The value of including thalamic atrophy as a clinical trial endpoint in multiple sclerosis

Multiple sclerosis (MS) features a substantial white matter (WM) pathology in the brain, which manifests as focal lesions and reduced volume (or atrophy) compared with healthy controls. In addition, extensive gray matter (GM) atrophy is strongly prevalent in MS and highly clinically relevant but can be difficult to measure, especially in a clinical setting.¹ Recent work has shown clear patterns of GM atrophy in patients with MS² that are focused on brain network hubs, i.e., regions that are strongly connected with the rest of the brain. These areas are important for cognitive decline and disability progression and include the thalamus³ and other regions belonging to the default-mode^2,4 and motor networks.² There has been a recent surge of interest in the thalamus, with some hope that thalamic atrophy and its associated dysfunction may be a treatment target of especially high potential³ because thalamic atrophy can be measured relatively easily. The value of including thalamic atrophy as a trial endpoint in clinical trials with disease-modifying treatment in MS is emerging.⁵