This book is being continuously revised because the research and information on how best to treat and manage persons with multiple sclerosis (MS) is rapidly changing and advancing.

Jean Martin Charcot described the clinical and pathological features of MS in 1868, and for the next century there was an understanding of the nature of the disease according to the clinical and laboratory methods of the day. It was believed to be a disease primarily affecting young adults that began with an attack of neurological symptoms. A number of attacks might occur, and these were noted to be related to scattered inflammatory lesions (plaques) in the white matter of the central nervous system (CNS). The inflammatory lesions were characterised by a breakdown of the myelin that surrounds the central axon of the nerves, but with relative preservation of the axons. After a long period when there were frequent attacks and remissions of symptoms, there was often a stage of slow progression of neurological deficit. This picture seemed to fit what physicians were seeing in most patients. However, in the last few years there has been a rapid expansion of the research effort to better understand the disease and its underlying mechanisms. This information has provided a different understanding of the disease, and new and innovative approaches to therapy and management.

We now see that MS does not start with the first attack, because there is evidence that there has been disease activity long before this, probably many years before. Although MS mostly affects young adults, it can also occur in children or much older adults. Patches of inflammation and demyelination certainly are present in the white matter of the CNS, and can be seen on magnetic resonance imaging (MRI), but there is increasing evidence that the changes in the disease are much more widespread than the scattered lesions would suggest, including in areas previously thought to be normal. The information from serial MRI studies also shows that there is a process of ongoing activity, even when the person does not notice any new symptoms.

For over a century the focus has been on the breakdown of the myelin sheath that surrounds the central axon of the nerve, but current interest centres on the axon and on the demonstration that there is subtle but important and widespread axonal change. This widespread axonal damage may be more important in causing the progression seen later in the disease. Although always regarded as a white matter disease, there is now evidence that changes may occur in the grey matter as well. From this brief outline it is clear that understanding of the underlying processes in MS is rapidly changing, and these clarified concepts are crucial in the development of new approaches to the disease. The complex immunological changes that affect the myelin and axons are becoming better understood, allowing the development of therapies that are focused on specific steps and pathways in the immune system and the development of beneficial new drugs for the benefit of people with MS.


There is also substantial new information about the genetic aspect of the disease, as well as the potential “triggers” that might precipitate the appearance of the disease in someone who is genetically predisposed to the disorder. It has long been noted that MS has a variable incidence in different parts of the world, and epidemiology research reveals possibilities for why some populations are more at risk than others. Studies of the natural history of the disease clarify the various patterns of MS that can occur. Using this natural history information, investigators will be able to better measure whether new therapies will alter the eventual outcome of the disease.

Almost all of the major advances in medicine have occurred in a steady, stepwise fashion, with new information and advances from basic research giving insights leading to the next stage. Subsequent research has led to other stages prior to the eventual “discovery.” Although patients and physicians are naturally waiting impatiently for major advances, the pace of change and advance is proceeding at an unparalleled rate, and the view is more hopeful than ever.