THE HISTOLOGY OF DISSEMINATED SCLEROSIS. 675 



" areolierte " areas ascribed to secondary disseminated sclerosis. It seems, therefore, 

 justifiable to assume that cases of true disseminated sclerosis clinically have as 

 their basal histological features areas of actual sclerosis, which have evolved 

 through a stage of fat granule cell formation, and areas which are in process of 

 a similar evolution. 



It might, however, further be contended that areas arising on the basis of an 

 increasing glia hyperplasia and those arising on an inflammatory basis are present 

 in the same case. Muller's explanation of this finding is that, to the primary true 

 disseminated sclerosis, due to developmental factors, a secondary form, due to toxi- 

 infective influences, is superadded. I have already admitted the presence in the same 

 case of areas arising in both ways, and also the presence of " areolierte" areas, and in 

 the foregoing section the possibility, that a uniform explanation of the development 

 of these three types of areas can be found, has been put forward. In view of the 

 essential importance of the difficulty of accounting for such types of areas, a brief 

 summary of the argument there presented will be given. The essential point in this 

 argument is related to the well-known fact that a common cause, according to the 

 intensity and duration of its action, may produce a very varying picture, and 

 therefore several factors, which cannot be strictly separated, are acting in concert. 



It is probable that when the causal agent diffuses through the blood-vessel walls 

 with average concentration and intensity, areas arise on the basis of (l) a primary 

 solution of the myelin — a result of the irritant action of the "noxa"; and (2) a 

 simultaneous glia reaction — the result of the stimulant action of the " noxa," and 

 that such areas pass through stages of fat granule cell formation, glia fibril formation, 

 to a complete sclerosis with very fine, dense glia meshes. On the other hand, if the 

 causal agent be of weaker concentration and intensity and acting over a longer time, 

 its stimulant action on the glia is solely in exercise : areas would then arise on the 

 basis of a gradually increasing glia hyperplasia. The comparative picture presented 

 by the end-result of each could be differentiated only by the possibly more 

 isomorphous character of the resultant sclerosis in the latter case. Further, the 

 " noxa " may be of stronger intensity and its irritant action predominate, so that areas 

 of a more acute myelitic character arise, in which the rapid degeneration of the myelin 

 sheath is accompanied by a destruction, not a mere swelling, of the axis cylinder. 

 Such areas, followed by a certain amount of secondary degeneration and later by a 

 reparatory sclerosis, are also found in disseminated sclerosis, but this is not the 

 normal evolution of an area. At the same time it is clear that a varying intensity 

 of the "noxa" might cause areas to arise, in which the resultant sclerosis shows all 

 transitions from a simple retention of the glia network — the so-called " areolierte " 

 areas of Muller, through areas with a certain but not complete degree of fibril 

 formation — in which the proliferated glia nuclei are the nodal points of radiating 

 fibrils to areas of complete sclerosis in which the glia meshes are very close. This 

 varying picture, seen best with glia stains, depends, therefore, not on different under- 



