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INTRASPINOUS TREATMENT (SWIFT-ELLIS) OF GENERAL PARALYSIS: A PRELIMINARY NOTE ON FOUR CASES TREATED BY THIS METHOD.
1103 in females of this type exists in the virgin condition across the mouth of the utero-vaginal " canal wherever this opens into a uro-genital sinus." Just as the labia minora are concealed in these animals, the hymen itself lies deep within the female passages, and so
hymen
FIG. 13.
observation. Nevertheless, all the conditions that are characteristic of the females of Type A could be reproduced simply by everting the vulva of Type B. (See Fig. 13.) Between this vulval orifice, surrounded byitslabiamajora, and the anus a bridge of tissue exists which constitutes the perineum, but the anatomical basis of this perineum is quite distinct in these animals. In Type A the perineum consists of the extroverted summit of the cloaca, but in females of Type B it is composed of the d cloacal margins that have met and united in front of the
frequently
escapes
anus.
W’e have already seen that in the male of this type the genital tubercle may be so completely concealed, and the of and end Lower vagina uro-genital sinus (vulva) sheath be so short, that the of a young pig. Note the likeness to the female may concealed hymen and One other labia minora. V, Vagina. be very great. H, Hymen. F, erethral condition remains to be conopening. LM, Labia minora. sidered. Females of Type A c, Clitoris. have already been described in which the genital tubercle approaches to a masculine degree of development, so much so that in some Primates it again becomes a urinary canal by the closure and union of the labia minora. Similarly in females of Type B these approximations to the male condition occur, and in some instances are far more profound than anything previously described. In some females of Type B it is not only the urinary, but even the genital canal, that is closed in and carried to the tip of the genital tubercle ; in this way the male and female condition becomes exactly similar. In some animals this condition is only temporary; in some, however, it is apparently permanent. [The condition present in the mole, the spotted hyaena, the South American hare, and some other animals was then
described.] UNIVERSITY
COLLEGE, LONDON.-The
report
of this College of the University of London for the year ending February, 1914, which has just been issued, shows that the number of students attending during the session 1912-13 was 2083 ; of these, 137 attended the department of the faculty of medical sciences. For the year ending August 31st, 1913, the total revenue of the College from all sources amounted to .S.66,694 2s. 8d., being an excess of expenditure over income of .8173 10s. 4d. Among the new buildings that are in progress are a large block for the new chemical laboratories and the building for the purpose of housing the department of applied statistics and eugenics, including the biometric and Galton laboratories. These buildings, however, cannot be completed until adequate funds are forthcoming. The total at present needed to complete the most pressing works in hand is .658.262, of which £28,652 are required for the new chemical laboratories. A special committee, with Prince Arthur of Connaught as president and the Hon. Rupert Guinness as treasurer, is occupied in the task of raising these funds.
INTRASPINOUS TREATMENT (SWIFTELLIS) OF GENERAL PARALYSIS: A PRELIMINARY NOTE ON FOUR CASES TREATED BY THIS METHOD. BY EDWARD MAPOTHER, M.D. LOND.,
F.R.C.S. ENG.,
AND
THOMAS BEATON, ASSISTANT MEDICAL
M.D., B.S. LOND.,
OFFICERS, LONDON COUNTY ASYLUM, LONG GROVE, EPSOM.
SINCE the description by Swift and Ellis at a meeting of the New York Neurological Society in April, 1913, of a new mode of treatment for parasyphilitic diseases of the nervous system by the injection into the spinal subarachnoid space of
salvarsanised serum, a considerable number of such have been treated by this method in America,1 but relatively few have been recorded in this country. The presence of the spirochaeta pallida can be demonstrated post mortem in a majority of cases of so-called parasyphilitic diseases of the nervous system, it has been cultivated from the brain tissue of the living general paralytic, and the rabbit has been infected by means These of the serum of the general paralytic. findings indicate that general paralysis is, at any rate in the majority of cases, a true syphilitic process depending upon the presence and activity of the organism itself. The difference between the course of general paralysis and that of other of the brain would appear to be lesions syphilitic due to the different distribution of the organisms in the two cases; in general paralysis they are found in the cortical and subcortical tissue spaces, away from the blood-vessels, and so, inaccessible to the influence of antisyphilitic remedies circulating in the blood stream, hence the failure of the treatment of the disease by intravenous administration of salvarsan as well as by the older antisyphilitic remedies. The cerebro-spinal fluid bears the same relation to the neurone as the lymph to the ordinary tissue of the body, and it is noteworthy that, after the mere introduction of salvarsan into the blood stream, the presence of arsenic in the cerebro-spinal fluid has never been demonstrated, whereas it is especially in that fluid that one finds chemical changes resulting from the altered metabolism of the neurone in general paralysis. A hopeful line of treatment for this disease would seem, therefore, to be an attempt to destroy the organisms by spirochaeticidal substances introduced directly into the cerebro-spinal fluid. The intraspinous injection of salvarsan itself is contraindicated by the meningitis to which it gives rise. It has, however, been demonstrated that the blood serum after intravenous injection of salvarsan possesses a strongly marked destructive action on the spirochæta—this action, in the opinion of most observers, being quite out of proportion to its actual salvarsan content-and such serum can be introduced into the subarachnoid space without any harmful effects. The readiest access for the introduction of the activated serum is afforded by lumbar puncture, this being the method described by Swift and Ellis and also that used by the present authors. Dr. Levaditi, Dr. Marie, and Dr. Martel have modified the procedure by introducing the serum under the cerebral dura through a trephine hole on cases
