While brain atrophyis considered a marker of advanced stages of MS, it also occurs in patients with clinically-isolated syndrome and radiologically-isolated syndrome. Brain atrophy is now an endpoint in many clinical trials Brain atrophy is now a recognized end- point in all Phase III clinical trials for MS. It can be evaluated using traditional MRI scans; however, limitations do exist. • Atrophy accumulates very slowly; therefore, longer follow-up studies (lasting longer than two years) are needed to detect significant changes. • In the short-term, DMTs that have immuno- suppressive properties appear to decrease brain volume due to the resolution of inflammation. This volume loss is not a sign of neurodegeneration, because there is no actual loss of brain volume. This phenomenon, which is known as “pseudo atrophy,” can last for up to one year after treatment with immunosuppressant DMTs. • Physiological factors and non-MS factors (e.g., dehydration, alcohol consumption, smoking, genetic variation, comorbidities, and age) can also decrease brain volume. Importance of early diagnosis and treatment MS is characterized by both inflammation and progressive neuroaxonal damage. When this damage occurs in the earlystages of MS, it maybemaskedbycompensatorymechanisms. The progressive damage maygo unrecognized untilitistoolateforinterventiontobebeneficial. As MS progresses, the balance between degenerative and reparative processes shifts, resulting in progressive neuroaxonal degeneration and increasing disability Because brain atrophy creates permanent damage and correlates with physical and cognitive disability, it is important that people with MS be treated with DMTs sooner 60 msfocusmagazine.org Medicine & Research Brain atrophy occurs early in the disease process Figure reprinted with permission from the Multiple Sclerosis Foundation and EW Associates, LLC.