In lieu of an abstract, here is a brief excerpt of the content:

FORM AND CAUSE IN MULTIPLE SCLEROSIS FRANCESCO PANSERA* Introduction Among the several unusual features of multiple sclerosis (MS) is the characteristic sharp definition of the plaque edge [1—6]. It is not obvious how a demyelinating lesion can have such a sharply demarcated border, especially if we consider the complex form of the oligodendrocytes and their spatial relations. Sharp edges are more apparent in the chronic, inactive plaque. Active plaques can have a sharp edge, or a less distinct border zone (periplaque ). Relatively indistinct margins are present especially in acute (Marburg type) MS, a rapidly fatal demyelinating disease which is considered a rare variant of MS. In acute MS the lesion is intensely inflammatory , and the destruction so severe that it extends in some degree to axons. In general, there is an inverse relationship between the activity of the plaque and the sharpness of its edge. We propose a model that explains the sharpness of the plaque edge, and gives clues to the etiology and pathogenesis of MS. Basic to consideration of the problem is the concept that myelin [7-9] has a dual nature : cellular, as a topologically coherent extension of the oligodendrocyte , and chemical, as a complex lattice of molecules. Model The indistinct borders that are commonly seen in destructive lesions are produced by a peripheral band in which destruction is partial. Sharpness of the borders is an inverse function of the width (W) of such band (Figure 1). The width is represented by the function W = D11 V. The author thanks Professors Lester Adelman and Piero Tosi for reviewing the manuscript . *Institute of Pathologic Anatomy and Histology, University of Siena, Via Tevere 20, 00198 Roma, Italy, (correspondence); and Laboratory of Neuropathology, New England Medical Center, Boston.© 1993 by The University of Chicago. All rights reserved. 0031-5982/93/3602-0799$01.00 306 Francesco Pansera ¦ Form in Multiple Sclerosis l_eSi0nW Unlnvolved tissue Fig. 1.—Model of the lesion edge. W = (length of the side of one square) · 13. Du is the diameter of the target unit of tissue U. This is the unit of tissue that is characteristically affected by the pathologic agent. The sum of the target units gives the macroscopic lesion. In most pathologies, U coincides with the cell. V is the number of units, on the axes of expansion of the lesion, included in the peripheral band in which the tissue destruction is not total. Units within this band can be either healthy or affected. V is a range: it is an index of the statistical variation in the pathologic involvement at the borders of the lesion. A sharp edge is the result of a low W. This could be due to a particularly low value of V associated with a normal (i.e., cell size) target unit U. However, it is difficult to imagine how demyelination can occur in such an ordered way, especially considering the complex histologic architecture of white matter. The chemical nature of myelin suggests a much simpler solution; in MS the size of the target unit U is smaller than the size of a cell. Considering a diameter of the order of 5 · 10"4 cm for small human cells, it can be estimated that in MS the target unit should have a diameter of the order of 5 · 10"5 cm or lower. Discussion The pathogenesis of MS is not known. Most ongoing research focuses on putative autoimmune or viral etiologies. Our semiquantitative model has implications for the theories of MS pathogenesis. First, it considers Perspectives in Biology and Medicine, 36, 2 ¦ Winter 1993 307 that the target unit, since it is of subcellular size, should be among the chemical components of myelin [7—9], including factors that sustain local myelinization. The target unit cannot be the oligodendrocyte, or the internode (which has length of the order of 10"2 to 10_1 cm [10, H]). Thus, in MS demyelination occurs on a molecular scale, rather than on a cellular one. Loss of oligodendrocytes is secondary to demyelinization, and not the primary event. The model is not incompatible with the theories of a preexisting defect in the myelin that makes it vulnerable to an etiologic agent. Second, according to...

pdf

Share