1 W. H. Hough and G. W. M’Caskey: Journal of the American Medical Association, Jan. 17th, 1914.
1104 each side of the
skull,2
the advantage claimed being
greater assurance that it should reach the cerebral cortex. However, such heroic surgery would not appear to be necessary as Dr. Cotton, in two cases of general paralysis which died during the course of treatment by the intraspinous method, found salvarsan in the ventricular fluid.3 It has also been shown that if phthalein be introduced by lumbar puncture into the subarachnoid space, and two hours later fluid is withdrawn simultaneously from the ventricles and through a lumbar puncture, phthalein is to be found in both, though the spinal fluid contains double the proportion found in the ventricular fluid.4 Further, it was noted by the late Dr. Loomis that after argyrol was introduced into the spinal subarachnoid space it was to be found at necropsy distributed over the cerebral cortex.5 The technique of the process as originally described by Swift and Ellis and as carried out by ourselves is briefly as follows. 1. The intravenous injection of 300 c.c. normal saline containing 0’4 grm. salvarsan neutralised with caustic soda. 2. One hour later the removal of 40 c.c. of blood. This is centrifugalised and 12 c.c. of the serum obtained is diluted with 18 c.c. of normal saline, the mixture being then heated for half an hour at 56° C. 3. The intraspinous injection, after removal of an equivalent quantity of cerebro-spinal fluid, of the 30 c.c. of this diluted serum prepared as The whole process was repeated four above. times at intervals of two weeks between Oct. 28th and Dec. 9th, 1913, and a final repetition was carried out on Jan. 5th, 1914. The Wassermann reaction was quantitatively estimated at Claybury Laboratory in specimens of blood taken before and after the intravenous injection of salvarsan on each occasion, and we may here note that there was never any difference in intensity in the two specimens. A similar estimation with an examination as cell content was perto the globulin and formed on samples of cerebro-spinal fluid removed before the intraspinous injection at each sitting. The method used for the estimation of the Wassermann reaction was that devised by Candler and Mann, and shortly to be published in the Archives of Nezcrology and Psychiatry, Vol. VI. The four patients selected for the treatment were cases showing but a very slight grade of deterioration, as it was felt that if arrest of the disease could be effected the results would be of much greater value if the process of actual destruction of the nervous elements had not preceded very far. The following is a short summary of the history of each case and of the conditions existing at the time of commencement of treatment. CASE I.—A male, aged 40, admitted on June 18th, 1913. Syphilis was admitted 20 years before ; no treatment and no secondary symptoms. First symptoms noted two and a half years before, consisting of attacks of vertigo and anxiety, decrease of sexual appetite, and outbursts of intemperance. More recently attacks of confusion with auditory and visual
hallucinations, persecutory delusions, and excitement. On admission he was in a confused state with partial amnesia for his recent excited periods, but with considerable insight into their morbid character and distress thereat. There was little genuine dementia, either intellectual or emotional. Before the commencement of treatment he varied considerably, showing at times marked confusion with hallucinations, and occasionally betrayed depression with suicidal tendencies. 2
Levaditi, Marie, and Martel: Comptes Rendus de la Société de Dec. 19th, 1913. W. Cotton : Journal of Nervous and Mental Disease, January, 1914.
