Table 1: Neuroimaging studies evaluating the relationship between cortical lesions, clinical disability and cognitive impairment.

StudyMethodNumber of patientsRelevant findings

Calabrese et al. 2007 [42]Cross sectional
1.5T; DIR
116 CIS, 163 RRMS, 101 SPMS
40 HC
Cortical lesions occur in greater numbers in SPMS than in CIS or RRMS.
Cortical lesion numbers are correlated with EDSS.
Calabrese et al. 2009 [62]1 yr longitudinal
1.5T; DIR
48 Benign MS
Benign MS patients have lower numbers of cortical lesions and lower cortical lesion volumes as compared to early RRMS, and do not accumulate a statistically significant number of new lesions over 1 year.
Roosendaal et al. 2009 [63]3 yr longitudinal
1.5T; DIR
7 HC
Cortical lesions increase significantly in MS patients over time and are associated with worse performance on neuropsychological measures.
Cortical lesions are most frequent in SPMS.
Calabrese et al. 2009 [64]Cross sectional
1.5T; DIR
70 RRMS Cortical lesion volume and number correlate with most, but not all, of the cognitive tests of Rao’s brief repeatable battery.
Cortical lesion volume is an independent predictor of the cognitive impairment index.
Calabrese et al. 2010 [65]3 yr longitudinal
1.5T; DIR
76 RRMS, 31 SPMSBaseline cortical lesion volume best predicted disability progression (as measured by EDSS) over the follow-up period.
Mike et al. 2011 [66]Cross sectional
20 RRMS, 6 SPMSCortical lesion number and volume independently predicted EDSS.
Cortical lesion number and volume independently predicted performance measured by the Symbol Digit Modality Test.
Only cortical lesion number predicted performance measured by the California Verbal Learn Test.
Nelson et al. 2011 [67]Cross sectional
39 MS
(Subtypes not specified)
Leukocortical lesion numbers are independently correlated with cognitive impairment, while purely intracortical lesions are not independent contributors.
The size of cortical lesions, not the tissue specific location, may better explain the correlation with cognitive impairment.
Calabrese et al. 2012 [68]3 yr longitudinal
1.5T; DIR
32 RRMS with epilepsy, 60 RRMS without epilepsyCortical lesion number and volumes are larger in patients with epilepsy than those without.
RRMS patients with epilepsy accumulate lesions at a faster rate than nonepileptic patients over 3 years.
Calabrese et al. 2012 [69]5 yr longitudinal
1.5T; DIR
157 RRMS, 35 Pediatric MS, 45 Benign MS, 44 PPMS, 31 SPMSHigher cortical lesion loads correlate with higher EDSS.
Patients with clinical progression have the highest rate of cortical lesion accumulation.
Cortical lesion volumes are independent predictors of disability progression and cognitive impairment.