Reflections on the pathogenesis of optic (retrobulbar) neuritis in multiple sclerosis

Abstract

-The conditions which lead to a plaque of demyelination in the retrobulbaroptic nerve are discussed. Growth of the plaque occurs along venules as small fingerlike sleeves which develop outwards from the contour of the plaque. This occurs slowly and at intervals; the very gradually expanding lesion remain for a long time clinically silent.It is here postulated that the change to clinical disease is induced if cells digesting myelin debris settle in a more distal part of the perivascular space of a vein, than during the subclinical phase. In sufficient numbers these cells will impede the movement of molecules from extra-cellular fluid surrounding nodes of Ranvier into cerebrospinal fluid. A restriction in this vital drainage pathway results in oedema causing distrubed signal transmission in neurons passing through the veins drainage territory. Depending on intensity this can induce the characteristics symptom of blurred vision.These concepts have been used to speculate on sequential changes in neurons and to relate them to various phases of the disease. This seems to be justified as the pattern evolved corresponds well with the clinical symptomatology.

Multiple Sclerosis: Prevention of serious illness — Vision of a desired future for newly ascertained patients

“…The intense demyelination occurring at the contour of an active plaque seems to be a secondary effect in a semi-secluded brainspace which has better diffusion pathways to the bloodstream than to cerebrospinal fluid. Plaque development -as a result of a circulating toxin (4) capable of entering the matrix of membranes and exerting an effect on myelin --has been discussed (5) and the circumstances leading to eye-symptoms have been explored (6). In this plaque-space completely different processes from those in surrounding white matter are under way (7,8).…”