Biologie, 3
4
W. Swift: Ibid.
5 Quoted by W. Leszynski: Ibid.
With regard to physical signs, speech was slow and clipped ; the pupils were contracted, unequal, irregular, and both quite immobile to light ; all movements were slow; there were tremors of the tongue and the hands ; station and gait were both unsteady and the knee-jerks were exaggerated. The Wassermann reaction was strongly positive in blood and cerebro-spinal fluid. CASE 2.-A male, age 33, admitted July lst, 1912. Syphilis was admitted 13 years previously ; two months’ treatment. He had felt dull and anergic for two years before admission, with depression due to quarrels with his wife who drank. On admission he was still depressed, self-accusatory and apprehensive, the result of auditory and visual hallucinations. At the date of commencement of treatment he had improved remarkably, and it was difficult to determine any abnormality, either intellectual or emotional. With regard to physical signs, articulation even of test sentences was normal ; the pupils were slightly irregular, rather large, and equal in size ; the left reacted very slightly to convergence, the right not at all ; both were quite immobile to light. There were marked tremors of the hands, tongue, and face ; coordination and sensation were normal; station and gait There was marked increase of knee and were normal. supinator jerks. Wassermann reaction was strongly positive in blood and cerebro-spinal fluid. CASE 3.-A male, aged 58, admitted on May 31st, 1913. Syphilis was admitted, but the date was not known. The first symptoms were noted 15 months before admission ; there was sudden onset of marked amnesia for current events. On admission there were instantaneous amnesia, fabrication, euphoria, complete lack of insight, and tendency to make ill-considered plans for the future. There was little general dementia ; he was capable of arithmetical deductions and of a correct and collected account of all events of his past, except those of the previous 15 months. At the time of commencement of treatment he showed practically no change. As to physical signs, speech was a little indistinct in articulation for consonants; the pupils were medium and unequal, the right being larger than the left, and were irregular and inactive to light. There were tremors of the tongue and hands ; movement of the limbs was clumsy ; station was steady, the gait a little unsteady ard spastic ; and the knee and supinator jerks were brisk. Wassermann reaction was strongly positive in blood and cerebro-spinal fluid. CASE 4.-A male, age 52, admitted on August 7th, 1913. Syphilis was denied and physical signs were absent. The first mental symptoms were noted 20 months before. After a fall while at work he developed numerous disconnected delusions, and since then he had done no work and had shown marked confusion from time to time. On admission the mental state varied a good deal. At times he showed no gross intellectual defects, though he was always apathetic and lethargic. There was also a marked incongruity between his apathy and his continual complaints as to his health. From time to No definite delusions could be elicited. he displayed considerable amnesia for his I time, however, past life and confusion as to his present surroundings. At the date of commencement of treatment, Oct. 28th, the confusional periods had ceased to occur, there was no amnesia, but he showed a general weakness ofjudgment. With regard to physical signs, the voice was monotonous, articulation was stumbling and explosive ; the pupils were medium, equal, and regular; reaction to light and accommodation was very slight. There were well-marked tremors of the face, tongue, and hands; overaction of the facial muscles and clumsiness of all movements. The ordinary gait was shuffling ; he could, however, walk heel-and-toe along a line with little difficulty. There was no Hombergism; the patellar and supinator jerks were very brisk. The Wassermann reaction was strongly positive in the blood and cerebrospinal fluid.
I
The reaction immediately following the treatment was slight and diminished in severity with each repetition, the symptoms noted being vomiting, dizziness, slight pain in the head, neck, back, and legs. The occurrence of these, however, was not constant. A rise in temperature, maintained for 30 hours on the first occasion and diminishing in range and duration on each successive occasion,
1105 was
observed.
All
four
patients
exhibited a no time
remarkable similarity in this respect; at
the condition of any of them alarming. An almost identical reaction, and no change in the patients’ condition, followed was
lasting a
set of
preliminary experimental procedures on Sept. 26th, 1913. These were designed to test individually the effect of different stages of the treatment, omitting the use of salvarsan, and they were as follows :Case 1, intravenous injection of 300 c.c. normal saline; Case 2, intraspinous injection of 30 c.c. normal saline; Case 3, intravenous injection of 300 c.c. normal saline and intraspinous injection of 30 c.c. normal saline; Case 4, intravenous injection of 300 c.c. normal saline and intraspinous injection of 30 c.c. diluted serum prepared in a manner
The
similar to that used in the actual treatment.
