Abstract
Cerebral gray matter (GM) atrophy has clinical relevance in multiple sclerosis (MS). Fingolimod has known efficacy on clinical and conventional MRI findings in MS; the effect on GM is unknown.
To explore fingolimod's treatment effect on cerebral GM atrophy over two years in patients with relapsing forms of MS.
Patients starting fingolimod [n=24, age (mean±SD) 41.2±11.6years, Expanded Disability Status Scale (EDSS) score 1.1±1.4; 58% women] were compared to untreated patients [n=29, age 45.7±8.4years, EDSS 1.0±1.2; 93% women]. Baseline, one and two year MRI was applied to an SPM12 pipeline to assess brain parenchymal fraction (BPF) and cortical GM fraction (cGMF). T2 lesion volume (T2LV) and gadolinium-enhancing lesions were assessed. Change was modeled using a mixed effects linear regression with a random intercept and fixed effects for time, group, and the time-by-group interaction. The group slope difference was assessed using the interaction term.
Over two years, cGMF remained stable in the fingolimod group (p>0.05), but decreased in the untreated group (p<0.001) (group difference p<0.001). BPF change did not differ between groups (all time-points p>0.05). T2LV increased over two years in the untreated group (p<0.001) but not in the fingolimod group (p≥0.44) (group difference p<0.001).
These results suggest a treatment effect of fingolimod on cerebral GM atrophy in the first two years. GM atrophy is more sensitive to such effects than whole brain atrophy. However, due to the non-randomized, retrospective design, heterogeneous between-group characteristics, and small sample size, these results require confirmation in future studies.
•Cerebral gray matter atrophy has clinical relevance in multiple sclerosis (MS).•Fingolimod has a known efficacy on MRI-defined lesions and whole brain atrophy in MS.•Fingolimod's effect on cerebral gray matter (GM) disease is unknown.•Our findings suggest treatment effect on GM atrophy over 2years.•GM was more sensitive to fingolimod's effects than whole brain atrophy or clinical measures.
