Table 2: Neuroimaging studies assessing the relationship between markers of diffuse damage in NAGM and clinical disability and cognitive impairment.

StudyMethodNumber of patientsRelevant findings

Rovaris et al. 2002 [70]Cross sectional
1.5T; DTI
34 RRMSAverage gray matter mean diffusivity correlates with cognitive impairment measured by the Symbol Digit Modality Test (SDMT).
Ranjeva et al. 2005 [71]Cross sectional
1.5T; MTR
18 CIS
18 HC
Decreased MTR in the parietal lobe (BA40) correlates with poorer performance on Paced Auditory Serial Addition Test (PASAT).
Agosta et al. 2006 [72]8-year longitudinal
1.5T; MTR
73 MS
(34 RRMS, 19 SPMS)
20 CIS
16 HC
Lower gray matter MTR-peak height at baseline is an independent predictor of accumulation of disability over 8 years as measured by the Expanded Disability Status Scale (EDSS).
Rovaris et al. 2006 [73]5-year longitudinal
1.5T; DTI
55 PPMSAverage gray matter mean diffusivity was an independent predictor of clinical deterioration as measured by EDSS.
Khaleeli et al. 2007 [74]Cross sectional
1.5T; MTR
46 PPMS
23 HC
Lower MTR in the right primary motor cortex correlated with disability as measured by EDSS.
Lower MTR in the right parietal and occipital cortices correlated with poorer performance on PASAT.
Amato et al. 2008 [75]Cross sectional
1.5T; MTR
47 Benign MS
24 HC
Reduced cortical MTR correlated with a variety of measures of cognitive impairment.
Fisniku et al. 2009 [76]Cross sectional
1.5T; MTR
41 MS
(31 RRMS, 10 SPMS)
28 CIS
19 HC
Reduced gray matter peak height MTR is the best independent predictor of disability as measured by EDSS, and only independent predictor of cognitive impairment as measured by the Multiple Sclerosis Functional Composite (MSFC).
Tovar-Moll et al. 2009 [77]Cross sectional
3T; DTI
24 MS
(13 RRMS, 11 SPMS)
24 HC
Elevated mean diffusivity within the thalamus correlated with performance on PASAT and EDSS.
Crespy et al. 2011 [78]Cross sectional
1.5T; MTR
88 CIS
44 HC
Gray matter MTR decrease is significantly associated with worse EDDS scores.
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