changes observed in the conditions of the
since the commencement of the treatment classified under the following heads: (1) changes in the mental state; (2) change in the physical signs of the disease ; and (3) changes in the Wassermann reaction. The changes in the mental state havee not been strikingly favourable. Case 1 passed through an attack of hallucinosis, both auditory and visual, without marked clouding of consciousness, immediately following the second repetition of the treatment and lasting about 14 days. Since then he has shown some tendency to euphoria, and though remembering his former hallucinatory periods and recognising their subjective character he is lacking in a correct insight into their gravity. His memory, however, remains good and he is more active and interested in his surroundings. Case 2 remains practically normal. Case 3 shows the same amnesia for current events and of all those since the manifest onset of the disease with the same tendency to fabrication. A few surprising instances of the retention of isolated memories, however, have been noticed. He looks brighter and shows no sign of progressive dementia. In Case 4 the patient’s general dulness persists unchanged, without evidence of progressive dementia. Confusional periods, such as were observed previous to the treatment, have not occurred lately. The changes in the physical signs are as follows. In Case 1 the tremors have entirely disappeared, and the station, gait, and coordination arenormal. The pupils are medium in size, equal, regular, and react almost normally in speed and extent. Some analgesia is present. In Case 2 the pupils now both react slowly to convergence and the left only to light; no other change is to be noted. In Case 3, about the beginning of February the pupils were practically normal in form and reactions, but since then have shown a tendency to return to their initial condition. There has been some diminution of tremors and some improvement in coordination. In Case 4 there was a temporary improvement in the condition of the pupils, but this has again disappeared. The tremors are gone and the tendon reflexes are a little less exaggerated. With regard to the Wassermann tests, the quantitative estimation of the Wassermann reaction in both blood and the cerebro-spinal fluid showed no change whatever: in all cases the reaction in both remains as strongly positive as it was before treatment. The cerebro-spinal fluid in addition was examined for the presence of globulin and excess of cells, and both those conditions were present throughout. As only five months have elapsed since the date of
patients may be
commencement of treatment, it is obviously impossible to draw definite conclusions. While it is true that in none of the four cases has any progressive deterioration in the mental state occurred, yet it must be remembered that remissions equalling in degree those seen in our patients occur in 7 per cent. to 8 per cent. of general paralytics ; moreover, the average duration of such remissions being 11 months, the arrest of progress in our cases is not yet sufficiently prolonged to constitute evidence that the evolution of the disease has been altered.6 With reference to the changes in the physical signs, it must be noted that alternating states of the reflex activity of the pupil to light occur in about one-third of cases during the first and second stages of the disease; too much stress, therefore, must not be laid upon such variations as have been observed in our cases.’ The improvement in the general coordination and the diminution of tremors is only such as commonly accompanies states of remission in the ordinary course of the disease. In our opinion the persistence of the Wassermann reaction in both blood and cerebro-spinal fluid is strong presumptive evidence of the failure of the treatment, for whatever may be the actual genesis of the reaction, it is now generally accepted as indicating the continued presence of the living spirochaeta. Furthermore, this persistence of reaction must be due to the presence of the organism under conditions rendering it refractory to salvarsan in the blood stream, and this is characteristic of the disease. An analysis of cases of general paralysis treated by this method described by other observers, mainly American, shows little ground for the generally hopeful attitude adopted in regard to the treatment, for none of them appear to have produced changes in the mental or physical conditions other than such as are to be seen with almost equal frequency during the untreated course of the disease, and, while in several of the published cases changes in the cell and globulin content of the cerebro-spinal fluid have been noted, in none has any claim been made that the Wassermann reaction has been abolished in either the blood or the cerebro-spinal fluid. Even if disappearance of the Wassermann had been found during treatment, the cure of the disease would be unproven, as periods in which the reaction is temporarily absent have been shown to occur during its ordinary course. Our thanks are due to Dr. F. W. Mott, the director of the Claybury Laboratory, and to Dr. J. P. Candler, who so kindly carried out the numerous examinations of the specimen fluids on each occasion. 6
H. L. Paine:
Paralysis of p. 684. 7
A Statistical Study of Remissions in General the Insane, Boston Medical and Surgical Journal, 1913,
De Montyel:
ROYAL
Archives de
Neurologie, June, 1905.
INSTITUTION.-On
Tuesday
next
at 3 P.M., Dr. Walter Wahl will deliver the first of two lectures on"Problems of Physical Chemistry "(1) "Study of Matter at High Pressures," and (2) " Study of Matter at Low Temperature." On Saturday, April 25th, Dr. T. E. Stanton commences a course of two lectures on ’’ Similarity of Motion in Fluids "—(1)’’The Theory of Similarity of Motion in Fluids and the Experimental Proof of its Existence," and (2) "The General Law of Surface Friction in Fluid Motion." The Friday evening discourse on April 24th will be delivered by Dr. Frank Watson Dyson, the Astronomer Royal, on" The Stars Around the North Pole," and on lst by Mr. E. F. Benson on A
(April 21st),
Criticism
on
Critics."
