The pathological substrate of MS [1,2]
MS is an inflammatory-mediated demyelinating disease of the central nervous system. For most MS patients, the clinical disease course starts with relapses with or without complete recovery. When symptoms exceed a clinical threshold, neurological disability may become evident. Over time, the disease may advance into secondary progressive MS, which is characterized by incremental progression of disability. Conceptually, the MS pathogenesis can be divided into two distinct but overlapping and connected phases: inflammation and neurodegeneration (see figure).
Conceptually, the MS pathogenesis can be divided into two distinct but overlapping and connected phases: inflammation and neurodegeneration [1,2].
Axonal loss most likely begins at disease onset and accumulates over time. Conversion of relapsing-remitting to secondary progressive occurs once axon loss surpasses the capacity of the central nervous system to compensate for loss of function. Neurodegeneration is considered the major cause of permanent neurological disability in MS patients (see figure).
Axonal deterioration in MS
Modified from Oksenberg JR, Barcellos LF. Genes Immun 2005; 6: 375-87 and Trapp BD, Nave KA. Ann Rev Neurosci 2008; 31: 247-69.