Part 7

Thus, =mentally=, the patient showed elation, grandiosity (millions of dollars to give away), intellectual weakness, disorder of memory, lack of judgment, rambling talk, speech defect, omission of letters in writing and spelling.

=Neurologically=, there was tremor of the lips, slight irregularity of the pupils, which however reacted well, and lively knee-jerks.

Mr. Twist had sought advice at our out-patient department in his thirty-third year. The records show that at that time he was somewhat depressed, and his speech was even then, according to his own statement, stammering. However, we found the W. R. at that time to be negative in the blood serum. It appeared that his mother had died of consumption; his father was said to have committed suicide. A brother had once recovered from an attack of depression, presumably an attack of manic-depressive psychosis. Accordingly, we thought at the time that the case was probably one of manic-depressive psychosis. Moreover, our routine serum W. R. failed to indicate any syphilitic process. As for the so-called stammering of speech, this appeared to be a matter of the patient’s own recollection rather than of our observation. In any event, the patient had gone into the country and appears to have entirely recovered; falling, again, however, into mental difficulties after a short period, and finally arriving at the hospital in the above-mentioned classical condition.

The W. R. in the blood serum proved again negative. The test was repeated a number of times; also, after salvarsan had been given. The salvarsan did not act provocatively, and the blood serum has remained consistently negative.

In cases of syphilis the W. R. is at times negative. Swift claims that in such cases an injection of salvarsan will often produce a positive W. R. if the blood is tested on several days following the injection.

The spinal fluid, however, did show a positive W. R. as well as a gold sol reaction of a “paretic” type. There were at the first examination 194 cells per cmm., there was a moderate excess of albumin, and a positive globulin test. In short, there was no question of any other diagnosis than GENERAL PARESIS.

1. How can the negative W. R. of the blood serum be explained? It is difficult or impossible to explain this. Figures differ as to the percentage of cases of general paresis with negative blood serum; perhaps 3 to 5% of these cases yield a negative serum W. R.

It is important to note the long preparetic period: at least a year and a half. Could our diagnostic methods be sharpened a trifle, such cases as these could be obtained early in this preparetic period and it might then be safe to promise good therapeutic results.

2. What is the nature of the preparesis of Dana? When Dana’s brief paper on preparesis was written, there was of course hardly any idea that cases of paretic neurosyphilis could be cured or would recover, except possibly vanishingly few _curiosa_ about which there would always rage a diagnostic question. Accordingly, Dana, having found certain cases that seemed to him to have early signs of paresis but had apparently been cured by treatment, proposed to call them cases of preparesis. His idea was that he would thereby not offend those who held that general paresis was theoretically a fatal disease. With modern work and the display of more and more atypical cases of neurosyphilis, and the observation of relatively numerous cures or remissions under treatment, the designation of preparesis for a separate entity, or even for a sub-form of neurosyphilis, becomes superfluous.

3. What is the percentage of cases of paretic neurosyphilis that show a negative serum W. R.? Among the best figures are those of Müller, who found that of 386 examples of paretic neurosyphilis, 379 showed all reactions positive, or 98.5%.

4. What is the meaning and value of the so-called provocative salvarsan injection? In practice, there may be a series of negative W. R.’s in the blood serum before a positive reaction is finally obtained, owing to technical difficulties or biological peculiarities. Where intensive work is being done upon the neurosyphilis problem, it is beyond question desirable to make the W. R. test upon at least three separate samples of blood drawn at intervals, for the second or third test may prove positive. This situation makes the interpretation of the so-called provocative salvarsan injection exceedingly doubtful; that is, the reaction might have been positive on repetition without the injection of salvarsan. The present case, as above stated, failed to yield a serum W. R. even after repeated tests and the “provocative.”

5. What is the significance of the irregular pupils in this group? Paretic neurosyphilis shows inequality of the pupils in a high per cent of cases. Irregularity of outline of the pupils is commonly thought to be an important sign and to suggest neurosyphilis. It is true that many cases of pupillary irregularity are syphilitic, but the sign is of little or no differential value since congenital malformations and relics of old injuries and adhesions may produce effects identical with those of neurosyphilis.

=DIFFUSE (that is, meningovasculoparenchymatous[5]) NEUROSYPHILIS is typically associated with six positive tests (serum Wassermann reaction, fluid Wassermann reaction, spinal fluid gold sol reaction, pleocytosis, positive globulin, excessive albumin); but one or more, and frequently several, of these tests are likely to run mild as compared with the tests in PARETIC NEUROSYPHILIS (“general paresis”). The clinical course of the diffuse (and especially the meningovascular) cases is likely to be protracted, with a good prognosis as to life (barring fatal vascular insults).=

=Case 14.= We shall present the case of John Jackson, a surveyor, 31 years of age, suffering from a left hemiplegia, with this in mind: To exhibit difficulties in diagnosis in the presence of an embarrassment of symptomatic riches.

