INTRODUCTION: The mechanism of action of fingolimod within the central nervous 
system and its efficacy in reducing/preventing both focal and diffuse grey 
matter (GM) damage in active multiple sclerosis (MS) are not completely 
understood.
METHODS: In this longitudinal, 2-year prospective, phase IV, single-blind study, 
40 MS patients treated with fingolimod and 39 untreated age, gender, and 
disability-matched MS patients were enrolled. Each patient underwent a 
neurological examination every 6 months and a 3T MRI at the beginning of the 
treatment and after 24 months. The accumulation of new cortical lesions (CLs) 
and the progression of regional GM atrophy were compared between the two groups.
RESULTS: At the end of the study (T24), the percentage of patients with new CLs 
(13.5 vs. 89%, p < 0.001) and the percentage of GM volume change was lower in 
the treated group (p < 0.001). The regional analysis revealed that the treated 
group had also less volume loss in thalamus, caudatus, globus pallidus, 
cingulate cortex, and hippocampus (p < 0.001), as well as in, cerebellum, 
superior frontal gyrus, and insular-long gyrus (p < 0.05). Patients with no 
evidence of disease activity were 60% in the treated group and 10% in the 
untreated group (p < 0.001).
CONCLUSIONS: These results suggest a possible protective effect of fingolimod on 
focal and diffuse GM damage.