Multiple sclerosis. Observations and reflections--a personal memoir.

The pathogenesis of MS has become better understood as a result of recent advances in several areas, particularly in epidemiology and neuro-imaging. A number of epidemiologically based conclusions need to be revised, most importantly the putative direct relationship between prevalence and latitude, and the concept that epidemics of MS have occurred in some parts of the world. It is now clear that genetic factors play a much more important role in the genesis of the disease than environmental factors, although the latter cannot be ignored. The existence of a genetic susceptibility, coupled with either protective or enhancing factors, which may be genetic or environmental, is recognized as being most important in individuals of northern European origin. Much evidence suggests that the disease is initiated by a viral illness (or possibly a vaccination) at some time before puberty. This first antigenic challenge results in the development of what is called the "MS trait", a systemic condition that may never develop into the actual disease and may be observed as well in the unaffected siblings of MS patients. The trait is almost certainly a manifestation of an alteration of the immune system; its most important effect is to render the blood-brain barrier more vulnerable to a variety of agents that will increase its permeability. In order for MS to involve the central nervous system, loss of integrity of the blood-brain barrier is an obligatory step, an observation which has now been amply confirmed by neuroimaging studies. This effect upon the blood-brain barrier appears to be non-specific, since it may result from such diverse causes as a viral infection, a vaccination, or mild trauma. Edema and inflammation follow, but myelinoclasia is not always a consequence; thus plaque formation may not occur and the initial lesion of MS may disappear without leaving a trace. The actual mechanism of myelinoclasia, and the role played in it by lymphocytes, remain unknown. Although the disease does affect the central nervous system, it may remain asymptomatic for a long time after the actual plaque is formed, even for the person's entire life.