The Connection of Intestinal 
Autotoxis with Certain 
Common Forms of Insanity. 
BY 
ALLAN McLANE HAMILTON, M.D., 
One of the Consulting Neurologists to the Manhattan State 
Asv lum, New York ; 
Corresponding Fellow of the Medical Society of London, etc. 
REPRINTED PROM THE 
Heto ITovft jf&etifcal Journal 
for October 31 and November lfy and 
21, 1S96. Reprinted from the New YorTc Medical Journal 
for October 31 and November 1J+ and SI, 1896. 
THE CONNECTION OF INTESTINAL AUTOTOXIS 
WITH CERTAIN COMMON FORMS OF INSANITY * 
By ALLAN McLANE HAMILTON, M. D., 
ONE or THE CONSULTING NEUROLOGISTS TO THE MANHATTAN STATE ASYLUM 
NEW YORK ; 
CORRESPONDING FELLOW OF THE MEDICAL SOCIETY OF LONDON, ETC. 
Until quite recently the therapeutics of mental dis- 
eases have been very primitive, in view of the patho- 
logical advances that have been made in so many differ- 
ent directions, and do not appear to have been seriously 
influenced by the important researches that have marked 
the last decade, so far as deranged metabolism is con- 
cerned. Even to-day the management of insanity nearly 
everywhere consists chiefly in quelling excitement by 
narcotics, overcoming depression by stimulants and ton- 
ics, and affording rest, isolation, and protection. 
I have for several years been impressed with the so- 
matic origin of various psychoses, especially those which 
were first classified and defined by Krafft-Ebing as “ ac- 
quired/’ and by others ascribed to certain epochs, and I 
have looked for some more direct and reasonable causes 
than those which are ordinarily alleged to exist, reach- 
* Read before the Medical Society of London, May 11, 1896. 
Copyright, 1896. by D. Appleton a>d Company. 2 
INTESTINAL AUTOTOXIS AND INSANITY. 
ing the conclusion that in very many instances the ex- 
istence of defective oxidation will explain the clinical 
features of numerous insanities which were formerly 
roughly classified with regard to their mental character- 
istics alone, as mania, melancholia, dementia, or still 
further particularized by the names which defined their 
periodicity, or the crisis at which they appeared, or the 
element of hereditary predisposition; although in a few 
exceptions, notably hepatic and rheumatismal insani- 
ties, the somatic element has been recognized. 
The defect of most classifications of an assigned eti- 
ology is that no serious attempt is made to satisfactorily 
connect the alleged cause with the symptoms and sat- 
isfactorily explain them. Granted that intrinsic defects, 
due to heredity, exist, no very clear or satisfactory ex- 
planation is given of what initial physical and sec- 
ondary psychic disturbances follow. A great deal has 
been written about increased or diminished tension of 
the cerebral arterial system, but to those familiar with 
the exciting causes or pathology of insanity the irregu- 
larity of cerebral hypersemia or anaemia must be mani- 
fest. Why a periodical mania should develop, subside, 
and reappear, the environment and other influences be- 
ing unchanged during the entire course, has not been 
definitely explained. Why a confusional insanity most 
unexpectedly follows a surgical operation when there is 
little or no shock, or a form of puerperal insanity ap- 
pears weeks after parturition, and when the danger of 
local sepsis has long disappeared, suggests the necessity 
of some fresh explanation. 
Before going further in this direction it may be well 
to say that my desire for more exact knowledge in re- 
gard to the pathology and setiology of such everyday dis- INTESTINAL AUTOTOXIS AND INSANITY. 
3 
orders as acute mania or melancholia was stimulated by 
the experience common to most of us, that, where psy- 
chic causes exist, not only the mental but the physical 
disturbance is usually entirely out of proportion to any 
cerebral shock or demand upon the brain, and it seems 
strange that where the most extreme kinds of mental 
strain exist in some individuals, they are attended by 
comparatively little or no general disturbance. I was 
led to reason that if subjects who are subjected to com- 
paratively superficial mental strain rapidly develop great 
physical derangement, disturbances of assimilation, 
feebleness, and emaciation, and die in a few weeks, there 
must be something beneath all this—something that has 
been simply lighted up or induced by the preparatory 
condition into which, perhaps, hereditary influences en- 
tered to some extent, or not at all. The observations of 
Herter and Smith point to the fact that that protean 
neurosis, neurasthenia, is closely connected with some 
form of disturbed intestinal function, and Eccles and 
Gautier clearly recognized the insufficient activity in the 
oxidation processes with the presence of the products of 
incomplete metabolism, and with an increase of the 
combined sulphates in the urine. The excellent work of 
Bouchard, Bodriguez, Chardon, and Chevalier Lavaure, 
and the more recent papers in your own coimtry of 
Macpherson, Eccles, St. John Bullen, and Turner, have 
led to the inquiry whether a large number of acute in- 
sanities are really not after all due to primal intestinal 
disorders, and if even the course of the chronic psy- 
choses must not he more or less modified by the same 
agencies: and whether, this being true, we should not 
in the future direct our treatment more than we have 
in the past to the care of the digestive organs, placing 4 
INTESTINAL AUTOTOXIS AND INSANITY. 
less reliance on the use of the conventional narcotics, or 
other familiar modes of treatment. 
With this end in view I made many months ago a 
series of investigations, the results of which have been 
based upon experiments with animals and clinical ob- 
servations conducted in the hospitals and asylums with 
which I have been connected, and in my own practice 
and elsewhere. More than fifty cases of different kinds 
of insanity have been observed, which include examples 
of acute and chronic melancholia and mania, simple 
delusional insanities, primal and terminal dementias, 
paralytic dementia, periodic, puerperal, and traumatic 
insanities, and the alcoholic and drug psychoses. The 
variation of the urine and fasces was noted, and all the 
cases were carefully watched. It would be impossible 
in a brief paper of this length to more than summarize 
my results, and it is my intention this evening to simply 
sketch the work that has been done. 
The experiments were undertaken to determine first 
whether there was any specific or noso-toxicity of the 
urine of the insane; and, if so, what the nature of such 
toxicity was; next, to discover, if possible, how impor- 
tant and general was the theory of uric-acid poisoning; 
and again, whether mental disorders were produced and 
modified by an autotoxaemia; whether the offending sub- 
stances were the leucomaines or the intrinsic products 
of putrescence in the intestines. According to Marie 
and Bose, the urine of insane persons possesses a toxicity 
which varies and is more or less identified with the dif- 
ferent forms of insanity. They found that it was in- 
creased in agitated melancholia, as well as in persecu- 
tory insanity and excitable mania, while there was only 
a normal amount in quiet mania, and the toxicity was INTESTINAL AUTOTOXIS AND INSANITY. 
