RQ^ML /^vf^ CoUese of l^f^v^imni anb burgeons; %ihxavv Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons http://www.archive.org/details/studiesuponcerebOOIawr studies upon the Cerebral Cortex in the Normal Human Brain and in Dementia Paralytica By 0. ALFREO LAWRENCE . BP^^^Sllbmitted in partial fulfilment of the requirements for the degree of t: Doctor of Philoscfphy in the Faculty of Pure Science, Columbia Univer- f- sity. Reprinted from the JOURNAL OF NERVOUS AND MENTAL DISEASES* VoL XXX, Nos. 9, to. U and 12 COLUMBIA UNn"^PS'TY DEPARTMENT OF PHYSiPLOny College of Physicians and Surgeons 437 WEST FIFTY NINTH STREET NEW YORK ALLIANCE PRESS COMPANY NEW YORK CITY J903 STUDIES UPON THE CEREBRAL CORTEX IN THE NORMAL HUMAN BRAIN AND IN DEMENTIA PARALYTICA.' By G. Alfred Lawrence, M.D., Ph.D., of New York. instructor in diseases of the mind and nervous system^ new "vork post-graduate medical school and hospital Introductory. The following contribution to the study of the cerebral cortex in the normal human brain as compared to that in dementia paralytica, does not include much that is new to the pathology of the latter, but aims to present the subject in a some- what different manner than has heretofore been done. The writer's perusal of many anatomical and pathological articles has often been unsatisfactory to himself, owing to many generalized statements of conditions found without any adequate illustrations of what was really to be seen. It has been the endeavor in this !-ticle to present and describe photomicrographs of actual sec- jns from a practically norrnal human brain histologically by way • f comparisori, and to follow these by photomicrographs of sec- ons of a brain of a well marked case of dementia paralytica. These photomicrographs have been supplemented by drawings. The possibilities as well as the limitations of photomicrography in preparations stained by the Nissl method, it seems to the writer, ire fairly well brought out in this article, and this was one of the Dbjects sought in its presentation. That photomicrographs show structure and arrangement in but one plane of limited thickness is true. It is also true, however, that they show exactly what is there and the exact relation to other parts, and there is no personal equation such as is bound to occur in any drawing. A drawing, on the other hand, is always more or less composite, does not show exact relationship, and involuntarily the point to be illus- trated is made to assume undue prominence. In work of this kind artefacts are constantly to be looked for and avoided, and the entire process of preparation, as well as the history of the case, must be also carefully considered before any conclusions should be drawn. 'Submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy in the Faculty of Pure Science, Columbia University. 2, G. ALFRED LAWRENCE. When it is considered how extremely thin the human cortex is, ^•5 to 3.5 milHmeters ; that its exterior surface is estimated at about 200,000 square millimeters ; that it is intricately arranged in convolutions of varying size and direction ; that it is exposed to injury prior to death, at the autopsy, during transportation, and also in the various manipulations of fixation, imbedding, section- ing, staining, decolorizing and mounting, it can readily be seen how artefacts may result by the time the specimen is prepared for examination. This was forcibly brought to the notice of the writer in the examination of some sections but a short time ago. Owing to a dull microtome knife the nuclei of a number of the cells were completely carried outside of the cell-body and the cell- bodies themselves broken and cracked in places. This was at first regarded as a pathological process until attention was called to the fact of the nuclei all being extruded in the same direction, and the breaks and cracks presenting a ragged and irregular ap- pearance. Even when the greatest care is used there will be a variation in thickness in different sections — one being somewhat thinner and the next correspondingly thicker than actually regis- tered by the microtome, although most carefully imbedded, so that variations in the thickness are also to be considered. Further- more, in fixation, shrinkage or swelling may occur, the latter being demonstrated by Donaldson ( 1891 ) , who placed fresh nerves in a solution made up of 2.5 per cent of potassium bichromate, plus one-sixth its volume of 95 per cent alcohol for three weeks. He then washed them for one day in water and placed them in 95 per cent, alcohol for three or four days, and finally in 80 per cent alcohol, using six olfactory bulbs, six olfactory tracts, and three pairs of optic nerves of the sheep. This was exactly the same treatment to which his specimens of human nerves had been sub- jected. The volume of specimens of olfactory bulbs subjected to this treatment and afterwards placed in 80 per cent alcohol was found to be 5.2 per cent greater than fresh specimens, those of the olfactory tracts 8.8 per cent greater, while the optic nerves showed but 2.6 per cent increase in volume. Imbedding in celloidin did not affect the volume, while some stains, as acid fuchsin, produced no change, whereas Delafield's hematoxylin caused swelling, and thus DEMENTIA PARALYTICA. 3 increase in volume. Hammarburg (195) found by experimenting with small blocks of cortical tissue that by accurate measurements blocks hardened in Miiller's fluid for three days showed a volu- metric increase of 11.7 per cent. Other blocks hardened in Mill- ler's fluid for three weeks, and then, transferred to alcohol and left in the latter for fourteen days, showed, on the other hand, a shrinkage in volume of 43 per cent. In alcohol, 95 per cent, at the end of twenty-four hours, a shrinkage in volume of 20.5 per Cent was observed. This shrinkage is furthermore found to vary with different blocks from the same region of the same brain, and it is found that there is no constant relation between pieces from brains of various grades of hardening. Thus thef method of fixa- tion must always be taken into consideration. Again, in staining under exactly similar conditions, one section on a slide will be found more intensely stained than another section on the same slide, or even one part of a section will be found more intensely stained than some other part of the same section. In the subsequent decolorization still greater variations may occur, for, if carried too far, important structures may be com- pletely decolorized. If carried to the other extreme it is impos- sible to differentiate the various parts. The only way to avoid either extreme is by repeated examination of the sections under the microscope while the process is being carried on, as under similar circumstances one section in a given time may become much more decolorized than another. In regard to mounting of sections stained by the Nissl method, as all were that have been employed in this article, xylol-damar has given the greatest satis- faction to the writer. With this mounting medium there was no subsequent shrinkage, and thus a resulting exposure of the sec- tions, also no decolorization was to be observed at later periods. In some sections mounted for over three years, no decororization was observed, even after several exposures to the intense light necessary for photomicrographic purposes, and frequent expo- sures to light in their examination under the microscope, Canada balsam was also used, but in time the sections were found par- tially or completely decolorized. Benzene-colophonium has a 4 G. ALFRED LAWRENCE. tendency to shrink and crack and thus expose portions of the sec- tions in some cases. It is desired to emphasize the importance of careful attention to all these details at the beginning of the article, in order to impress upon the reader the necessity of the greatest care and conservatism in the interpretation of any changes found in the specimens under observation, and, furthermore, the correct in- terpretation of the same. Before going on to the main subject of the article, a brief historical review of work in this line will be given. Historical. The first study of the internal structure of the nerve cells began over fifty years ago when Remak (1841) called attention to a fibrillary structure inside the axis cylinder and cell- body of certain nerve cells. Later, Max Schultz (1872) studied nerve fibers and cells from various parts of the central nervous system of different animals with elaborate descriptions of his find- ings. He dealt with a description of the fibrillary appearance of the interior of the cell-body largely. This doctrine of the nerve cell was afterwards strongly supported by Boll (1873), Schwalbe (1885), and Ranvier (1878). Opposite views were, however, held by Arndt (1874), and Key and Retzius (1876). Arndt, in 1874, described the structure of the spinal ganglion cells and spoke of the presence in them of different kinds of elementary spherules which varied in size and general appearance. Key and Retzius stated that the ground substance of the spinal ganglion cells was homogeneous, but that in it numerous strongly refrac- tive, round, oval granules were present, and they thought the ap- pearance of a concentric striation or fibrillation could be simu- lated through the arrangement of the granules in rows. Flem- ming (1-882) saw granules within the cells which would stain with nuclear and azo dyes and hematoxylin, but nevertheless affirmed a fibrillary structure of the central cells and of a tortuous or much curved threadwork within the spinal ganglion cells be- tween the granules. In recently published articles (1896) he still maintains that fibrils exist inside the nerve cell protoplasm. Dogiel (1893) has also expressed himself in favor of the views of a fibrillary structure for certain at least of the nerve DEMENTIA PARALYTICA. 5 cells. In 1885 Nissl published the first of a series of articles in which he calls particular attention, in tissues hardened in alcohol and stained in basic aniline such as majenta red and methylene blue, to certain structures. By Nissl's method these are brought especially well into view, and their arrangement in the protoplasm and their significance for the function of the cell can be studied. These structures had been previously observed by Flemming and Benda (1882), but by less perfect methods. Nissl at first stained tissues hardened in alcohol with magenta red or meth- ylene blue, and cleared in oil of origanum. This has been modi- fied in several ways, so that at present his treatment is as follows : Small blocks of tissue are hardened in 96 per cent alcohol and fastened by Weigert's method with gum arable, without imbed- ding. The sections are received in 96 per cent alcohol and stained in a watch glass. The stain is to be heated over the spirit flame until small bubbles arise which make a crackling, noise (65° to 70° C.) ; sections are then transferred to aniline-oil-alcohol until differentiated. The process of differentiation is ended when no more coarse clouds of color go off into the fluid. The section is then transferred to the slide, dried with filter paper, after which some drops of oil of cajeput are applied, and the sections are again blotted with filter paper. A few drops of benzene are poured on the sections, blotted again, and finally some benzene- colophonium added, a cover glass placed over the section, and the slide heated until all the benzene gas has been driven off. Upon cooling, the section is thus permanently mounted. The stain is made as follows : Methylene blue, B. pat., 3.75 grams; Venetian soap, 1.75 grams; distilled water or soft water, 1,000 c. c. The differentiating or decolorizing fluid has the fol- lowing composition: Aniline oil, colorless, 10 parts; alcohol,. 96 per cent, ninety parts. Nissl obtains his aniline oil directly from the factory at Hochst and keeps it carefully protected from the light. The benzene-colophonium is prepared by pouring benzene upon colophonium (white rosin) and alowing it to stand for from twenty-four to thirty hours. This results in a fluid transparent mass which can be brought to the desired thickness either by the 6 G. ALFRED LAWRENCE. addition of more benzene or by allowing it to evaporate, and then it is ready for use. In mounting, while driving off the benzene gas by heating over the flame, the material may catch fire, but if the flames are blown out immediately no injury is done, and the alterations produced by the burning are quite characteristic and easily recognizable. The above description has been given in detail as it is the classical method, which, as above and with various modifications to be described later, has been used by the writer in this article. This method distinguishes within the cell- body always two and sometimes three constituents. One of these constituents of the protoplasm stains entirely blue by this method, and is spoken of by Nissl as the stainable or visible formed part of the nerve cell. The second part remains entirely unstained, and is spoken of by him as the unstainable or the visible unformed part of the nerve cell-body. In addition to the above, in many nerve cells, pigmentary deposits are visible which have been especially studied recently by Rosin ( 1896) . Nissl has prepared a somewhat elaborate classification of cells according to the character and ar- rangement of the stainable portion to the non-stainable portion of the cell-body in different cells in different parts of the central nervous system. This stainable substance shows a series of dif- ferent forms ; smaller and larger granules of regular or irregular shape, arranged in groups or rows, These stainable masses are sometimes arranged in threads, smooth or rough, and varying in thickness, course, and length. Often larger structures, regularly or irregularly shaped, are seen, which stain with varying degrees of intensity, some appearing homogeneous, others showing a complex internal construction difficult to describe. Three varieties of these larger bodies are especially to be noted, (i) the so-called ''nuclear caps" (Kernkappen), stainable masses in the form of regular or irregular cones hollowed out like a cap and corresponding to one pole of the nucleus upon which it rests. There may be two such caps within one cell-body at opposite poles, and occasionally, according to Nissl, three such caps may exist within a single cell. (2) So-called "wedges of division" (Verzweigungs-Kegeln), stainable masses completely filling the angle at the point of division of a nerve cell process. DEMENTIA PARALYTICA. 7 (3) Spindles, oblong spindle-shaped stainable bodies, thick in the middle and thinner at both ends, the latter sometimes tapering off into rhread-like filaments. These spindles may be one or two- sided. Any one of these forms may be vacuolated. Nissl makes a rather elaborate classification of these ganglion cells according to their internal morphology, after spending years in the most exact investigations of various nerve cells in the different nerve centers of man and animals. He has come to the conclusion that definite types or variations of nerve cells exist which are constant not only in the same animal but often exist characteristically in homologous localities in a whole series of animals. According to him, all the cells in the nerve centers, except the so-called chromo- phile nerve cells, can be divided into two main classes. The first class includes the nerve cells which possess a well marked cell- body surrounding the nucleus completely on all sides, the proto- plasm having a distinct contour. These are called somatochrome nerve cells. The second class (sub-divided into two groups, cyto- chrome and caryochrome) includes those cells in which, in Nissl preparations, the nucleus is most in evidence, the nucleus has a clear contour, but only indications of a cell-body are present, an appearance due to either the scanty development of the cell-body or to the predominance in it of the unstainable substance. These cells often look as if they were naked nuclei, though by Golgi's method it can be shown that they may possess definite axones and dendrites. In some of these cells the stainable sub- stance may be present, but very unevenly distributed, at different points in the cell, the nucleus appearing as if only partially sur- rounded by protoplasm. Nissl classifies these cells with such an ill-defined cell-body, the nucleus appearing only partially sur- rounded and not exceeding in size the nucleus of a neuroglia cell or of an ordinary leucocyte, as "granules" (Korner) or cyto- chrome nerve cells. These cells are present in great numbers in the granular layer of the cerebellum, also in the cerebral cortex and the olfactory bulb — ^being different varieties and not identical. The second subgroup of cells, in which the cell-body is only indi- cated but the nucleus is of the size of an ordinary nerve cell, or at least larger than that of a neuroglia cell, he designates as 8 G. ALFRED LAWRENCE. caryochrome nerve cells. There are varieties of these as in the substantia gelatinosa Rolando, and those of the ganglion ha- benula — these types being designated at present by letters of the Greek alphabet. A majority of the nerve cells fall in the first group — the somatochrome cells — w^here the cell-body, in the light of morphology, has apparently greater relative importance than the nucleus. In this group are a series of types of nerve cells to be distinguished from one another partly through differences in the nuclei, but chiefly through different relations of the stainable and unstainable constituents of the cell-body. These somatochrome cells were originally divided by Nissl into four groups,, but now he includes them all in three groups as follows : Group I. Arkyochrome nerve cells: — stainable portions of cell-body in Nissl preparations in the form of a network, branches of which appear to be distinctly connected. Nissl notes, however, that in many of these cells processes can be made out into which the distinct network of the perinuclear part of the cell-body can go over, thus forming a parallel-striped arrangement. These arkyochrome cells Nissl subdivides into enarkyochrome forms and ampharkyochrome forms. The former shows the stained constituents arranged in the form of a network, which differs from the latter in that the intensely stained radiating nodal points of the network are connected in the cell-body by deeply stained thick bridges so that a further connected network of very deeply stainable substances is observable. Both these sub-groups of cells are widel}^ distributed throughout the central nervous sys- tem. The former have been observed by Nissl in the spinal cord, but are most numerous in the large dorsal nucleus at the proximal end of the medulla. What he formerly classified as Group III, arkyostichochrome nerve cells, are now included in this first group (1897a).- He describes these cells as presenting a striated appearance with a network-like structure united in a most intricate manner. The Purkinje cells of the cerebellar cortex were given as typi- cal examples of cells of this sort. (See Plate IX, Fig. 27). Group II. Stichochrome nerve cells, stainable substance ar- DEMENTIA PARALYTICA. 9 ranged in strise, running in same direction, and usually parallel to contour of cell-body, in part also with surface of nucleus. These strise, made up of different stained elements, threads, spin- dles and granules, are more or less isolated and in rows. Nissl describes four types of these cells represented by (i) nerve cells of motor nuclei, (2) large cells of cornu Ammonis, (3) certain cells of cerebral cortex, and (4) certain cells of spinal ganglia. Group III. Gryochrome nerve cells, stainable substance en- tirely made up of small granules distributed in threads or heaps. Nissl does not give an illustration of these cells, but states that they are to be found particularly but not exclusively in the corpus striatum. Nissl states further that transitional forms exist which are difficult to definitely classify, but that the cells of a wholly definite structure are situated throughout, the animal series in homologous localities. He has also shown that all these types of cells may, under certain circumstances, show different, staining relations (1894a), that is, the individual members of a certain group of cells belonging to one type .may be palely,, moderately, or intensely stained. This difference seems to depend upon the concentration of the stainable substance in the cell-body. The darkly stained ceils he designates as pyknomorphous cells, in which stainable portions are arranged relatively most closely ; intermediate stages are designated as parapyknomorphous cells ; while very feebly stained cells are designated as apyknomor- phous, in which stainable masses are not arranged close to one another but are somewhat widely separated by the non-stainable constituents of the cell-body. Nissl furthermore mentions that often the nucleus shows modifications which correspond in greater or less degree to the staining intensity of the cell-body, so that in an apyknOmorphous cell the unstained nuclear sub- stance is relatively more abundant than in the pyknomorphous cells. This holds in the somatochrome cells, and to a less degree in the caryochrome and cytochrome cells. Supposed to be more or less in the nature of an artefact are the so-called chromophile nerve cells which one finds often single or in small groups along with the other nerve cells, but in which the stainable substance seems to be evenly diffused throughout lO G. ALFRED LAWRENCE. the cell-body, making it impossible to distinguish a stainable from an unstainable constituent in the cell. Nissl (1896c) states that they are always relatively smaller than pyknomorphous cells. The explanation of these forms is not as yet entirely satisfactory, but they are supposed to be due to the action of the reagents em- ployed, though under certain circumstances they may have a pathological significance. Another nomenclature has been intro- duced by Flesch (1897), in which he speaks of chromophilic cells and chromophobic cells with transitional forms, and attributes the differences to variations in the internal chemistry of the cells, this latter depending in part upon differences in the devolopment, in part upon differences in metabolism or function. Von Lenhossek (1895) gives a very accurate description of the appearances within the cells of the ventral horn of the spinal cord and in the cells of the spinal ganglia. He has found that thionin stains as well if not better than methylene blue, and Barker (1899) has obtained similar results, but states that crys- talline deposits have been more frequent in preparations stained with thionin than in those stained with methylene blue. In ma- terial hardened in Lang's solution or other corrosive sublimate solutions, the writer has at times detected crystalline deposits, whether stained with thionin, methylene blue or methylene violet, and attributed the same to the fixative fluid and not to the stain at all, as no crystalline deposits have been observed with other fixative agents-— alcohol, formalin, and Van Gehuchten's fluid- regardless of which stain was used. It would be interesting to know whether corrosive sublimate fixation was used by Barker in the above mentioned preparations. Van Gieson uses polychrome to a considerable extent as a stain, but it seems to the writer to give a paler and less distinct stain than either methylene blue or methylene violet, and has a tend- ency to fade after a time. Referring to von Lenhossek again, he objects to the term "granules" for the stainable substance, the masses being ordinarily much too coarse to be so designated. He has given accurate descriptions of their characteristics and ar- rangement in various animal species. This stainable substance of Nissl he designates as "chromophile corpuscles," and later uses the term "tigroid masses" (1896). DEMENTIA PARALYTICA. II Do Quervain (1893) has suggested that the chromophiUc bodies or corpuscles are aggregations of fine granules, but von Lenhossek refuses to admit that all such bodies represent aggre- gations of minute granules. Schaft'er (1893) first described the peculiar behavior of the axone and adjacent portion of the cell- body known as the axone hillock as regards Nissl staining, this space being entirely free from this stainable substance of Nissl. With Kronthal's method the axone and axone hillock stain in- tensely in methylene blue, but Benda (1895) found that when specimens thus prepared were cleared in creosote this region lost its color and only the stainable substance of Nissl in the cell-body and dentrites retained its color. He found one exception, how- ever. In the basal axones of the pyramidal cells of the cerebrum, especially of those known as the giant pyramidal cells of Betz, just at the beginning where a collateral is coming off at right angles, a small wedge-shaped granule, triangular in section, takes up the methylene blue, the axone itself not staining at all. These dif- ferent results obtained by differences in technique emphasize the writer's previous statement of the necessity of a full knowledge of the history of the case and every detail of technique before com- ing to any conclusions in a given case. With this brief review of the more important literature on the internal structure of the nerve cell we will now turn to the ar- rangement of the cells in the cortex. To go into the literature of this subject in detail would be sufficient material for an article in itself, so that it will be passed over as briefly as possible. Table I shows the arrangement of the cells as described by the more im- portant contributors to this subject. As early as 1782 Gennari divided the cortex at the posterior pole of the cerebrum into three layers, an external and internal gray layer separated by a white layer (so-called line or band), the "line of Gennari." Vicq d'Azyr, in 1786, described this region as also made up of an inner and outer gray layer between which was a white layer (line or band), the "line of Vicq d'Azyr." Meckel, in 1812, stated that the gray layer of the cortex is single in all parts but the occipital region and cornu Ammonis. In the occipital region a band of white substance, the line of Vicq d'Azyr, separates the gray substance into an 12 G. ALFRED LAWRENCE. external and internal gray layer, so that the structure of this part of the brain is more complex than the rest of the external cortical region. Coming down to 1840 Baillarger first examined the cortex carefully, and described three gray and three white layers, or six layers in all, alternating gray and white. From his descriptions the line of Gennari or Vicq d'Azyr, in the occipital region, received the additional name of the "line of Baillarger." In 1841 Remak examined the cortex microscopically as well as macroscopically, but without the use of staining agents, and de- scribed a four-layered type made up of two gray and two white layers alternating with one another. Somewhat later (1852) Kolliker described a three-layered plan, the inner layer appearing of a yellowish red color, the mid- dle of a grayish color, and the outer of a whitish color. Berlin, in 1858, first used stains in his work, hardening pieces of the cortex in chrome salt and staining with carmine. He de- scribed six layers as the type, the upper five from the character and arrangement of the cells and the lower as a layer free from cells. He describes the layers from within outwards toward the surface, reversing the usual order of all other authors, and' lead- ing to considerable confusion, unless this fact is carefully noted. Clarke, in 1863, described eight layers as the common type, and Luys the following year, 1864, described just one half that num- ber, or four layers, as the common type. Arndt, in 1867, de- scribed a five-layered type, and Meynert in the same year divided the cortex into a motor and a sensory region, the former anterior to the fissure of Rolando, and the latter posterior to the same. He described five layers as the common type, and eight layers as the type in the occipital region. Cleland, in 1870, described rather a complex arrangement of the cortex into a four-layered type, the third layer being separated from the fourth by what he designated as the "primary pale band." The "deep pale band" is included in and forms the lower part of the fourth layer. Henle in the same year described a four-layered type made up of (i) the outer layer, (2) outer spherical cell layer, (3) pyramidal cell layer, and (4) inner spherical cell layer. Charcot, the fol- lowing year, 1871, described the layers of the cortex as five in DEMENTIA PARALYTICA. 