Nevertheless, most immunologists currently subscribe to the notion that MS is mediated by a T-cell sensitization to some component of myelin. This idea is supported by numerous lines of evidence, including the observation that T cells initiate the lesions of experimental allergic encephalomyelitis (EAE), which is assumed to be an approximate animal model of MS, as suggested originally by Waksman and Adams. It has been difficult, however, to produce a relapsing experimental form of the illness that would simulate MS. Although the entry of autoreactive T cells into the CNS results in a perivascular inflammatory reaction, its relationship to MS is unclear. Conceivably, intense T-cell stimulation is in itself sufficient to induce demyelination but it is also possible that the primary target of the immune reaction is the myelin sheath or some component thereof and that the T-cell infiltration is a reaction to demyelination. Most investigators believe that an additional insult is required, as illustrated by the EAE animal model, in which myelin alone is not a sufficient factor but always requires an adjuvant immune stimulus. EAE is clearly an imperfect model; it is not a naturally occurring disease but one in which a demyelination of the CNS is induced in susceptible animals in a single episode by autologous myelin antigens. The inducing antigen in EAE is known, whereas the putative antigens in MS are not.
Also incorporated into most theories of the immune pathogenesis is an alteration of the blood–brain barrier, represented by adhesion of lymphocytes to endothelial cells in the nervous system. Whether this is an active interaction or a passive event triggered by antigenic attraction is not clear; nonetheless, these cell–vascular interactions have been incorporated into pathogenic theories and are the basis of newer treatments for MS. Always in the background is the element of genetic susceptibility, presumably making certain individuals prone to these immunologic events as noted in the earlier sections.
The foregoing data notwithstanding, the immune mechanisms in MS are not fully specified and the autoimmune hypothesis is not beyond challenge. It is noteworthy that the prevalence of other diseases of presumed autoimmune origin in some series is no higher in MS patients than in the general population (De Keyser). However, various epidemiologic studies differ on this point and some have found an increase in autoimmune diseases in affected patients and in their families.
Physiologic Effects of Demyelination
The main physiologic effect of demyelination is to impede saltatory electrical conduction of nerve impulses from one node of Ranvier, where sodium channels are concentrated, to the next node. The resulting failure of electrical transmission is thought to underlie most of the abnormalities of function resulting from demyelinating diseases of both the central and peripheral nerves. As an example, the delay in electrical conduction in the optic nerve (found by using pattern-shifting visual stimuli in MS patients) raises a number of points about the pathophysiology of demyelination. When the demyelinating process is acute and reversible within a few days, the block in nerve fiber conduction is obviously physiologic rather than pathologic; in such a brief period, recovery is unlikely to have been a result of remyelination; recovery is probably a result of subsidence of the edema and acute inflammatory changes in and around the lesion. Remyelination probably does occur, but it is a slower process and partial at best, and its functional effects in the CNS are possibly expressed as a slowing of nerve conduction, which, if present in an eye with normal vision, may account for the reduction in flicker fusion and in the perception of multiple visual stimuli (Halliday and McDonald). It is clear, however, that many of the plaques in the cerebral hemispheres that are visualized on MRI are unaccompanied by corresponding symptoms. Either there has been complete remyelination in these plaques, sufficient to support clinical functioning, or, in the acute stage, the plaque may represent edema rather than demyelination.