5 
much reduced in purely stuporose and senile conditions. 
As the result of their experiments upon animals, hyper- 
thermy and anaesthesia, auditory hyperaesthesia, dimin- 
ished reflexes, pyschomotor disturbances, and agita- 
tion ensued; hut their conclusions, however, were doubt- 
ed by Seglas and Ballet, who contended that there was 
nothing distinctive in the findings. For the purpose of 
satisfying myself as to the possible extent of noso-tox- 
osis, I selected six patients, from whom the urine was 
obtained weekly, and conducted a series of experiments 
to determine whether there was any uniformity or pe- 
culiarity, hut with negative results. 
Rabbits were chosen and kept closely under observa- 
tion for a number of days, and, although some of them 
manifested rather striking nervous symptoms, as well as 
the hyperthermy observed by the authors referred to, 
the results were neither constant nor characteristic. 
Two of the patients whose urine was injected were 
melancholics, one was a case of acute mania, another of 
chronic mania, a fifth of paretic dementia, and the sixth 
of periodical insanity. The resulting effect seems to 
depend very much upon the increased specific gravity of 
the specimen, and on the evidences of intestinal dis- 
orders and malnutrition. The urine of the paretic was 
always exceedingly toxic, which property was possessed 
by that of the periodic patient, whose urine showed a 
large amount of indican, while in only one of the other 
cases of mania in which the specific gravity of the urine 
was high, was there any result effected by its injection. 
In these dense urines there was an increase of the com- 
bined sulphates and urea. Large quantities, amounting 
to forty cubic centimetres of the urine of the melan- 
cholic, were injected without any apparent effect, so I 6 
INTESTINAL AUTOTOXIS AND INSANITY. 
was forced to abandon the idea that the excreta, in cer- 
tain forms of insanity, presented specific toxic qualities. 
The only interesting psychic manifestation besides an 
apparent stupidity was the causation, in the rabbit that 
had received the injection of urine from the paretic pa- 
tient, of rather a curious condition, which led me to 
believe that hallucinations of vision existed. There was 
absolutely nothing, however, that could be regarded as 
uniform, although frequent injections were made. So 
far as the influence of uric poisoning is concerned, I 
am clearly of the opinion that it has not as much to do 
with the genesis of mental disease as is alleged for it by 
the more enthusiastic, but in those cases in which it is 
supposed to play an setiological part it is a very grave- 
question whether its presence is not indicative of an- 
other kind of poisoning, which is the result of the de- 
structive metabolism of nuclein, the amount of uric 
acid measuring the amount of leucocyte activity, and 
we are confronted with the query whether the initial 
destruction is not due after all to a primary intestinal 
disorder. The symptoms produced by the injection 
of urea and uric acid into animals, as detailed by Bou- 
chard, though possessing a certain uniformity, have too 
limited significance in view of the varying symptoms 
which enter into the clinical picture of various insani- 
ties due to the absorption of putrescent substances. 
One distinguished writer has announced that melan- 
cholia especially is due to the accumulation of the sec- 
ond of these substances, and that one of its important 
features is the increased arterial tension, an assump- 
tion which I do not think is always tenable, though it 
may occasionally exist, for my own experience teaches 
me that there are many cases of this mental disease INTESTINAL AUTOTOXIS AND INSANITY. 
7 
where the arterial condition is the reverse. So far as 
the influence of retained leucomaines is concerned, there 
seems to be much more reason to believe that, in the 
subjects where there is the retention of the physiological 
products of waste, disorders of the nervous system gen- 
erally ensue. Salomon has found that when parax- 
anthin was introduced into the blood stream of the 
smaller animals, states were induced resembling some of 
the psychoses observed in man, and I am informed that 
he has produced in a mouse a condition, so far as ob- 
jective appearances are concerned, closely resembling 
stuporous melancholia. His experiments in 1892, and 
those of Mendel subsequently, prove that it was possi- 
ble to produce symptoms similar to those of katatonia 
by the injection of this substance into white mice, dogs, 
and cats. Vaughan injected a small quantity of hypox- 
anthin into a frog, which some hours afterward became 
convulsed. Eemembering that paraxanthin and heterax- 
anthin are the organic analogues of the vegetable alka- 
loids caffeine and theobromine—one being a dime- 
thylxanthine and the other a methylxanthine—the natu- 
ral speculation may arise whether the effect upon the 
nervous system of the latter might not be duplicated 
in the organic extracts, although Vaughan and others 
have concluded that the organic alkaloids obtained from 
ptomaines, or rather diamines, have not the identical 
physiological effects of such vegetable alkaloids as atro- 
pine, morphine, coniine, etc. 
At my request, Dr. E. E. Smith, of New York, pre- 
pared a quantity of hypoxanthin in the following man- 
ner: 
Liebig’s extract of beef was dissolved in a large vol- 
ume of water, and lead acetate added till no further pre- INTESTINAL AUTOTOXIS AND INSANITY. 
8 
cipitate was produced; the solution was filtered, the fil- 
trate treated with hydrogen sulphide till the lead was 
precipitated, and this filtrate evaporated to a small vol- 
ume and the creatine crystallized in the cold. The 
evaporation of the crystals was aided by the subsequent 
addition of several volumes of an eighty-eight-per-cent, 
alcohol. The mother liquor, after removal of the alco- 
hol, was precipitated with ammonia and silver nitrate, 
the precipitate dissolved in nitric acid of specific gravity 
1.1 by the aid of heat, and the solution cooled, when 
crystals of hypoxantliin silver nitrate separated out. 
This salt was suspended in water, decomposed with hy- 
drogen sulphide, and the filtrate evaporated to a small 
volume, whereupon hypoxanthine nitrate crystallized 
out. 
Microscopical examination of the crystals of hy- 
poxanthine nitrate showed the characteristic form with 
the exception only of one or two acicular crystals, 
doubtless mere traces of adenin. 
