Physical disability and cognitive impairment evolution in benign multiple sclerosis: a five years prospective study

Background. Benign multiple sclerosis (BMS) definition is generally based on a minimum disease duration (DD) during which a maximum expanded disability status scale (EDSS) score is reached. However, EDSS does not account sufficiently for cognitive deficits, which may be as disabling as motor impairment Objectives. To study prospectively the evolution of physical disability and cognitive performance of BMS patients Methods. Among 300 patients seen at Verona MS Center between January and June 2008, 36 patients with relapsing-remitting (RR) course, DD ≥10 years, and EDSS score ≤2.0 were defined BMS cases. Of these, 24 gave consent for inclusion in the study along with 13 sex- and age-matched non-benign MS (n-BMS) patients with RR course, DD≥10 years and EDSS score from 2.5 to 4.5. The two groups were followed for 5 years with neurological examination at least every year and neuropsychological assessment at baseline and at study conclusion. Conventional MRI analysis was done for patients who had a brain scan with the same protocol in 2008 and 2013. Results. At inclusion BMS subjects were 41±8 years old (mean±standard deviation) with median DD of 15 years (range 11-29) and median EDSS score 1.5 (range 0-2), while n-BMS patients were 46±8 years old, had median DD of 16 years (range 10-27) and median EDSS score 3.0 (range 2.5-4.5). At baseline 16% of patients in both groups failed two or more neuropsychological tests. After 5 years, 23 BMS and 12 n-BMS patients had completed the study. The EDSS score worsened in 8% and 46% of cases, respectively (p=0.008), while the proportion of patients with ≥2 failed neuropsychological tests at 5 years increased at 25% in both groups. BMS and n-BMS patients who failed ≥2 tests had a significantly worse work and financial status both at baseline and at 5 years follow-up even after excluding subjects with EDSS score >3.5. Brain MRI T2 lesion location and number increase over time were not significantly associated with neurological and cognitive outcomes. Conclusions. Patients classified as having BMS according to widely used criteria had better physical disability outcome at 5 years compared to n-BMS cases. However, rates of initial cognitive impairment and neuropsychological decline over time did not differ between the two groups, including the possible impact on work and social functioning. Neuropsychological testing is essential even in MS patients with minimal or no physical disability given the distinct trajectories followed by disease progression in cognitive and motor domains.