The patient arrived at the hospital, in the first place, because he had been threatening a woman who lived next door to him. He believed that this neighbor had been talking about him and circulating reports against him. Excited by these ideas, he had threatened to cut her throat.

Now the occurrence of hemiplegia in adult life before the approach of senium is always suspicious of syphilis, and this suspicion we naturally entertained from the beginning. However, there was upon the scalp a crooked linear furrow about six inches long, running from the vertex to the right parietal eminence. Another furrow about an inch long was present upon the forehead. These furrows appeared to be of a bony nature and were not tender. There was evidence of an old decompression operation on the right side of the head; there were also large scars on both sides of the neck, evidently the result of old operations; and there were numerous palpable glands—the largest about the size of a lima bean—all firm and not tender.

It seems that at the age of eight, according to the patient’s mother, Jackson had received a head injury and had remained unconscious for three weeks. Upon recovery, he had to relearn both to walk and to talk; however, he was able to begin school where he left off. He became more nervous and irritable after the accident than previously. Nothing further had developed until, at about 25 years of age, a tubercle was discovered in his eye (the right pupil was smaller than the left, reacting more slowly; right iris bound down by adhesions, with white opacity of anterior chamber). For two years, 25 to 27, the patient was under medical treatment for tuberculosis, and at the conclusion of this period numerous glands were removed from the neck and diagnosticated tuberculous. However, the neck did not heal and he carried bandages upon it for two years.

At 28, the patient’s mother described the occurrence of a slight shock, with head retraction, for a minute or two, and inability to speak. Thereafter there had been five or six similar attacks, less severe, and without loss of speech. The attacks were never accompanied by convulsive movements. Then occurred a paralytic stroke, leaving the patient with a left hemiplegia, which had somewhat improved. Mentally, the patient had gone down hill, becoming less alert and more apathetic, and to some extent amnestic. One had to consider, accordingly, the somewhat doubtful possibility of post-traumatic and post-operative conditions, and the question of tuberculosis (possibly errors in diagnosis; the lungs showed no evidence of tuberculosis).

=Physically,= the signs of a left hemiplegia were appropriate. Spasticity on the left side was found; there were Babinski, Gordon, Oppenheim reflexes and ankle clonus on the left side (all absent on the right). Speech defect was present. =Mentally,= aside from the delusions noted at the beginning of our analysis, a striking feature was the patient’s childishness. While reciting delusions, the patient was overactive and evinced a somewhat childish interest. Arithmetically, Jackson had preserved a fair ability but his apathy and lack of interest interfered with tests, and possibly also with the exercise of memory. As above noted, we were compelled to maintain the suspicion of syphilis throughout despite the attractive hypotheses of traumatic and post-decompressive effects and cerebral tuberculosis. A history of the acquisition of syphilis an unknown number of years before admission entered to strengthen the suspicion of the syphilitic nature of the mental symptoms.

TYPICAL LABORATORY FINDINGS IN NEUROSYPHILIS (NONNE, 1915) ─────────────┬─────────┬─────────┬─────────┬───────────────┬─────────── DIAGNOSIS │ W. R., │ W. R. │ SPINAL │ PHASE I, │PLEOCYTOSIS │ BLOOD │0.22 CC. │ FLUID, │ GLOBULIN │ │ SERUM │ BLOOD │ 1.0 CC. │ │ │ │ SERUM │ │ │ ─────────────┼─────────┼─────────┼─────────┼───────────────┼─────────── PARESIS OR │POSITIVE │POSITIVE,│POSITIVE,│POSITIVE, │POSITIVE, TABOPARESIS│ IN │ 85–90% │ 100% │ 95–100% │ ABOUT 95% │ ALMOST │ │ │ │ │ 100% │ │ │ │ │ │ │ │ │ TABES (not │POSITIVE,│POSITIVE,│POSITIVE,│POSITIVE, │POSITIVE, combined │ 60–70% │ 20% │ 100% │ 90–95% │ 90% with │ │ │ │ │ paresis) │ │ │ │ │ │ │ │ │ │ CEREBROSPINAL│POSITIVE,│POSITIVE,│POSITIVE │POSITIVE almost│POSITIVE SYPHILIS │ 70–80% │ 20–30% │ ALMOST │ always; │ ALMOST │ │ │ ALWAYS │ NEGATIVE only│ ALWAYS │ │ │ │ EXCEPTIONALLY│ ─────────────┴─────────┴─────────┴─────────┴───────────────┴─────────── CHART 8

The W. R. proved positive in blood and spinal fluid. The gold sol reaction was of the syphilitic type; 37 cells were found per cmm.; there was a slight amount of globulin and a slight excess of albumin.

