Gray matter atrophy is related to long-term disability in multiple sclerosis.
OBJECTIVE
To determine the relation of gray matter (GM) and white matter (WM) brain volumes, and WM lesion load, with clinical outcomes 20 years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis (MS).


METHODS
Seventy-three patients were studied a mean of 20 years from first presentation with a clinically isolated syndrome (33 of whom developed relapsing-remitting MS and 11 secondary-progressive MS, with the rest experiencing no further definite neurological events), together with 25 healthy control subjects. GM and WM volumetric measures were obtained from three-dimensional T1-weighted brain magnetic resonance images using Statistical Parametric Mapping 2.


RESULTS
Significant GM (p < 0.001) and WM atrophy (p = 0.001) was seen in MS patients compared with control subjects. There was significantly more GM, but not WM atrophy, in secondary-progressive MS versus relapsing-remitting MS (p = 0.003), and relapsing-remitting MS versus clinically isolated syndrome (p < 0.001). GM, but not WM, fraction correlated with expanded disability status scale (r(s) = -0.48; p < 0.001) and MS Functional Composite scores (r(s) = 0.59; p < 0.001). WM lesion load correlated with GM (r(s) = -0.63; p < 0.001), but not with WM fraction. Regression modeling indicated that the GM fraction explained more of the variability in clinical measures than did WM lesion load.


CONCLUSIONS
In MS patients with a relatively long and homogeneous disease duration, GM atrophy is more marked than WM atrophy, and reflects disease subtype and disability to a greater extent than WM atrophy or lesions.
Fisniku
Leonora K
LK
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, UK. l.fisniku@ion.ucl.ac.uk
Chard
Declan T
DT
Jackson
Jonathan S
JS
Anderson
Valerie M
VM
Altmann
Daniel R
DR
Miszkiel
Katherine A
KA
Thompson
Alan J
AJ
Miller
David H
DH
D000328:Adult; D001284:Atrophy / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D015331:Cohort Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology / Q000503:physiopathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D011379:Prognosis; D012720:Severity of Illness Index; D013995:Time