With this product I conducted a series of experi- 
ments on rabbits and monkeys. Hypoxanthine was 
mixed with the food and given in doses varying from 
ten to fifteen centigrammes at intervals of an hour, 
until a hundred and fifty centigrammes were given, 
without any satisfactory results so far as the production 
of symptoms of any kind was concerned. Of four rab- 
bits, only one presented toxic symptoms, and to a Java 
monkey as much as fifty centigrammes were given with- 
out any apparent effect. The susceptible subject was a 
lively nervous rabbit weighing three pounds and a half, 
to whom twenty centigrammes were given in bran. 
Within five minutes after taking it, the animal mani- 
fested some excitement, rubbed its paws vigorously, and INTESTINAL AUTOTOXIS AND INSANITY. 
9 
was restless and disturbed by noise or jarring of the 
floor; its ears became exceedingly congested and its re- 
flexes were affected by the slightest tap. This irrita- 
bility gradually subsided, so that at the end of two hours 
it became dull and stupid, and did not resist pinching 
or other forms of stimuli. Its paws could be pricked 
with impunity and without any apparent evidence of 
feeling. Its pupils were widely dilated, and the pupil- 
lary reflex was lost, while there seemed to be retinal 
insensibility, for it did not mind a lighted match or 
the application of an irritant. When with much urging 
it was made to move, it dragged its hind legs, and there 
was no effort to escape. It remained in a condition of 
torpor for over an hour and gradually resumed its nor- 
mal condition of liveliness. The same rabbit subse- 
quently manifested identical phenomena when twenty 
cubic centigrammes of a fifty-per-cent, solution were in- 
troduced into the circulation. 
It would appear that the intestinal toxalbumins have 
more to do with the production of disturbance of the 
nervous system than the leucomaines, which undeniably 
have an effect, though not a very marked one. Selmi 
obtained ptomaines from the urine of a paretic patient 
which, when injected into an animal, produced convul- 
sions, and according to Vaughan and others most of the 
ptomaines produce convulsions and other forms of hy- 
pcrkinesis. 
A study of the cases that have formed the basis of 
observation for the past year unquestionably bears out 
the assumption that disturbances of the gastro-intestinal 
tract, more often than is generally supposed, are attend ■ 
cd by bacterial necrosis and the introduction into the 
general circulation of certain very virulent toxic agents 10 
INTESTINAL AUTOTOXIS AND INSANITY. 
whose effects are expended mainly upon the nervous 
system. I think I am safe in saying that nearly all the 
rapidly developing confusional insanities have this ex- 
planation, and we must, therefore, he on the alert for 
such a cause, even when the case has commonplace fea- 
tures. No other alternative has presented itself so 
strongly to my mind as that of intestinal putrefac- 
tion, and in all the patients whose urine was exam- 
ined a decided increase in the amount of indican was 
found, even when the diet was carefully regulated. 
A sudden and rapid development of incoherence, 
then, with malassimilation, highly colored urine, and 
delusions that are unsystematized, clearly suggests an 
inquiry into the condition of the organs of digestion, 
and the first step should consist in a complete examina- 
tion of the urine and faeces. Even in the chronic in- 
sanities the occurrence of acces and convulsions has, 
in my experience, been attended with some defect of me- 
tabolism, and the determination of the sulphate ratio has 
afforded me great help in diagnosis. 
Turner, in an admirable paper, determined that the 
ratio of the preformed and aromatic sulphates in gen- 
eral paresis, while not very markedly increased in the 
early stages, became decidedly so in the established dis- 
ease or coincidently with the acces, the ratio rising and 
afterward subsiding. 
It would appear, from my own cases, that those 
usually showing little or no excess of combined sul- 
phates include examples of chronic delusional insanity, 
chronic melancholia, and some of dementia. In indi- 
viduals Avhose mental condition was one where im- 
perative concepts played the chief part, the urine 
showed nothing that was unusual, at least so far as INTESTINAL AUTOTOXIS AND INSANITY. 
11 
absorption of intestinal putrefactive products was con- 
cerned. 
From the data obtained from all available sources, 
my own cases and others, it would appear not only that 
the ratio of the sulphates between themselves and to the 
urea, and the presence of indican in considerable 
amount, are indications of intestinal putrefaction, which 
no doubt influence the course of various insanities, but 
that a large increase of the combined sulphates has 
much to do with the genesis of various psychoses, and 
Bence Jones has noted this in delirium, while Regis 
and Chevalier Lavaure recognize the gravity of septic 
poisoning in other well-known mental conditions, but 
so far, though our knowledge is somewhat crystallized, 
the matter is still unsettled, and there is much to be 
learned with regard to the importance of the sulphatic 
ratio. My investigations convince me that the presence 
of indican in the urine of the insane has the most sig- 
nificance, so far as constancy is concerned, for in nearly 
all the cases which were not simply evolutional it has 
been discovered in excessive quantities, in connection 
with the development or as a feature of an exacerbation 
of an existing mental disorder. 
What is an excessive quantity? may be asked. The 
reply is: Any amount that can be detected in the urine by 
Jaffe’s test, even if a weak reaction is obtained. Smith 
fixes the harmful amount at anything more than five 
milligrammes in twenty-four hours, and the color may 
vary from a light pink to a deep purple. In two or three 
of my cases the appearance of indican was nearly always 
coincident with the outbreak of new symptoms or the 
intensification of old ones, and it always marked the ex- 
istence of a putrefactive process, bearing out the axiom 12 
INTESTINAL AUTOTOXIS AND INSANITY. 
that the presence of indol indicates bacterial death in 
the intestines. As regards the special connection of 
urinary findings of this kind with different kinds of 
mental disease, it would appear that in all forms with 
loss of weight and depression the sulphate ratio be- 
tween the combined and preformed sulphates was lower 
than in health. It has been pointed out by Senator 
that an abundant appearance of indican under these cir- 
cumstances indicates starvation, and, from the lowered 
quantity of preformed sulphates found in cases of in- 
anition, Herter and Smith agree with him. In melan- 
cholia especially, the amount of indican depends upon 
whether the disease is of the stuporous or agitated va- 
riety, the quantity of this substance found not being so 
great in the former. In one of the series of cases in 
Bloomingdale Asylum, examined by Dr. Dodd, it was 
absent only once" in a series of seventeen examinations, 
and always existed in large quantity with a correspond- 
ing decrease in the sulphate ratio, the latter varying 
from one half to one twelfth. In such cases of melan- 
cholia the blood-corpuscles and haemoglobin seem to 
undergo a decided diminution, which has been ob- 
served in other conditions where anaemia existed in as- 
sociation with the increase of the combined sulphates 
and the presence of large quantities of indigo blue. I 
believe it was the late Sir Andrew Clarke who first 
pointed out the connection between anaemia and the 
absorption of the products of intestinal putrefaction. 
