Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Due to its high prevalence, MS is the leading cause of non-traumatic neurological disability in young adults in the United States and Europe. The clinical disease course is variable and starts with reversible episodes of neurological disability in the third or fourth decade of life. This transforms into a disease of continuous and irreversible neurological decline by the sixth or seventh decade. Available therapies for MS patients have little benefit for patients who enter this irreversible phase of the disease. It is well established that irreversible loss of axons and neurons are the major cause of the irreversible and progressive neurological decline that most MS patients endure. This review discusses the etiology, mechanisms and progress made in determining the cause of axonal and neuronal loss in MS.
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