1 3 number, (i) superficial layer, (2) small pyramidal cell layer, (3) larger pyramidal cell layer, (4) granular cell layer, and (5) fusiform cell layer; approximating that used by many of the subsequent authors. Lewis, in 1876, described five layers as the type for the motor area and six layers as the type for the sensory area. Major in the same year, 1876, described six layers as the common type, and Krause, also in the same year, described seven layers as the common type. Betz, in 1881, made the division into five layers as the type for the motor area, but divided the sensory region into eight layers as the type — a classification somewhat similar to Meynert's, but with a different nomenclature. Golgi, in 1883, using his impregnation method, divided the cortex into three layers as the type, (i) superficial or small pyramidal cell layer, (2) middle .or larger pyramidal cell layer, and (3) internal or irregular cell layer. Schwalbe, in 1885, de- scribed a curious arrangement of the cortex into four layers, the upper two known as the "outer Hauptzone" or chief zone, and separated from the lower into two layers, known as the "inner Hauptzone" or chief zone, by the "boundary zone" or "line of ^aillarger;" Obersteiner's (1887) division into a five-layered •type is similar, except as to the nomenclature, to that of Char- cot's common type, Lewis' motor type, and Betz's motor type. Cajal, in 1890, recognized the same three layers as Golgi in the .common type, but added a fourth layer, which he called the first or molecular zone, then followed the second, or zone of small pyramidal cells ; the third, or zone of large pyramidal cells, and •the fourth, or zone of polymorphous cells ; thus making four layers in all. Golgi's first layer is thus seen to include the first and second layers of Cajal. In the occipital lobe, Cajal describes an additional layer of vertical fusiform cells between the first or molecular layer and the layer of small pyramidal cells, the other layers being similar to his common type, and thus making fi:ve layers in this region. Gowers, in 1893, adopted practically the same division into a five-layered motor type and six-layered sen- sory type as described by Bevan Lewis in 1876. Hammarberg, in 1895, described six layers as the type, with numerous varia- tions in. different parts of the cortex. Edinger, in 1896, describes 14 G. ALFRED LAWRENCE. four layers, similar to Cajal as the type, and Starr (1896), in his atlas of nerve cells, also describes a similar arrangement. Nissl (1898) describes a four-layered type as follows: First, or layer poor in cells ; second, or layer of pyramidal cells containing 2 equals layer of small pyramidal cells (equals 2 of Meynert's layers) plus 3 equals layer of larger pyramidal cells (equals 3 of Meynert's layers) ; third, or layer of small cells (equals 4 of Meynert's layers) ; and fourth, or internal (6) plus external (5) zone of the layer of medullated fibers (equals 5 of Meynert's layers). Region 5 equals ganglion cell layer, and region 6 equals spindle cell layer of Hammarburg. It will be seen that there is much variation and not a little confusion in adjusting these various arrangements and classifications to one another, and in order to simplify the matter as much as possible the writer sug- gests that as the large and small pyramidal cells are so inter- mingled and merged into one another, they should be included in one layer, thus making three layers the common type, as fol- lows : First, or superficial layer, corresponding to the first layer of Cajal and Edinger; second, or pyramidal cell layer, corre- sponding to the second and third layers of Cajal and Edinger; and third, or spindle cell layer, similar to the fourth layer of Cajal and Edinger. This arrangement differs from Golgi's three- layered type in that the latter recognized no superficial or tangen- tial fiber layer, but includes this as the upper part of his first, or layer of small pyramidal cells, whereas in the writer's arrange- ment one pyramidal cell layer includes both the large and small pyramidal cell layers of Golgi. The third layer ,of Golgi and of the writer are the same as the fourth layer of Cajal and Edinger. This classification into three layers as the type will be used for convenience in the subsequent description of the plates. That there are variations from the type in difiPerent parts of the cOrtex, of course, is recognized by all who have worked in this field to any extent, and, furthermore, specialized parts of the cortex have a specialized arrangement, as the cornu Ammonis, for example. In turning now to the pathological investigations by means of the Nissl stain (1898), they are found to have been exhaustive and varied, including most parts of the central nervous system DEMENTIA PARALYTICA. 1 5 in both man and animals and in many forms of disease. A brief review only will be given of the contributions containing descrip- tions of researches by Nissl's stain in that form of mental de- rangement known as dementia paralytica, or general paresis. Nagy (1894) carried on his investigations by means of the Nissl stain, and found the greatest changes in dementia paralytica, in- cluding various stages of cell degeneration up to complete de- struction of the same — the cells most altered being those of the frontal lobes, and least changed those of the occipital lobes. Changes of a high grade were also shown in the cells of cases dying after severe epileptic insanity — here the gyrus rectus and cornu Ammonis being affected the most. In chronic forms of in- sanity similar changes were found, but the number of cells en- tirely destroyed was undoubtedly smaller than in the above men- tioned forms of illness. In acute hallucinatory confusional insanity only the beginning stages of alteration were found ; simi- larly in mania. He finally states that each form of mental de- rangement showed the highest grade of change in which the clinical picture of the worst suffering was present, while in the curable forms there were found corresponding slight changes. Belmondo (1896) employed the Nissl method in investigating the alterations in the nerve cells in dementia paralytica, and did not find changes of great gravity — at most the cell protoplasm being much diminished and disintegrated 5 now and then pigmen- tary atrophy, as much in the Rolandic region as the frontal lobe, is found, and in other parts a diffuse chromatolysis is to be seen. He condemns the expression meningo-peri-encephalitis, which im- plies a conception of an inflammatory process. Boedecker and Juliusburger (1897) examined sections of cortex from the central and parietal convolutions of three cases of dementia paralytica by the Nissl method. They found thick- ening of the pia with septa projecting into the cortex, containing blood vessels whose walls showed no special thickening but were surrounded by rich deposits of pigment granules, which latter were also found here and there, distant from the septa in the cortical network. In regions most affected the cortex did not present its well known layering. There was to be seen a thickly- 1 6 G. ALFRED LAWRENCE. compressed granular crowding with different shaped granules ; thin, spindle-shaped, round, or oval, with strongly colored ones lying adjacent to those only slightly colored. There was increase of blood vessels and hypertrophy of the interstitial network, with corresponding decrease in the number and size of the cells. Many cells were considerably diminished in size, markedly shrunken, entirely without processes, and intensely colored. At times a differentiation into nucleus and granular cell-body was not possible, owing to complete chromatolysis, and very seldom were cells found with a strongly colored nucleus, strongly colored fine granules about the same, with larger granules at the peri- phery of the cell-body — a partial chromatolysis. By the Marchi method these investigators determined a de- generation of the fibers from these cells extending into the spinal cord. They conclude the process to be an intense degeneration and proliferating one, going on hand in hand — degeneration of the cells and proliferation of the interstitial network, with increase of blood vessels. Crisafulli (1897) notes a great variety of changes in dementia paralytica. The cellular changes are most advanced and diffuse in the ' frontal lobes, but are not limited to that region. He examined sections from the frontal, parietal, occipi- tal and temporo-sphehoidal lobes of both hemispheres. He found pallor, granular disintegration, and loss of chromatic substance. Often the cell-bodies were atrophied or contained an excess of yellowish pigment, and their numbers were reduced. The nuclei were often eccentric, and all stages of the destruction of the nucleus were observed. While the alterations shown by Nissl's method were not less constant than those demonstratable by other methods, Crisafulli does not consider them characteristic of the disease or in any way different from those seen in some other mental diseases. They are, however, more or less grave and diffuse and not limited to a single cortical center; with varying degrees of degeneration of the nerve cells. He further states that, -provided the nerve cell element degeneration is not greatly advanced, it is impossible to find any alteration of the blood ves- sels, and, finally, that when the psychosomatic condition of the paralytic is not greatly aggravated and death intervenes from DEMENTIA PARALYTICA. tj Other causes, it is possible that the pathological report will note some elements which are not degenerated, although there may be various alterations. His article is illustrated by eight figures showing cells in various conditions of degeneration, Angladi (1898) reports a case of acute dementia paralytica in which death occurred after a series of epileptiform convulsions when the patient was at the age of thirty-seven years. The autopsy showed peri-encephalitis. Preparations were made from the ascending frontal convolutions and the anterior part of the frontal lobe of the left hemisphere. He states that not a single one of the pyramidal cells preserved its normal characteristics, and the transformation in the great majority of cases semed to be various stages of the same process — various stages of chro- matolysis, vacuolization, eccentricity of the nucleus up to rupture of the cell wall and extrusion of the nucleus and, finally, com- plete destruction and disappearance of the cell. The chromatic substance is first attacked, and some few cells relatively healthy showed about the nucleus the first stages of dissolution. De- struction of the achromatic network was shown by formation of vacuoles at the periphery of the cell, increasing gradually up to complete destruction of the substance of the cell. The nucleolus becomes vacuolated and disappears. The nucleus is attacked by central chromatolysis and disappears in situ, or becomes eccentric, or the cell-body may rupture and the nucleus be ex- truded, becoming irregular, compressed or shriveled. The con- tour of the cells is always irregular, and the prolongations either broken or tortuous. He states that the cells of the medulla and cord show identical alterations. Angladi finally concludes by stating that we do not know whether these lesions are the cause or the result of the malady, and asks the question, "Are the lesions primary or secondary to an alteration of the vessels or interstitial tissue?" Berger (1898) examined the anterior horn cells of the spinal cord in twelve cases of dementia paralytica and found lesions affecting principally the chromatic substance in 83 per cent of the cases. He failed to find a strict parallel between these cellu- lar lesions and those of the fibers and cortex, or between them 1 8 G. ALFRED LAWRENCE. and the clinical symptoms of the disease. He illustrates his article by figures of these cells. Nissl (96a), in 1896, stated that he maintains the same posi- tion as Kraepelin, namely, that one sees in dementia paralytica a general disease with the histopathology directed especially to the cortex. The pathological changes in the blood vessels are obscure, and the relation of the glia to the blood vessels is complicated, also the condition of the lymphatic vessels. Sorne authors regard the disease as an inflammatory process, others that a chronic in- terstitial inflammation enters into it, others that it is a parenchy- , matous process, and still others that it is a histopathological pro- cess in which the specific tissue is diseased primarily. Nissl notes that an inflammation without the blood vessels sharing in it can- not be thought of. He states that the appearance of the paralytic cortical disease can be present without the blood vessels being diseased and without the blood vessels containing any elements, of an inflammatory process. Also there may be a high grade of disease of the 'tissue (Gewebe) in excess of any disease of the blood vessels, and only a slight involvement of the tissue, and vice versa, a severe tissue damage with only insignificant disease of the blood vessels. Also direct inflammatory blood vessel changes with infiltration of the walls of the same with leucocytes and "mastzellen," which may rarely pass out into the adjacent regions. In some cases this inflarnmatory alteration of blood ves- sels results in a massive production of decay of numerous neurones. These inflammatory changes in the blood vessels have nothing directly to do with the chief paralytic process, and are only found in the cortex when sepsis-producing bacteria are present. It therefore follows that the paralytic cortical disease can be regarded either as the result of disease of the blood vessels or as an inflammatory process. Almost all cases of dementia paralytica show a slight or severe disease of the blood vessels. There may be also a leptomeningitis, disease of the beginning part of the aorta, an injury to the diploe, brittleness of the bones, or there may be a general arterio-sclerosis. If it is not a disease of the arteries or an inflammatory process, it may be a primary disease of the glia or of the cortical neurone. Changes in glia DEMENTIA PARALYTICA. I9 are progressive in kind (mitosis of glia nuclei, hypertrophy of gha cells, and increase of glia fibers) with regressive changes in .the cortical neurone — an acceptation that results of investigation directly contradict, since we find in the most luxuriant increase of glia that the nerve cells are only slightly or not at all changed, and vice versa, in the most severe nerve cell changes the increase of glia. may be only slight. The acceptation of a primary glia fiber increase is absurd, since the glia fibers are an intercellular substance. Nissl therefore concludes that the cortical disease of dementia paralytica is a primary disease of the cortical neurone ; at the same time with the regressive changes in the cortical neu- rone goes the progressive changes in the glia cells.. Histo- pathological investigations of paralytic cortical disease has to deal chiefly with the following difficulties : ( i ) a paralytic diseased cortex and the, to us, available cortex of the dead paralytic are two different things. Entire series of original circumstances that damage the neurones of the cortex without having anything to do directly with the paralytic process is to be noted, as the com- plete closure of a blood vessel which only indirectly bears upon the original process. Also death of a paretic froni typhus fever, septic pyemia, etc. The problem is extremely difficult, as there is no specific disease of the cortical cells, and, furthermore, there is no paralytic cortical cell disease, although there is a paralytic cortical disease. The kind of disease of the cortical tissue is worthy of being pointed out. (2) It is not sufficient to know that the cortical neurone is diseased, but it is important to know which cortical neurones are damaged. ■ Attention to the kinds of nerve cells directly diseased is important for the real conception of the disease process, and also for the critical examination of the plan of the cortex and its functions. ' Nissl differentiates the following forms of disease of the cells of the cortex in dementia paralytica : ( i ) Acute progressive disease. In certain cases the disease ends with the complete destruction of the elements of the cortex. (2) The chronic disease progresses slowly, restilting in either a pigmentary degeneration or in a decay of the cell-body and nucleus, and ends with so-called cell sclerosis. (3) The severe disease of the cortex which runs either an acute or sub- 20 G. ALFRED LAWRENCE. acute course and terminates with the death of the cell. The necrotic cells persist commonly either bleached out or having the appearance of colliquation or of vaucolization of the ground work. (4) The combined form of the disease, in which the cell may be acutely diseased without either a cure following, or, on the other hand, the ordinary course being taken that terminates with the destruction of the cell. Midway in its course the disease process is arrested and takes on the symptoms of the chronic disease. The severe cortical cell disease is entirely overlooked by former authors. It differs in that the nucleus is also involved and a pro- cess of liquefaction takes place in the same. It becomes smaller, shrunken, the contours become homogeneous and tinged, the nu- cleolus sinks to the nuclear wall, which latter is irregular and shriveled into folds, the network cannot be distinguished, and vacuoles and crystals may be formed. In the necrotic cells cal- careous deposits may be found, as is seen in other cortical cell diseases, as sclerotic elements. These chalky or calcareous con- cretions occur in the form of fine granules, crumbs, placques, or stalactitic masses, which are intensely colored with methylene blue. The entire cell may be bleached or only a single part, as some of the fine dendrites or only a single dendritic process, or only the nucleus, or, finally, only the nucleur membrane. This calcifi- cation, moreover, is an exceedingly important phenomena, since we are entitled to conclude that partially calcified cells are no longer functionally active and are necrotic. Under similar condi- tions in acute diseases we recognize the phenomenon of death in the affected cells. If one places the preparations in alcohol after twelve hours postmortem, any mistake in this direction may be obviated. Whoever grasps the histopathology of the cortical cells will guard against any mistake in regard to the above mentioned death phenomena. Ewing, in 1898, used the Nissl method in observations upon the changes found in ganglion cells of the cen- tral nervous system in various pathological conditions, and stated that various grades of chromatolysis were found in the cortical cells in dementia paralytica. Ballet (1898) exhibited sections from the paracentral lobule of both a normal and a paretic brain, stained by the Nissl method. DEMENTIA PARALYTICA. 21 In the normal brain, under a magnification of forty-five diameters, the four layers of Schwalbe and Ramon y Cajal were easily dis- coverable, but in the paretic sections, in marked contrast, they were recognized with difficulty ; also in the latter, great numbers of capillaries were noted in the third layer and white subcortical substance, the nerve cells were less numerous, and in all cases less distinct and lost in the midst of a mass of nuclei. At 130 diame- ters the contrast was still more marked, and at 250 diameters vascular lesions were noted consisting of enormous dilatation of the capillaries and arterioles, the investment of these vessels by a casing of lymphatic corpuscles which distended the adventitious sheaths, and the accumulation of pigment at certain points, par- ticularly in the neighborhood of the bifurcations. These altera- tions are also revealed by hematoxylin and picro-carmine, and have been described for a long time by all observers, but the Nissl method shows the changes more clearly than any of the others. In addition to these changes one may mention the multiplica- tion of the white corpuscles and their migration from the vessels by diapedesis, as due in part perhaps to the proliferation of cellu- lar elements of the neuroglia which accumulate in the interstitial tissue, principally in the neighborhood of the vessels or about the nerve cells. At 600 diameters one easily distinguishes the small white cells (lymphocytes), with small nuclei deeply colored and with but a small amount of protoplasm ; large white globules with protoplasm somewhat abundant and with voluminous nuclei irregular in form and less impregnated than those of the lympho- cytes by the methylene blue; and, finally, polynuclear leucocytes. But interest in Nissl's method is chiefly in the study of the lesions of the nerve cells. At 600 diameters one sees the profound altera- tions undergone by these cells. In examining the elements of the third layer (large pyramidal cells) or the giant cells of Betz, there is a tendency in them to lose their triangular shape and become oval or rounded, the protoplasmic prolongations are atrophied and but slightly visible, the chromophilic granules for the most part undergo a process of disintegration and are reduced to a sort of fine powder or dust, or are entirely dissolved in the mass of proto- plasm. The author then discusses the nature of the process. 