In all the melancholic and other patients in which the 
coincidence existed, the variations in the haemoglobin 
and red corpuscles were closely connected with the ab- 
sorption of toxic substances, the extent of which was an- 
nounced by the increase of the combined sulphates, INTESTINAL AUTOTOXIS AND INSANITY. 
13 
while the physical appearances were those of malnutri- 
tion. Such a case was that of a young lady whose fee- 
bleness and exhaustion were extreme, and were coin- 
cident with a mental condition manifested by an initial 
neurasthenia, with digestive disorders, depressing delu- 
sions, self-accusation, and attempted suicide. The 
hcemoglobin was reduced to thirty per cent., and the 
red corpuscles to less than three hundred thousand. 
This state existed in connection with a low sulphate 
ratio and a constant output of indican, notwithstand- 
ing the fact that appropriate diet was ordered. The 
course of treatment, in which nuclein-forming agents 
and lavage and intestinal washing figured, cured her 
in two weeks, after arsenic and iron and forced feeding 
had failed. 
Some forms of melancholia are undoubtedly due to 
autotoxis dependent upon impaction and coprgemia, al- 
though the passage of an apparently sufficient amount 
of fecal matter may incline the observer to ignore the 
existence of constipation as a cause. If the urine of 
such patients is examined, a large excess of aromatic 
sulphates will he found, with increased indigo blue and 
possibly skatol. Two such cases have made a great 
impression upon me, for the reason that, notwithstand- 
ing the passage of what looked like fair-sized stools, 
which to all appearance contained the recognized debris 
of food taken within twenty-four hours, such was not 
the case, and a certain accumulation existed which gave 
rise to a melancholia of an almost stuporous kind at 
first, hut which subsequently became excited after a 
week or two, and was quickly cured by the recognition 
of the obstruction and its removal. In this case the 
increase of ethereal sulphates was enormous, the pres- 14 
INTESTINAL AUTOTOXIS AND INSANITY. 
ence of indican being detected in large quantities. After 
the bowels were emptied and naphthalin was given, the 
delusions, which were more or less systematized, quickly 
disappeared, and the urine became normal. It would 
seem that circumstances sometimes modify the course 
of a chronic melancholia by favoring the increased 
elimination of more or less toxic products, so that an im- 
provement in the mental state is witnessed, at least for 
a time. In a case reported by Eccles, an attack of in- 
fluenza in a melancholic caused an increase in the 
elimination of urea and the leucomaines, with a coin- 
cident improvement of the mental depression, which, 
however, reappeared when the pyrexia subsided. 
By far the most suggestive cases in which autotoxis 
from intestinal disorder plays a part are those of acute 
excitement, especially where there is rapidly developing 
incoherence and confusion. These, in my experience, 
have, as a rule, been associated with corresponding evi- 
dences of intestinal disorder such as have been de- 
scribed. Lively and generally fleeting illusions and 
hallucinations and delusions developing after insomnia, 
loss of appetite, and constipation, the delusions being 
unsystematized, are features, and if such derangement 
be connected with urinary findings of the character I 
have mentioned, and the clinical evidences of physical 
disturbance, I think the intestinal disturbance may be 
always looked upon as a cause. 
The more sudden and active are the manifestations 
when unsystematized delusions or hallucinations are ex- 
pressed, the more positive are, in my experience, the in- 
dications of autotoxis. So characteristic, for instance, 
are the loquaciousness and incoherence that Jacobson, 
who has described the toxic insanity of nephritis, has INTESTINAL AUTOTOXIS AND INSANITY. 
15 
applied the name of “ Verwirrheit ” to the confusion, 
which is almost allied to delirium. Acute hallucinatory 
insanity is often expressed by pseudaphasic confusion, 
and is often undoubtedly due to the cause I have men- 
tioned, and there are even cases of extreme neurasthenia 
in which consciousness is more or less affected, and 
where there is no special delusional system. Occasional 
remissions of some duration are possible in these forms 
of general derangement, during which the patient recog- 
nizes his false ideas and speaks of them. In some of these 
cases pseudaphasic confusion is expressed as the result 
of misleading auditory hallucinations which the patient 
is unable to correct. To the excited psychoses belong 
certain short-lived varieties of mental disturbance of 
this kind attributed to shock, and denominated trau- 
matic insanity, in which such confusion is a character- 
istic. To this class belongs a case recently seen by me 
in consultation with Dr. Lusk, of New York. 
The patient was a woman, thirty-seven years of age, 
who went into St. Vincent’s Hospital on January 28, 
1896. She had had some irregular menstruation with 
slight uterine haemorrhages between the menstrual pe- 
riods, and once or twice in her life had had epileptic 
convulsions. The condition of the heart and lungs was 
negative. Abdominal and vaginal examination revealed 
the presence of a fibrous tumor, which was removed by 
operation on January 29th, on that day the tempera- 
ture being normal and the pulse 90, hut the urine 
had a specific gravity of 1.035, and contained abundant 
urates. 
After the operation no untoward results occurred 
until the next day, when there were restlessness, insom- 
nia, flatulence, and a slight rise of temperature, which 16 
INTESTINAL AUTOTOXIS AND INSANITY. 
continued, so that on the evening of the 31st it had 
reached 103°. She was troubled with abdominal dis- 
comfort, eructations of gas, and increased nervousness. 
The bowels moved for the first time on February 1st, 
the amount of faeces being very small; on the 2d the 
enema brought away a large movement. She became 
flighty on the evening of the 2d, and had delusions and 
terrifying hallucinations of a persecutory nature; the 
temperature meanwhile varied between 101.2° and 102°, 
with broken and uneasy sleep procured only by mor- 
phine and chloral. 
The urine was now superficially examined, showing 
an abundance of urates with high specific gravity (1.025), 
no albumin, and sugar. Her incoherence almost 
amounted to delirium, and she cried, and was excited 
and anxious to leave her bed. For several days there 
was no particular rise of temperature, there being no 
greater advance than 102.8°, with a corresponding ra- 
pidity of pulse. The intestinal disturbance still con- 
tinued, and was very general. She did not recognize 
persons, hut called them by wrong and fanciful names, 
and had no idea where she was. She had been fed with 
nutritive enemata and milk, and on the 14th a critical 
examination of the urine was made at my suggestion, 
which disclosed the following appearances: 
A moderately large amount of indican and a low- 
ered ratio of preformed and combined sulphates; the 
combined sulphates measured by the Salkowski-Bau- 
mann method being 0.25 gramme, and the preformed 
sulphates 0.45 gramme in the urine of twenty-four 
hours, while the urea was reduced to 11.81 grammes in 
the same period. 
