The pressure of the cerebrospinal fluid is from three to five times as great as in normal individuals. The albumen content of the fluid is increased about six times (Kraepelin). The increase in the globulin content has been very frequently referred to in the literature of general paresis. Kraepelin states that it also occurs in tabes, syphilis, brain abscess, occasional cases of extra medullary tumors, multiple sclerosis and in some infectious diseases. He attaches a great deal of importance to the increase in the cellular elements of the spinal fluid. "Cases with repeated normal findings are so rare that the correctness of the diagnosis may be justly doubted." The Wassermann findings no longer require comment. The colloidal gold test of Lange is equally well known. Nowhere else in psychiatric procedure does the laboratory render such valuable diagnostic assistance as is the rule in cases of general paresis. A positive Wassermann reaction in the spinal fluid, the presence of an increase in the albumen and globulin content, with a marked lymphocytosis in the cerebrospinal fluid and a positive gold test, is quite sufficient evidence on which to base a definite diagnosis. The results of an examination of the spinal fluid for diagnostic purposes at the time of autopsy are highly unreliable. An increase in the cell count, which may be misleading, is found in the spinal fluid of non-paretics in all cases after death. The number of cells depends entirely on the time of examination. It is not at all unusual to find from one to three hundred per cubic millimeter when a count is made from twenty-four to forty-eight hours after the death of the patient.[176] Another interesting fact is that the presence of sugar always shown by Fehling's solution during life cannot be demonstrated postmortem, at least after the lapse of a few hours.[177] The significance of this change is not clear. Nor is the increase in the globulin content of the spinal fluid, when taken alone, pathognomonic of either general paresis or syphilis, as was pointed out in 1909.[178] One of the most elaborate studies ever made of the spinal fluid, that of F. W. Mott, shows that this increase is due to degenerative processes of the nervous system which may be due to a variety of causes.[179]
In no other psychosis do we find such clear-cut pathological findings at autopsy as are readily demonstrable in general paresis. We are very largely indebted to the exhaustive researches of Nissl and Alzheimer, (1904)[180] for our information on this subject. Macroscopically adhesions of the dura to the calvarium and of the pia to the cortical substance are quite common. Opacities of the meninges are practically always present. Pachymeningitis hemorrhagica, externa or interna, is common, often with the formation of extensive hemorrhagic membranes. Ependymitis may be readily observed in the floor of the fourth and lateral ventricles. There is usually a reduction in the general brain weight, with atrophy of various parts, usually one side or the other of the cerebrum. The sulci are widened and the frontal lobes are often noticeably smaller in size. Less frequently the temporal, parietal or occipital regions are affected. Often there are localized foci of atrophy with cyst formation. The ventricles are frequently widely dilated, with an increase of cerebrospinal fluid.
Microscopic examination always shows a more or less diffuse leptomeningitis with a markedly thickened pia infiltrated with lymphocytes and plasma cells. In the superficial layers of the cortex there is a neuroglia proliferation with characteristic "spider cells." There is an obvious disturbance of the normal layering of the cortex which is very striking. The adventitia of the vascular walls shows an extensive infiltration by lymphocytes and particularly by plasma cells which are often very numerous. Rod cells or "stäbchenzellen" as described by Alzheimer are very noticeable as are also satellite cells or free nuclei. The neurones are often diminished in number and frequently show the "acute" or "grave" alterations described by Nissl, as well as shrinkage, sclerosis, pigmentary deposits, vacuolization, etc. The characteristic axonal alteration originally described by Turner as occurring in central neuritis is sometimes observed. Degeneration of the nerve fibres may be brought out by proper staining processes. Intimal thickening of the vessel walls and a capillary proliferation or budding should also be mentioned. Foci of softening sometimes are to be found in the cortex. The presence of occasional gummata is now conceded, although formerly denied by Alzheimer. The changes in the cerebellum are not essentially different, but are usually not so conspicuous. In the cord a pachymeningitis and leptomeningitis are usually present, as well as the vascular changes described above. The important findings, however, are the degeneration of the posterior columns and lateral tracts, or mixed forms involving both of these. Owing doubtless to defects in staining technique, the demonstration of the treponema is difficult and unsatisfactory. It must be admitted that some of the above histopathological changes in themselves, the cell alterations, for instance, do not, when considered alone, prove the existence of general paresis. The whole picture as shown by the microscope, however, leaves no room for argument. The postmortem diagnosis is absolutely conclusive.