22 G. ALFRED LAWRENCE. some authors (Magnan, Mierzijewski, Mendel) claiming the primary disease to be that of the neuroglia framework — an inter- stitial encephalitis. Others on the contrary (Tuezeck, Ziegler, Binswanger, Joffroy, Pierret) claim it affects primarily the nervous tissue, either the nerve fibers or the nerve cells ; thus being a parenchymatous encephalitis. The . more Ballet studies the pathological anatomy of dementia paralytica the more he is con- vinced that the first and most important lesions are those of the blood vessels. These are seen in every case, while those of the cells are inconstant, variable in degree, and subordinated to those of the vessels. This is not to say th9,t the cellular alterations may be, as some authors claim, the result of the mechanical choking of the cells by the proliferating interstitial tissue which makes their pathology more complex, but he thinks the result is due less to the compression by the thickened neuroglia than to the difficulties of assimilation, owing to either the circulatory obstruction or the action of the toxines carried by the blood. Ballet then discusses the relation of syphilis to dementia paralytica, and states that the pathological anatomical findings in the two cases are practically identical, and advocates a syphilitic etiology for the disease. In this historical review of the literature on the pathological conditions found in dementia paralytica by the employment of the Nissl method, it is to be noted that but few of the contributions were accompanied by figures illustrating the various pathological findings described in the text. Technique. Turning to the technique employed in this work, first will be described a method used in transporting material con- siderable distances in the minimum amount of space, and prepar- ing the same in the shortest possible time. On several occasions the writer was enabled to secure more than one brain at th-e same time, and at a considerable distance from the laboratory. ~ It was desired to place small blocks from various parts of each of the brains in various fixative media in the shortest possible time, and to put them into the smallest possible space for transportation. The smallest size of tin boxes known as "Miller's patent seariiless box" (Fig. A) were secured at trifling cost at Eimer & Amend's, in New York city; though any small box would answer the purpose. These measured but 2.5 c. c. in diameter and 1.25 c. c. in depth. One gross of these boxes occupy DEMENTIA PARALYTICA. 23 only a space of 15 c. c. square by 5 c. c. in depth. By piercing a hole in both the cover and bottom of these boxes a free circulation of the fixative medium is secured — as mentioned, any other small box or phial admitting of the free circulation of the fixative me- dium could be used ; but these chanced to be the most convenient and available receptacles to the writer. By placing a bit of ab- sorbent cotton or cheesecloth in both the bottom of the box and in the cover the specimen is perfectly protected. A square box of black pins (Fig. B), such as can be secured at any drygoods store at trifling cost, was purchased. Small squares of cardboard were cut out and numbered in duplicate, using a lead pencil. Each Fig. A. number, with its single duplicate, was placed upon a pin and re- turned to its position in the box. The various fixative fluids desired were carried in small glass jars with ground glass covers. All these preparations are made in advance so that at the autopsy, upon removing the brain, small pieces can be taken from any part of the cortex, each one placed in a separate small tin box with a number from one of the pifts. The other or duplicate number is 24 G. ALFRED LAWRENCE. left upon the pin, and the latter thrust into the space on the brain surface from which the block was taken (Plate I, Fig. i). The small tin box is then thrown into whatever fixative fluid is desired, and the fluid entrrs and fills up the interior by means of the open- ings above described, the whole process taking less time than re- quired in explanation. In this way a large number of blocks can Fig. B. be taken from one or more brains without any possibility of con- fusion, and in a minimum amount of time, and likewise take up a minimum amount of space, requiring no writing or labeling of specimens at the time. After all blocks desired are removed the brain is carefully placed upon cotton in a tin pail of the required size in whatever fixative fluid is desired, and other brains can be treated similarly. At the laboratory subsequently the exact locality from which blocks were taken can be noted at leisure in the most accurate DEMENTIA PARALYTICA. 25 manner. The writer has by this method taken blocks from vari- ous parts of two separate brains, placed them in half a dozen different fixative fluids, and packed them up, together with the tw^o brams in tin pails of suitable diameter, placing everything in a hand bag of medium size, and carried the same many miles on the train without the slightest inconvenience or knowledge by others of the contents ot the hand-bag. The fixative agents em- ployed in this work were alcohol absolute, alcohol 95 per cent, formalin 10 per cent solution (40 per cent formaldehyde, i part by volume, water 9 parts by volume). Van Gehuchten's fluid (alcohol absolute (5o, chloroform 30, and glacial acetic acid 10 parts by volume), and Lang's solution (mercuric chloride 5 grams, sodmm chloride 6 grams, acetic acid 5 grams, and water 100 grams). The most satisfactory results have come from fixa- tion in Van Gehuchten's fluid, and the alcohols. In the employ- ment of the latter more or less shrinkage results, but this can be recognized, and the chromatic substance within the cell is usually well marked. Van Gehuchten's fluid was used as follows : Small blocks, not more than .3 to .5 c. c. in thickness, were immersed in Van Gehuchten's fluid and left for twelve hours. They were then placed in 95 per cent alcohol, where they remained until desired for use. No changes in the contour of the cells were observed to result, and the chromatic substance in these cells was well shown in the subsequent staining. Blocks to be imbedded were then placed in absolute alcohol, and, for the paraffin method, trans- ferred to xylol, and left in the latter for several hours till thor- oughly permeated. They were then placed in paraflin — melting point about 50° C., for from 45 minutes to one hour, and then transferred to another paraflin bath of the same melting point for the same length of time, so as to secure complete penetration and the removal of all xylol. The blocks were then imbedded and sub- sequently sectioned by a Minot microtome serially. The sections were made varying in thickness from 2 to 15 microns, those from 6 to 10 microns being found best for study of the arrangement and internal structure of the cells. The celloidin method was also employed, but it was more difficult to secure thin sections when desired, and especially to arrange them serially. A thin smear of tgg albumin was placed upon a perfectly clean slide, several con- secutive sections placed upon the same, and then a small quantity 26 G._ ALFRED LAWRENCE. of water by means of a pipette allowed to flow under the sections. This was gently warmed upon the water bath or over an alcohol lamp until the sections were perfectly flattened out. The water was drawn off and the sections allowed to dry. This treatment permitted all subsequent manipulations with the sections upon the slides, without their floating off or becoming disturbed or injured. The slides were then placed in xylol to dissolve out all paraffin and run down in successive grades of alcohol from absolute alco- hol to 2P P^r cent alcohol, and from the latter immersed in water. The sections were then stained upon the slide by means of an aqueous solution of methylene blue, as given by Nissl (methylene blue, 3.75 grams; A^enetian soap, 1.75 grams, and distilled water I,ooo c. c), or by a i per cent aqueous solution of methylene violet or a i per. cent aqueous solution of thionin. . A counter stain of erythrosin was used in some cases after treatment with methylene blue, giving the achromatic substance a pink color in contrast to the blue color of the chromatic substance. The routine method was to gently heat the slide covered with the stain for two minutes over an alcohol lamp, keeping the slide in constant mo- tion, and only allovv'ing it to becorne sufficiently heated so that the steam would come from the surface, but no bubbling of the dye in solution. The dye v/as then gently washed off, the slide im- mersed in water, and then run up into 30, 50, 70, 80, 95 per cent, alcohol, absolute alcohol plus xylol equal parts, xylol, and finally mounted in xylol-damar. Some slides were placed, after immersion in water following the staining process, in anilin-oil 10 parts, absolute alcohol 90 parts, and subsequently treated as described by Nissl, and finally mounted in benzene-colophonium. The first method, however, gave the most satisfactory results in the hands of the writer, and which, as seen, embodies various modifications of the original Nissl method. Sec- tions prepared in the routine method above described have been frequently examined under the microscope, also frequently ex- posed to sunlight, and at times to the powerful rays of the electric arc in the photomicrographic work, but were in nowise faded or injured after a period of two years from the time of preparation. In the micrographic work the most painstaking care was em- ployed in every detail of the work. Achromatic objectives of various power with compensating eye-pieces in different combina- DEMENTIA PARALYTICA. 27 tions were used so as to produce different magnifications up to 1,400 diameters. Oil-immersion lenses were not used, as the above combination secured the greatest possible depth under such high powers. The time of exposure varied from a few seconds in the low power photomicrographs to five minutes in some of those magnified 1,400 diameters. Material. Some twenty brains were secured, and sections made from various parts of them all and studied in connection .with this article. Three brains of cases electrocuted at Ossining, I and in which the autopsy occurred immediately afterwards and ;the material placed in various fixative media, were secured. The photomicrographs representing the practically normal brain histo- logically in the first part of this article were taken from one of [these brains, marked A (Plate I, Pig. i), a man thirty-six years of age who had been confined in Sing-Sing State Prison for over two years and leading the regular routine prison life during that iperiod. The autopsy was held immediately after death by electro- ■cution. The body was well nourished, and no pathological condi- [tion of the central nervous S3^stem or other organs was found. ■ Small blocks, .3 to .5 c. c. in thickness, from various convolutions I of the brain were placed in the various hardening or fixative i agents described above, and the brain itself immersed in 95 per icent alcohol. The blocks were subsequently imbedded in paraffin, [sectioned serially, stained, differentiated, and mounted as already • described. l '-.Brains from three cases of dementia paralytica were also se- cured and studied. Sections from the one marked B (Plate X, Fig. 29) were used to illustrate this article in its pathological por- tion. The paralytic dement from which brain B was taken was a lawyer, had a collegiate education, was single, no history of syph- ilis, and family history negative. Was native of the United States. The disease began at about the age of twenty-eight years with the usual change of character, followed by grandiose ideas and maniacal excitement. Asylum treatment for over a year caused his symptoms to clear up sufffciently so that he was dis- charged. For nearly two years he was in a fairly quiet condition. He then broke out in a long period of excitement, lasting over a year, followed by terminal dementia lasting for one and a half years before death, which latter was uncomplicated. Duration of ZS G. ALFRED LAWRENCE. the disease was thus over five and a half years, during which period there was a remission lasting two years, in which he did not require asylum treatment. There was contracture of both arms and legs for three months preceding death. Mentally he was a little brighter during that time. At death the body was immediately placed upon ice, and the autopsy performed fifteen hours later. The body weighed 78 pounds at death and was Plate I, Fig. i. flexed. Two small cavities, each the size of a pea, were found in the apex of the right lung. The lymphatics were somewhat en- larged. Heart was atrophied. There was meningeal thickening. The ependyma in the posterior part of the floor of the fourth ven- tricle was very slightly granular. The membranes were anemic, and there was no edema or fluid. The convolutions, especially in the region of the central convolutions, are widely separated from one another ; but, as will be described later, this is largely due to mechanical causes in subsequent fixation. In addition to these brains over a dozen were secured from other sources, mostly from the New York City Morgue, of persons who had committed DEMENTIA PARALYTICA. 29 suicide or died suddenly from accident or homicide, with autopsy performed within a few hours after death. Normal Cortex. The descriptions and plates herein contained, and illustrating the normal human cortex, are not intended to give the ide^ of being in any way a complete exposition of such a vast subject; but it has been the aim to give photomicrographs with accompanying descriptions of typical sections and cells from vari- ous regions of the cortex, as a basis of comparison with sections taken from corresponding regions of the cortex in a case of de- mentia paralytica. Neither is this contribution intended to be in the nature of an atlas, being much too limited in scope for such a work; but to illustrate as far as practicable the structures found in what can be considered a fairly normal brain, with the condi- tions founa in a brain of one dying from dementia paralytica. Various regions of the normal cortex from brain A, one of the electrocuted cases (Plate I, Fig. i), with its accompanying plates will be first described, and then will follow a like description of the corresponding region with its accompanying illustrations of the brain of the case of dementia paralytica, brain B (Plate X, Fig. 29). Plate I, Fig. i, above referred to, shows the left hemi- sphere of Brain A, natural size ; a normal brain, with well marked convolutions and sulci. The small pieces of cardboard with their contained figures show the particular point from which the subse- quent blocks were taken, and also illustrate the method of exact localization of blocks described under the heading of technique. Frontal Region. — Turning now to the several cortical re- gions, various portions of the first, second and third frontal convolutions were examined in different brains, and typical of this region is the section shown in Plate I, Fig. 2, which, with minor modifications, is similar to that of all portions of this re- gion, and will now be described in detail. The block from which this section was taken comprised a part of the external surface of the first, or superior frontal convolution, including the entire width of the gyrus for a distance of .4 cm., and taken from the position shown by the figure i, Plate I, Fig. i. The gyrus at this point measures .6 cm. in width, so that the actual size of this sec- tion is .6 cm. in width by .4 cm. in depth, and it is 6 2-3 microns in thickness. The block at autopsy immediately after death was placed in Van Gehuchten's fluid, where it remained for twelve hours, when 30 G. ALFRED LAWRENCE. it was placed in alcohol 95 per cent until ready for use. It was then imbedded in paraffin, sectioned serially with a Minot micro- tome, stained for two minutes in warm methylene blue, decolor- ized in alcohol, cleared in xylol, and mounted in xylol-damar. Plate I, Fig. 2, referred to above, shows the, section under a magnification of 14 diameters. The section has been broken in manipulation, but shows the general striated arrangement of the cells radiating outward from the white medullary center to • Plate I, Fig. 2.' ■ '■ the surface ; also the layering of the cortex. The strip of cor- tex outlined in ink on the plate at a is that porti' n shown in Plate II, Fig. 3, under a magnification of 160 diameters. The outer pale layer, the thicker cellular layers,' and the inner med- ullary white portion can easily be differentiated even with this magnification. The outer layer is found to be fairly uniform in thickness in this section, but we will find later that there may be a consider- able variation, not only in the thickness of this layer, but also' of the other layers, and consequently of the entire cortex. The radial arrangement of the cells from the medullary white sub- stance is especially well shown under this magnification, and a more general and comprehensive view of both the normal ar- DEMENTIA PARALYTICA. 31 rangenients and of derangements and disturbances due to path- ological changes can be made out under this magnification than by higher powers in which but minute areas are seen. These latter high magnifications are of course also necessary for the complete study of all the details of such variations or patholog- ical changes. Plate'II, Fig. 3, magnified 100 diameters, is that it- ,-4 J. C- i-o X portion of the section outlined in ink in Plate I, Fig. 2 at a. De-- colorization has been carried on here to such a degree as to make many of the cells appear somewhat pale and 'washed out, and to cause a complete decolorization of many of the neuroglia cells. This, however, admits of a better study of the arrange- ment of the internal structure of the cells, as a too deep coloriza- tion does not sufficiently differentiate the chromophilic granules and network. The outer surface of the cortex is here seen to be smooth and regular. Immediately beneath is the first or superfi- ,32 G. ALFRED LAWRENCE. cial layer, pale in color, .25 mm. in thickness, and characterized by a paucity of cells irregularly arranged and appearing upon a colorless background, which we know from sections treated by the Weigert method to be made up of large numbers of densely packed nerve fibers and processes. In the plate are seen for the most part neuroglia cells, but under a high power here and there nerve cells are found, rounded, spindle-shaped, or polygonal in form, with a nucleus filling up almost the entire cell-body, and with no visible dendritic processes, or at most but one or two extending vertically or at right angles to the surface of the cortex. The cell-body contains but a small mass of chromophilic substance, usually forming a narrow band about the nucleus with thickenings where the dendritic processes are given ofif. The cells with no visible processes of course may have such extending in a direction outside of the plane of the section. Fig. C shows one of these cells containing no visible processes, with a rounded cell^body, a large rounded nucleus almost filling up the same and surrounded by a uniformly thin band of chromatic substance. Fig. D shows another cell from this same region with a single proces vertical to the surface of the cortex. Here again the large rounded nucleus almost fills up the cell-body and is surrounded by a thin band of chromatic substance thickened at the point where the dendritic process is given off, and extending into the same for a short distance. Fig. E shows a similar cell, but with two processes extending in a nearly horizontal direction. The thin chromatic band is here thickened at both extremities. The greatest diameter of the ■ cell in Fig. D is vertical, while in Fig. E it is horizontal, in Fig. C of course being practically uniform. Occasionally cells are seen with one process vertical and the other horizontal, as in Fig. F, this being polygonal in shape. The nuclei in all of these cells are well defined, large, and contain a small amount of chroma- tin in the form of a poorly differentiated network, and at some point containing a distinct nucleolus. According to Nissl's clas- sification of nerve cells these would be known as karyochrome nerve cells. The neuroglia cells are smaller, rounded or oval in shape, contain a nucleus, and are much more numerous in this layer than the comparatively scarce nerve cells. The second or pyramidal cell layer, to simplify the layering of the cortex to the greatest extent, as previously described, is made to include both the large and small pyramidal cells. This measures in the plate (Plate II, Fig. 3) 1.40 mm. in depth. This layer thus includes the large and small pyramidal cell layers and the ganglionic cell layer of Hammarberg, and the large and small pyramidal cell layers of Golgi and of Cajal. (See Table I.) Hammarberg (1895) in his description of this region states that the layer of DEMENTIA PARALYTICA. 33 small pyramidal cells does not form a distinct layer, but grad- ually passes over into that of the third layer of large pyramidal cells, so that the two in his division make a layer .80 mm. in depth. He further states that the under border of the third layer is difficult to determine, so that there is no distinct fourth layer. This fourth layer is then described as containing small pyramidal cells less thickly distributed than in the layer above, intermingled with which are some smaller irregular cells, giving the appearance of a region poor in cells ; and he notes further that in many places the difference is so slight that it does not make a separate layer. His fifth layer is described as a .70 mm. thick ganglion cell layer, made up of somewhat larger and more closely packed pyramidal cells. These layers, — second, third, fourth and fifth layers of Hammarberg, are all included in this second layer of the writer, and in this section measures about 1.40 mm. in thickness. It is made up of pyramidal cells varying in size in all parts of the layer, so that in any region, ex- cepting a band below the middle portion to be described later, pyramidal cells of different size may be seen in close proximity. As a rule, however, the larger pyramidal cells are found mostly in the deeper portion of the layer. But here as elsewhere are to be seen the small pyramidal cells interspersed. There are also to be seen some rounded and irregular cells throughout this layer. Just below the middle of this second layer is seen a belt some .30 mm. in width, in which small pyramidal cells decidedly predominate and containing but few larger and medium sized pyramidal cells. This region is comparable to the fourth layer of Hammarberg, but as it contains no elements differing from the region above and below, but simply varies in the relative number and size of the same, it does not seem to the writer worthy the designation of a separate layer with the resulting increase in the number of layers. Both above and below this belt large and small pyramidal cells are intermingled ; the large pyramidal cells increasing in proportion from above downward. Fig G (G of Plate H. Fig. 3) shows the details of structure of one of these small pyramidal cells under a high magnification (x 1,300. No. 3 ocular, 1-12 in. oil immersion objective, Leitz). By focussing in different planes the large, broad, apical, den- dritic process is seen extending vertically towards the surface of the cortex. It contains chromophilic granules arranged . with the long axis parallel to the axis of the cell. The cell-body is in the form of a pyramid with rounded sides. The large nucleus is irregularly oval with the long axis parallel with the long axis of the cell. The nucleolus is centrally located and surrounded by the slightly stained nuclear contents. From the lower portion of the cell-body are given off three dendritic processes, one of which subsequently branches into two processes, at which point 34 G. ALFRED LAWRENCE. a mass of chromatin is seen, one of the so-called "wedges of division" (Versweigungs-Kegln) of Nissl. These dendritic processes contain no chromophilic granules, but at the point where they are given ofif from the cell-body are found aggrega- tions of chromophilic granules which also surround the nucleus on either side, their long diameter extending in general parallel with the long axis of the cell. Plate II, Fig. 4, is a photomicro- graph of this same cell as stated, indicated by the letter G in Plate II, Fig. 3, and shown in Fig. G of the text as already de- scribed. In order to secure a focus by which the cell processes Plate II, Fig. 4. could be seen even faintly the nucleus and nucleolus are almost entirely out of the plane of focus, the latter showing faintly how- ever. Immediately about the nucleolus there is a slightly pale area, a portion of the nucleus. The contents of this cell-body itself present for the most part the appearance of a very dark, almost homogenous, intensely stained chromatic substance, and gives only a partial idea of the real structure and arrangement of the granules as seen in Fig. G. The contour of the nucleus cannot be distinctly made out, nor the relative position of the nucleolus in the same. The individual chromophilic granules DEMENTIA PARALYTICA. 