Neurophysiological evidence for long-term repair of MS lesions: implications for axon protection

Abstract

After recovery from the acute stage of optic neuritis, a marked prolongation in the latencies of visual evoked potentials (VEPs) is typically observed. We have conducted three studies (one cross-sectional, two prospective), aimed at elucidating the progressive shortening of VEP latency, which frequently ensues over the following months or years. This has been shown to be a progressive process and a prevalent tendency in the patient population, proceeding for more than 2 years in spite of the fact that very little functional improvement in vision occurs after the first few months. We argue that the underlying process of repair is most likely to involve remyelination of demyelinated optic nerve axons. Rather than restoration of visual function (which may be virtually complete after as short a period as 3 months), the main importance of the long-term myelin repair process may consist in protecting demyelinated axons from subsequent, permanent degeneration. In the VEPs of the acutely unaffected fellow eyes followed up over 3 years, we observed an asymptomatic deterioration, possibly due to insidious processes of demyelination and/or axonal degeneration. Even in the relapsing/remitting stage of MS, therefore, there is electrophysiological evidence for involvement of clinically asymptomatic axons, which, in the later stages, may be manifested as progressive functional deterioration.