We made a diagnosis of CEREBROSPINAL SYPHILIS rather than general paresis on account of, first, the slow course of the disease; second, the vascular type of the cerebral insult, hardly typical of paresis; and third, the mild spinal fluid reaction. Treatment will hardly cure the hemiplegia, at least so far as restoration of cerebral tissues lost in the insult is concerned. We were perhaps entitled to consider that, as in the cases of Petrofski (17), O’Neil (19), Robinson (45), the meningitic process could be arrested. Unfortunately, our treatment of 20 injections of salvarsan over a period of 10 weeks, followed by a number of months of bi-weekly injections of mercury salicylate, proved incapable of making any change in the mental and physical picture or in the laboratory findings.

1. Can we explain the apparently poor reaction to treatment of the cerebrospinal syphilis in the case of Jackson by supposing a more deep-seated involvement than the meningovascular involvement indicated by the hemiplegia and the signs in the fluid? Autopsied cases in our experience show focal parenchymatous involvements that have not caused obvious clinical symptoms at any time during the course of the disease. These symptomatically silent lesions may have been present.

2. What is the comparative prognostic value of seizures in paretic neurosyphilis and in such a meningovascular case as that of Jackson? Paretic seizures are often and indeed characteristically recovered from. Moreover, autopsies in paretic neurosyphilis characteristically show no gross focal destructive lesions to correspond with the seizures. The paretic seizures are apparently more irritative than paralytic. However, the seizures of the meningovascular group of neurosyphilis are also, though less commonly, recovered from, so that the differential diagnosis on the basis of the outcome of seizures is not safe. Rarely paretic neurosyphilis itself also develops seizures from which no recovery is made.

3. What is the relation of neuropathic heredity to neurosyphilis? The family history of John Jackson is undoubtedly poor, since his father died of diabetes and a paternal uncle was insane; and on the mother’s side, the grandmother died of tuberculosis and an aunt died insane. This general question was more interesting in the days before the syphilitic nature of general paresis and of allied diseases was known. However, we may still hold perhaps that not only syphilis but also various intoxications, especially alcoholism, do flourish upon a neuropathic soil. This question, like that of Krafft-Ebing’s celebrated claim of the relation between syphilization and civilization, needs revision in the light of more extensive applications of the W. R. in larger and larger groups of persons under various community conditions.

=The SIX TESTS (serum Wassermann reaction, fluid Wassermann reaction, pleocytosis, gold sol reaction, globulin, excess albumin) are likely to run STRONGER in PARETIC NEUROSYPHILIS (“general paresis”) than in DIFFUSE (especially meningovascular) NEUROSYPHILIS; in particular, the gold sol reaction is likely to prove “paretic” rather than “syphilitic.” The clinical course of paretic neurosyphilis (“general paresis”) is likely to terminate in death within a few years.=

=Case 15.= Pietro Martiro was a well developed and nourished man, 30 years of age, who had been doing erratic things and acting peculiarly for a few weeks before entering the hospital. In the hospital, Martiro proved to be very excitable and given to violence. He had marked delusions of grandeur, saying he was worth many millions of dollars, was the greatest singer in the world, the greatest athlete in the world, and the like.

=Physically=, there was no disorder except overactivity of some reflexes. The diagnosis of GENERAL PARESIS offered no difficulties, and it was confirmed by the laboratory tests (positive serum and fluid W. R., “paretic” gold sol reaction, 42 cells per cmm., an excess of albumin, and a positive globulin test).

=Treatment=: The perfect physique of this case and the extremely brief clinical duration (a few weeks) would naturally suggest a probably favorable outcome. However, cases with marked delusions of grandeur have very frequently proved to be cases with extensive brain tissue loss as shown in certain studies with Danvers material.

In any event, the treatment in this case proved unavailing. Enormous doses of salvarsan, twice a week, aided by mercury and potassium iodid, were given. Although other cases had been helped by such intensive treatment, Martiro went steadily downhill, nor was there the slightest diminution in the intensity of any of the spinal fluid reactions. After 50 injections of salvarsan over a period of 30 weeks without improvement, treatment was discontinued. A few months later, the patient died.