35 cannot be distinguished excepting at the base of the right lateral dendritic process. The apical dendritic process appears as a mere shadow, owing to its being out of the plane of focus. The basal dendritic process show almost as well as in Fig. G, except- ing the branching of the one at the left which is but faintly indi- cated. The small mass of chromatin at this point — the so-called "wedge of division," of Nissl — is also but faintly indicated. The general contour of the cell, points from which the dendritic processes are given off, and position of the nucleolus are accu- rately represented. Had a plane been selected showing the nu- cleus accurately some of the processes would have been entirely out of focus. Other cells adjacent to the one just described are seen to be less deeply stained and the chromatin is seen in the form of larger and smaller indistinctly rounded or elongated granules. It will thus be seen that there are hmitations, and serious Hmitations too, in the use of photomicrographs, es- pecially under high powers, in such a study as this. It would require several photomicrographs at various planes to bring out all the details shown in the single Fig. G, which of course is a composite taken by focussing in all planes under a magnification of 1,300 diameters, and showing certain, but not all, details of the different planes. Of course outlines are not so' distinct in the real cell as must necessarily be made to appear in a drawing, and this latter might be compared to a dissection in which cer- tain parts are brought out prominently at the expense of the normal appearance of the whole in life. No one would hesitate to say, however, that Fig, G gave a much better idea though not an exact representation of the cell, than Plate II, Fig. 4, and that drawings are essential accompaniments of such plates in the full elucidation of a subject of this kind. These cells are known as stichocrome nerve cells of the somatochrome class. Fig. H shows one of the large pyramidal cells (the largest to be seen in the plate) under the same magnification as in Fig. G (x 1,300. No. 3 ocular, 1-12 in. oil immersion objective, Leitz). The internal structure of the large pyramidal cells is found to be made up of distinctly stained chromophilic substance in larger and smaller irregular granules, some so fine and closely ar- ranged as to completely fill up the cell-body, thus presenting a uniform field of closely packed minute granules without any spe- cial relation to one another. In other cells the granules are coarser and present a somewhat parallel arrangement about the nulceus and extending up into the main apical process for some distance and also into the basal lateral processes in the same general parallel manner. In other pyramidal cells there is a fine chromophilic network with larger and smaller aggregations of chromatin as nodes or enlargements of the network. In this figure the cell-body is pyramidal in shape with rounded contour 36 G. ALFRED LAWRENCE. merging above into the large apical dendritic process, which is finally lost to view as it enters another plane. Below at the base, both to the right and left, are given off several dendritic processes, some of which are seen to branch a short distance from the cell-body. The large, slightly oval nucleus is centrally situated somewhat nearer the base of the cell than the apex, and contains a large, eccentrically placed nucleolus, surrounded by the pale, slightly strained, for the most part homogenous, Plate II, Fig. 5. nuclear protoplasm. Within the cell-body about the nucleus and extending into the apical process, and to a less extent into the basal dendritic processes, are chromophilic granules of rounded or elongated shape, and having a tendency to be ar- ranged in groups in places. Especially at the point where a den- dritic process is given off is frequency to be found a mass of these granules. Often a wedge or cap of chromophiHc sub- DEMENTIA PARALYTICA. 37 Stance is seen at the point where a dendritic process is to be given off, as at a, or where a process divides into two branches, as at h, the latter being one of the so-called "wedges of division" of Nissl. The granules vary in size and shape and are arranged in general in a direction parallel to the long axis of the cell- body and of the long axis of the dendritic process when extend- ing into the same. About the nucleus they are often arranged parallel to its wall. Five dendritic processes are given off from the base of this cell, three of which are seen to divide into two branches each; at h, showing one of the so-called "wedges of division" of Nissl, referred to above. Plate II, Fig. 5 is a pho- tomicrograph of this same cell indicated by the figure H in Plate II, Fig. 3, and already described and shown in Fig. H; here under a magnification of 1,400 diameters. The body of another somewhat smaller pyramidal cell is seen just behind the apical dendritic process of this cell and part of it almost in the same place, so that it is difficult to differentiate the two. It will be seen that the nucleus and nucleolus are in good focus, but that the basal dendritic processes, excepting at their origin from the cell-body, can scarcely be distinguished. The shape of the nucleus, size and position of the nucleolus, and arrangement of the chromatin within the same is as well shown as in the figure. Also the shape and contour of the cell-body. The den- dritic processes, however, as mentioned above, are out of the plane of focus, so that only a very hazy, indefinite indication of the beginning of three of them can be made out. The large one at the left can scarcely be determined at all. The more central one at the left is faintly outlined, and at the point of bi- furcation the so-called "wedge of division" of Nissl (B) is seen, but the division itself cannot be determined. Of the three pro- cesses given off from the base at the right the beginning of the one most centrally located can be very faintly seen and a faint/ outline of the other two, appearing as one in the photomicro- graph is seen. The apical dendritic process is so merged with the body of the cell just below it that it is difficult to determine its outline. The cell protoplasm is more differentiated however than in the preceding plate (Plate II, Fig. 4). Here chromophi- lic bodies are seen at the base on the right where the dendritic processes are given off, indicated by A both here and in Fig. H. Chromophilic granules are also seen fairly well indicated to the right and above the nucleus, in larger and smaller bodies without sharp outlines, which is the condition actually found in the cell. They are not sharply and definitely outlined as shown in Fig. H, which in that respect is not accurate, but merely diagrammatic. At the left and below the nucleus in the basal por- tion of the cell-body these chromophilic bodies are so closely 38 G. ALFRED LAWRENCE. aggregated as to give almost a homogenous dark appearance to that portion of the cell, and it is only by carefully focussing in various planes that the chromophilic bodies are made out. Here again the photomicrograph without the accompanying drawing would give one only a partial knowledge of the struc- ture of this cell. Cells of this type are to be classified as large stichochrome nerve cells of the somatochrome class. Inter- spersed among these larger and smaller pyramidal cells in this layer are some small irregular and rounded cells consisting of a large nucleus containing a nucleolus, and surrounded by a cell- body containing in the smaller cells a very narrow rim of finely granular chromophilic substance, in some places so nar- row as to be scarcely discernible. In other cells the cell-body is much more developed surrounding the nucleus and giving off several protoplasmic processes which go out in various direc- tions. Neuroglia cells similar to those of the first layer are found interspersed among the nerve cells in all parts of the sec- tion. Small portions of capillary blood vessels are shown as at I in the plate (Plate II, Fig. 3, I) where the vessel is seen to di- vide into two branches below, and also at 2 (Plate II, Fig. 3, 2), showing a single small capillary extending only for a short dis- tance in this plane. The walls are seen to be exceedingly thin, made up of a single layer of nucleated cells, and containing red blood corpuscles. The walls of these blood vessels stand in marked contrast to the thickened and tortuous walled vessels found in the cases of dementia paralytica later to be described. Below this is the third, or spindle cell layer about 1.20 mm. in thickness in this section. The spindle cells in this layer con- tain a large nucleus, with a distinct nucleolus, but no nuclear net work could be made out. The nuclei in many of them pre- sent the appearance of being too large for the cell-body, so that often, as in Fig. I, the cell-body seems to be bulged out on one side to accommodate the large nucleus, giving an eccentric form, and resulting in a spindle with one side very promi- nent and the opposite side quite flattened. The chromatic sub- stance is arranged in no definite network and contains no dis- tinct chromophilic bodies, but consists of minute particles close- ly aggregated about the nucleus, especially at each pole and found in a lesser amount and in variable quantities in the re- mainder of the cell-body. In Fig. J the nucleus is situated ec- centrically at one end of the cell-body, so that most of the other cell contents are at the opposite end with a narrow band of closely aggregated chromophilic substance surrounding the nu- cleus at both ends. The nucleus in this cell is more elongated and oval in shape, with distinct nucleolus and otherwise pale, slightly stained contents. Other cells as Fig. K are more or DEMENTIA PARALYTICA. 39 less irregular in shape, in this case having the form of an irreg- ular inverted pyramid containing a large rounded nucleus near the base which is surrounded by a narrow band of dense chro- matic substance. About this is an irregular chromatic network containing nodal thickenings at some points. The nucleus con- tains a distinct nucleolus, but otherwise pale and but slightly stained contents. A large dendritic process is seen given ofif below and two dendritic process go off from the base and to one side. Fig. L shows another irregular shaped cell with a den- dritic process given off from one side in addition to those from MMMM w .-;<:-J^: HHi r ■■•■*^::::i \ ■ i J ;^. i '---i J!' ■ Ki?i ..'••J '■ : .-<■■■ .. ■y^'vVi^.f;;-- ■^■■■ UV;, 1 . 'f . ■« '; ^'■"tf ■i5.vi-;i^A!daaiiJy>- "^?:tH Plate II, Fig. 3. Plate III, Fig. 8. Plate VII. Fig. ig. Plate XIII, Fig. 41. Plate Vll, Fig. 21. DEMENTIA PARALYTICA. 65 upper portion of the convolution already described. In the second layer, however, the greatest difference is found. The large, Betz cells practically disappear in the lower third of this convolution, although large pyramidal cells simulating them in general struc- ture, but lacking the size, are found in the middle portion of this layer. In this lower third of the convolution the second layer as seen in this section is 1.50 mm. in thickness, and the large pyram- idal cells are seen arranged in irregular groups in its middle portion. Below them is seen a region a averaging .25 mm. in thickness in which small pyramidal cells are almost exclusively found. Below this larger pyramidal cells are seen, but not in great numbers. The divison between this and the lower or spindle cell layer is not well marked, the latter measuring .90 mm. in thick- ness. The cells here are irregularly polygonal or spindle shaped and do not differ from those in the same region in the upper part of this convolution. The total thickness of the cortex at this point is 2,65 mm., exactly the same as of the section shown in Plate III. Fig. 8. Counts of the nerve and neuroglia cells were made in this region in exactly the same manner as in the previously described regions. This section, as above stated, is ten microns in thickness and stained with methylene violet and in seven fields of 36 sq. mm. each from various portions of the second and third layers, the average number of nerve cells to each square milli- meter of surface of the ocular net-micrometer was found to be 1.08, multiplied by 100 gives 108 as the average number of nerve cells to each square millimeter of surface of the section in the second and third layer. The nerve cells in the first layer were so few and scattered that no counts of the same were made. In eight fields of 36 sq. mm. each from various portions of the three layers of the cortex in this section the average number of neu- roglia cells to the square millimeter of surface of the ocular net- micrometer was 2.48, multiplied by 100 gives 248, as the average number of neuroglia cells to each square millimeter of surface of the cortex of this section. Here again it will be seen that the methylene violet stain shows a larger number of neuroglia cells — 248, while the nerve cells — 108, are but slightly in excess of the average number in the two previously described sections of the upper portion of the anterior central convolution, and slightly less in number than in the sections described from the frontal con- volution (Table II.). Passing now to the region posterior to this, we come to the posterior central convolution of this central or motor region. This posterior central convolution is regarded as a transition region between that anterior to the fissure of Rolando, or motor region, and that posterior to the same region, or sensory region of those authors who divide the cortex into a sensory and motor type 66 G. ALFRED LAWRENCE. of cortical lamination. The first and third layers here are prac- tically the same as in the region anterior to the fissure of Rolando. The second layer, however, lacks the regularity of the correspond- ing layer in the above mentioned region, but as will be seen in the plate (Plate VII. Fig. 19), there is nothing new or different in this layer from the corresponding layer in the plates already de- scribed. The large Betz cells seen only in limited portions of the region just anterior to this and contained in but a very small por- tion of this so-called motor region are replaced here by some Plate VI, Fig. 18 smaller sized, irregularly situated pyramidal cells, singly or in groups, and of similar internal structure, and mostly to be found in the middle and lower portion of the layer. As typical of this posterior central convolution, a section was taken from a block including the middle portion of this convolution in its entirety for a distance of 4 cm. (5, Plate I. Fig. i). The section is 6 2-3 microns in thickness, fixed in 95 per cent, alcohol, and stained with methylene blue, technique otherwise similar to all other sections. Plate VI. Fig. 18, is a photomicrograph of this section, magnified 14 diameters. The convolution here presents a peculiar mechanical DEMENTIA PARALYTICA. 6j formation, causing a great variation in thickness of the cortex in different portions, being over twice as thick at h as at the point a, from which latter point Plate VII. Fig, 19 was taken. This condi- tion is not an artefact, as under high magnification no indication of disturbance of the relations of the cells is to be observed. At the vertex, however, there is an artificial break in the first and upper part of the second layer at two points. The first layer is seen to vary in thickness, being thicker at the acute angle below h, and gradually becoming thinner as it approaches the vertex, to become again thicker below a. The general radial direction of the cells is well seen, especially at the vertex and anterior aspect, as at a. Ar h it is not quite so well made out, but exists to a fairly well marked degree when examined under a higher power. Pyramidal cells of considerable size are seen in some parts of this layer, more especially in the middle portion, but in no case do they approach in size to the Betz cells, nor are they for the most part situated in the same portion of the cortex. The third layer is thin and soon lost to view in the medullary white substance. Plate VII. Fig. 19, is a photomicrograph of the strip a enclosed in ink lines in Plate VI. Fig. 18, and magnified 100 diameters. The first or upper layer at this point is somewhat irregular in contour and averages .20 mm. in thickness. It contains neuroglia cells and some scattered nerve cells similar in appearance and structure to those described in Plate II. Fi. 3, for the same region. The second or pyramidal cell layer is especially interesting, owing to the irregularity of the distribution of its cells. At the upper portion the small pyramidal cells are seen closely aggregated together. Below this these cells become more scattered, and irregularly in- terspersed among them are medium sized and larger pyramidal cells. Some of the larger of these have a tendency to be ar- ranged singly or in groups and have an internal structure similar to the giant pyramidal or Betz cells found in parts of the anterior central convolution and in the posterior part of the first frontal convolution. The chromophilic granules are, however, of smaller size though similarly arranged in some of the cells. About the middle of this layer, opposite a, is seen another region in which the small pyramidal cells predominate, and in which there are scarcely any larger pyramidal cells. Just below this again are seen large pyramidal cells arranged singly and in groups, forming the lower portion of this second layer which measures about 1.45 mm. in thickness and below gradually merging into the third or spindle cell layer. In addition to the spindle cells there are many irregular polygonal cells founds in this layer which at this point is about .60 mm. in thickness and only partially shown in the plate ; the upper two-thirds being seen here. The lower third, not shown, is similar and gradually merges into the white medullary 68 G. ALFRED LAWRENCE: substance. The entire cortex is thus 2.25 mm. in thickness at this point, whereas, as above mentioned at point b in Plate VI. Fig. 18, it is over 5 mm. in thickness. Taking into consideration the varia- tions found in different parts of the same area, often quite near together, and considering the general type of arrangements, it does not seem to the writer that this area varies to a very marked degree from the general type, or at least to such an extent as to be especially marked off from the other regions of the cortex. There is certainly a greater variation between dift'erent regions of the anterior central convolution as in the upper and lower portions, where some parts have no Betz cells and others have thern vari- ously distributed, as well as other differences, than between this region and the frontal region as a whole. Those who separate the cortex into two types, — an anterior or motor type, and a posterior or sensory type, — regard this convolution as the transition region between the two. An examination of sections, both anterior and posterior to this convolution, shows that the same general plan of arrangement is carried out in all parts of the external surface of the cortex with only miiior differences which do not seem sufficient to make such a marked distinction applicable anatomically, and certainly not histologically. The size and form of the cells and their general arrangement differs but slightly from that of the region anterior and posterior, with the exception of the Betz cell groupings in localized portions of the former. Nerve cell and neuroglia cell counts were m'ade with the ocular net-micrometer here in this region in the same manner as in the other previously described sections. Eight fields of thirty-six square millimeters each, from various portions of the second and third layers of the cortex, were examined and 185.5 nerve cells were found to be the average number for each square millimeter of surface of the section. In the same manner the neuroglia cells were counted in eight fields from all three layers of the cortex and 109.2 neuroglia cells were found to be the average number for each square millimeter of surface of the section in the cortex. Here methylene blue was the stain employed with the resulting low average number of neuroglia cells, whereas the average number of nerve cells is found to be higher than in any of the previously described sections anterior to this region, and it will be seen sub- sequently that it is also higher than that found for the region posterior as well although the section is 6 2-3 microns in thick- ness, and some already described are 10 microns in thickness (Table II.). This, however, bears out the statement previously made that sections between six and ten microns in thickness con- tain practically all nerve cells that can be seen in one plane. Parietal Region. — Posterior to the region just described we come to the parietal region, made up of the superior parietal, DEMENTIA PARALYTICA. 69 supra-inarginal, and supra-angular convolutions. The general arrangement of the layering of the cortex is fairly uniform throughout this region and the section represented in Plate VII, Fig. 20. from a block taken from the supra-marginal convolu- tion is typical of this region (7, Plate I. Fig. i). The block was fixed in Van Gehuchten's fluid, stained with methylene violet, and other technique as for previous regions. The actual size of this section is 7 mm. in its greatest width, and 8 mm. in length, and it is 6 2-3 microns in thickness. As seen in the photomicograph, c. A .^ \ ■ / / <9 p ■ \ \ ■ ,4 Plate VII, Fig. 20 magnified 14 diameters, the convolution is wider above at the surface than deeper down in the sulcus. At the point a is seen the position of the strip from which the photomicograph repre- sented in Plate VII, Fig. 21 was taken. At h and c, owing to the greater angle, the cortex is considerably thicker than at a. The shape of the convolution here is seen to be different again from any of the preceding, thus giving a somewhat different mechanical arrangement, with a broad flattened vertex and shorter anterior 70 G. ALFRED LAWRENCE.. and posterior aspects. At the lower portion, on the right, a part of the cortex was cut away in removing the block. In the vicin- ity of a there are some minute artefacts, causing an irregularity of the surface here, and small fragments are partially torn away at two points. The first, or superficial layer, is fairly uniform in thickness, excepting opposite a, which will be discussed more fully in describing the next plate (Plate VII, Fig. 21), and upon the posterior and anterior aspects, where this layer is slightly thicker. The radial arrangement of the cells of the second layer is well shown, and the cortex is seen to be thicker at the angles b and c, as before mentioned. Throughout the middle and lower part of this layer well developed pyramidal cells are seen, some almost approaching in type small Betz cells. The third layer pre- sents nothing unusual, and gradually passes over into the white medullary substance. Plate VII, Fig. 21, shows the strip indi- cated in ink opposite a in Plate VII, Fig. 20, under a magnifica- tion of 100 diameters. The first or superficial layer is seen to be irregular at this point, about 20 mm. in thickness at the right of the plate, then increasing rather suddenly to .25 mm. for a short distance, when the outline suddenly descends, decreasing the layer at this point to .15 mm. It then gradually increases until, at the left of the plate, it is .22 mm. in thickness. The extreme thickness near the center, although the surface is only slightly torn at several points and scarcely noticeable, yet has the appear- ance of an artefact, due no doubt to the unequal pressure in the manipulation of removal, when the brain was in its natural soft condition, prior to any post-mortem changes. A short distance below the surface at this point the cortical substance itself is seen slightly broken, thus confirming the artificial nature of the irregu- larity and increase in depth. The nerve and neuroglia cells are similar to those found in this layer in the regions anterior to this. The second or pyramidal cell layer is 1.60 mm. in thickness, and contains small pyramidal cells exclusively in the upper portion. Very soon, however, larger pyramidal cells appear, and at about the middle of the layer are the greatest in size and most numerous of the layer. Some of these large pyramidal cells in point of size and structure appear intermediate between the large and giant pyramidal or Betz cells. They also tend to be arranged singly or in groups, with smaller cells about them. Just below the middle of this layer, at a, is found a region .20 mm. in thickness, con- spicuous by the almost entire absence of large pyramidal cells, and made up for the most part of small pyramidal cells. Below this large pyramidal cells again appear, intermingled with the small pyramidal cells, and the layer gradually passes over into the lower or spindle-cell layer. The pyramidal cells have the same internal structure as those in the region anterior to this, in the DEMENTIA PARALYTICA. 