The ratio of uric acid and urea was 1 to 38. INTESTINAL AUTOTOXIS AND INSANITY. 
17 
Naphthalin was suggested and given in doses of 
four grains every two hours, being preceded by calomel 
and soda. Her condition, which had up to this time 
been almost continuously one of incoherence, promptly 
cleared up, and she but occasionally expressed delu- 
sions. The next day the temperature fell to 98.8°, and 
remained normal thereafter. She recognized that she 
had been irrational, and after the 23d there was little 
mental disturbance left, the specific gravity of the urine 
falling and showing a rapid decrease in all abnormal 
constituents, while her stools, which had been of a clay 
color, were well formed and regular. The sulphate 
ratio became normal, and the total sulphates were prop- 
erly proportionate to the urea; the ratio of uric acid to 
urea was 1 to 50. 
Another case in which the condition of the urine 
bore a very close relation to the variation of the mental 
symptoms was that of a young married lady, who upon 
two previous occasions, one far apart from the other, 
had manifested symptoms of an alternating character, 
there being usually an initial melancholia and succeed- 
ing light mania, which increased and had to be con- 
trolled by morphine and hyoscyamine. Her periods of 
mental derangement generally extended over several 
months, and seemed to hear close connection with a 
more or less profound disturbance of digestion, and 
were distinctly modified by the menstrual periods. The 
attacks of 1893 and 1894 were managed in the ordinary 
way, and there was a general amelioration of the symp- 
toms and final subsidence, the convalescence occurring 
after removal from home. In 1895, after a protracted 
neurasthenia, she was affected with a maniacal condition 
marked by very great muscular violence, incoherence, 18 
INTESTINAL AUTOTOXIS AND INSANITY. 
and lively delusions, some of which were erotic and un- 
systematized. So extreme was her condition as to need 
the services of three nurses, and, despite their uninter- 
rupted care, she became filthy and destructive, tearing 
her clothes, breaking such objects as she could lay her 
hands upon, and requiring dangerous quantities of hy- 
oscine for the production of quiet. Her condition was 
exceedingly variable, and when she was not engaged in 
impulsively destroying things about her and assaulting 
her nurses, she scribbled and wrote incessantly, and there 
was almost constant verbigeration. Her bodily con- 
dition was one which gave me a great deal of worry, for 
she rapidly lost flesh, and this despite the fact that 
large quantities of food of a condensed and apparently 
suitable kind were taken. 
Repeated examinations of the urine and the feces 
showed a very decided disturbance of gastric and intes- 
tinal digestion, and her symptoms kept pace with the 
variations in these processes. Her mental state, which 
was most irregular and apparently uninfluenced by any- 
thing in her surroundings, revealed an interesting con- 
dition of affairs, which was so constant and consistent 
as to convince me that the insanity was kept up by the 
absorption of some toxic material. Her periods of ex- 
citement and confusion were always attended by a re- 
duction in the amount of urine excreted, by an increase 
in the ratio of preformed and aromatic sulphates and indi- 
can, and by the presence of those signs of impaired diges- 
tion which indicated an intestinal putrefactive process. 
Certain psychical prodromes of attacks after periods of 
comparative lucidity were nearly always immediately 
connected with the presence of an increased sulphate 
ratio. At one time, before this connection was realized, INTESTINAL AUTOTOXIS AND INSANITY. 
19 
the prognosis was exceedingly bad, because of the ex- 
traordinary condition of physical exhaustion. 
This patient had received up to this time nearly all 
the approved restorative agents and tissue builders that 
were available, and one twelfth of a grain of the hy- 
drobromide of hyoscine daily. When this point was 
reached, the diet was restricted, nitrogenous substances 
being excluded as far as possible, and thorough intes- 
tinal disinfection was obtained by means of charcoal, 
salicylic acid, and the carbonate of guaiacol, the patient 
meanwhile being given large draughts of water, and her 
lower bowels flushed by the long rectal tube, with a mild 
solution of boric acid. At regular intervals she took 
calomel purges, and a preparation of the red marrow of 
the small hones of the calf, to which reference will pres- 
ently he made. The good result was almost immediate. 
Excitement subsided, and there was a rapid return of 
self-control, with the disappearance of the delusions, 
and a general subsidence of all mental disturbance. Con- 
tinued and sufficient sleep was obtained for the first time 
in months, and the patient rapidly recovered. Within 
a few days after the intestinal antisepsis had been es- 
tablished, the urinary condition became apparently nor- 
mal, the ratio of sulphates resuming its normal stand- 
ard, and the specific gravity of the urine was promptly 
lowered, while the indican disappeared. A distinct and 
decided gain in color and flesh was inaugurated, and in 
three weeks after treatment the red blood-corpuscles 
had increased fifty per cent., while the percentage of 
haemoglobin, as measured by the Reichert instrument, 
rose to 105. 
The causation of puerperal fever by the death of the 
Bacterium coli has been demonstrated by Budin, who 20 
INTESTINAL AUTOTOXIS AND INSANITY. 
has studied the febrile disturbance in connection with 
faecal accumulation. Undoubtedly, many puerperal in- 
sanities have some such explanation as this, especially 
those of the maniacal variety, which often develop in 
a very few days after parturition. A case I have recently 
seen was one in which there was absolutely no ascertain- 
able local infection and in which there was no unusual 
rise of temperature, and a rapid recovery took place after 
the establishment of intestinal antisepsis. 
Alcoholic insanity, as well as other forms, where acute 
or chronic variations prevail, must, I am convinced, be 
studied with regard to the conditions of the intestines, 
and it does not do to ascribe its origin altogether to gen- 
eral exhaustion or to circulatory changes, or to the well- 
known effects of alcohol upon the nervous tissue, al- 
though undoubtedly all these conditions exist at some 
time or other, and in different cases play a part. If we 
stop a moment to consider the clinical features of acute 
alcoholic insanity, we shall find many of the symptoms 
of a rapidly developing toxaemia, quite apart from that 
effect upon the nervous system which may be produced 
by the agent itself. The cerebral hypersesthesia, rapid 
changes in perverted perception, the development of the 
peculiar hallucinations in which rotten substances, 
worms, bad odors, or other horrors appear, often figure; 
the hyperkinesis, cephalalgia, malaise, etc., and the an- 
tecedent history of gastric intestinal disorders, the pres- 
ence of abundant aromatic sulphates, urea and indican 
in the urine, and possibly skatol, the foul small stools 
or diarrhoea, the final unstable and changing delusions, 
exhaustion and death, are suggestive. When we con- 
sider that the proteids have passed undigested through 
the small intestines, and have accumulated below, where INTESTINAL AUTOTOXIS AND INSANITY. 
