[Physiopathology of the clinical manifestation of multiple sclerosis. Electrophysiological hypotheses]

Abstract

Clinical manifestations of multiple sclerosis cannot always be correlated with the type of lesion present. Plaques in certain regions may be clinically silent whereas, inversely, some neurological disorders appear not to be related to a demyelinization process. The pathophysiology of neurological symptoms and signs in multiple sclerosis may therefore be related to two other factors: 1) membrane phenomena observed in demyelinated fibers and leading to partial or complete conduction block, or 2) conduction blocks due to pathological phenomena that fail to provoke anatomical demyelinization. Demyelinization induces a sudden drop in impedance of the axon membrane which is responsible for the conduction block. Redistribution of sodium ionophores in the demyelinated axon enables transmission of certain messages but in a slower and unreliable manner. Sensitivity of demyelinated fibers to temperature and the extracellular ionic environment provides an explanation for the transient, recurrent stereotyped reactions provoked by fever, physical exercise or digestion. In the absence of demyelinization, a conduction block could be the result of either a minimal lesion at the paranodal myelin with denudation of the specialized parts between axon and glia,or of humoral blocking factors--of debatable specificity--or cellular factors that have been demonstrated recently. The existence of such mechanisms suggests the need for revision of the notion of acute episodes of multiple sclerosis. Finally, knowledge of the mechanisms involved in nerve conduction along demyelinated fibers suggests the possibility of therapy to restore conduction of these fibers by acting on extracellular ionic concentrations or directly on membrane ionic canals.