A consideration of the subject of general paresis without some reference to the juvenile form, first described by Clouston in 1877, would be manifestly incomplete. Although this term may be applied to a type of the disease acquired in childhood, it is usually used as referring to hereditary syphilis. Symptoms generally appear at or before the age of puberty. As a general rule the child is more or less defective mentally from birth, although this is not always true. Ordinarily the course of the disease is one of progressive deterioration, with an occasional episode of excitement. Convulsive seizures are frequent, and contractures are often noted. These cases are likely to be mistaken for idiocy and overlooked. The duration usually extends over a period of several years. The pathology is practically the same as that of the adult form of the disease. Almost invariably a positive Wassermann is obtained on examining the blood of the parents. It is equally interesting to note that the children of syphilitic parents often show a positive Wassermann reaction without any evidence of paresis, or at least for some time before it develops.
The only question remaining at this time is whether general paresis and cerebral syphilis are separate and distinct disease entities. For many years this was held to be the case. Certainly gummata and other syphilitic processes are to be found in the brain where there is no such pathological picture as characterizes general paresis. In any event the latter must be recognized as a very well defined form of syphilis of the nervous system. In view of the very definite etiology, symptomatology and pathology of general paresis, the various clinical differentiations of Kraepelin and other writers are looked upon by many as not being of very great importance. In any and all clinical types, however described, we are unquestionably dealing with the same sharply circumscribed disease process. This subject is one of academic interest only.
The American Psychiatric Association in its classification of psychoses made no attempt to differentiate types. For purposes of statistical study the following suggestions appear in the manual:—
"The range of symptoms encountered in general paralysis is too great to be reviewed here in detail. As to mental symptoms, most stress should be laid on the early changes in disposition and character, judgment defects, difficulty about time relations and discrepancies in statements, forgetfulness and later on a diffuse memory impairment. Cases with marked grandiose trends are less likely to be overlooked than cases with depressions, paranoid ideas, alcoholic-like episodes, etc.
"Mistakes of diagnosis are most apt to be made in those cases having in the early stages pronounced psychotic symptoms and relatively slight defect symptoms, or in cases with few definite physical signs. Lumbar puncture should always be made if there is any doubt about the diagnosis. A Wassermann examination of the blood alone is not sufficient as this does not tell us whether or not the central nervous system is involved."
A study of the statistics of the thirteen New York state hospitals in the "pre-Wassermann" days and before we had acquired our present accurate knowledge of the pathology of general paresis shows that there were 84,152 admissions during the fourteen years ending on October 1, 1888. Of this number 5,697, or 6.76 per cent, were diagnosed as general paresis. In the same hospitals, from 1912 to 1919 inclusive, 6,374 cases of general paresis were reported,—12.71 per cent of the 49,640 first admissions. During the years 1918 and 1919 that disease constituted 13.19 per cent of all admissions. This apparent increase undoubtedly is due to the fact that modern methods have materially improved facilities for accuracy of diagnosis. It is not at all probable that the admission rate has doubled during the period in question for any other reason. In the Massachusetts hospitals during the year 1919, only 7.90 per cent of the first admissions were diagnosed as general paresis. There was, however, an unusually high rate of cerebral syphilis. In twenty-one hospitals in fourteen other states, reports based on the present classification show a total of 18,336 admissions, mostly in 1917, 1918 and 1919. Of this number 1,233, or 6.72 per cent, were cases of general paresis. Thus, in a total of 70,987 admissions based on the present classification of psychoses as used by the American Psychiatric Association there were 7,845 cases of general paresis in all,—a percentage of 11.05. It is, of course, a well-known fact that general paresis is largely a psychosis of densely populated communities. This is readily shown by the New York statistics. During the year 1919, 9.6 per cent of the admissions at Binghamton were cases of general paresis. The percentage at Buffalo was 15.5; at Gowanda, 17.3; Hudson River (Poughkeepsie), 9.0; at Middletown, 3.7; Rochester, 8.6; St. Lawrence (Ogdensburg), 9.2; Utica, 10.1; and Willard, 13. In the institutions caring for the insane of New York City 16.3 per cent were reported at the Manhattan State Hospital, 13.5 per cent at Kings Park, and 14.7 per cent at Central Islip. The percentage at the other institutions, except at Buffalo and Gowanda, which care almost entirely for residents of the city of Buffalo, is determined very largely by the transfer of patients from the hospitals of New York City and the metropolitan district. General paresis constitutes approximately ten per cent of the commitments in the city of Boston. On the other hand, we find an admission rate of 2.3 per cent for the Vermont State Hospital (1917 and 1918), 1.5 per cent for the Central State Hospital, Virginia (1919), 2.5 per cent for the Columbia State Hospital (South Carolina) (1918), and a period of two years at the Spencer State Hospital, West Virginia (1917 and 1918) with 262 admissions and no cases of general paresis. Of 2,895 first admissions reported by the Ohio state hospitals for the year ending June 30, 1920, 438, or 15.12 per cent, were cases of general paresis. It is interesting, at least, to note that Letelier[181] showed an admission rate for this disease of seven per cent at the Casa de Orates at Santiago, Chili.