21 
tliey lie enfolded in a congested and feeble gut, it is not 
difficult to appreciate the fact that they form a rich field 
for bacterial attack, with the resultant introduction into 
the system of an amount of toxic material sufficient to 
produce a most serious change in the functions of the 
brain and cord. The alcoholic extracts of faecal matter, 
according to Bouchard, are far more toxic than ordinary 
putrid matter, so it will be appreciated how readily 
skatol, indol, and other alkaloids of the faeces may be 
introduced in such quantities as to do much mischief. 
The successful treatment of the cases of alcoholic insan- 
ity that have come under my notice certainly goes far 
to strengthen this view. 
The insanity developing after very acute diseases, es- 
pecially influenza, is probably primarily dependent upon 
the intestinal congestion and derangement of the mu- 
cous membrane, which is a part of the general disorder 
elsewhere, but in typhoid fever, where specific intes- 
tinal regions are attacked, it does not appear that there 
is any undue appearance of indol in the urine, although 
the appearance of post-febrile insanity in this disease 
would make this seem impossible, at least in a small 
number of cases. 
The practical management of these cases not onh 
includes the provision of an absolutely suitable diet, 
but the use of antiseptics, and recourse to mechanical 
means for the purpose of cleansing the gastric tract. 
That the lower bowel is the seat of infection appears to 
be very well established by the experiments of Bau- 
mann, who found that when a fistula was made in the 
portion which included the lower portion of the small 
intestine, there was a disappearance of the indol, phenol, 
and the other ethereal sulphates from the urine, but that 22 
INTESTINAL AUTOTOXIS AND INSANITY. 
when the intestinal contents were allowed to pass through 
the lower natural outlet, the putrefactive products were 
largely increased and their presence was again detected 
in this fluid. This discovery shows the necessity for 
thoroughly washing out the lower bowel from as high 
a point as possible, and a long rectal tube should always 
be used for this purpose. 
Macpherson’s plan, tried with some success, is based 
on a recognition of the fact that when the antiseptic 
power of the acid of the gastric juice is impaired, there is 
an indication for the use of intestinal antiseptics with 
primary recourse to hydrochloric acid. Macpherson re- 
sorted first to lavage, which was followed by a dose of 
calomel at night, a saline purge in the morning, and the 
subsequent administration of naphthalin in doses, at 
first of thirty grains daily, which were increased to eighty 
grains. 
In my selected cases I used a variety of intestinal 
antiseptics, the list including naphthalin, salol, and the 
carbonate of guaiacol, charcoal, borax, and the salicylate 
of sodium. Several cases were put upon small repeated 
doses of calomel. These drugs were faithfully tried, 
and although with naphthalin I sometimes obtained ex- 
cellent results, and in one case of traumatic insanity very 
prompt ones, I found that upon several occasions it gave 
rise to diarrhoea, great muscular weakness, and twice 
strangury, and the urine was colored with hydroquinone. 
The administration of phenol or its derivatives may, 
under some circumstances, mask the results of urinary 
examination, as was the case in a recent experience. The 
patient had submitted himself to treatment by a physi- 
cian for a supposed tuberculous affection, receiving in- 
jections of a preparation which contained phenol and INTESTINAL AUTOTOXIS AND INSANITY. 
23 
pilocarpine. A few days after treatment he became 
wildly insane and attempted suicide. An examination 
revealed an entire absence of the preformed sulphates 
and indican, hut a very large amount of combined sul- 
phates. In this case the phenol entirely changed the 
urinary findings, as it always does. There was no intes- 
tinal disorder or there would have been indican, and the 
conclusion was reached that all the mental derangement 
was due to the pilocarpine. 
Salol was unreliable and of slight service, and was 
often passed in an unchanged condition in the faeces. 
Even with this drug administered in large quantities, 
it was apt to he found in small round balls in the faeces, 
and it is therefore recommended that all intestinal anti- 
septics should be given in small and repeated doses. 
Naphthalin, if administered in capsules, which, as 
a rule, is necessary because of its offensive odor, is some- 
times passed in an unaltered state. My experience is that 
of Herter and Smith, that there is no agent which ap- 
proaches salicylate of sodium, so far as its antiseptic ad- 
vantages are concerned, and I have given it in from ten 
to fifteen grains, thrice daily, and found it of especial 
value in melancholia and other insanities where the cere- 
bral condition is one of anaemia. The use of this drug, 
which produces a condition of increased arterial tension, 
is rather against the theory that uric acid produces cere- 
bral symptoms, for not only is it of service because of its 
antiseptic action, hut in the anaemic brain of melan- 
cholia it certainly brings about an improvement through 
accession of new blood and nutritive material. 
In insanity of a toxic nature there is, as we know, 
a destruction of haemoglobin, and a very greatly reduced 
number of red corpuscles. This condition of affairs is 24 
INTESTINAL AUTOTOXIS AND INSANITY. 
not only met with in the acute insanities due to the 
absorption of putrefactive products of intestinal indi- 
gestion, hut in old insanities as well, and Johnson-Smyth 
found the red corpuscles reduced to 4,070,000 and the 
hemoglobin to fifty per cent, in the case of secondary 
dementia. 
So far as the nutrition of the individual is concerned, 
I have had the best results with a combination which is 
a rapid producer of nuclein, and when we appreciate the 
fact that in the majority of these cases there is a de- 
struction of the coloring matter, as well as other blood 
elements, the provision of some agent rich in this sub- 
stance is an absolute necessity. 
Eemedial measures of this kind consisted in the use 
of a combination of a glyceride of the red marrow of 
small hones with bullock’s blood, the amount of glycerin 
being regulated both in quantity and temperature so that 
coagulation does not take place during its preparation. 