71 lars^est ones the chromophilic granules simply being larger and more conspicuous ; thus these cells come under the same classifi- cation, according to Nissl, as those in the frontal and central con- volutions. The third or spindle-cell layer is .70 mm. in thickrress, and not distinctly separated from the layer above. The arrange- ment of the cells and their form and size, as well as the internal structure, is in no way ditterent from the corresponding layer in the cortex anterior to this. The total thickness of the cortex here is then 2.50 mm., being .25 of a mm. thicker than in the section of the posterior central convolution previously described, .15 mm. less in thickness than the section shown in Plate III. Fig. 8, from the anterior central convolution, and .35 mm. less than in the sec- tion of the first frontal convolution shown in Plate II, Fig. 3. The variation in thickness is thus seen to be slight and no greater. and even not so great as can be found in contiguous portions of any one convolution. In other parts of the parietal region the arrangement of the cortical lamination is similar to that de- scribed above with minor modifications, due to differences in shape, etc., of the convolutions. Here nerve cell and neuroglia cell counts were made in the same manner as in previous regions, and the average number of nerve cells to the square millimeter of surface of the section was found to be 104, w^hereas the average number of neuroglia cells for the same area of surface of the sec- tion w'as 180.90. This is the lowest average of nerve cells in any region of this, brain, with the exception of the upper portion of the anterior central convolution. The methylene violet stain makes the average number of neuroglia cells quite high, however, though considerably less than in the upper portion of the anterior central convolution. Temporal Region. — Below the parietal region just discussed W'C come to the three temporal convolutions — the first, second and third. Here the general arrangement of the cortical laminations and the cell structure is practically the same in the three convolu- tions, and bears a striking resemblance to that found in the frontal region. A block was. taken from the anterior portion of the first temporal convolution near the apex (6, Plate I, Fig. i), the entire width of the convolution and for a distance of .4 cm. The actual size of the section from this block represented in the photomicro- graph r Plate A'll. Fig. 22) is 8.5 mm. at the wddest point, and 8.5 mm. in length on the right, and 6 mm. in length on the left, and it is 6 2-3 microns in thickness. The block was fixed in Van Gehuchten's fluid, stained w'ith meth}lene blue, all the other details of technique being similar to that employed for previously described sections. This photomicrograph is magnified 14 diam- eters, and here the shape of the gyrus is seen to be somewhat similar to that in Plate Yll, Fig 20, but broader above, and also 72 G. ALFRED LAWRENCE. with a broader base. The vertex is flattened similarly, resulting in the more acute anglg at b and the slightly obtuse angle at c, at which points the cortex is thicker than at the vertex or the anterior or posterior aspects. The cortex is seen to be uniformly thicker along the surface, opposite d, than upon the opposite aspect at and above and below a. The first or superficial layer is thicker at c than in other portions, and is somewhat b'-oken in places along the vertex. The second layer varying in thickness, being thickest at the points mentioned above, where the entire G \ b ■ D ■\ '4 ■^ • t * Plate VII, Fig. 22 cortex is thickest, shows the radial arrangement of the cells very well, especially at the vertex and opposite a and b. The larger nerve cells appear quite conspicuous in the middle and lower por- tion of this layer in places. The third layer is quite uniform, dis- appearing in the white medullary central substance. Plate VIII, Fig. 23, shows the strip a of Plate VIII, Fig. 22 at a magnification of 100 diameters. Here the dififerentiation has been carried to about the same stage as in Plate II, Fig. 3, and the paucity of neuroglia cells is equally as apparent. Again the general arrange- DEMENTIA PARALYTICA. 73 nient of the cells in the two plates is remarkably similar. The first or superficial layer is here .25 mm. in thickness, and contains, for the most part, neuroglia cells and a few scattered nerve cells. The second or pyramidal cell. layer measures 1.65 mm. in thick- ness, as compared to 1.40 mm. in Plate II, Fig 3, being thus slightly thicker than in the latter. The cells are arranged prac- tically the same, however, the small pyramidal cells above inter- mingled with larger pyramidal cells in increasing numbers deeper down in the layer. Here again, at a point somewhat deeper than in Plate II, Fig". 3. is to be found a region at a, of the same thick- ness — .30 mm., where small pyramidal cells arc found almost ex- clusively, followed again by a region containing large pyramidal cells in considerable numbers in addition to small pyramidal cells. This layer finally passes over into a narrow (.40 mm. thick) third or spindle-cell layer. This layer is also similar to that of Plate II, Fig. 3, with the exception of its depth, the latter having a spindle or irregular cell layer, measuring 1.20 mm. in thickness. As will be seen by referring to Plate I, Fig. 2, the strip a repre- sented in Plate II, Fig. 3, was taken from the point of greatest curvature, where the cortex is usually the thickest, whereas Plate VIII, Fig. 23, was taken from the point a shown in Plate VIII, Fig. 22, from the side of the section where the cortex is thinner. The entire depth of the cortex is found to be 2.30 mm., as com- pared to 2.85 mm. in Plate II, Fig. 3, a difference of .55 mm. There are no larger pyramidal cells here intermediate in size be- tween the Betz cells and the ordinary large pyramidal cells, as were noted singly or in small groups scattered in the central and parie- tal convolutions already described, and, as we shall see, also occur in the occipital convolution. The internal structure of these cells and their classification are similar to that for the cells described in Plate II, Fig. 3. Nerve and neuroglia cell counts were made from this section, which, as above mentioned, is 6 2-3 microns in thickness and stained with methylene blue. Seven fields of 36 sq. mm. each gave an average of 146 nerve cells to each square millimeter of surface of the section, and eight fields of the same size gave an average of 131.90 neuroglia cells to each square milli- meter of surface of the section. It will be seen upon comparing these figures with those from sections of regions more anterior and above, that they show a larger number of nerve cells than in the sections from the regions anterior to the fissure of Rolando, but a, less number than that for the posterior central convolution, and more than from the parietal region. The neuroglia cells are about the same in number as in Plate II, Fig. 3 of the frontal region. " Occipital Region. — Coming to the posterior pole of the ex- ternal cortex, the typical structure of the occipital lobe is repre- 74- G. ALFRED LAWRENCE. sented by Plate VTII, Fig. 24, a section magnified 14 diameters from a block taken from the point indicated by the figure 8, Plate I, Fig. I. The section is 6 2-3 microns in thickness, is 6 mm. in width at the widest portion, and 7 m.m. in length, stained with methylene violet, fixed in Van Gehuchten's fluid, other technique as previously described. This convolution is seen to be quite dif- ferent in shape from the two previously described of the temporal and parietal regions, having a broader base and narrower rounded vertex. The cortex is seen to be thickest on the lateral aspect b, thinner on the opposite lateral aspect c, and thinnest at the vertex in the vicinity of a; the central white medullary substance being reduced to a minimum. The outer layer varies in thickness, being thickest at c. Above this it is broken away for a short distance, is quite thin at the vertex, and becomes somewhat thicker on the lateral aspect b. Above b the section is seen to be cracked, an artefact resulting from its fixation upon the slide, also at c numer- ous small breaks are noticed, due to the microtome knife. Oppo- site a, and enclosed in ink lines, is the segment of this section, represented in Plate IX, Fig. 25, under a magnification of 100 diameters. The radial arrangement of the cells is well made out at the vertex, but not quite so readily seen on the lateral aspects of the gyrus here, but under a higher magnification can be dis- tinctly made out. About the middle of the second layer, especially at the vertex, some very large pyramidal cells are to be seen singly or in groups, and approaching the Betz cells in type in some cases. The third or lower layer presents nothing unusual, and disappears below into the white medullary substance of the interior of the gyrus. Plate IX, Fig. 25, is a photomicrograph of the segment a, enclosed in ink lines in Plate VIII, Fig. 24, at a magnification of 100 diameters. Here the cortex is found thinner than in any of the preceding plates, measuring scarce 2 mm. in thickness. The first layer averages only .15 mm. in thickness, and in structure and arrangement of the cells is similar to this layer in the preceding plates. The second layer measures 1.15 mm. in thickness, containing small pyramidal cells above and quite closely packed together, but increasing in size below and being somewhat more scattered. About the middle of this layer a number of large cells are seen, many singly, but some arranged in groups in places. Some of these are even larger than those found in the parietal convolution, and are intermediate in size between the Betz or giant pyramidal cells and the large pyramidal cells. These latter are not very numerous in this region, the small pyramidal cells making up by far the greatest part of the cellular elements of this layer. Below the middle of this layer is to be found a region, at a, almost exclusively made up of small pyramidal cells about .25 mm. in width. Between this and the lower border large pyram- DEMENTIA PARALYTICA. 75 idal cells are again found intermingled with the smaller. The third or spindle cell layer is here .70 mm. in thickness, containing larger and smaller spindle and irregularly polygonal cells, the lower border being gradually lost in the white medullary sub- stance below. The nerve cells are found quite numerous and closely aggregated in this region, as counts by the same method Plate VIII, Fig. 24. and manner as in all previous sections, give here an average of 164 nerve cells to the square millimeter of surface of the section, and 199 neuroglia cells, the section being 6 2-3 microns in thick- ness and stained with methylene violet. The cells are thus seen to be more numerous than in any other region of the external surface of the hemisphere, with the exception of the posterior cen- tral convolution. The fact of the greater number of the pyramidal 76 G. ALFRED LAWRENCE. cells being- small, permits of their closer aggregation, and no doubt is an important factor in the result of the nerve cell counts. The number of neuroglia cells averages higher than in any other region posterior to the fissure of Rolando, but they are less in number than in the anterior central convolution. This includes the plates of the external surface of the cortex, but for the purpose of comparison, several plates will be intro- duced from other parts of the central nervous system. The first of these is a photomicrograph, Plate IX, Fig. 26, of several large Plate IX, Fig. 27. pyramidal cells from the layer of large pyramidal cells of the hippocampus major or cornu ammonis; between the alveus, repre- senting the white medullary substance of the ordinary gyrus, and the stratum radiatum containing the apical dendrite processes of these hippocampal pyramidal cells. This plate and the two follow- ing are not presented as a basis of comparison with similar regions of the pathological brain subsequently to be described, but to give an idea of the appearance of these cells in a normal brain as seen in a photomicograph of a Nissl preparation magni- DEMENTIA PARALYTICA. 11 fied 1,400 diameters, as distinct types in Xissl's classification. These large cells of the cornu ammonis are given as one of the four types of Group II of the stichochrome nerve cells in his classification ; the other three types being ( i ) the nerve cells of the motor nuclei, (2) certain cells of the cerebral cortex, and (3) certain cells of the spinal ganglia. In shape these cells ap- Plate IX, Fiff. 26. proach the larger pyramidal cells of the external surface of the cortex, second layer, but are somewhat more slender, of a narrow pyramidal shape, have fewer basal dendritic processes, and a long, somewhat slender, apical dendritic process. The chromatic sub- stance here is made up of very small granules fusing into larger 78 G. ALFRED LAWRENCE. and smaller masses in places, so that in the photomicrograph it is difficult to differentiate and determine their arrangement accu- rately. In some of the cells, as in the cell to the extreme right of the plate, and partially out of the field, the rounded and linear granules above the nucleus, and extending into the apical process, are seen to have a general parallel arrangement. The nuclei of these cells are large, and contain a large, well marked nucleolus and a more or less irregular chromatic network. As this section was stained with methylene violet, numerous neuroglia cells are distinctly seen scattered among the pyramidal nerve cells. From the cerebellar cortex a photomicrograph was taken of two Purkinje cells, magnified 1,400 diameters, and shown in Plate IX, Fig. 27. The section from which this photomicrograph was taken was situated on the external surface of the left hemisphere, cut transversely to the horizontal axis of the same, fixed in alcohol 95 per cent, stained with methylene blue : other technique similar to that of previously described plates. The section is 10 microns in thickness. These Purkinje cells were given by Nissl as typical examples of what he formerly described as Group II, arkyosti- chochrome nerve cells of the somatochrome class, in which was presented a striated appearance, with a network-like structure, united in a most intricate manner, thus having characteristics of both the arkychrome and the stichochrome cells. He now classi- fies them as one of the types of Group I, the arkyochrome nerve cells. In the Purkinje cell, to the right, the base of each of the two large dendritic processes is seen, one going off to the right, the other to the left, subsequently to divide and subdivide in the internal layer, not shown in the plate. The Purkinje cell 10 the left shows only one of these processes in this plane, that going off to the left which divides in the same manner as above de- scribed for the other cell. The large rounded nucleus, with its centrally placed nucleolus, is fairly well shown in the cell to the right, and contains a fine network of chromatic substance. The chromatic substance of the body of the cell is made up of larger and smaller irregularly-rounded chromophilic bodies, arranged in an indefinite network extending up into the base of the dendritic processes. A nuclear cap is seen above the nucleus of the Pur- kinje cell on the right. The closely-packed fine granular cells of the granular layer of the cerebellum are seen just below these two Purkinje cells, and are included in the class of cytochrome nerve cells in Nissl's classification. They contain a nucleus almost filling the cell body, and which is surrounded by only a very nar- row rim of chromatic substance. Within the nucleus is a nucleo- lus, and in some of these nuclei several irregularly-arranged chro- matic granules are also seen. Between the Purkinje cells is a small nerve cell with rounded body and an apical dendritic pro- DEMENTIA PARALYTICA. 79 cess. It contains a nucleus, nucleolus, and some chromophilic granules irregularly arranged in the cell-body. The last photomicrograph in the series of the normal histo- logical material is that shown in Plate X, Fig. 28. of a typical multipolar ganglion cell from the anterior horn of the lumbar enlargement of the spinal cord, under a magnification of 1,400 Plate X, Fig. 28. diameters. The segment of cord from which the section was taken was fixed in Van Gehuchten's fluid; this section is 6 2-3 microns in thickness and stained with methylene violet. This cell is, according to Nissl's classification, an arkyochrome nerve cell, Group I, of the somatochrome class, the chromophilic bodies being bo G. ALFRED LAWRENCE. arranged more in the. form of a network than in a parallel ar- rangement in the cell-body, though within the dendritic processes these bodies are more or less distinctly parallel in arrangement. The cell -body is irregularly polygonal in outline, with five large dendritic processes going off in different directions, and contain- ing at the base, and for a considerable distance, linear-shaped chromophilic bodies, arranged in a more or less parallel niaririer and spreading out and connected with the cell-body network. This latter is made up of irregularly-rounded and elongated chromo- philic bodies, arranged in an irregular network. The nucleus is large, rounded, slightly eccentric in situation, and contains a large rounded nucleolus and a pale indefinite network of chromatic substance. Numerous neuroglia cells are seen scattered about, singly or in groups, in the immediate vicinity of this cell. Part of another large ganglion cell is seen at the upper portion of the plate, on the left. This concludes the very brief discussion of the cortex of the normal brain, in which an endeavor has been made to present typical sections of the main divisions of the external surface of the cerebral hemisphere by means of photomicrography, upon which the greatest care was employed, in order to give an accurate idea of the usual appearance to be seen under the microscope in the study of such sections in contradistinction to the common diagrammatic figures that one usually associates with such work, and which do not show the actual arrangement and structure, but rather the ideal or embodyment in one figure of what is to be found in parts of many. The writer, on the other hand, does not wish to be understood as not favoring diagrammatic or schematic figures in work of this kind, as he regards them as highly im- portant and a valuable accessory to photomicrography and accu- rate drawings in the proper conception of the intricate structure and arrangement of the various portions of the nervous system as well as other systems. That there are minor variations from these plates in the dififerent regions has been repeatedly stated, but the variation is only a minor one, and does not depart suffi- ciently from the type to be considered as more than a modifica- tion. Furthermore, in going over the various plates from the different regions it will be seen that there is a general uniformity of arrangement and structure of the cells, and that one region does not vary to any great extent from that of any other region. This is well illustrated by comparing the plates from the frontal region with those of the temporal region, in which it would be difficult to determine the one from the other. The Betz cells in parts of the motor cortex are a conspicuous modification, but when we consider that only a small part of the motor area con- tains these cells, and again that these cells, though large, represent Plate IX, Fig. 25. Plate XI, Fig. 31. Plate XI. Fig. 33 Plate XI V, Fig. 43. Plate XV, Fig. 45, Plate XV, Fig. 47. DEMENTIA PARALYTICA. 8l but a miinrte fraction of the total number of cells in the cortex at this point it will be seen their presence makes but a slight modi- fication in the general cortical arrangement as a whole. The pyramidal cells intermediate in size between the large pyramidal cells and the Betz cells are of especial significance to the writer as perhaps indicating that, with increased specialization of func- tion, carried on through long periods of time, increased specializa- tion of the structure and size of the cortical cells is going on hand in hand, and that perhaps the so-called Betz cells, now almost entirely limited to certain portions of the central convolu- tions, some time in the future may be found in all parts of the cortex. Their large size, with resulting large amount of proto- plasm in the cell-body and large nucleus, the comparatively enor- mous amount of 'chromatic substance, as possibly stored up food products, all point to great capacity for storing up nervous energy to be given out when indicated as powerful efferent impulses, or, on the other hand, the capacity of receiving as equally powerful different impulses. Increased specialization in mental activity may result in greater numbers of nerve cells being set apart and increased in size and capacity for carrying out special functions. Paretic Brain. — Turning now to Brain B, the case of demen- tia paralytica, from which all the succeeding plates were taken, we see in Plate X, Fig. 29, a photograph of the left hemisphere of the brain, natural size. The macroscopic appearance at first sight would seem to indicate that there was marked atrophy and shrink- age in parts of several convolutions, especially the anterior central and frontal convolutions ; but a careful study of the sections taken from these regions shows this not to be altogether the case, or at least only to a slight degree. As any one who has studied brain topography to any extent well knows, there is much variation, not only in the shape and arrangement of any given convolution, but also in its size, so that great care should be observed in not mis- taking such normal variation for atrophy. A study of the various plates shown here under a magnification of 14 diameters, con- taining' the entire cross section from the several convolutions in the brain and comparing them to the preceding brain will make this point clear. Here and there a considerable quantity of the cortex has been torn away with the pia mater, whereas in many places small depressions are seen in which only a very small por- tion of the superficial layer of the cortex has been torn away. The convolutions are here well marked and the sulci very deep, so that there is a large area of cortical surface. The sulci in the middle portion of the hemisphere are widely open, owing to the support being placed only in the middle of the median surface of the hemisphere, so that the weight of the poles, anterior and posterior, caused these latter to become depressed, resulting in this con- 82 G. ALFRED LAWRENCE. spiciions widening of the' central sulci. The posterior pole of the brain — the occipital lobe — is practically normal macroscopically, and it will be seen later also microscopically, there being none or but very slight pathological changes in the cortex in that region. This photograph of the brain was taken before any blocks were removed, it having been previously fixed in 95 per cent alcohol. As each block was removed the exact location was noted and indi- cated in the photograph by the letters of the alphabet, and the place from which the block was taken enclosed in ink lines. Frontal Conz'ohition. — This portion of the cortex is repre- sented bv the block K, taken from the external surface of the first Plate X, Fig. 29. frontal convolution in its middle third, the exact location being seen in Plate X, Fig. 29, K. The photomicro2:raph seen in Plate X, Fig. 30, was taken from a section 10 microns in thickness, and is magnified 14 diameters. The gyrus here is somewhat narrow, and the sulci on either side were quite open and deep, and from the macroscopic appearance one might at first be inclined to think that there was some atrophy of the gyrus ; but a detailed study of sections from this region shows that this is not the case. Block K was fixed in 95 per cent alcohol ; this section is i cm. in length, .63 cm, in width at its widest part, and, as above stated, 10 microns in thickness, being stained with methylene blue ; the DEMENTIA PARALYTICA. 