May
hymen
FIG. 13.
observation. Nevertheless, all the conditions that are characteristic of the females of Type A could be reproduced simply by everting the vulva of Type B. (See Fig. 13.) Between this vulval orifice, surrounded byitslabiamajora, and the anus a bridge of tissue exists which constitutes the perineum, but the anatomical basis of this perineum is quite distinct in these animals. In Type A the perineum consists of the extroverted summit of the cloaca, but in females of Type B it is composed of the d cloacal margins that have met and united in front of the
frequently
escapes
anus.
W’e have already seen that in the male of this type the genital tubercle may be so completely concealed, and the of and end Lower vagina uro-genital sinus (vulva) sheath be so short, that the of a young pig. Note the likeness to the female may concealed hymen and One other labia minora. V, Vagina. be very great. H, Hymen. F, erethral condition remains to be conopening. LM, Labia minora. sidered. Females of Type A c, Clitoris. have already been described in which the genital tubercle approaches to a masculine degree of development, so much so that in some Primates it again becomes a urinary canal by the closure and union of the labia minora. Similarly in females of Type B these approximations to the male condition occur, and in some instances are far more profound than anything previously described. In some females of Type B it is not only the urinary, but even the genital canal, that is closed in and carried to the tip of the genital tubercle ; in this way the male and female condition becomes exactly similar. In some animals this condition is only temporary; in some, however, it is apparently permanent. [The condition present in the mole, the spotted hyaena, the South American hare, and some other animals was then
described.] UNIVERSITY
COLLEGE, LONDON.-The
report
of this College of the University of London for the year ending February, 1914, which has just been issued, shows that the number of students attending during the session 1912-13 was 2083 ; of these, 137 attended the department of the faculty of medical sciences. For the year ending August 31st, 1913, the total revenue of the College from all sources amounted to .S.66,694 2s. 8d., being an excess of expenditure over income of .8173 10s. 4d. Among the new buildings that are in progress are a large block for the new chemical laboratories and the building for the purpose of housing the department of applied statistics and eugenics, including the biometric and Galton laboratories. These buildings, however, cannot be completed until adequate funds are forthcoming. The total at present needed to complete the most pressing works in hand is .658.262, of which £28,652 are required for the new chemical laboratories. A special committee, with Prince Arthur of Connaught as president and the Hon. Rupert Guinness as treasurer, is occupied in the task of raising these funds.
INTRASPINOUS TREATMENT (SWIFTELLIS) OF GENERAL PARALYSIS: A PRELIMINARY NOTE ON FOUR CASES TREATED BY THIS METHOD. BY EDWARD MAPOTHER, M.D. LOND.,
F.R.C.S. ENG.,
AND
THOMAS BEATON, ASSISTANT MEDICAL
M.D., B.S. LOND.,
OFFICERS, LONDON COUNTY ASYLUM, LONG GROVE, EPSOM.
SINCE the description by Swift and Ellis at a meeting of the New York Neurological Society in April, 1913, of a new mode of treatment for parasyphilitic diseases of the nervous system by the injection into the spinal subarachnoid space of
salvarsanised serum, a considerable number of such have been treated by this method in America,1 but relatively few have been recorded in this country. The presence of the spirochaeta pallida can be demonstrated post mortem in a majority of cases of so-called parasyphilitic diseases of the nervous system, it has been cultivated from the brain tissue of the living general paralytic, and the rabbit has been infected by means These of the serum of the general paralytic. findings indicate that general paralysis is, at any rate in the majority of cases, a true syphilitic process depending upon the presence and activity of the organism itself. The difference between the course of general paralysis and that of other of the brain would appear to be lesions syphilitic due to the different distribution of the organisms in the two cases; in general paralysis they are found in the cortical and subcortical tissue spaces, away from the blood-vessels, and so, inaccessible to the influence of antisyphilitic remedies circulating in the blood stream, hence the failure of the treatment of the disease by intravenous administration of salvarsan as well as by the older antisyphilitic remedies. The cerebro-spinal fluid bears the same relation to the neurone as the lymph to the ordinary tissue of the body, and it is noteworthy that, after the mere introduction of salvarsan into the blood stream, the presence of arsenic in the cerebro-spinal fluid has never been demonstrated, whereas it is especially in that fluid that one finds chemical changes resulting from the altered metabolism of the neurone in general paralysis. A hopeful line of treatment for this disease would seem, therefore, to be an attempt to destroy the organisms by spirochaeticidal substances introduced directly into the cerebro-spinal fluid. The intraspinous injection of salvarsan itself is contraindicated by the meningitis to which it gives rise. It has, however, been demonstrated that the blood serum after intravenous injection of salvarsan possesses a strongly marked destructive action on the spirochæta—this action, in the opinion of most observers, being quite out of proportion to its actual salvarsan content-and such serum can be introduced into the subarachnoid space without any harmful effects. The readiest access for the introduction of the activated serum is afforded by lumbar puncture, this being the method described by Swift and Ellis and also that used by the present authors. Dr. Levaditi, Dr. Marie, and Dr. Martel have modified the procedure by introducing the serum under the cerebral dura through a trephine hole on cases
