Myelin content changes in Clinically Isolated Syndrome and Relapsing- Remitting Multiple Sclerosis: Associations with lesion type and severity of visuomotor impairment

•MESE sequence quantifies myelin and intra-extracellular water content in CIS and RR-MS.•Myelin water content decreases in NAWM and focal lesions of RR-MS.•Intra-extracellular water content increases in NAWM and focal lesions of RR-MS.•Myelin and intra-extracellular water changes in right periventricular NAWM correlate with poor visuomotor performance. Cognitive disturbances occur in patients with Relapsing Remitting Multiple Sclerosis (RR-MS) and Clinically Isolated Syndrome (CIS). The Multi-Echo-Spin-Echo (MESE) T2-weighted sequence quantifies demyelination, the pathological hallmark of MS, but has not been used for the documentation of the potential relationship between anatomically specific demyelinating changes and cognitive impairment in MS. To identify markers of regional demyelination in patients with RR-MS and CIS in relation to clinical variables and severity of cognitive impairment. 37 RR-MS patients, 39 CIS patients and 52 healthy controls (HC) were examined using the MESE sequence. Long T2 and myelin water fraction (MWF) values were measured, serving as indices of intra/extracellular water content and myelin content, respectively, in focal white matter lesions and 12 normal appearing white matter (NAWM) areas of the patients and HC. A comprehensive neuropsychological assessment was administered to all patients. RR-MS patients showed widespread long T2 increases and MWF reductions in NAWM, compared to the respective values of HC (p < 0.001), which correlated with total lesion volume. Among RR-MS patients illness duration correlated negatively with MWF in right hemisphere frontal and periventricular NAWM areas (and positively with corresponding long T2 values). MWF values were lower in the CIS, as compared to the HC group, in the temporal, frontal and periventricular NAWM areas. Focal demyelinating lesions displayed variable higher T2 and lower MWF values, compared to NAWM, closely corresponding to their intensity on T1 sequences. Reduced MWF values and increased long T2 values in right periventricular NAWM were significantly associated with poor visuomotor performance. The MESE sequence affords accurate estimation of myelin and water content in NAWM and focal lesions in RR-MS and CIS patients, by means of the MWF and long T2 values, respectively, providing a sensitive index of demyelination associated with visuomotor deficits.