83 other technique being the same as for all the other plates. The shape of the section is somewhat that of a truncated pyramid, broader at the base and narrow at the rounded vertex. This me- chanical arrangement makes the cortex thicker at the vertex than on the lateral aspects. At a, and enclosed in ink lines, is the segment represented in Plate XI, Fig. 31. The first or superficial layer is seen to vary somewhat in thickness, being thicker on the Plate X, Fig. 30. lateral surface below b, with another thickened portion below a, a third just to the left of the vertex, and finally at the lower part of the left lateral aspect. The second or pyramidal cell layer does not show quite as distinct arrangement of the cells in a radial direction as in the corresponding region of the normal cortex, and there is especially to be noted the numerous portions of minute capillaries of varying size and tortuosity, singly or branched. This second layer passes over into the indistinct third layer, \^ich is lost below in the pyramidal-shaped white medul- lary cenier, which also contains numerous capillaries. Plate XI, 84 G- ALFRED LAWRENCE. Fig. 31, is a photomicrograph, magnified 100 diameters, of a segment corresponding in position to a of a section adjacent to and from the same block as that shown in Plate X, Fig. 30. The section is 6 2-3 microns in thickness, and of the same length and breadth as that shown in the preceding plate. Decolorization has been carried on to a considerable extent, about to the same degree as in Plate II, Fig. 3, and thus causing the plate to appear rather pale. Additional causes are the paucity of large pyramidal cells in the second layer, and the shrunken condition of many of the cells, as well as other pathological alterations. The upper layer averages .20 mm. in thickness, and contains for the most part scattered neuroglia cells. The second or pyramidal-cell layer is 1.80 mm. in thickness. Here is to be found a very similar ar- rangement of the cells to that in the corresponding region of the normal brain A. In the upper portion are to be seen the small pyramidal cells in considerable numbers, just below the super- ficial layer. Then they become more scattered, with a tendency to an arrangement into larger and smaller irregular groups, the cells becoming larger in the deeper portions. A little below the middle of this layer is found a narrow strip at a, where the small pyramids predominate almost to the entire exclusion of the larger ones, which latter, however, are seen above and below. Below this again are to be seen the larger pyramids, which finally give way to the irregular and spindle cells of the third layer. The nerve cells themselves show various changes. Many of them appear to be atrophied or shrunken, this process varying in degree in different cells. This in many cases has resulted in the forma- tion of larger or smaller pericellular spaces as seen about many of these cells, as at P in this plate and in Fig. P of the text, for instance. Here a large pericellular space completely surrounds the cell. The basal dendrites are represented by only one small shrunken process given off at the left and extending but a short distance. The body of the cell is shrunken and irregular in con- tour. A large mass of yellowish pigment is seen at the base to the right. A small amount of finely granular chromophilic substance is found about and above the nucleus. The nucleus itself is dis- placed downward into the base of the cell-body, to the extreme left. It is small, irregular in outline, and contains a well defined nucleolus but no chromatic substance. The apical process is shrunken and irregular in direction, and contains traces of chro- mophilic substance in places. The chromatic substance in the large majority of these cells has become diffused and decreased in amount in variable degrees, so that a large number of the cells present the appearance of chromatolysis up to almost complete disappearance of chromatin in some of them. These latter present a pale, washed-out appearance, as shown by the cell marked Q in DEMENTIA PARALYTICA. 85 this plate and seen enlarged in Fig. Q, where only a small amount of chromatin is found in the apical process and a slight amount of pigment in the lower part of the base. Some cells show loss of chromatin only about the nucleus, and are spoken of as in- stances of central chromatolysis. Others have a disappearance of chromatin at the periphery of the cell-body only, and this condi- tion is known as peripheral chromatolysis. The nuclei of many of these cells are found frequently displaced to one side, crowded into the base of a dendritic process, near the base of the cell-body, or near the base, or up into the proximal portion of the apical process. Many of these are irregular in shape and diminished in size. Quite a large pt-oportion of the larger pyramidal cells con- tain light yellowish pigment in variable quantity and usually at the base of the cell, often extending into the base of a dendritic process. The cell P, above described, in addition to the pericellu- lar space, demonstrates these last two points, the nucleus being crowded into the base of the dendritic process given off on the left and a considerable deposit of pigment being found at the base and extending into the right dendritic process. The cells contain- ing this pigment are marked with a cross, adjacent to them, in this plate. It will be seen that they are to be found mostly in the middle and lower portion of this layer, and also some few scattered irregular-shaped cells in the third layer. The dendritic processes in many of these cells end abruptly beyond their base, and in but few cases can they be traced to any great distance from the cell- body. The apical process shares in this general atrophy, and often is curved and irregular in direction, instead of presenting a regular straight course towards the periphery of the cortex. In some cells the nucleus is difficult to distinguish, the limiting mem- brane being indeterminable and the nucleolus appearing to be in the midst and surrounded by only the cell-body, and usuallv in an eccentric position. Numerous blood vessels are here to be seen, all, with thickened walls and pursuing a tortuous course. Large perivascular spaces are also seen about many of these blood ves- sels, as at d, for instance. The third, or spindle or irregular cell layer -is here .90 mm. in thickness, and is made up of irregular and spindle cells, some of the former, as some of the cells of the second layer, contain pigmentary deposits. Here also the chromatin is found in diminished quantity, and various stages of chromatolysis are seen. The nucleus is diminished in size in many cases and does not appear to be as prominent a factor as in the normal cells of this region. The cells as a whole appear smaller in size and more or less atrophied, containing less proto- plasm in the cell-body. as well as a diminished amount of chro- matin. The blood vessels are here also found to have thickened walls, and are tortuous in direction. At e is seen one of these 86 G. ALFRED LAWRENCE. vessels, with thickened walls and surrounded by a large perivas- cular space. The entire thickness of the cortex at this point is found to be 2.90 mm. ; almost the same as in the corresponding region in Brain A, as seen in Plate 11, Fig. 3. Counts were made of the nerve and neuroglia cells in various parts of this section in the same manner as in the previous sections, and in eight different fields of 36 sq. mm. each of the ocular net-micrometer from vari- ous portions of the two lower layers for the nerve cell counts, and in all three layers for the neuroglia cell counts. There was found to be an average of 100 nerve cells and 56.90 neuroglia cells to each square millimeter of surface of this section. The small num- ber of neuroglia cells being due to the methylene blue stain em- ployed and differentiation carried on to a considerable degree in a section 6 2-3 microns in thickness. In the section shown in Plate X, Fig. 30, 10 microns in thickness, and more deeply stained, the number of nerve cells is not quite so great, whereas the num- ber of neuroglia cells is almost six times as great, although the two sections are quite near together and from the same block. This is due to the neuroglia cells in Plate XI, Fig. 31, being al- most completely decolorized in the greater differentiation, where- as the cells, although paler, yet were not decolorized, and can all be made out. The same method of using the ocular net-microm- eter was employed here as in all the other plates, and counts were made from eight different fields of thirty-six squares each from different parts of the second and third layers of this section, and the average number of nerve cells was found to be 82.91 to the square millimeter of surface of the section, as compared to 100 for the same area in Plate XI, Fig. 31, so that there are on an average less nerve cells in this section, 10 microns in thickness, than in the section from which Plate XI, Fig. 31 was taken, which was but 6 2-3 microns in thickness, the same stain being used in both cases. The nerve cells, however, are more deeply stained in this latter section, and appear more distinct, and there are also more large cells. The neuroglia cells in eight different fields of thirty-six squares each from various parts of the three cortical layers average 303 to the square millimeter of surface of the sec- tion, as contrasted to 56.90 to the square millimeter in Plate XI, Fig. 31. Here increased thickness makes a difference in favor of this plate, and in addition to that the deeper stain with less decolorization cause all the neuroglia cells to appear more promi- nent. As stated before it was found that sections from 6 2-3 to 10 microns in thickness contain all the nerve cells to be seen in one plane. As the neuroglia cells are much smaller in diameter and often arranged in dense clusters, there may be a greater number in a section 10 microns in thickness than in one 6 2-3 microns in thickness. (See Table II.) DEMENTIA PARALYTICA. 87 Central Region. — Turning' to the region posterior to the one just discussed, we come to the central re2,'ion, or motor area, made up of the anterior and posterior central convolutions. Typical of the anterior central convolution in its upper portion is the section rep'"esc nted in Plate XI. Fi^". 32, under a magnification of 14 diameters. The exact location of the block from which this sec- tion was taken is indicated by the ktter D in Plate X, Fig. 29. The wide separation of the convolutions f^om one another, with resulting gaping sulci, is especially marked in this region. As Plate XI, Fig. 22- previously mentioned, this is largely due to mechanical agencies, a central support permitting the opposite poles, owing to their weight, to become depressed and force open the sulci in this region during the process of hardening or fixation. In the re- moval of the pia mater, small portions of the adhering cortex have been removed in places. This is seen just below the letter O, and in many places in the convolutions both anterior and posterior to this. By referring back to Plate TIT, Fig. 7 of the normal brain 88 G. ALFRED LAWRENCE. it will be seen that this section was taken from approximately the same relative position of the convolution as that seen in Plate III, Fig. 7, and, furthermore, the two convolutions are quite similar in shape ; this convolution being somewhat broader and less rounded at the vertex than that of the normal brain, however. The outer cortical layer is here more irregular and torn than in Plate III, Fig. 7, and at the vertex of the convolution at b the outer part of the first layer is seen stripped off for some distance. This, of course, is an artefact, the detached part being more adherent to the stripped off pia than to the cortex below. This outer layer furthermore presents a somewhat irregular contour, being broken in places as at c and d. The layer is thicker oppo- site a, and on the left lateral aspect, than elsewhere. The second or pyramidal cell layer shows the general radial direction of the cells, but not so well marked as in Plate III, Fig. 7. The chief point of interest, however, is almost complete disappearance of the Betz cells, which are seen so prominently in this region in the normal brain in plates of this magnification (14 diameters). In photomicrographs of 100 diameters we will find this disappear- ance is not complete, and that the cells, although much atrophied and. pale, so as to scarcely appear under the lower power, are much more apparent here, and are seen in all stages of dissolution. In this plate only scattered Betz cells are seen singly or in small groups at wide intervals, and these few are small, shrunken and, for the most part, pale. Fig. R is a drawing of the large Betz cell marked R in this plate. The nucleus is quite centrally situ- ated, with a large distinct nucleolus and some faint chromatic substance. Some few chromophilic bodies are seen interspersed among the finely granular chromatic substance. The cell pro- cesses are pale, irregular, and soon terminate at a short distance from the cell-body. No pigment is found in this cell. Figs. S and T show two other near-by cells, the former containing an eccentric nucleus, irregular, shrunken cell-body, with some pig- ment at the left of the nucleus. The processes being irregular and short. The cell in Fig. T is much shrunken and distorted, the nucleus irregular, a small nucleolus, and but little diffuse chro- matic substance. There are no basal processes, and the apical process is narrow and irregular in direction. Numerous capil- laries are seen with thickened walls, and some with perivascular spaces. The third layer is indistinct, and fades into the white medullary substance, where many large capillaries with thickened walls, tortuous course and perivascular spaces are found. At a, and enclosed in ink lines, is the segment of this section, corre- sponding in position to that seen in Plate XI, Fig. 33. This sec- tion is 8 mm. wide, 6.5 mm. long, and 10 microns in thickness, fixed in 95 per cent alcohol, stained with methylene violet, and DEMENTIA PARALYTICA. 89 other technique similar to all the other sections. Plate XI, F*^. 33, is the photomicrograph magnified 100 diameters of a segment corresponding to a of Plate XI, Fig. 32, and from a section taken from the same block, and but a short distance from the above. At this point the first or outer layer measures .25 mm. in thick- ness, whereas in Plate XI, Fig. 32, it would measure at least .40 mm. in thickness. It contains numerous neuroglia cells, with here and there a small pale nerve cell in which is situated a small nucleus surrounded by a mere trace pf chromatic substance. Be- low this is the second or pyramidal cell layer, measuring 1.30 mm. in thickness. In the upper parts the pyramids are seen to be small and quite closely packed together. About the middle of the layer they are seen to be much larger and more scattered. Below this again, at a, is seen a region containing for the most part only small pyramids, and this finally merges into the lower portion of this layer, where are seen the large and giant pyramidal cells. These latter, or Betz cells, are seen in irregular groups or "nests," consisting of from one to several (six or more) cells. All of these cells show a diminished amount of chromophilic substance and no distinct granules. Various stages of advanced chromatolysis are seen, from a general diffusion of the chromatic substance to almost complete absence of the same. The cells are for the most part shrunken, the nuclei small and indistinct, displaced in many cases, and the cell processes atrophied and tortuous. Many of these larger cells contain a varying amount of yellowish pigment. Fig. U shows the cell marked U in the plate. No processes are seen, the cell-body is shrunken and contains but a small amount of diffused chromatin, showing no structure and pale in color. The nucleus is small, shrunken and indistinct, with a pale nucleo- lus. No pigment is to be seen in the cell. To the left of the cell- body is a small pericellular space. Several neuroglia cells are seen in apparent direct contact with the cell-body and others in the pericellular space and the wall of the latter. The cell just below and to the left of this in the plate is similar in regard to the amount of chromatin, is pale, and the nucleus and nucleolus are not visible. Three processes are seen given off at the base, but atrophied and extending for only a short distance. A small peri- cellular space is seen about this cell also. The cell just below and, to the right of this, and marked V in the plate and seen in Fig. V, shows the same grade of chromatolysis. The remnant of a shrunken and atrophied process is seen at the base on the right. The shrunken nucleus, with pale nucleolus, is centrally situated, and below this are found diffused pigmentary deposits. Through- out the cell-body, less in the upper than in the lower part, is scattered pale diffuse chromatic substance, and without any definite arrangement. A narrow pericellular space is seen along 90 G. ALFRED LAWRENCE. the right side of this cell. The general contour and lack of struc- ture are seen in Fig. V. Here, too, neuroglia cells are seen lying upon and in close juxtaposition to the cell-body. Numerous blood vessels with thickened and tortuous walls and perivascular spaces are seen throughout this layer. The third or spindle or irregular cell layer here measures .90 mm. in thickness, and is made up of shrunken spindle and irregular cells, pale, and containing but a small amount of diffuse chromophilic substance. Many of them are surrounded by pericellular spaces of varying size. The letter Plate XI, Fig. 34. W indicates one of these spindle cells seen in the drawing, Fig. W. The polar processes are here filamentous, and distorted in direc- tion, the cell-body shrunken and containing but a small amount of diffuse chromatic substance, so that it is pale in color, the nucleus is small and indistinct, and contains a small nucleolus. The cell-body is partially surrounded by a distinct pericellular space, with a neuroglia cell upon the edge at one point. Numer- ous blood vessels with thickened walls and perivascular spaces are also seen in this layer. The entire depth of the cortex here is 3.05 mm., all three layers being slightly thicker than in Plate III, Fig. 8, of Brain A, the first layer being .05 mm., the second .15 DEMENTIA PARALYTICA. 91 mm., and the third .20 mm., thicker than in the latter. As varia- tions of this extent are found in sections of convolutions in close proximity, and even in different parts of the same section in any brain, it seems doubtful to the writer whether we can attach any special significance to such a slight variation, due possibly to me- chanical causes, acting in embryonic or even post embryonic life. Counts of the nerve and neuros:lia cells here show a decided fall- Plate XII, Fig. 35. ing off in number of the former. This section is 6 2-3 microns in thickness and stained with methylene violet. The same method with the ocular net-micrometer was used, counting the nerve cells in eight different fields of thirty-six square millimeters, each in various parts of the second and third cortical layers, and the neuroglia cells in the same number of different fields in all these cortical layers. The average number of nerve cells to each square millimeter of surface of the section was found to be but 39.60, whereas the average number of neuroglia cells to the same area was found to be 204. The number of nerve cells is thus seen to be much diminished as compared to Plate III, Fig. 8, the corre- sponding region of the normal brain A, where there are an aver- 92 G. ALFRED LAWRENCE. age of 95 nerve cells to the square millimeter of surface of the section. The number of neuroglia cells is also less here, being 204 in this plate in comparison to 293 in Plate III, Fig. 8. The latter section is. however, 10 microns in thickness, as compared to 6 2-3 microns for this plate, and as previously noted, owing to the small size and close aggregation of the neuroglia cells, more would be normally found in the thicker section, although this Plate XII, Fig. 36. hardl}- accounts for the great difference, as both were stained in the san.e manner with methylene violet. Plate XI, Fig. 34, is a photomicrojraph, magnified 14 diameters, from a section taken from the point L of the upper portion of the anterior central con- vokition of Brain P> (see Plate X, Fig. 29), and as seen by refer- ring to this latter, is from a more inferior portion of this gyrus DEMENTIA PARALYTICA. 93 than the section represented in Plate XI, Fig. 32. This section was fixed in 95 per cent alcohol, is 6 2-3 microns in thickness, and stained with methylene violet. The first la3'er is seen to be fairly uniform in thickness at the lower two-thirds, as seen at c. Above, and at the vertex, and also along the anterior aspect of the con- volution, as at d, the surface is more or less torn and irregular, due to carrying away of small fragments with the adherent pia. By referring to Plates XI, Fig. 32, and XIII, Fig. 39, the varia- tions in shape and mechanical arrangement of the convolution in adjacent portions will be noted. In Plate XI, Fig. 32, the vertex is broadly rounded and somewhat flattened. In Plate XIII, Fig. 39, the vertex is more narrow and pointed, while in this plate, intermediate in position between the above two plates the vertex is less pointed. Large perivascular spaces are noted in many places throughout this section, especially marked in the upper portion to the left of the vertex, where but a fragment of the blood vessel is to be seen only at the lowest point of an enormous perivascular space. The radial arrangement of the cells is but poorly shown, the Betz cells seem to have disappeared almost en- tirely in the second layer, in marked contrast to the plates of the same magnification of Brain A. (Plates III. Fig. 7; I\', Fig. 9, and lY, Fig. 11.) Under a high magnification, however, the rem- nants of many of these Betz cells can be made out, showing vari- ous pathological changes. The other nerve cells also show a wealth of pathological change of varying degree and kind to which the nerve cell is subjected — all grades of chromatolysis, pigmentation, atrophy, and shrinkage of the nerve cells and pro- cesses, with larger or smaller pericellular spaces. Numerous capillaries, with thickened walls and perivascular spaces, are seen scattered throughout the various parts of the section. The actual size of this section is 8 mm. wide at the point opposite d. 8.5 mm. long, and 6 2-3 microns in thickness. At the points a and h are seen the Betz cells, shown under a magnification of 1,400 diame- ters in Plates XII, Fig. 35, and XII, Fig. 36. The former of these is a photomicrograph as stated, under a magnification of 1,400 diameters of the nerve cell, indicated by the letter a in Plate XI, Fig. 34. By referring to this latter plate, and then to Plate X, Fig. 29, we can locate almost the exact position of this cell in the cortex of Brain B. The cell-body is seen shrunken and deformed, lying in a pericellular space partially surrounding it. The nucleus is eccentric, being crowded over to the extreme edge of the cell-body on the right side. It is also shrunken and indis- tinct, but contains a well-marked and prominent nucleolus. The apical process above and to the right appears quite sharply de- flected at a point but a short distance from the base, but this is not really the case, as the portion from a to the edge of the plate 94 G. ALFRED LAWRENCE. is one of the walls of a blood vessel, the opposite wall not being seen in this plate at all. At the point a, this apical dendritic process appears to come in direct contact with this portion of the wall of the blood vessel, and is there lost to view. The other dendritic processes— seven in all — are shrunken, and contain a small amount of diffuse chromatin. Within the cell-body the chromatin is considerable in amount, and quite generally diffused in fine granules throughout the cell-body, lacking any definite structural arrangement. There is a somewhat greater amount at the base to the left and below the nucleus, and also at the upper part of the cell-body. Above and to the left of the nucleus, where the cell-body appears most pale, and extending into the base of the dendritic processes here, is a considerable mass of yellowish pig- ment. Numerous neuroglia cells are seen in the vicinity of this Betz cell. Plate XII, Fig. 36, is also a photomicrograph, magni- fied 1.400 diameters, of another of these Betz cells trom the point h of Plate XI, Fig. 34. Here there is but Httle diffuse chromatin, confined principally to the base of the dendritic process given off on the right. All the lower part of the cell-body, excepting this portion, contains palely yellow pigment. The nucleus is displaced almost to the extreme edge of -the cell-body, and lies just below the two neuroglia cells seen at a. The nucleolus, on this account, can not be determined at this plane. On microscopic examination the nucleus is found to be shrunken and indistinct. Numerous neuroglia cells are seen upon and in the immediate vicinity of this cell. The basal dendritic process b, which is but faintly seen here, owing to its lying in a somewhat lower plane, has eight neuroglia cells in close apposition to it. The dendritic process on the right can be traced for some distance, is somewhat shrunken, and con- tains no chromatic substance. Another small dendritic process is given off from the base opposite the point c, and being in a lower plane, only its base is seen here. It is colorless, and extends but a short distance from the cell-body. The apical dendritic process contains no chromatin, and. as seen, has several neuroglia cells surrounding it a short distance from its base. A large pericellu- lar space almost entirely surrounds the cell, excepting at the base to the left. Plates XII, Fig. 37, and XII, Fig. 38, are photomi- crographs of the same magnification (1,400 diameters), taken from an adjacent section of the same block as the two preceding plates, and are also 6 2-3 microns in thickness. This section was prepared in exactly the same way, with the exception that methylene blue was used as the stain instead of methylene violet. This will be at once apparent upon noticing the neuroglia cells, which are here pale and washed out, many to the point of com- plete decolorization, so as not to be seen at all. The Betz cell in the center of Plate XII, Fig. 37, is seen surrounded by a large DEMENTIA PARALYTICA. 