Multiple sclerosis (MS) is the leading cause of neurological disability in young women in the USA and Europe and the second leading cause of such disability in young men. Major advances have been made in the past two decades in understanding the pathogenesis and immunobiology of MS resulting in major advances in the treatment of the disease over the past 15 years. These advances are the consequence of advanced neuroimaging, molecular biology and immunological techniques. However, the disease remains generally incurable. Further advances will depend on developing more selective immunotherapeutic strategies, particularly involving B cells and regulatory T cells as well as developing therapeutic strategies to prevent neurodegeneration and to induce repair in the central nervous system (CNS) of patients with MS.

Key Concepts:

• MS is the leading cause of neurological disability in young women in North America and Europe.
  
• Although there is good evidence that MS results from both genetic and environmental factors, the exact nature of those factors remains uncertain.
  
• Although often classified as a disease of myelin, recent research clearly demonstrates the immune attack on the CNS destroys neurons, axons and oligodendroglia; therefore MS is more properly considered an inflammatory disease of the CNS.
  
• Although classically considered an autoimmune disease driven by autoaggressive T cells, clinical data suggests B lymphocytes also play a key role in the pathogenesis of MS.
  
• Mechanisms of immune attack on the CNS may vary from patient to patient but in general include both cellular and humoral mechanisms.
  
• Brain magnetic resonance imaging (MRI) has fundamentally changed our understanding of disease activity in MS patients. It is now known that much of the damage to the CNS is not apparent clinically in the early phase of the disease, but contributes to the long-term disability of the disease.
  
• Recently, major advances have been made in developing therapies that can slow the progression of MS. However, no cure has yet been found.
  
• Neurodegeneration appears to be a consequence of the immune attack on the CNS and may result in continued progression of disability even if the immune attack on the CNS is inhibited.
  
• Recently it has become clear that the brain in MS patients is constantly attempting to repair the damage done by the immune attack both through remyelination and cortical remodelling. In fact, these processes appear to explain the clinical appearance of stability in MS patients at a time when the MRI demonstrates ongoing inflammation and damage.
  
• Advances in our understanding of the pathogenesis and treatment of MS has significant implications for other inflammatory diseases of the nervous system.