1 W. H. Hough and G. W. M’Caskey: Journal of the American Medical Association, Jan. 17th, 1914.
1104 each side of the
skull,2
the advantage claimed being
greater assurance that it should reach the cerebral cortex. However, such heroic surgery would not appear to be necessary as Dr. Cotton, in two cases of general paralysis which died during the course of treatment by the intraspinous method, found salvarsan in the ventricular fluid.3 It has also been shown that if phthalein be introduced by lumbar puncture into the subarachnoid space, and two hours later fluid is withdrawn simultaneously from the ventricles and through a lumbar puncture, phthalein is to be found in both, though the spinal fluid contains double the proportion found in the ventricular fluid.4 Further, it was noted by the late Dr. Loomis that after argyrol was introduced into the spinal subarachnoid space it was to be found at necropsy distributed over the cerebral cortex.5 The technique of the process as originally described by Swift and Ellis and as carried out by ourselves is briefly as follows. 1. The intravenous injection of 300 c.c. normal saline containing 0’4 grm. salvarsan neutralised with caustic soda. 2. One hour later the removal of 40 c.c. of blood. This is centrifugalised and 12 c.c. of the serum obtained is diluted with 18 c.c. of normal saline, the mixture being then heated for half an hour at 56° C. 3. The intraspinous injection, after removal of an equivalent quantity of cerebro-spinal fluid, of the 30 c.c. of this diluted serum prepared as The whole process was repeated four above. times at intervals of two weeks between Oct. 28th and Dec. 9th, 1913, and a final repetition was carried out on Jan. 5th, 1914. The Wassermann reaction was quantitatively estimated at Claybury Laboratory in specimens of blood taken before and after the intravenous injection of salvarsan on each occasion, and we may here note that there was never any difference in intensity in the two specimens. A similar estimation with an examination as cell content was perto the globulin and formed on samples of cerebro-spinal fluid removed before the intraspinous injection at each sitting. The method used for the estimation of the Wassermann reaction was that devised by Candler and Mann, and shortly to be published in the Archives of Nezcrology and Psychiatry, Vol. VI. The four patients selected for the treatment were cases showing but a very slight grade of deterioration, as it was felt that if arrest of the disease could be effected the results would be of much greater value if the process of actual destruction of the nervous elements had not preceded very far. The following is a short summary of the history of each case and of the conditions existing at the time of commencement of treatment. CASE I.—A male, aged 40, admitted on June 18th, 1913. Syphilis was admitted 20 years before ; no treatment and no secondary symptoms. First symptoms noted two and a half years before, consisting of attacks of vertigo and anxiety, decrease of sexual appetite, and outbursts of intemperance. More recently attacks of confusion with auditory and visual
hallucinations, persecutory delusions, and excitement. On admission he was in a confused state with partial amnesia for his recent excited periods, but with considerable insight into their morbid character and distress thereat. There was little genuine dementia, either intellectual or emotional. Before the commencement of treatment he varied considerably, showing at times marked confusion with hallucinations, and occasionally betrayed depression with suicidal tendencies. 2
Levaditi, Marie, and Martel: Comptes Rendus de la Société de Dec. 19th, 1913. W. Cotton : Journal of Nervous and Mental Disease, January, 1914.
