CELL CHANGES IN THE CENTRAL NERVOUS SYSTEM UNDER VARIOUS NATURAL AND EXPERIMENTAL CONDITIONS. FIRST PAPER: PARATHYROID TETANY

1. Complete thyroparathyroidectomy was performed on thirteen dogs, with the result that all except one developed typical tetany in some degree within one to fourteen days. The one not showing these symptoms was killed on the twenty-second day after the operation, to be used as an operated control. The tissue from three normal dogs supplied the necessary control material. 2. The symptoms of parathyroid tetany suggest an acute affection of the nervous system, especially of the nerve centres. This fact is strongly supported by microscopic alterations found in the nerve cells, the degree of which corresponds very closely to the acuteness of the attacks. These pictures point to a condition of general toxaemia. 3. Not all cells of a single animal or even of a single nerve-nucleus are affected to the same extent, so that for the same animal various steps in the reaction can be recognised. The alterations cannot be considered as the result of activity alone, but are interpreted as being produced by the same agent or agents which act as stimuli upon the neuromuscular mechanism. 4. A careful study of the nerve cells from Nissl preparations has been made, taking representative sections from the spinal cord, medulla oblongata, cerebellum, pons, mid-brain, thalamus, and cruciate gyrus. 5. The nerve cells of dog C, the operated control, are well within the normal. In the remaining twelve animals definite although varying degrees of alterations were found in these elements. In general, one might say that these changes are proportional to the acuteness of the tetanic affection. The milder grades of tetany, although extending over several days, are less drastic in their effects as measured by nerve-cell reaction than more acute attacks of a few hours' duration. 6. Sufficiently graduated stages are represented to warrant an account of the course of the affection. Early in the chromatolytic reaction, as measured by the severity of the symptoms, there is a stage of absolute hyperchromatosis with shrinkage of the cells, after which the amount of stainable material gradually diminishes through fragmentation and dissolution. This begins in the perinuclear region and spreads towards the periphery until a stage is reached in which normal staining Nissl substance can no longer be demonstrated. 7. The nucleus, on the other hand, seems to maintain its integrity to a greater extent. Except that it is slightly swollen and clouded, it appears to be normal. Complete degeneration of the cells, with karyorrhexis or karyolysis, was not seen; and in very few cells, if any, did it appear that the alterations were beyond repair had it been possible to restore the normal condition of the animal. 8. Shifting of the nucleus toward the periphery, although occasionally seen, occurred no more frequently in the experimental than in the control tissues. Vacuolisation of the cytoplasm commonly accompanied the most acute affection, particularly in the Purkinje cells and granule cells of the cerebrum. This was often associated with perivascular and pericellular œdema. 9. The associated hyperpyrexia was roughly proportional to the severity of the tetanic spasms, and followed rather than preceded the latter. This increase in body temperature is sufficient by itself to produce changes in the nerve cells, and undoubtedly exaggerates the condition of general poisoning. But this alone cannot account for the nerve-cell alterations, since these occur in milder form in animals whose temperature remains about normal. 10. This work offers insufficient proof of the conclusion that there is an increase in the number of glia cells, or that the processes can be seen for greater distances from the cell-bodies. Little importance is attached to these findings of other observers.