Table 3: Neuroimaging studies evaluating the relationship between gray matter atrophy, clinical disability, and cognitive impairment.

StudyMethodNumber of PatientsRelevant Findings

Chen et al. 2004 [79]1 yr longitudinal
1.5T; cortical thickness
24 RRMS, 6 SPMSCortical thickness decreased 3.13% ± 2.88%/year in patients with progressive disability. In stable patients 0.06 ± 2.31%/year change in cortical thickness.
Tedeschi et al. 2005 [80]Cross sectional
1.0T; GMF
427 RRMS, 140 SPMS
104 HC
GMF is the most significant MRI variable in determining final disability as measured by EDSS.
Morgen et al. 2006 [81]Cross sectional
1.5T; NGMV
19 HC
Patients with low cognitive performance showed more extensive cortical volume loss than HC in the frontal, temporal, and parietal lobes.
Houtchens et al. 2007 [82]Cross sectional
1.5T; NTV
26 RRMS, 5 SPMSCognitive performance in all domains was correlated with thalamic volume in MS group ( 0.506–0.724, ) and EDSS ( , ).
Fisher et al. 2008 [83]4 yr longitudinal
1.5T; GMF
7 CIS, 36 RRMS, 27 SPMS
17 HC
GMF correlated with both the MSFC and EDSS. Increasing contribution of GM atrophy to whole brain atrophy as MS advances.
Fisniku et al. 2008 [84]Cross sectional
1.5T; GMF
29 CIS, 33 RRMS, 11 SPMS
25 HC
GMF, not white matter volume, correlated with clinical disability as measured by EDSS and MSFC.
Horakova et al. 2009 [85]5 yr longitudinal
1.5T; NGMV
181 Early RRMS
27 HC
NGMV and age were the best predictors of progression of EDSS.
Rocca et al. 2010 [86]8 yr longitudinal
1.5T; NTV
20 CIS, 34 RRMS, 19 SPMS
13 HC
Baseline thalamic atrophy significantly correlates with deterioration in EDSS score.
Audoin et al. 2010 [87]Cross sectional
1.5T; regional GMV
62 CIS
37 HC
Right cerebellar atrophy correlated with EDSS scores but no correlation between regional atrophy and cognitive status.
Calabrese et al. 2010 [88]Cross sectional
1.5T; Cortical thickness
100 RRMS
42 HC
A widespread pattern of cortical thinning is the best predictor of cognitive impairment as measured by the Rao’s Brief Repeatable Battery
Calabrese et al. 2010 [89]Cross sectional
1.5T; Cortical thickness, DGMV
152 RRMS
42 HC
Significant atrophy of striatum, thalamus, superior frontal gyrus, and inferior parietal gyrus in fatigued patients compared to nonfatigued patients
Calabrese et al. 2011 [90]4 yr longitudinal
1.5T; Cortical thickness
105 CIS
42 HC
CIS with atrophy of the superior frontal gyrus, thalamus, and/or cerebellum doubled the risk of conversion to MS.
Roosendaal et al. 2011 [91]Cross sectional
1.5T; NGMV
95 CIS, 657 RRMS, 125 SPMS,
NGMV was the strongest predictor of disability and cognitive impairment as measured by EDSS and PASAT.
Nocentini et al. 2012 [92]Cross sectional
1.5T; GMF, regional GMV
13 RRMS, 5 SPMSSignificant associations found between scores on the SDMT and LDCR-CVLT with regional GM atrophy in prefrontal, parietal, temporal, and insular cortex
Amato et al. 2012 [93]Cross sectional
1.5T; NCV
29 RIS, 26 RRMS
21 HC
In RIS, lower NCV correlated with worse cognitive performance.
Batista et al. 2012 [94]Cross sectional
59 RRMS, 27 SPMSBoth NCV and deep gray matter volumes are significantly correlated with cognitive impairment. Thalamic atrophy plays significant role in IPS slowing.
Zivadinov et al. 2013 [95]2 yr longitudinal
1.5T; NCV
136 RRMSSignificant cortical atrophy occurs in early RRMS over 2 years and is associated disability progression.

Label: IPS: information processing speed. GMF: gray matter fraction. GMV: gray matter volume. MSFC: multiple sclerosis functional composite. NCV: normalized cortical volume. NDGMV: normalized deep gray matter volume. NGMV: normalized gray matter volume. NTV: normalized thalamic volume. RIS: radiologically isolated syndrome. SDMT: symbol digit modality test. LDCR-CVLT: long delayed cued recall-California Verbal Learning Test.