With this preparation I have been enabled to. prevent 
waste, and build up my patients much more rapidly 
than with any of the other more popular restorative 
agents, and its use at two of the large hospitals for the 
insane in New York was attended by an increase of red 
corpuscles to the extent of fifty per cent., and depressed 
states were quickly helped.* 
The possible conclusions are, I think, the following: 
1. Urines rich in indican contain very little or no 
preformed sulphuric acid, and are toxic. 
2. When the sulphate ratio is materially changed, it 
* The preparation which has been called carnogen by its manufac- 
turers was that used in the Hudson River State Hospital in Poughkeep. 
sie. See Dr. Pilgrim’s article in the American Medico-surgical Bulletin 
for June 6, 1896. INTESTINAL AUTOTOXIS AND INSANITY. 
25 
is likely to indicate autotoxis in connection with an in- 
crease in the amount of combined or ethereal sulphates. 
3. Such indications are generally found with acute 
insanities, in which rapidly developing symptoms occur. 
4. Fugacious and changing illusions and hallucina- 
tions, unsystematized delusions, confusion and verbi- 
geration in connection with insomnia, pallor, intestinal 
indigestion, constipation, and rapid exhaustion are due 
to autotoxis. 
5. Paranoiac states, or those in which concepts are 
the features, chronic stuporous conditions, and certain 
forms of dementia have little to do with the formation of 
intestinal products of putrefaction. 
6. Various post-fehrile, traumatic, alcoholic, or drug 
insanities are those in which autotoxis is most constant. 
7. The variations in the excretion of combined sul- 
phates keep pace with the changes in the progress of an 
established insanity, acces and epileptoid attacks be- 
ing directly connected with putrefactive processes. 
8. The most successful treatment consists in lavage, 
intestinal douches, gastric and intestinal antisepsis by 
means of hydrochloric acid, borax, salicylate of sodium, 
charcoal, guaiacol, or naphthalin in small repeated doses. 
The administration of a combination of the red marrow 
from the small bones, blood, and glycerin. 
Bibliography. 
Senator. Centralblatt. f. d. med. Wissensch., 1872. 
Salomon. Archiv fur Anat. und Phys., 1882; 
Archiv fur Anat. und Phys., 1885, p. 570. 
Spitzka. On Insanity. 
Thudicum. Grundziige der anatom, und Min. 
Chemie, 1886, pp. 15, 246. 
Salkowski. Zeitschr. f. physiolog. Chemie, Bd. x, 
1886, S. 266. 26 
INTESTINAL AUTOTOXIS AND INSANITY. 
Baumann. Zeitsclir. f. pliysiolog. Chemie, Bd. x, 
1886, S. 126. 
Yon Jaksch. Clinical Diagnosis (Translation), pp. 
158, 160. 
Betencourt-Rodrigues. Transactions of the Inter- 
national Congress of Mental Medicine, 1889. 
Chevalier-Lavaure. These de Bordeaux, July, 1890. 
Gaston Lyon. These de Paris, 1890. 
Charpentier. Annales medico-psychol., October, 
1890. 
Fayal. These de Lyon, 1890. 
Johnson-Smyth. Journal of Mental Science, Octo- 
ber, 1890. 
Ayres. Medical Times, July, 1891. 
Herter and Smith. New York Medical Journal, Sep- 
tember, 3, 1892. 
Maepherson. Journal of Mental Science, 1893, vol. 
xxxix, p. 37. 
Herter and Smith. New York Medical Journal, 
June 22, 29, July 6, 13, 20, 1895. 
Kegis. A Practical Manual of Mental Medicine, 
1895, p. 102. 
Turner. Journal of Mental Science, 1895. 
F. St. John Bullen. Journal of Mental Science, 
April, 1895. 
Ferraud. Bulletin general de therapeutique, livr. i, 
p. 3, 1896. 
Eccles. Lancet, January, 1896. 
Discussion. 
The President congratulated the society upon the 
presence of so distinguished an authority as the au- 
thor, a courtesy which he hoped would he reciprocated 
by the reading of a paper by an Englishman before 
the Academy of Medicine of New York at some future 
date. He recalled the excellent work done by the au- 
thor during the last twenty years in the department of 
medicine with which he himself was most associated. 
The paper opened out new and original ground, though 
he supposed the author himself would admit that much INTESTINAL AUTOTOXIS AND INSANITY. 
27 
of it was speculative. Many of his conclusions, indeed, 
could not at present be implicitly received and accept- 
ed, and autotoxis would not drive out of the field all the 
older methods of dealing with this class of cases, though 
it might prove a valuable help in treatment. He re- 
called the fact that Dr. Lauder Brunton had pointed 
out the resemblance which exists between the languor 
associated with indigestion and the effects of curare poi- 
soning, and that he had suggested that these symptoms 
might be due to the absorption of poisonous matter 
from the intestines, probably of the nature of ptomaines. 
It was only necessary to suppose an excessive production 
of these ptomaines or their imperfect destruction by the 
liver, which, under ordinary circumstances, prevented 
them reaching the circulation, to understand that this 
failure to protect might have far-reaching consequences. 
They had only to imagine this to see that in the long 
run a condition might be engendered which might cul- 
minate in melancholia with stupor, evidently strictly 
analogous to the autotoxis to which the author had in- 
vited their attention. That the production of these bod- 
ies in the intestine might be enormously increased in cer- 
tain states had been clearly demonstrated, and he him- 
self was inclined to believe that their presence in excess 
in cases of intestinal catarrh might readily give rise to 
the mental consequences associated with this condition. 
He pointed out that there was a well-known type of hy- 
pochondriacal melancholia associated with catarrh of 
the transverse and ascending colon in which the mental 
characteristics were out of proportion with the lesions, 
cases in which there was no family history, and the 
symptoms yielded readily to a visit to Carlsbad or Marien- 
bad. He had often thought that the symptoms in these 
cases might he due to excessive production of ptomaines 
in the intestine or to their imperfect destruction by the 
diseased liver. The possibility of putrefactive changes 
in the intestine and the consequent production of pto- 
maines were, of course, very great and very varied. He 
mentioned that, according to Mr. J. Murray, of the 28 
INTESTINAL AUTOTOXIS AND INSANITY. 
