.5] years), worse performance on the Multiple Sclerosis Functional Composite correlated with voxelwise GM volume loss in the middle cingulate cortex (P < .001) and a cluster in the precentral gyrus bilaterally (P = .004). In addition, worse performance on the Paced Auditory Serial Addition Test correlated with volume loss in the auditory and premotor cortices (P < .001), whereas worse performance on the 9-Hole Peg Test correlated with GM volume loss in Brodmann area 44 (Broca area; P = .02). Finally, voxelwise GM loss in the right paracentral lobulus correlated with bowel and bladder disability (P = .03). Thus, deficits in specific clinical test results were directly associated with localized GM loss in clinically eloquent locations.

Conclusions And Relevance: These biology-driven data indicate that specific disabilities in MS are associated with voxelwise GM loss in distinct locations. This approach may be used to develop disability-specific biomarkers for use in future clinical trials of neuroprotective treatments in MS.

Citing Articles

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Voskuhl R, MacKenzie-Graham A Front Mol Neurosci. 2022; 15:1024058.

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References

Amunts K, Schleicher A, Burgel U, Mohlberg H, Uylings H, Zilles K . Broca's region revisited: cytoarchitecture and intersubject variability. J Comp Neurol. 1999; 412(2):319-41. DOI: 10.1002/(sici)1096-9861(19990920)412:2<319::aid-cne10>3.0.co;2-7. View

Binkofski F, Buccino G, Posse S, Seitz R, Rizzolatti G, Freund H . A fronto-parietal circuit for object manipulation in man: evidence from an fMRI-study. Eur J Neurosci. 1999; 11(9):3276-86. DOI: 10.1046/j.1460-9568.1999.00753.x. View

Nour S, Svarer C, Kristensen J, Paulson O, Law I . Cerebral activation during micturition in normal men. Brain. 2000; 123 ( Pt 4):781-9. DOI: 10.1093/brain/123.4.781. View

Thompson P, Mega M, Woods R, Zoumalan C, Lindshield C, Blanton R . Cortical change in Alzheimer's disease detected with a disease-specific population-based brain atlas. Cereb Cortex. 2000; 11(1):1-16. DOI: 10.1093/cercor/11.1.1. View

Morosan P, Rademacher J, Schleicher A, Amunts K, Schormann T, Zilles K . Human primary auditory cortex: cytoarchitectonic subdivisions and mapping into a spatial reference system. Neuroimage. 2001; 13(4):684-701. DOI: 10.1006/nimg.2000.0715. View

Ge Y, Grossman R, Udupa J, Babb J, Nyul L, Kolson D . Brain atrophy in relapsing-remitting multiple sclerosis: fractional volumetric analysis of gray matter and white matter. Radiology. 2001; 220(3):606-10. DOI: 10.1148/radiol.2203001776. View

Rizzolatti G, Fogassi L, Gallese V . Neurophysiological mechanisms underlying the understanding and imitation of action. Nat Rev Neurosci. 2001; 2(9):661-70. DOI: 10.1038/35090060. View

Mazziotta J, Toga A, Evans A, Fox P, Lancaster J, Zilles K . A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM). Philos Trans R Soc Lond B Biol Sci. 2001; 356(1412):1293-322. PMC: 1088516. DOI: 10.1098/rstb.2001.0915. View

Peterson J, Bo L, Mork S, Chang A, Trapp B . Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol. 2001; 50(3):389-400. DOI: 10.1002/ana.1123. View

10.

Ashburner J, Friston K . Why voxel-based morphometry should be used. Neuroimage. 2001; 14(6):1238-43. DOI: 10.1006/nimg.2001.0961. View

11.

Chard D, Griffin C, Parker G, Kapoor R, Thompson A, Miller D . Brain atrophy in clinically early relapsing-remitting multiple sclerosis. Brain. 2002; 125(Pt 2):327-37. DOI: 10.1093/brain/awf025. View

12.

Benedict R, Bakshi R, Simon J, Priore R, Miller C, Munschauer F . Frontal cortex atrophy predicts cognitive impairment in multiple sclerosis. J Neuropsychiatry Clin Neurosci. 2002; 14(1):44-51. DOI: 10.1176/jnp.14.1.44. View

13.

Hanakawa T, Honda M, Sawamoto N, Okada T, Yonekura Y, Fukuyama H . The role of rostral Brodmann area 6 in mental-operation tasks: an integrative neuroimaging approach. Cereb Cortex. 2002; 12(11):1157-70. DOI: 10.1093/cercor/12.11.1157. View

14.

Fisher E, Rudick R, Simon J, Cutter G, Baier M, Lee J . Eight-year follow-up study of brain atrophy in patients with MS. Neurology. 2002; 59(9):1412-20. DOI: 10.1212/01.wnl.0000036271.49066.06. View

15.

De Stefano N, Matthews P, Filippi M, Agosta F, De Luca M, Bartolozzi M . Evidence of early cortical atrophy in MS: relevance to white matter changes and disability. Neurology. 2003; 60(7):1157-62. DOI: 10.1212/01.wnl.0000055926.69643.03. View

16.

Sailer M, Fischl B, Salat D, Tempelmann C, Schonfeld M, Busa E . Focal thinning of the cerebral cortex in multiple sclerosis. Brain. 2003; 126(Pt 8):1734-44. DOI: 10.1093/brain/awg175. View

17.

Benedict R, Weinstock-Guttman B, Fishman I, Sharma J, Tjoa C, Bakshi R . Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden. Arch Neurol. 2004; 61(2):226-30. DOI: 10.1001/archneur.61.2.226. View

18.

Dalton C, Chard D, Davies G, Miszkiel K, Altmann D, Fernando K . Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. Brain. 2004; 127(Pt 5):1101-7. DOI: 10.1093/brain/awh126. View

19.

Hayasaka S, Phan K, Liberzon I, Worsley K, Nichols T . Nonstationary cluster-size inference with random field and permutation methods. Neuroimage. 2004; 22(2):676-87. DOI: 10.1016/j.neuroimage.2004.01.041. View

20.

Amato M, Bartolozzi M, Zipoli V, Portaccio E, Mortilla M, Guidi L . Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment. Neurology. 2004; 63(1):89-93. DOI: 10.1212/01.wnl.0000129544.79539.d5. View