Notes on the pathogenesis of multiple sclerosis

Abstract

A multifactorial genetic susceptibility determines the risk of acquiring multiple sclerosis (MS). This risk is modified by environmental factors. A viral antigenic challenge, either infectious or vaccinal, causes a genetically susceptible person to develop the MS trait, a systemic asymptomatic condition which does not affect the nervous system. It consists of an activated immune system and increased vulnerability of the blood-brain barrier (BBB). MS may never progress beyond this stage. A second antigenic challenge results in an immune response by means of the phenomenon of molecular mimicry and leads to an alteration of the BBB, an obligatory step in the pathogenesis of the disease. Other occurrences such as trauma or electrical injury, termed facilitators, may also cause this change in the BBB. The exact mechanism for the BBB alteration is unknown, but it allows the penetration into the brain parenchyma of cellular and non-cellular elements of the blood and the formation of the initial MS lesion, i.e., inflammation and edema of the myelin sheath. This stage is fully reversible, but may also proceed to plaque formation by a mechanism which is not yet understood. Myelinoclasia releases myelin components that get into the blood via the altered BBB and elicit an immune response from activated lymphocytes, which may then be involved in further attacks on the myelin sheath and lead to a self-perpetuating progressive illness.