The physiopathology of multiple sclerosis

Introduction Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, predominantly, but not exclusively, involving the normal-appearing white matter. From an immunological point of view, chronic inflammation in MS can be thought of as an inflammatory process with a disordered resolution phase. We still do not know why inflammation in MS does not resolve, but there are several possible explanations. The persistence of inflammatory central nervous system (CNS) infiltrates could be caused by long-lasting “danger signals.” Although many viruses have been implicated as possible danger signals in MS, there is no conclusive evidence that any pathogens have such a role. The most recent and perhaps attractive candidate is the Epstein–Barr virus, which has been found to be associated with MS both in children and in adults. Moreover, Aloisi and colleagues found in CNS elevated numbers of B cells infected by the virus, an observation that, if confirmed, would indicate a pathogenic role of the virus. The pathological substrates of neurological dysfunction in MS are demyelination and axonal loss. In myelinated fibers, saltatory conduction of action potentials is determined by clustering of voltage-sensitive sodium channels within axon membranes at nodes of Ranvier and, to a much lesser extent, beneath the myelin sheaf. Demyelination may produce multiple functional alterations, reported in Table 2.1. Conduction block almost invariably occurs if the length of the demyelinated area exceeds 5 mm.