Gray matter (GM) pathology is an important component of the multiple sclerosis (MS)
disease process. Accelerated gray matter atrophy has been observed in MS patients,
but its relationship to neurological disability is not defined. This study was done
to determine the relationship between whole brain, GM, and white matter (WM) atrophy
and MS disability progression.
Patients with MS and Clinically Isolated Syndromes (CIS), and age- and gender-matched
healthy controls were entered into an observational protocol. Baseline brain parenchymal
fraction (BPF), GM fraction, and WM fraction, and change over 4 years were correlated
with sustained disability progression over the entire study duration. Disability progression
was measured using the Multiple Sclerosis Functional Composite (MSFC) and the Expanded
Disability Status Scale (EDSS).
Seventy MS and CIS patients and 17 HCs were studied for an average of 6.6 years (range,
3.6-7.8 years). At the final visit, 7 patients were classified as CIS, 36 as relapsing-remitting
MS (RRMS), and 27 as secondary progressive MS (SPMS). Baseline whole brain, GM, and
WM atrophy predicted EDSS >6.0 at the last study visit. Twenty-one (33%) patients
worsened using the EDSS to define disability progression; 29 (46%) worsened using
MSFC to define disability progression. Patients with MSFC progression had significantly
higher GM atrophy rates compared with patients who were stable on MSFC. White matter
atrophy was similar in patients with and without disability progression. Atrophy rates
were not different in patients with or without disability progression defined using
EDSS.
Whole brain, GM, and WM atrophy predicted MS disability progression observed over
the next 6.6 years. Gray matter atrophy rates over 4 years correlated with disability
progression measured with the MSFC, but not EDSS. This indicates that MSFC defined
disability progression is more closely linked to brain atrophy than EDSS defined disability
progression, and provides important new insight into the poor correlation between
MRI and clinical disability in MS. The findings confirm the clinical relevance of
gray matter atrophy in MS.