Biologie, 3
4
W. Swift: Ibid.
5 Quoted by W. Leszynski: Ibid.
With regard to physical signs, speech was slow and clipped ; the pupils were contracted, unequal, irregular, and both quite immobile to light ; all movements were slow; there were tremors of the tongue and the hands ; station and gait were both unsteady and the knee-jerks were exaggerated. The Wassermann reaction was strongly positive in blood and cerebro-spinal fluid. CASE 2.-A male, age 33, admitted July lst, 1912. Syphilis was admitted 13 years previously ; two months’ treatment. He had felt dull and anergic for two years before admission, with depression due to quarrels with his wife who drank. On admission he was still depressed, self-accusatory and apprehensive, the result of auditory and visual hallucinations. At the date of commencement of treatment he had improved remarkably, and it was difficult to determine any abnormality, either intellectual or emotional. With regard to physical signs, articulation even of test sentences was normal ; the pupils were slightly irregular, rather large, and equal in size ; the left reacted very slightly to convergence, the right not at all ; both were quite immobile to light. There were marked tremors of the hands, tongue, and face ; coordination and sensation were normal; station and gait There was marked increase of knee and were normal. supinator jerks. Wassermann reaction was strongly positive in blood and cerebro-spinal fluid. CASE 3.-A male, aged 58, admitted on May 31st, 1913. Syphilis was admitted, but the date was not known. The first symptoms were noted 15 months before admission ; there was sudden onset of marked amnesia for current events. On admission there were instantaneous amnesia, fabrication, euphoria, complete lack of insight, and tendency to make ill-considered plans for the future. There was little general dementia ; he was capable of arithmetical deductions and of a correct and collected account of all events of his past, except those of the previous 15 months. At the time of commencement of treatment he showed practically no change. As to physical signs, speech was a little indistinct in articulation for consonants; the pupils were medium and unequal, the right being larger than the left, and were irregular and inactive to light. There were tremors of the tongue and hands ; movement of the limbs was clumsy ; station was steady, the gait a little unsteady ard spastic ; and the knee and supinator jerks were brisk. Wassermann reaction was strongly positive in blood and cerebro-spinal fluid. CASE 4.-A male, age 52, admitted on August 7th, 1913. Syphilis was denied and physical signs were absent. The first mental symptoms were noted 20 months before. After a fall while at work he developed numerous disconnected delusions, and since then he had done no work and had shown marked confusion from time to time. On admission the mental state varied a good deal. At times he showed no gross intellectual defects, though he was always apathetic and lethargic. There was also a marked incongruity between his apathy and his continual complaints as to his health. From time to No definite delusions could be elicited. he displayed considerable amnesia for his I time, however, past life and confusion as to his present surroundings. At the date of commencement of treatment, Oct. 28th, the confusional periods had ceased to occur, there was no amnesia, but he showed a general weakness ofjudgment. With regard to physical signs, the voice was monotonous, articulation was stumbling and explosive ; the pupils were medium, equal, and regular; reaction to light and accommodation was very slight. There were well-marked tremors of the face, tongue, and hands; overaction of the facial muscles and clumsiness of all movements. The ordinary gait was shuffling ; he could, however, walk heel-and-toe along a line with little difficulty. There was no Hombergism; the patellar and supinator jerks were very brisk. The Wassermann reaction was strongly positive in the blood and cerebrospinal fluid.
I
The reaction immediately following the treatment was slight and diminished in severity with each repetition, the symptoms noted being vomiting, dizziness, slight pain in the head, neck, back, and legs. The occurrence of these, however, was not constant. A rise in temperature, maintained for 30 hours on the first occasion and diminishing in range and duration on each successive occasion,
1105 was
observed.
All
four
patients
exhibited a no time
remarkable similarity in this respect; at
the condition of any of them alarming. An almost identical reaction, and no change in the patients’ condition, followed was
lasting a
set of
preliminary experimental procedures on Sept. 26th, 1913. These were designed to test individually the effect of different stages of the treatment, omitting the use of salvarsan, and they were as follows :Case 1, intravenous injection of 300 c.c. normal saline; Case 2, intraspinous injection of 30 c.c. normal saline; Case 3, intravenous injection of 300 c.c. normal saline and intraspinous injection of 30 c.c. normal saline; Case 4, intravenous injection of 300 c.c. normal saline and intraspinous injection of 30 c.c. diluted serum prepared in a manner
The
similar to that used in the actual treatment.
