There is still substantial inconsistency between clinical disabilities and findings on brain networks and lack of longitudinal study in Multiple Sclerosis (MS). We aimed to elucidate how topology alters and how disability progression affects the structural and functional organizations over 2-years using graph theory approach in relapsing-remitting MS (RRMS). RRMS patients have encountered with lack of improvement in PASAT over 2-years. Structural connectivity was more sensitive to show a relationship with a cognitive function over 2-years than the rs-fMRI and MEG functional metrics in RRMS patients. These findings underline the difficulties associated with functional imaging studies in MS.