The present investigation was primarily directed to the study of neurofibrillary changes 'net with in the subjects of various forms of mental disease: but it was not long before it was found to be necessary to extend the line of investigation and to study their arrangement in the healthy state; as in a subject on which there is so much debate, a description of conflicting results by observers who frequently hold
diametrically opposite views is unsatisfactory and often misleading. It was then arranged to make a comparative study of the subject and to also ascertain the arrangement in man - and contrast the difference between human embryo and adult. I regret to say however that I have been,as yet, unable to carry out the last part of my plan because of the difficulty of obtaining suitable material, either from the human embryo or from the healthy adult. Attention has therefore been directed to various lower animals and to the changes met with in the insane.
The chief methods used have been those of Bethe and Lugaro; the former as representing the teaching of independent fibrils; the latter as representative of !, the teaching that the arrangement of the achromatic substance within the nerve cells is essentially an anastomosing reticulum. Other methods have been employed, notably that of Ramon -y-- Cajal, described as is No. 3. method and intended by its author to chiefly how the pericellular structures.
The research has been carried out at the laboratory of this asylum and I have had no hint or help with regard to either the choosing of the subject or the prosecution of the investigation.
As a result of these observations it is seen that the achromatic structure of the cells undergoes very profound alterations in the various diseased mental states, and that the changes in these various states bear a close resemblance to one another and also to those recorded by other observers as the result of experimental investigation. But whilst the general nature of the changes, as might be expected, is the same throughout, the intensity varies in the different groups of cases. In dementia associated with cerebral softening the pathological alterations have reached their height; the superficial cell layers are practically all destroyed and the cells of the ganglion layer are affected to a greater degree than in other conditions. The extracellular fibres also show the diseased conditions of varicosity and variation in size. Chronic brain atrophy also exhibits appearances which must have a profound affect on the functional activity of the units concerned. The case of melancholia associated with diabettes mellitus is very striking and remarkable for the total absence of stained cells, but the fact of its being a single case and so unconfirmed scarcely gives it the significance that similar changes found in other cases of diabettes mellitus would confer upon it. In the meantime therefore it can only be regarded as an interesting condition. The presence of pigmentation in the cells is an almost universal condition; the amount is often so large as to totally fill the cell to the exclusion of other structures. It is of the pale yellow variety except in some conditions of dementia with cerebral softening when it was noted to be bright yellow colored. The question of the origin of nerve cell pigment which is so frequently met with in diseased conditions is still unsettled. It is very frequently found at the part of the cell at which there is supposed to be greatest functional activity, but this part may be quite free of it and accumulations occupy the base of the apical process or the peripheral parts of the cell. It appears as if it might result from the breaking down of some element of the cell and that the metabolism had not advanced sufficiently to allow of its absorption: that is to say it is a product of partial breaking down of cell structure. It is usually contained in a reticulum the meshes of which are large, irregularly rounded or angled, and the fibrils which form the meshwork thicker than those of the physiological cell reticulum. Marinesco thinks that the pigmentary reticulum is distinct from that of the cell and its general appearance tends to confirm that view. That it tends to undergo a physiological increase in old age is a well known fact but that it is also unusually increased whenever almost any profound change affects the cells is also established on sure foundation, especially if the lesion is of a chronic nature and associated with disease of the vessels. This implies a gradual interference with the normal nutritional supply to the tissues; and it is easily conceivable that such a reduction of nutrition would result in diminished metabolism within the cells and so to an accumulation of partially reduced effete bodies which appear as yellow colored pigment. The question however is one for still further histo-chemical investigation.