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


METHODS
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.


METHODS
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
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.
Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles.
Allan
A
MacKenzie-Graham
Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles.
Florian
F
Kurth
Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles.
Yuichiro
Y
Itoh
Department of Biomathematics, David Geffen School of Medicine at University of California, Los Angeles.
He-Jing
HJ
Wang
Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles.
Michael J
MJ
Montag
Department of Biomathematics, David Geffen School of Medicine at University of California, Los Angeles.
Robert
R
Elashoff
Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles.
Rhonda R
RR
Voskuhl
D000293:Adolescent; D000328:Adult; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D006233:Persons with Disabilities; D004964:Estriol / Q000627:therapeutic use; D005260:Female; D000068717:Glatiramer Acetate / Q000627:therapeutic use; D066128:Gray Matter / Q000000981:diagnostic imaging* / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D012044:Regression Analysis; D012720:Severity of Illness Index; D055815:Young Adult
D000068717:Glatiramer Acetate; D004964:Estriol