95 pericellular space. All the processes, four in number, including the apical dendritic process, are pale, and terminate but a short distance from the cell-body. The nucleus is eccentrically situated near the wall at the left, is small, and contains a large nucleolus, but no nuclear network. Within the cell-body finely granular chromatic substance is found at the base below and to the right of Plate XII, Fig. Z7- the nucleus. There is no pigment present. This cell presents an advanced stage of partial chromatolysis. Above and to the right is an almost indeterminable mass, which, under the 1-12 inch oil- immersion objective, appears to be the remnant of a capillary, surrounded by a large perivascular space. Other cells are seen here in various stages of disintegration, surrounded by large peri- cellular spaces, some containing none or onlv the remnants of den- 96 G. ALFRED LAWRENCE dritic processes, indistinct and shrunken nuclei, some distinct nu- cleoli and others none at all, and all in a more or less advanced state of chromatolysis, with but little of the diffused stained chro- matic substance present. The neuroglia cells that are visible at all are pale and poorly stained, while many are almost or corn- Plate XII, Fig. 38. pletely decolorized. Plate XII, Fig. 38, is a photomicrograph of a Betz cell on the same section and but a short distance from the cells of the preceding plate, and under the same magnification (1,400 diameters). Here there is almost complete chromatolysis, there being but little finely granular, diffuse chromatic substance scattered in the cell-body, slightly more at the base than above the nucleus. The latter is small, rounded, centrally situated, and DEMENTIA PARA LYTIC A. 97 contains a large, rounded, distinct nucleolus. - The three basal pro- cesses are narrow, pale, and terminate at no great distance from the cell-body. The apical process is pale and slender, extending for some little distance before coming" to an end. Part of a pale, atrophied cell is seen to the right of the same. The ghosts of several neuroglia cells may be seen here, but most of them are completely decolorized. Plate XIII, Fig. 39, as will be seen by referring to Plate X, Fig. 29, is from the lower portion of the upper third of the an- terior central convolution, from the point marked O, and is magni- fied 14 diameters. This section, as already mentioned, is found to Plate XIII, Fig. 40. vary somewhat in shape from that of the preceding sections shown in Plate XI, Fig. 32, and Plate XI, Fig. 34, being narrower and more pointed at the vertex. From the strip marked a, and enclosed in ink. the structure and arrangement of the nerve cells were carefully studied, and both nerve and neuroglia cell counts made and will be referred to again later. The irregularity and difference in thickness of the first layer in different parts is to be noted, being especially thick at h, where it almost presents the appearance of an artefact, but under a high power no derange- ment of the structure can be made out. At a the laver is seen to 98 G. ALFRED LAWRENCE. be very thin, owing to some of the surface of the cortex having remained adherent to and been stripped off with the thickened pia mater. Large perivascular spaces are to be especially noticed in the subcortical portion of the section. Here is to be noted the almost entire absence of the Betz or giant pyramidal cells in the ixjwer part of the second layer, although some large pyramidal cells are to be found, they are not, however, so large -nor are they arranged in such distinct groups as in the region higher up. Un- der higher magnification the remnants of some of these Betz cells are seen in various stages of necrosis and disintegration. The cortex lacks the distinct striated appearance seen in the sections of the normal cortex. This layer passes indistinctly into the third or spindle cell layer, which in turn is lost in the white medullary substance below. Numerous capillaries are seen, many with thickened walls and perivascular spaces throughout the section. This section was fixed in 95 per cent alcohol, sectioned 10 microns in thickness, stained with methylene violet, with other technique similar to that of all the previous sections. The actual size of the section is 9 mm. at its greatest width and 13 microns in length. The strip a varies from that of Plate XI, Fig. 33, only in the number and arrangement of the cells in the second layer. At this point the three layers are respectively .20 mm., 2.00 mm., and .90 mm. in thickness. The first layer contains some few scattered irregular nerve cells and numerous neuroglia cells. The second layer contains small pyramidal cells above, increasing in size until a little above the middle of the layer is a strip some .30 mm. in width, in which are to be seen large pyramidal cells arranged singly or in irregular groups. Some of these cells almost ap- proach the giant pyramidal cells in size. Many of them show but a slight shrinkage and contain an almost normal amount of chro- matic substance. The chromophilic bodies, however, are not as numerous or as large as in the normal brain. Other cells show a complete absence of chromophilic bodies, but contain the chro- matic substance diffused throughout the cell in minute particles. Still others are pale, and contain but little chromatic substance. The nuclei are larger, less eccentric, and there is a less degree of atrophy of the cell-body and processes. Below this is a region of small pyramidal cells with only a few scattered larger pyramidal cells merging into the lower part of the layer, where large pyrami- dal cells are again seen scattered irregularly among the smaller cells. These large pyramidal cells are somewhat smaller than the giant pyramidal or Betz cells seen in the upper part of this con- volution. These cells show more advanced pathological changes, in some cases marked atrophy and shrinkage with large pericellu- lar spaces, atrophy of the dendritic processes, eccentricity and shrinkage of the nucleus, pigmentary deposits, complete absence DEMENTIA PARALYTICA. 99 of or but a small amount of diffuse chromatic substance. The third layer presents the same general appearance as in the pre- ceding plate (XI, Fig. 33), with many cells much shrunken and atrophied and little or no chromatic substance within the same, and surrounded by pericellular spaces of varying size. Numer- ous large and small capillaries are seen scattered throughout this Plate XIII, Fig. 39. section, with thickened walls and surrounded by larger or smaller perivascular spaces. The entire depth of the cortex here is 3.10 mm., the second layer being slightly thicker than in Plate XI, Fig. 33. The nerve cells were found to average but 36.50 to the square millimeter of surface of the section here ; less than in any of the other plates, whereas the neuroglia cells average 289 to the square millimeter of surface of the section, almost as great a num- iOO G. ALFRED LAWRENCE. ber as in the previous sections of the same thickness, ten microns, and stained with methylene violet. The most conspicuous differ- ence between this and Plate XI. Fig. 33, higher up in the convolu- tion, is the arrangement of the large pyramidal cells, the absence of the typical Betz cells, and on the whole less advanced pathological changes. Plate XIII, Fig. 40, is a photomicrograph magnified fourteen diameters of a section from the block B of Plate X, Fig. 29, and is thus seen to be situated a little above the middle of the posterior central convolution. This section is 6 2-3 microns in thickness, 8 mm. in length, and 9 mm. in width at the widest point, was fixed in 95% alcohol, stained with methylene blue, and other technique similar to that of all previously described sections. This section at the vertex, especially to the left, shows the striated ap- pearance of cell arrangement very well, but upon the anterior and posterior aspects of the gyrus it is but indistinctly shown. The first layer is fairly uniform in thickness with broken spaces here and there, especially about the entrance of capillaries. This layer is somewhat thicker in certain places than in others. At a, for in- stance, it is thicker than at the vertex. This section has a broad, flattened vertex with considerable cortical area on both the anterior and posterior surfaces. The cortex opposite the angles c and b is somewhat thicker than elsewhere. This mechanical arrangement admits of a large, broad mass of fibres from various parts of this and the adjacent regions of the brain, leaving from and entering into relations with the cells of this portion of the cortex. The section is broken (an artefact) at the left and numerous capillaries are found scattered throughout all the cortical layers and also the white medullary center. The segment represented in Plate XIII, Fig. 41, was taken from a point corresponding to a, but from an adjacent section of the same block, and is magnified 100 diameters. It is from relatively the same position as the segment shown in Plate VII, Fig. 19, the strip a of Plate VI, Fig. 18, of the normal brain, but, as will be seen by referring to the latter, the shapes of the two sections are quite different. The distribution and arrange- ment of the cells in this plate is somewhat different from that in Plate VII, Fig. 19, also. In this latter, as already described, some large pyramidal cells are irregularly distributed in parts of the upper half of the second layer, followed by a narrow region made up almost exclusively of small pyramidal cells to be followed by larger pyramidal cells in the lower portion of this layer. In this plate, however, there are but few of the larger pyramidal cells in the upper portion of the second layer, there being practically only small pyramidal cells in this upper portion with the larger pyra- mids mostly in the lower portion of this second layer. The cell seen in the lower part near the center (a, Plate XIII, Fig. 41), approaches in size to the Betz cell type. The first or superficial DEMENTIA PARALYTICA. lOI layer here contains nothing but capillaries and neuroglia cells and is .25 mm. in thickness. The second or pyramidal cell layer is 1.40 mm. in thickness and shows not only numerous capillaries with irregular and thickened walls, but also the cells in variom pathological conditions. Chromatolysis is complete in many of these cells as in the large pyramidal cell marked a for instance, where only traces of minute finely powdered chromatin can be seen in some parts of the cell-body. Here also the nucleus is indistinct, with a well marked nucleolus, and the basal processes are much atrophied, terminating but a short distance from the cell-body. A small pericellular space is seen at the base of this cell-body. Many cells show eccentricity of the cell nucleus, shrinkage of the cell- body, various grades of chromatolysis, pigmentation, atrophy, and distortion of the dendritic processes and are surrounded by peri- cellular spaces. The capillaries are numerous, have thickened and irregular walls, and are surrounded by perivascular spaces of varying "size and' extent. Numerous neuroglia cells are also inter- spersed about the cells and capillaries in this layer. The third or ipindle cell layer is only partially seen in this plate, and is about .90 mm. in thickness (only upper portion shown in Plate XIII, Fig. 41), and is similar to that in preceding plates of the motor region, and contains for the most part shrunken and irregular spindle and polygonal shaped cells, with numerous neuroglia cells and capillaries interspersed among them. Most of these cells show the various pathological processes mentioned above for the pyramidal cells. The cortex here thus measures 2.55 mm. in thickness, almost the same as for the two upper layers in Plate VII, Fig. 19, but here the third layer is .90 mm. in thickness as compared to .60 mm. in the above mentioned plate of the normal brain. Nerve and neuroglia cell counts were made here with the result that an average of 59.91 nerve cells and 134.37 neuroglia cells were found to the square millimeter of surface of the section as compared to an average of 185.50 nerve cells and 109.20 neu- rogHa cells for the same area in the strip of cortex represented in Plate VII, Fig. 19, of the corresponding region of the normal brain. Both sections were 6 2-3 microns in thickness and both stained with methylene blue. The difference in nerve cells is very marked, whereas the difference in number of neuroglia cells is not so great, and as the technique was identical throughout in the preparation of the two sections, the marked pathological pro- cess shown in this latter, it seems to the writer must be attributed as the cause of this difference to a large extent at least. Parietal Region. — Plate XIV, Fig. 42, is a photomicrograph magnified fourteen diameters, of the parietal region from the point H. in Plate X, Fig. 29, this being a part of the supra-angu- lar gyrus and from the same relative part of the gyrus as the I02 G. ALFRED LAWRENCE. corresponding plate (VII, Fig. 20) of the normal brain. The section was fixed in 95% alcohol, stained with methylene violet, and treated otherwise as the preceding plates. This section measures 6 mm. in width, 16 mm. in length, and is 6 2-3 microns in thickness. Its shape is long and narrow and quite different from that of Plate VII, Fig. 20. At the vertex of the convolution Plate XIV, Fig. 42. the first layer has geen cut away with the paraffin in preparing the block for sectioning serially with a Minot microtome, and, of course, this condition is an artefact. The first layer is seen to be fairly uniform in thickness with this exception. In the second layer it is difficult to determine the well marked striated arrange- ment of the cells, as seen in Plate VII, Fig. 20. Numerous peri- vascular and pericellular spaces are seen with or without the capil- DEMENTIA PARALYTICA. IO3 laries or cells, as the case may be. The third layer is indistinct and fades away into the white medullary center which also con- tains many pericellular and perivascular spaces. No doubt the fixation in 95% alcohol has produced some shrinkage, but by no means all, as the plates of the occipital convolution just posterior to this show a much less degree of shrinkage than is here present and not only every block taken from this brain was fixed in ex- actly the same way, but also some of the blocks from Brain A. At a and surrounded by ink lines is the segment of the section shown under a magnification of 100 diameters in Plate XIV, Fig. 43, and as is here seen is taken from the lateral aspect near the vertex, instead of from the vertex as in the corresponding plate of the normal cortex (Plate VH, Fig. 21). The first layer averages .25 mm. in thickness and contains numerous capillaries with thickened walls, and tortuous course with larger and smaller perivascular spaces. Numerous neuroglia cells are scattered throughout this layer. The second layer is here 1.50 mm. in thickness. Here, too, are seen numerous capillaries with thick- ened walls, irregular course, and large perivascular spaces. In the upper half of the layer the small pyramidal cells gradually are intermingled with larger pyramidal cells as the lower portions are reached, until just above a the largest pyramids of the sec- tion are seen singly or in groups in a comparatively narrow zone. Below and opposite a is a narrow zone, some .25 mm. in width in which there are practically no large pyramidal cells. Below this again is a very narrow zone at the lower part of this layer in which some few large pyramidal cells are seen scattered among the smaller and irregular cells. These cells present all stages of chromatolysis, pigmentation, shrinkage of the cell-body and pro- cesses and irregularity in direction of the latter, eccentricity and shrinkage of the nucleus and larger and smaller pericellular spaces. Numerous neuroglia cells are scattered throughout the layer. The third, or spindle cell layer, measures scarce .50 mm, in thickness and contains for the most part shrunken and irregular spindle cells in larger or smaller pericellular spaces, in many in- stances in various stages of chromatolysis. Numerous neuroglia cells in many cases appearing in direct contact with the cell-body are seen in this layer, as well as in the above layer. The vascular changes are also similar. The entire depth of the cortex here is thus 2.25 mm., somewhat less than in Plate VII. Fig. 21, but about the same as on the lateral aspect of this latter plate. Nerve and neuroglia cell counts were made here in the same manner as in previous sections, and it was found that there was an average of 68.63 nerve cells and 192.70 neuroglia cells to each square millimeter of surface of the section as compared to 104 nerve cells and 180.90 neuroglia cells in the corresponding region of Brain A, I04 G. ALFRED LAWRENCE. both sections being of the same thickness and stained in the same manner with methylene violet. Temporal Region. — Turning to the region below this we come to the temporal region represented here by a section from the first temporal convolution near its anterior extremity, from the ! J L-:^ Plate XIV, Fig. 44. point / in Plate X. Fig. 29, and shown under a magnification of fourteen diameters in Plate XIV. Fig. 44. This convolution is also much narrower than the corresponding convolution of Brain A, seen in Plate VIII, Fig. 22, thus having a somewhat dissimilar mechanical arrangement. To the right is seen the first temporal fissure and a portion of the second temporal convolution. The convolution measures 5.5 mm. in width and 8 mm. in depth from DEMENTIA PARALYTICA. 105 the vertex to the point on the level with the bottom of the first temporal fissure and is 6 2-3 microns in thickness. The convolu- tion at this point is seen on the right to curve around and fuse with the second temporal convolution, being free above at h, which is the lower boundary of the fissure of Sylvius at the be- ginning of the posterior branch. At a and enclosed in ink lines is the segment of the section shown in the following plate under a magnification of 100 diameters. The first or superficial layer is quite uniform in thickness, broken in several places, especially above h on the superior surface. The second layer shows the striated arrangement of the cells only very indistinctly at some few points and contains many pericellular and perivascular spaces, some with and others without contents. The third layer is indis- tinct and fades into the white medullary center which is narrow and passes inferiorly over to connect on the right with that of the second temporal convolution. In Plate XV, Fig. 45, strip a of Plate XIV, Fig. 44, under a magnification of 100 diameters, the pathological conditions are seen to be well marked. The section is 6 2-3 microns in thick- ness and stained with methylene violet. Here the first layer aver- ages about .20 mm. in thickness and to the right a fragment of a blood vessel is seen at the surface, but penetrating the cortex in a different plane. In the center and reaching into the second layer is a large capillary with thickened walls, with larger caliber above and smaller below, being somewhat funnel shaped and sur- rounded by a large perivascular space. Some smaller fragments of capillaries and neurogha cells are scattered about in the layer. The second or pyramidal cell layer is 1.50 mm. in thickness and presents very much the same general plan of arrangement as the corresponding region in the normal brain, as seen in Plate VIII, Fig. 23, and also in the region of the first frontal convolution, as seen in Plate II, Fig. 3, and XI, Fig. 31. Small pyramidal cells almost exclusively are seen in the upper part of the layer below this gradually increasing in size to the middle of the layer. Then opposite a is a narrow strip some .20 mm. in thickness in which there are small pyramidal cells almost exclusively. Below this again and in the lower part of this layer are larger pyramidal cells, intermingled with smaller pyramidal and irregular shaped cells. Here, too, the majority of the cells are seen shrunken and surrounded by larger and smaller pericellular spaces. Various stages of chromatolysis, shrinkage and eccen- tricity of the nucleus and atrophy of the cell processes are to be observed. The blood vessels show the same pathological condi- tions as in the upper layer and numerous neuroglia cells are in- terspersed thickly everywhere. The third layer is .80 mm. in thickness and presents the same io6 G. ALFRED LAWRENCE. pathological conditions of the cells and blood vessels as previously described for this layer in Plate XIV, Fig. 43, of the parietal region. The entire depth of the cortex here is 2.50 mm., some- what thicker than the corresponding region of Brain A. Nerve and neuroolia ceil counts were also made here and in a similar manner, an average of 56.74 nerve cells and 205.90 neuroglia Plate XV, Fig. 46. cells being found to the scjuare millimeter of surface of the cor- tical portion of this section, as compared to 146. nerve cells and 131.90 neuroglia cells to the square millimeter of the surface of the cortex in the corresponding region of Brain A. In the latter methylene blue was the stain used, the thickness of the sections being the same in both cases, and as has been seen in every in- stance the metlnlene violet stain has greater affinity for the neu- roglia cells than the methylene blue, whereas, the nerve cells stain about the san:e with the one as with the other. DEMENTIA PARALYTICA. 