Ongoing Axonal Injury in Chronic Active Lesions in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic disease of the CNS that is characterized by the accumulation of focal inflammatory demyelinating lesions. In the acute phase, lesions are typified pathologically by a dense infiltrate of activated microglia/macrophages/lymphocytes, demyelination, and transected axons.1,2 Subsequently, some lesions become chronic inactive, whereas up to 57% of lesions show persistent inflammation,1,2 and are defined as chronic active. These lesions feature a hypocellular inactive core, whereas iron-laden activated microglia/macrophages, ongoing demyelination, and axonal loss are localized at their rim. Of note, chronic active lesions lack the substantially abnormal blood–brain barrier permeability that typically characterizes acute lesions,1,2 thus reflecting a more compartmentalized pathologic process that is more difficult to visualize on MRI.