Ms as a Neurodegenerative Disease ( a Thought Experiment ) : the Clinical Evidence * —

Several important questions about the early stages of the pathophysiology of multiple sclerosis (MS) are currently unresolved. Some of these questions include the relative importance of central versus peripheral mechanisms in initiating lesion formation; whether MS begins with myelinforming cells or immune cells; whether lesions are relatively heterogeneous or homogeneous; and the role of axonal injury in the development of MS. Recent histopathologic studies of very early MS lesions have demonstrated oligodendrocyte apoptosis and activation of microglia that precede the demyelination or the infiltration of T and B lymphocytes. Some researchers have identified distinct MS subtypes that vary in immune cell infiltration and the role of complement fixation and immunoglobulin G in lesion pathology. Others have argued that MS lesions are actually quite similar at all but the earliest stages. Axonal pathology is an important feature of early MS, as transected and degenerating axons are evident in large numbers in tissue samples obtained from early MS lesions. Gray matter lesions have long been recognized in MS and may be closely associated with progressive forms of the disorder. Remyelination has been shown to occur in MS lesions even when macrophages are present. The degree of remyelination varies considerably from patient to patient, but may be extensive in approximately 20% of cases. (Adv Stud Med. 2008;8(9):305-308)