THE HISTOLOGY OF DISSEMINATED SCLEROSIS. 667 



of cells, or even on different cells of the same type. The changes which occur in the 

 tissues of inflamed areas are, therefore, of two types, degenerative and regenerative 

 respectively. Both of these occur simultaneously in different orders of cells, e.g. 

 the parenchyma of an organ may undergo degenerative change while its connective- 

 tissue basis is proliferating. If we apply this to the changes in disseminated 

 sclerosis, we can conclude that " there are certain principles underlying the 

 inflammatory process which enable us to recognise in it different degrees of one 

 process rather than several independent series of reactions." This shows that a 

 common cause, according to the intensity and duration of its action, may produce 

 a very varying picture. 



If we assume as the causal agent in disseminated sclerosis a circulating toxin, 

 it has been stated previously that this toxin must be in such weak concentration 

 that it produces no recognisable injury on the vessel wall in passing through it. 

 This weak toxin is further assumed to have an affinity for myelin, and it produces, 

 in the immediate neighbourhood of the vessel from which it has passed out, a 

 simple primary degeneration or solution of the myelin, with a proportionate 

 reaction on the glia — thus its injurious action is exercised on the myelin sheath, 

 its stimulant action on the glia. As this diffusion extends and the toxin mixes 

 with the tissue fluid and becomes more dilute, its stimulant action would be more 

 in evidence, and when the toxin tends to exhaust itself, i.e. at the peripheral zone 

 of the primary area, there would be a solely stimulant action on the glia, an 

 action which extends, therefore, beyond the area of degeneration of the myelin. 

 This stimulant action of the toxin seems to us to account for two of the histo- 

 logical data brought forward by Muller in evidence of a primary glia change : 

 (l) that at the periphery of the area we have a glia nuclear proliferation ; and (2) 

 that this extends between the normal myelinated fibres at the margin of the area. 

 These two data may possibly be partly explained by the secondary glia proliferation 

 occasioned by the degeneration of the nerve fibres, but for our present purpose 

 it is necessary to emphasise the stimulant action of the primary causal factor on 

 the glia — a stimulus which increases according to its dilution. The development 

 of such an area is that pointed out in tracing the evolution of an area through a 

 stage of fat granule cell myelitis. 



If we assume, further, that the concentration of the toxin is still more dilute 

 from the commencement, the degenerative action on the myelin would be almost 

 in abeyance, and the stimulant action on the glia would be its sole effect. A 

 slowly-increasing glia hyperplasia could then result, which would lead secondarily 

 to a myelin degeneration partly by direct compression and chiefly by the alterations 

 in the blood and lymph circulation in the area. Such a stimulus would thus lead 

 to an area of sclerosis through stages of a " gradually increasing glia hyperplasia," 

 which we have previously outlined. If such an assumption is justifiable, the two 

 types of areas are not two individually distinct processes, the latter developmental 