107 Occipital Region. — Plate XV, Fig. 46, is a photomicrograph magnified fourteen diameters of a section taken from the block / of Plate X, Fig. 29, situated in the upper portion of the lateral aspect of the occipital convolution. The section is 5 mm. wide, 8 mm. in length and 6 2-3 microns in thickness, was fixed in 95% alcohol, and stained with methylene violet. As may be observed, upon the posterior aspect, the sulcus is very shallow, the cortex here fusing with that of the adjacent gyrus not far from the vertex, whereas anteriorly the sulcus is well marked and quite deep. The first or outer layer is thicker both on the posterior and anterior aspects than at the vertex and is quite uniformly regular in outline. The second layer is well marked and shows the striated arrangement of the cells quite as well as in Brain A, at this point. Numerous large cells, some of which quite approach the Betz cells in size and structure, are seen scattered in the middle and lower portions of the layer. The third or spindle cell layer below is gradually lost in the white medullary substance. Through- out the entire section the cells and their arrangement are well made out, the capillaries although having thickened walls and somewhat tortuous are less conspicuous, the pericellular spaces smaller and less numerous, and most of the cells are fairly normal and show no distinct pathological changes. At a and enclosed in ink lines is the position of the segment in the adjacent section from which Plate XV, Fig. 47, was taken. This latter corre- sponds most favorably with Plate IX, Fig. 25, from the corre- sponding region of the normal brain and some of the nerve cells here in Plate XV, Fig. 47, are larger and more numerous than in the corresponding section from Brain A. The first or outer layer is uniform in outline and measures here but .15 mm. in thickness. It contains numerous neuroglia cells and some scat- tered small nerve cells similar to those described in Plate II, Fig. 3, and seen in the text as Figs. C, D, E, and F. The second or pyramidal cell layer is of special interest and measures 1.40 mm. in thickness, being somewhat deeper than in Plate IX, Fig. 25, but with a similar arrangement of cells. Above are small pyra- midal cells only, then larger pyramidal cells are seen in the deeper portions until about the middle of the layer is a region containing very large pyramidal cells, same as the one indicated by the letter X, for instance, being similar in size and structure to the Betz cells. Below this at a is a region .30 mm. in thickness in which numerous small pyramidal cells are alone seen. Below this again is a narrow zone containing some larger pyramidal cells scattered amongst the small pyramidal and irregular cells. The cell marked in the plate by the letter X is seen magnified in Fig. X, It is very large, contains irregularly elongated and linear chromophilic bodies of considerable size and arrangement in a I08 G. ALFRED LAWRENCE. more or less parallel direction to the cell-body and extending into the dendritic processes. The nucleus is large, rounded, distinct, and centrally located with a distinct rounded nucleolus and inde- finite chromophilic network within. No processes are given off at the base in this plane, but a large process is given off upon the right at the level of the nucleus and soon divides into two branches. Another process is given off to the left on the oppo- site side of the cell -body at a level just above the nucleus. The apical dendric process contains numerous linear chromophilic bodies extending for some distance into the same. This is a stichochrome nerve cell of the somatochrome class, and, in size and structure, is similar to the Betz cell. The two cells to the extreme right are similar in structure but not as large as the above. There are no pathological changes to be determined in the cells of this layer. Several small capillaries are seen with somewhat thickened walls, indicating that possibly the blood ves- sel changes are the first to be found in the disease, but of course much more extended observation and study would be required to determine the full relation of all these pathological processes to one another. The third or spindle cell layer is here .90 mm. in thickness and made up of spindle and irregular polygonal cells, quite normal in appearance for the most part; some, however, showing slight' shrinkage, pericellular spaces, and slight begin- ning chromatolysis. Some capillaries with thickened walls and perivascular spaces are to be observed here also. The entire thick- ness of the cortex measures 2.45 mm. being .45 mm. thicker than in Plate IX, Fig. 25. Nerve and neuroglia cell counts were made here with the results that 62.50 nerve cells and 215.01 neuroglia cells were found on an average to each square millimeter of sur- face of the cortex here, as compared to 164. nerve cells and 199. neuroglia cells in the same area of the corresponding section of Brain A, both sections being 6 2-3 microns in thickness and stained with methylene violet. From a study of the above plates from these two brains, the cortex in Brain A, would seem to be thinner and more compact, whereas, the cortex of Brain B, on an average measures somewhat thicker, yet the cells seem more scattered, so that a very much higher average of nerve cells is to be found in the former, far more it seems to the writer than could be accounted for by the possible destruction of some of the cells in the sections of Brain B, due to pathological agencies. The careful detailed study of the sections from various parts of the different regions of Brain A, practically normal from a histological standpoint, and of corresponding sections of Brain B, a case of advanced dementia paralytica in the manner as described DEMENTIA PARALYTICA. 109 in this article has led the writer to the following conclusions : I. Photomicrography is a useful and valuable adjunct to such work, giving greater accuracy in relations of parts to one another than is possible in drawings and showing conditions as they actu- ally appear to the eye of the observer in each particular plane when the sections are seen under the microscope. Powers of 14 or 20 diameters show very well relations of the layers to one another, and also the relation of the groups of large cells ; such as the Betz cells in the central regions, for instance. Powers of 100 diameters are well adapted to the study of the more minute detail of these relations of the layers and of various cells to one another, and also some of the morphology of the individual cells can be made out. Powers of 1,000 to 1,500 diameters show the internal structure of the cell to excellent advantage, but only in the very limited plane at which the object is focussed. On the other hand, the disadvantage of photomicrography is that everything is shown in any one plane so that special parts or structures are not brought out as prominently as in schematic drawings, and on this account all such work should be accompanied by such drawings to make it more complete. It is furthermore often quite difficult to obtain any one plane showing most of the cell structure, to say nothing of all of the same. II. Artefacts of many kinds are to be found in such work, and should be carefully avoided and eliminated in every instance be- fore definite conclusions are drawn from any series of observa- tions. Pressure and other mechanical causes acting before death, that due to manipulation at autopsy, artefacts resulting from fixa- tion, imbedding, sectioning, staining, decolorizing, and even mounting, are all possibilities, and are often most difficult to deter- mine in contradistinction to the pathological changes. III. The method of transporting- material by means of small metallic boxes or similarly sized phials, permitting of a free cir- culation of various kinds of fixative fluids, without injury, and also permitting of subsequent exact localization, the process re- quiring a minimum of time and space is, to the mind of the writer, of decided practical value in such work. This method is fully described in the text under the heading of "Technique." IV. Nerve and neuroglia cell counts have been alluded to no G. ALFRED LAWRENCE. above, but a few remarks upon method may be of value. The method of counting the same from photomicrographs of moderate magnification is not accurate, as cells may overlap or be arranged in dense groups or their images may not all be sufficiently distinct so as to differentiate them properly, especially does this apply to the neuroglia cells, which are very small and often closely aggre- gated. Photomicrographs magnified a thousand diameters or more, although showing all the cells visible, are much too limited in area. For these reasons the use of the ocular net-micrometer was found to be the best and most accurate for this work, using a stage micrometer to determine the relation of the ocular field to the actual size of the section. In this way the exact number of nerve and neuroglia cells can be determined for -any number of fields and an average obtained for any area, as was done in vari- ous plates in the brains employed in this work, as seen in Table II. As will be noted by referring to this latter, there is considerable variability in ihe number of nerve and neuroglia cells not only in different cortical regions but also from adjacent sections of the same region. The stain is seen to play an important role here in the resulting average number of neuroglia cells, methylene violet having a greater affinity for these cells than methylene blue. Sections stained by the latter cannot always be depended upon to show all the neuroglia cells. In comparing the normal paretic brain there is marked diminution of the nerve cells in the latter as compared to the former, whereas the neuroglia cells, making due allowance for variability, are somewhat increased in number in the paretic brain. V. The thickness of the layers is not constant in different parts of the same gyrus, nor even in different portions of a single transverse section of a gyrus, to say nothing of different regions of the cortex. In the same way there is greater or less variability in the shape and mechanical arrangement of each gyrus in con- trast to the other gyri making up the surface of the hemisphere and different parts of the same gyrus vary in this respect. This will be best observed by referring to the several plates of both Brains A and B, magnified 14 diam.eters, and of the various regions of the cortex. VI. After a quite extended perusal of the literature upon the DEMENTIA PARALYTICA. ill structure of the cortex as presented in the first portion of this article, the writer incHnes to the view of a three-layered type of cell arrangement in the cortex, as the type with, of course, varia- tions in special parts, as the cornu ammonis, for instance. This is shown in Table I, and brief is as follows: i, or superficial layer, containing- but few nerve cells, many neuroglia cells, and many chiefly tangential fibers. The first two elements only are seen with the Nissl stain, whereas the latter element is most conspicu- ous with Weigert's stain, and for this latter reason Ramon y Cajal designated it as the tangential fiber layer ; 2, or pyramidal cell layer, to reduce the layering of the cortex to its lowest terms, and including the small, large, and giant or Betz pyramidal cells all in this one layer ; 3, or spindle cell layer, including both the spindle cells which are in the majority and the less numerous irregular pol3^gonal cells. Below these three layers is the sub-cortical white medullary substance. VII. The study of the internal structure of the normal brain from a histological standpoint (Brain A) by the Nissl method shows four principal types of nerve cells : ( i ) The small rounded nerve cells of the first layer with or without one or more dendritic processes — rarely more than two, containing a rounded nucleus almost fillmg the body of the cell, this latter surrounded by a partial or complete narrow band of finely granular chromophilic substance. The neucleus contains a well marked neucleolus and slightl}' stained protoplasmic substance. These are co-called kar- yochrome nerve cells of Nissl's classification. (2) The pyramidal cells of the second layer, of which there are four varieties (a) the small pyramidal cells, (b) the large pyramidal cells, (c) cells in- termediate in size and structure between the large pyramidal cells and the typical giant pyramidal or "Betz" cells, and (d) the giant pyramidal or "Betz" cells. In the smaller pyramidal cells it is difficult to distinguish distinct chromophilic granules, but the chromatin is arranged in larger or smaller finely granular masses in various parts of the cell-bod}^ sometimes aggregated about the nucleus, at other times near the base or dendritic processes. The larger pyramidal cells, however, have the increasing amount of chromatic substance arranged in more or less- distinct larger and smaller chromophilic granules, and these arranged in a direction 112 G. ALFRED LAWRENCE. parallel to the surface of the cell-body. Still larger in size and more distinct in the arrangement of chromophilic granules in this general parallel manner are the intermediate variety of these pyramidal cells, which, although larger than the average pyramidal cell are considerably smaller than the typical Betz cell, and have a wider range of distribution not only in the vertical extent of the second layer of the cortex, but also in the different regions of the cortex, being found in the central, parietal, temporal, and occipital regions. Finally the largest in size and most distinct in structure, especially in the arrangement of the chromatic substance, are the giant' pyramidal or Betz cells, in which larger size, large distinct nucleus and nucleolus, and also large parallel arranged chro- mophilic granules are seen in the cell-body, and often extending far up into the dendritic processes. These are localized, for the most part, in the lower portion of the second layer in certain areas of the central convolution and the posterior portion of the superior frontal convolutions. These pyramidal cells as a whole can best be designated as stichochromc nerve cells of the somatochrome class in Nissl's classification, although the smaller pyramidal cells may simulate more the gryochrome nerve cells of this same class, owing to the indistinct arrangement of the chromatic -substance. (3) The spindle cells found in the third layer and containing a very large nucleus with well marked nucleolus. The nucleus is often so large that it seems disproportionate to the size of the latter. The chromatic substance here is finely granular and ar- ranged in irregular masses or heaps about the nucleus, and ex- tending into the base of the dendritic processes, these latter, usu- ally two in number and opposite, producing a bipolar condition. These cells are gryochrome nerve cells of the somatochrome class. (4) Finally irregular or polygonal nerve cells are found in the second and third layers. These cells are irregular in shape, with three or more dendritic processes, a large nucleus containing a well marked nucleolus. In the cell-body are irregular finely granular masses of chromatic substance similar to the spindle cells in this respect, so could fall in the same classification as gryo- chrome nerve cells of the somatochrome class. In the cerebellum, the Purkinje cells, with their chromatic substance more or less arranged in a network, are classified as arkychrome nerve cells of DEMENTIA PARALYTICA. II3 the soniatochronie class, whereas the small nerve cells of the granu- lar layer, with small nucleus, appear only partially surrounded by the cell-body, are classified as cytochrome nerve cells. The four types of cells above mentioned, as found in the cerebral cortex, were seen in all the regions of the external surface of the hemi- sphere studied. In addition to these cellular elements of the nerv- ous tissue the neuroglia cells of the interstitial tissue were every- where to be seen, and in the walls of the blood vessels the vascular cellular elements were also to be found. VIII. Previous investigators, in the study of the cerebral cor- tex in dementia paralytica by the use of the Nissl method, have noted the following pathological changes : Various stages of cell degeneration up to complete destruction of the same, consisting of diminution, disintegration, and vacuolization of the cell proto- plasm, all stages of chromatolysis up to complete disappearance of the chromatic substance, shrinkage with deformity of the con- tour of the cell-body, atrophy of the dendritic processes, various degrees of pigmentation and pigmentary deposits in the cell-body, also adjacent to blood vessels; shrinkage with diminution in size, irregularity, compression, vacuolization, and eccentricity of the nucleus with even extrusion of the same from the cell-body by the rupture of the cell wall, or complete sclerosis of the nucleus with homogeneous and tinged contents or crystalline deposits, nucleolus displaced to nuclear wall or indistinguishable or vacuolated, cal- careous deposits in the form of fine granules, crumbs, placques, or stalactitic masses intensely colored with methylene blue and found in the bodies of the sclerosed cells, part or whole of cell entirely bleached, complete necrosis of cells, reduction in number of nerve cells, thickening of pia with septa projecting into the cortex, granular crowding of variously stained granules, obscure layering of the cortex, multiplication of white corpuscles, proliferation of neuroglia cells, increase in and dilatation of capillaries and arteri- oles, with thickening of walls of same by encasement of latter with lymphatic corpuscles, and finally proliferation of interstitial net- work. The writer has observed all of these changes excepting the following: vacuolization of the cell protoplasm was not ob- served in the paretic material examined in this work, no pigment- ary deposits were observed outside of the nerve cell bodies, al- 1 14 G. ALFRED LAWRENCE. though varying amounts were found in many of the nerve cells. No vacuolization of the nucleus or extrusion of the same was found here, no crystalline or calcareous deposits were made out in any of the cells, no septa were observed penetrating from the thickened pia into the cortex, multiplication of white corpuscles was not observed, and proliferation of neuroglia cells as seen from the nerve and neuroglia cell counts as tabulated in Table 11. seems to have existed to but a slight extent in small localized places, as about some of the necrosed nerve cells. The writer does not mean to say that this may not occur in some cases, for on the contrary he is inclined to think it may occur under certain conditions, either localized or more general. Also no prolifera- tion of the interstitial network was observed here. About the nerve cells pericellular spaces of greater or less extent were ob- served in many cases. In some only a small portion of the cell- body, or a single dendritic process, was surrounded by a limited space ; in many, however, a large portion of all the cell-body was thus surrounded. Perivascular spaces were also observed of varying size and extent about many of the blood vessels of the cortex. Pigmentation, in addition to being present in many of the nerve cells of the first and second layers of the cortex in the central regions, was also observed in cells of these layers in the frontal region as well ; also in the parietal and temporal regions, but not in the occipital region. The pathological process here was most severe in the central and frontal regions, extending to a lesser extent, but still very marked, into the temporal and parietal regions, whereas the occipital region almost entirely escaped and appears practically normal. In the regions involved in this case the disease seems to be a chronic disease of the nerve cells with pigmentary degeneration and a necrosis of the cell-body, partial or complete, with accompanying involvement of the blood vessels. The relation of the vascular and cell changes to one another and the order of procedure in time is one that the writer believes re- quires much more extended investigation before it can be answered satisfactorily. In conclusion the writer gratefully acknowledges the kindly interest, suggestions, and assistance offered by Professor H. Fair- field Osborn, Professor Bashford Dean, Dr. Oliver S. Strong, and Dr. Edward Leaming, of Columbia University; Dr. Ira Van 9«nnari 1782 Vlcq d'Azyr 1786 Mockel 1612 Baillargar 1840 R« 1« Cosimon Typo Occipital Region Conmon Typo Occipital Region ConunQD Typo Occipital Region ConsnGi) Type Conme Kxtornal dray I Bxtomal Oray Kxtemal Gray I Sxtemal -. White I Layer We Rinde Oray I Layer Layer Gray I Layer Layer Oray I Layer Layer White 11 Layor External Oray II Layer Striae Exteme or in Lino of Baillarger Orauefi Srauei Sch: Weil ] ZwiscI Whito Layer «r II Line of Qonnari Whito Layer or II Lime of Ticq d'Azyr Intomal Sray III Internal aray III Intornal Oray III Uiddle Oray IT Layer Layer Layer Layer ■itriao V Srauei SnbstE Interne eelatl Schl stomal Oray VI Layer White Central Substance White Subs Sentral tance White Sobs Central tance White Centra] Substance Weiss a Subs Crisafulli, E. "Studio comparativo clmico istologico sulla paralisi generale progressiva." Ann. di Neurolog. 14, P- 255. Also: Ulteriore con- -;!^' ■"v;f" '^' ■-Sff" .==■.... -as- ;^™^ 'sa* B d?si - -a- .!»?.._. =5;- ■as" .rA -. -•■::f ;™=;;- ,;;£^- — ;!S- aif ^ "5; . : ^L .^:; iid^-^- »J3- 'T^ °';l;ls' '?:r '=;;;ir .„ °*sffi^ *"""' Z z. 3 r I T ■ :l, -i- "^."" ""'S™°' "*'»■■ »~:.;rs;r ~r]~" •issr X "" "sr ■■sr" -•ss- -i"jf.- sra" 5- 51 s. ~' ■ 3: "S! :,T ~ .KSr -S?"- "f" 3° "?•'» „15L. •S" ■>nS!" -S" "W "OS .?|::r.J Ir ,„ ■■311- SI 3, ( - srnl ■ .S. L!;0~:. f' Z ■si'.. ■Bi" ^„ "S" ..2lKr Iff" ■srs. "S" 11" w "ir 4. ,^,^^ sr «;•• ,^., Siiii" l "5 — "i:e^ -Si" .1,'.. "f" m: s ■■?"" ■■sa- -ffi- ffiw;. £ "°";r sS. t^lr '■","■,;"" S" sr £'■ ™ sr "t" "tr z £ 1: ins. -a sr 1! 2S?' ™i £r- "K.SS- -11 .™ •iK.S'- Sv- «&Ss= "~=™ "™^° "■-" ~"r: ^s:^ !rr:" ■"tiffiif _™~!_ .us:. lir~~ j?5. #j "— ■ Si. . .s. •IS. -■?~,_ JSs!. «^^ DEMENTIA PARAL YTICA. 1 1 5 Giesen, former Director of the New York State Pathological Insti- tute; Dr. H. T. 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"Anat- omic et physiologie du cerveau," 123, 117 pp., 35 pi. (1786.) Von Lenhossek, M. "Der feinere Bau des Nervensystems im Lichte neuesten Forschungen." 2te Aufl., Berlin (1895). "Ueber Nervenzellenstructuren." Vorhandl. d. Anat. gesellsch., Jena (1896), Bd. X, S. 15-21. EXPLANATION OF PLATES. Plate I. Fig. i. Brain A. Left hemisphere. Electrocuted case, nor- mal histologically. Plate I. Fig. 2. Brain A. Suture from point indicated by the figure I in Plate I. Fig. i. Section 6 2-3 microns in thickness stained with methylene blue and magnified 14 diameters. Plate II. Fig. 3. Brain A. First frontal conv. Strip a of Plate I, Fig. 2, magnified 100 diameters. Plate II. Fig. 4. Brain A. First frontal conv. Cell G. of Plate II, Fig. 3 magnified 1400 diameters. Plate II. Fig. 5. Brain A. First frontal conv. Cell H of Plate II, Fig. 3 magnified 1,400 diameters. Plate III. Fig. 6. Brain A. First frontal conv. Group of spindle cells / of third layer of cortex shown at / in Plate II, Fig. 3 magnified 1,400 diameters. Plate III. Fig. 7. Brain A. Ant. cent, conv. Upper third, taken from point indicated by the figure 2 in Plate I., Fig. i. Section 10 microns in thickness stained with methylene violet, and magnified 14 diameters. Plate III. Fig. 8. Brain A. Ant. cent. conv. Upper third. Strip a of Plate III, Fig. 7 magnified 100 diameters. Plate IV. Fig. 9. Brain A. Ant. cent. conv. Uppe- third. Section DEMENTIA PARALYTICA. II9 frt m same block and adjacent to that shown in Plate III, Fig. 7. Section 10 microns in thickness, stained with methylene blue, and magnified 14 diameters. Plate IV. Fig. 10. Brain A. Ant. cent. conv. Upper third. Strip a of Plate IV, Fig. 9, magnified ico diameters. Plate IV. Fig. 11. Brain A. Ant. cent. conv. Upper third. Sec- tion taken from same block and adjacent to that shown in Plate IV, Fig. 9. Section 10 microns in thickness, stained with methylene blue, and magni- fied 14 diameters. Plate IV. Fig. 12. Brain A. Ant. cent. conv. Upper third. Giant pyramidal cell from lower portion of second layer of cortex from section adjacent to that shown in Plate III, Fig. 7. Section 10 microns in thickness, stained with methylene violet and magnified 1,400 diameters. Plate V. Fig. 13. Brain A. Ant. cent. conv. Upper third. Portion o of Plate IV, Fig. 11, magnified 825 diameters. Plate V. Fig. 14. Brain A. Ant. cent. conv. Upper third. Two giant pyramidal cells from lower portion of second layer of cortex from section adjacent to that shown in Plate IV, Fig. 9. Section 10 microns in thickness, stained with methylene blue and magnified 1,400 diameters. Plate V. Fig. 15. Giant pyramidal cell from Ant. cent. conv. Upper third, lower part of second layer from approximately the same region as the cells shown in Plate V, Fig. 14, and stained with methylene blue. Sec- tion 10 microns in thickness, and magnified 1,400 diameters. Plate VI. Fig. 16. Brain A. Ant. cent. conv. Lower third, taken from point indicated by the figure 4 in Plate I, Fig. i. Section 10 microns in thickness, stained with methylene violet, and magnified 10 diameters. Plate VI. Fig. 17. Brain A. Ant. cent. conv. Lower third. Strip a of Plate VI, Fig. 16, magnified 100 diameters. Plate VI. Fig. 18. Brain A. Post. cent. conv. Middle third. Sec- tion taken from the point indicated by the figure 5 in Plate I, Fig. i. Sec- tion 6 2-3 microns in thickness, stained with methylene blue, and magni- fied 10 diameters. Plate VII. Fig. 19. Brain A. Post. cent. conv. Middle third, upper portion. Strip a of Plate VI, Fig. 18, magnified 100 diameters showing first and second layers and upper portion only of third layer. Plate VII. Fig. 20. Brain A. Supra-marginal conv. of parietal re- gion taken from point indicated by the figure 7 in Plate I, Fig. i. Sec- tion 6 2-'j microns in thickness, stained with methylene violet, and magni- fied 14 diameters. Plate VII. Fig. 21. Brain A. Supra-marginal conv. of parietal re- gion. Strip a of Plate VII, Fig. 20, magnified 100 diameters. Plate VIII. Fig. 22. Brain A. First temp. conv. taken from point indicated by the figure 6 in Plate I, Fig. i. Section 6 2-3 microns in thick- ness, stained with methylene blue, and magnified 14 diameters. Plate VIII. Fig. 23. Brain A. First temp. conv. Strip a of Plate VIII, Fig. 22, magnified 100 diameters. Plate VIII. Fig. 24. Brain A. Occipital conv. taken from point indi- cated by the figure 8 in Plate I, Fig. i. Section 6 2-3 microns in thickness, stained with methylene violet and magnified 14 diameters. Plate IX. Fig. 25. Brain A. Occipital conv. Strip a of Plate VIII, Fig. 24, magnified 100 diameters. Plate IX. Fig. 26. Brain A. Large pyramidal cells from layer of large pyramidal cells of the hippocampus major or cornu ammonis. Sec- tion 6 2-3 microns in thickness, stained with methylene violet, and mag- nified 1,400 diameters. Plate IX. Fig. 27. Brain A. Purkinje and granular cells from cortex Date Due i. 1 1 1 i f) RC381 U3 Lavtfrence