=PARETIC NEUROSYPHILIS (GENERAL PARESIS)=

=PHYSICAL SYMPTOMS=

EARLY HEADACHE VISUAL DISORDER HYPALGESIA ADIADOCHOKINESIS ATAXIA NASOLABIAL FLATTENING VOCAL CHANGE SPEECH DISORDER WRITING DISORDER LOSS OF MANUAL DEXTERITY PUPILLARY CHANGES REFLEX CHANGES SEIZURES LATE: PARALYSIS, CONTRACTURE

CHART 9

=PARETIC NEUROSYPHILIS (GENERAL PARESIS)=

=MENTAL SYMPTOMS=

INTAKE IMPAIRED CONSCIOUSNESS CLOUDED FATIGUABILITY INCREASED HALLUCINOSIS RARE AMNESIA—RECENT! CHRONOLOGY AND STORAGE IMPAIRED. FABULATION OVER-SUGGESTIBILITY JUDGMENT IMPAIRED FANTASTIC DELUSIONS INSIGHT INTO ILLNESS NIL EARLY IRRITABILITY OR HEBETUDE QUICK SHIFTING EMOTION CHARACTER CHANGE CONDUCT SLUMP

CHART 10

1. What is the duration of paretic neurosyphilis (“general paresis”)? If we omit the doubtful, early, and prodromal stages and count the beginning of the disease with the occurrence of definite symptoms, we find (Kraepelin) that almost half the patients with pronounced paretic signs die within the first two years of their disease. Kraepelin’s observations upon 244 cases are as follows:

Year: 1 2 3 4 5 6 7 8 9 10 14 Cases: 51 63 52 41 22 4 5 2 2 1 1

The average duration of the disease in months has been calculated as varying from 24 to 32 months. Juvenile paresis runs a slower and more insidious course. The duration of paresis, according to many observers, diminishes with the increasing age of the patient. It is now held that a combination of tabes with paresis does not prolong the duration of the paresis. As noted above in the discussion of Case Harrison (9), our conceptions of the characteristic duration of paretic neurosyphilis must alter with the increase of our knowledge due to the early application of laboratory tests.

2. What is the significance of the term _general paresis_? The case of Martiro is, of course, a good instance to show that the term is sometimes a misnomer. The characteristic generalized motor incapacity denoted by the term _general paresis_ is shown in patients in the institutions for the chronic insane in their last few months of life. The term _paresis_ is perhaps to be preferred to the term _paralysis_ because the paralysis is not complete but partial; but perhaps the best reason is that the word _paresis_ is a shorter word. When the mental side is to be emphasized, the term _paralytic dementia_ is employed. In this book we have used the term _paretic neurosyphilis_ to mean a more precise statement of the etiology of general paresis (general paralysis, paralytic dementia). The lay term, _softening of the brain_, like the terms _metasyphilis_ and _parasyphilis_ is in the present phase of our knowledge to be eschewed.

3. If this fatal case be typical of general paresis (for more favorable results, see Part V), what is the toll of deaths from this disease in the community at large? A striking statement may be quoted from Dr. Thomas W. Salmon’s “Analysis of General Paralysis as a Public Health Problem:”

“With the information in our possession at the present time, we are able to state that not fewer than 1000 persons in whom general paralysis is recognized die in New York State every year. Let us compare this with the lives lost from some other important preventable diseases. It means that _one in nine_ of the 6909 men who died between the ages of 40 and 60 in New York last year died from recognized general paralysis and that _one in thirty_ of the 5299 women who died in the same age-period died from this disease.

“The number of deaths from general paralysis in New York last year about equalled the number of deaths from typhoid fever. The following table gives the number of deaths due to the ten most important specific infectious diseases. Of course, deaths in measles, typhoid fever and scarlet fever will be found also under the names of some of the complications of these diseases, but it should be remembered that these primary diseases are not invariably fatal as general paralysis is. Many of the patients with measles who died from bronchopneumonia would have recovered but for this complication, while the paretics with bronchopneumonia would have died even if this complication had not arisen. No attempt is being made to compare the _prevalence_ of general paralysis with that of other diseases—we are trying only to estimate its share in the _mortality_.

“1. Tuberculosis (all forms) 16,133 2. Pneumonia 9,302 3. Bronchopneumonia 7,217 4. Diphtheria and croup 1,854 5. Influenza 1,381 6. Measles 1,071 7. Typhoid Fever 1,018 _General paralysis (recognized)_ 1,000 8. Scarlet fever 837 9. Whooping cough 818 10. Syphilis 782”

=PARETIC NEUROSYPHILIS (GENERAL PARESIS)=

=CHARACTERISTICS=

AMNESIA QUICK SHIFTING EMOTIONS CHARACTER CHANGE CONDUCT SLUMP NERVOUS DISORDERS SPEECH DISORDERS PUPILLARY CHANGES REFLEX CHANGES SEIZURES CEREBROSPINAL FLUID PICTURE

CHART 11

=SYPHILITIC PSYCHOSES=

SYPHILITIC NEURASTHENIA GUMMA SYPHILITIC PSEUDOPARESIS APOPLECTIC CEREBRAL SYPHILIS SYPHILITIC EPILEPSY SYPHILITIC PARANOIA TABETIC PSYCHOSIS HEREDITARY PARESIS

KRAEPELIN, 1910

CHART 12