Cortical functional reorganization and its relationship with brain structural damage in patients with benign multiple sclerosis

Background: Patients with multiple sclerosis (MS) who have a favourable clinical status several years after disease onset are classified as 'benign'. In many cases brain tissue damage does not differ between benign MS and the 'classical' MS forms. Objective: To assess whether the favourable clinical course in benign MS could be explained by the presence of an efficient functional cortical reorganization. Method: Twenty-five right-handed patients with benign MS (defined as having Expanded Disability Status Scale <= 3 and disease duration > 15 years) underwent functional MRI during a simple motor task (right-hand tapping) to assess movement-associated brain activation. This was compared with that of 10 patients with relapsing-remitting MS and 10 normal controls. Benign MS patients also underwent conventional brain MRI and magnetization transfer imaging, which was compared with an identical examination obtained 1 year before. Quantitative structural magnetic resonance measures were baseline and changes over time in T2-lesion volume, magnetization transfer ratio in T2 lesions and normal-appearing brain and total brain volume. Results: Movement-related activation was greater in patients with benign MS than in those with relapsing-remitting MS or normal controls, extensively involving bilateral regions of the sensorimotor network as well as basal ganglia, insula and cerebellum. Greater activation correlated with lower T2-lesion magnetization transfer ratio, and with decreasing brain volume and increasing T2 lesion volume. Conclusions: The results suggest that bilateral brain networks, beyond those normally engaged in motor tasks, are recruited during a simple hand movement in patients with benign MS. This increased activation is probably the expression of an extensive, compensatory and tissue-damage related functional cortical reorganization. This can explain, at least in part, the favourable clinical expression of patients with benign MS.