This study examines the long-term effectiveness of a combined cognitive-behavioral and neuropsychological intervention in a woman of 19 years old with multiple sclerosis, by evaluating functional neuroimaging, neuropsychological and psychometric testing. The results showed a partial improvement in some brain areas and brain inflammatory activity. There was an increase in attention, verbal memory, and nonverbal executive functioning as well as in the emotional state at posttest and one-year follow-up. This study indicates the need for including components of both cognitive-behavioral therapy and neuropsychological rehabilitation based on an individualized and tailored plan in standard treatments for multiple sclerosis. Future studies should further develop these contributions.