changes observed in the conditions of the
since the commencement of the treatment classified under the following heads: (1) changes in the mental state; (2) change in the physical signs of the disease ; and (3) changes in the Wassermann reaction. The changes in the mental state havee not been strikingly favourable. Case 1 passed through an attack of hallucinosis, both auditory and visual, without marked clouding of consciousness, immediately following the second repetition of the treatment and lasting about 14 days. Since then he has shown some tendency to euphoria, and though remembering his former hallucinatory periods and recognising their subjective character he is lacking in a correct insight into their gravity. His memory, however, remains good and he is more active and interested in his surroundings. Case 2 remains practically normal. Case 3 shows the same amnesia for current events and of all those since the manifest onset of the disease with the same tendency to fabrication. A few surprising instances of the retention of isolated memories, however, have been noticed. He looks brighter and shows no sign of progressive dementia. In Case 4 the patient’s general dulness persists unchanged, without evidence of progressive dementia. Confusional periods, such as were observed previous to the treatment, have not occurred lately. The changes in the physical signs are as follows. In Case 1 the tremors have entirely disappeared, and the station, gait, and coordination arenormal. The pupils are medium in size, equal, regular, and react almost normally in speed and extent. Some analgesia is present. In Case 2 the pupils now both react slowly to convergence and the left only to light; no other change is to be noted. In Case 3, about the beginning of February the pupils were practically normal in form and reactions, but since then have shown a tendency to return to their initial condition. There has been some diminution of tremors and some improvement in coordination. In Case 4 there was a temporary improvement in the condition of the pupils, but this has again disappeared. The tremors are gone and the tendon reflexes are a little less exaggerated. With regard to the Wassermann tests, the quantitative estimation of the Wassermann reaction in both blood and the cerebro-spinal fluid showed no change whatever: in all cases the reaction in both remains as strongly positive as it was before treatment. The cerebro-spinal fluid in addition was examined for the presence of globulin and excess of cells, and both those conditions were present throughout. As only five months have elapsed since the date of
patients may be
commencement of treatment, it is obviously impossible to draw definite conclusions. While it is true that in none of the four cases has any progressive deterioration in the mental state occurred, yet it must be remembered that remissions equalling in degree those seen in our patients occur in 7 per cent. to 8 per cent. of general paralytics ; moreover, the average duration of such remissions being 11 months, the arrest of progress in our cases is not yet sufficiently prolonged to constitute evidence that the evolution of the disease has been altered.6 With reference to the changes in the physical signs, it must be noted that alternating states of the reflex activity of the pupil to light occur in about one-third of cases during the first and second stages of the disease; too much stress, therefore, must not be laid upon such variations as have been observed in our cases.’ The improvement in the general coordination and the diminution of tremors is only such as commonly accompanies states of remission in the ordinary course of the disease. In our opinion the persistence of the Wassermann reaction in both blood and cerebro-spinal fluid is strong presumptive evidence of the failure of the treatment, for whatever may be the actual genesis of the reaction, it is now generally accepted as indicating the continued presence of the living spirochaeta. Furthermore, this persistence of reaction must be due to the presence of the organism under conditions rendering it refractory to salvarsan in the blood stream, and this is characteristic of the disease. An analysis of cases of general paralysis treated by this method described by other observers, mainly American, shows little ground for the generally hopeful attitude adopted in regard to the treatment, for none of them appear to have produced changes in the mental or physical conditions other than such as are to be seen with almost equal frequency during the untreated course of the disease, and, while in several of the published cases changes in the cell and globulin content of the cerebro-spinal fluid have been noted, in none has any claim been made that the Wassermann reaction has been abolished in either the blood or the cerebro-spinal fluid. Even if disappearance of the Wassermann had been found during treatment, the cure of the disease would be unproven, as periods in which the reaction is temporarily absent have been shown to occur during its ordinary course. Our thanks are due to Dr. F. W. Mott, the director of the Claybury Laboratory, and to Dr. J. P. Candler, who so kindly carried out the numerous examinations of the specimen fluids on each occasion. 6
H. L. Paine:
Paralysis of p. 684. 7
A Statistical Study of Remissions in General the Insane, Boston Medical and Surgical Journal, 1913,
De Montyel:
ROYAL
Archives de
Neurologie, June, 1905.
INSTITUTION.-On
Tuesday
next
at 3 P.M., Dr. Walter Wahl will deliver the first of two lectures on"Problems of Physical Chemistry "(1) "Study of Matter at High Pressures," and (2) " Study of Matter at Low Temperature." On Saturday, April 25th, Dr. T. E. Stanton commences a course of two lectures on ’’ Similarity of Motion in Fluids "—(1)’’The Theory of Similarity of Motion in Fluids and the Experimental Proof of its Existence," and (2) "The General Law of Surface Friction in Fluid Motion." The Friday evening discourse on April 24th will be delivered by Dr. Frank Watson Dyson, the Astronomer Royal, on" The Stars Around the North Pole," and on lst by Mr. E. F. Benson on A
(April 21st),
Criticism
on
Critics."
May