THE HISTOLOGY OF DISSEMINATED SCLEROSIS. 585 



groups of three, four, or more granule cells, thus forming interlacing bundles of fibrils 

 (figs. 2 and 329). In the elongated meshes formed by this interlacing there would 

 seem to be a gradual compression of the granule cells, for many seem to undergo a 

 gradual breaking up in situ. The nuclei become hyperchromatic and crenated, and 

 the definition of the cell membrane is lost, till finally only nuclei are left with a few 

 traces of vacuolated protoplasm around them. These nuclei remain long in these glia 

 meshes, and add to the nuclear abundance of the areas at this time. With the 

 gradual disappearance of the fat granule cells the interlacing bundles of fibrils gradu- 

 ally become more parallel (fig. 330) ; the glia cell nuclei diminish in volume as their 

 protoplasm is differentiated into fibres ; the axis cylinders, which have survived the 

 early swelling, are now more defined (fig. 33l), though many are still swollen and 

 weakly stained ; and, finally, the numerous vessels in the fibrillar tissue, which up till 

 now have had their sheaths widened and filled with cell elements, gradually undergo 

 the regressive changes already described. 



For the stage of complete sclerosis, reference may be made to the area described 

 under heading 1 (figs. 3, 4, and 331-336). 



Weigert sections of such an area, during its evolution, show the successive 

 changes of diffuse swelling of the myelin sheath, gradual loss of staining, and, finally, 

 a negative picture with at first numerous fragments and granules, retaining the 

 hsematoxylin stain, scattered throughout the tissue. The transition zone is often a 

 broad one on all sides, and both at its upper and lower limits it is wedge-shaped, 

 the lateral margins of the wedge forming a zone in which all the changes are 

 characteristic of an advancing process. If such an area undergoes complete sclerosis, 

 this wedge-shaped zone shows (l) a looser structure than the central area — its fibril 

 formation being not nearly so dense — and (2) a marked nuclear proliferation, of small 

 and large glia cells, which extends for a short distance into normal tissue. 



Marchi sections (figs. 319-323) and frozen sections, stained with Scharlach R. 

 (figs. 18-20), reveal very beautifully the gradual changes in a degenerating nerve 

 fibre — the presence of fine granules and globules or small and large irregular particles. 

 Those changes may take place in a portion of a nerve fibre which in its subsequent 

 course stains normally and then again shows degenerative changes. At the stage of 

 maximum development of fat granule cells both Marchi and Scharlach R. specimens 

 show their almost tubular arrangement in the tissue, and as the tissue becomes 

 cleared, the arrangement in long rows around the longitudinal vessels, and in the 

 vessels, cut transversely, which reach the pia. In the latter their numbers gradually 

 diminish as the pia is reached, and those that are left pass into the lymph spaces 

 in the inner layers of the pia (fig. 315). In the stages of advancing and complete 

 sclerosis, fat granule cells are left for a long time in the walls of the vessels radiating 

 from the sclerosed area : the transition zone also shows a complete layer of such cells 

 in the tissue spaces. As the process becomes stationary, these also are drained away, 

 leaving the whole area and the transition zone staining lighter than the normal tissue, 