British Museum, there were 128 genera of microbes 
and 169 fungi which thrived and flourished in fsccal 
matter; many of them were peculiar to particular kinds 
of fasces, 45 to the horse, 35 to the dog, 28 were peculiar 
to birds, and 21 to the fasces of man. It was clear, there- 
fore, that fasces afforded a very favorable and congenial 
nidus for fungoid and bacterial growth, and any change 
in the physical contents of the lower bowel or any 
change in their environment interfering with the fun- 
goid struggle for existence, by giving advantage to one 
variety, might allow of the production of an excessive 
amount of certain poisons, followed by symptoms of 
poisoning. ITe asked whether the brain itself might not 
provide poisons, seeing that poisonous ptomaines had 
been proved to develop in cerebral matter after death, 
and it was possible that under certain conditions of 
malnutrition similar products might be produced at an 
earlier period. Muscles were known to develop various 
alkaloids during life which might, under particular cir- 
cumstances, even determine a fatal effect. It was also 
worthy of consideration whether the epileptiform seiz- 
ures which checkered the course of the later stages of 
general paralysis might not be due to autotoxis. There 
was a gradual degradation of nutrition and possibly in- 
cipient decomposition of albuminous tissues which might 
produce substances acting as poisons on the nerve cells, 
producing a special train of symptoms along with a rise 
of temperature. Selbing had shown that ptomaline was 
found in the general paralytic and in pneumonia, and 
one was familiar with the fact that washing out of the 
lower bowel was often the means of arresting the epi- 
leptiform attacks which characterized the later stages 
of general paralysis. He supposed the author would ad- 
mit that the subject was at present better fitted for the 
laboratory than for academical discussion. His title, in- 
deed, was very comprehensive, for it might be made to 
include all forms of moral and intellectual auto-intoxica- 
tion, a phenomenon which resulted from undue egotism 
and the concentration of the energies on selfish or de- INTESTINAL AUTOTOXIS AND INSANITY. 
29 
grading objects. Ideal microbes and emotional pto- 
maines would lead them too far afield, and be would, 
therefore, not enter upon their discussion. 
Dr. Haig said it was now nearly eight years since 
he had first called attention to the presence of an ex- 
cess of uric acid in the urine of cases of mental depres- 
sion and of epileptic convulsions, etc., and he was still 
of the opinion that the symptoms in such diseases, now 
referred by some to intestinal putrefaction, were really 
due to the presence of an excess of uric acid in the 
blood. The uric acid altered the circulation throughout 
the whole body; the altered circulation in the brain ac- 
counted for the mental symptoms, and that in the stom- 
ach and intestines caused putrefaction to take the place 
of digestion. He had been much interested in what the 
author had said about the beneficial effects obtained by 
the use of calomel, because calomel cleared the blood 
of uric acid. It would, therefore, tend to prevent the 
modification of the intestinal circulation, which was the 
cause of the putrefaction. Salicylate of sodium also 
cleared the blood of uric acid and so prevented its exert- 
ing its usual effects. In one of the cases on which the 
author had laid considerable stress, he noticed that the 
patient got better when the regimen was changed, but 
they had not only changed the diet but given antiseptics 
and washed out the intestines as well. He had laid great 
stress upon these things hut had said little about the 
diet. His own idea was that they gave far too much 
nitrogenous fond, and when this was discontinued and 
the introduction of uric acid put a stop to, the patient 
got well. Many patients suffering from mental disease 
had been cured simply by diet, without any attention 
being paid to intestinal putrefaction. The points about 
uric acid which he wished specially to bring to the notice 
of those interested in mental diseases were the well- 
marked clinical signs of its excess in the blood—viz., 
high blood pressure and scanty urine. In some of the 
author’s cases he had noticed scanty urine, and this, no 
doubt, meant an abundance of uric acid in the blood. 30 
INTESTINAL AUTOTOXIS AND INSANITY. 
If they controlled that either by diet or by drugs they 
would control the circulation and the mental disease. 
Dr. Andeiezen said there was no doubt that one 
source of the poisons which generated insanity was in- 
side the body during life (poisons of endogenous origin). 
From bacteriological study we knew that actual toxines 
could be obtained from the cultures of various patho- 
genic bacilli—such as those of cholera, typhoid, tetanus, 
etc., which, injected into the body of man or animals, 
produced the special and characteristic phenomena of 
the disease in question (Koch, Pouchet, Brieger, and 
others’ researches). Deferring to the intestinal poisons 
arising from constipation, it was well known that in 
those accustomed to a daily evacuation of their bowels 
a comparative slight delay (a few hours to one day) was 
sufficient to bring about headache and depression of 
spirits, which immediately passed off when the bowels 
were relieved. The mere retention of faecal matter, even 
for a few hours, permitted of the passage of a certain 
quantity of poison into the blood. He found it difficult 
to explain this circumstance on the hypothesis of uric- 
acid formation. An excess of uric acid would doubtless 
also give rise to much the same effects, but the rapidity 
with which the effects followed mere faecal retention 
showed that the source of the symptoms must be re- 
ferred to the intestines. It was very important also to 
bear in mind what Dr. Lauder Brunton had shown—viz., 
that a great amount of toxic matter might be produced 
from disorder of the stomach, as in various gastric ca- 
tarrhs. Dr. Andriezen mentioned certain cases of lis- 
teria with dilated stomach, in which washing out the 
stomach and giving small doses of naphthalin (five 
grains) had brought about a very prompt recovery. 
Of course, other cases of hysteria, those with a different 
pathogenesis, did not react to this kind of treatment. 
In the cases of hypochondriacal melancholia without 
neurotic taint or history he could bear out what the 
President had stated, and he believed that these belonged 
fo much the same category as the hysteria noted above, INTESTINAL AUTOTOXIS AND INSANITY. 
31 
only the changes were more extensive and severe, and 
the mental symptoms correspondingly increased. Toxic 
absorption from the gastro-intestinal tract, with or with- 
out morbid changes in the portal blood, could produce 
chloroses and anasmias of various degrees, and in some 
cases of pernicious anaemia such poisons (different dia- 
mines) had been found in the faeces by Hunter. The 
sluggish movements in the gastro-intestinal tract and 
its lowered vitality in melancholia favored the develop- 
ment of ptomaine-producing micro-organisms. Such 
cases showed an increase of the aromatic sulphates in 
the urine—a good index of the amount of intestinal 
putrefaction going on. In epilepsy and in general paral- 
ysis the accumulation of such toxines in the blood fa- 
vored and brought on convulsive attacks. The tendency 
of chronic Bright’s disease to intensify existing symp- 
toms of toxaemia and even to favor acute convulsions 
(i. e., poisoning of the cerebral centres), as in pregnant 
women, was pointed out, and the importance of it in the 
clinical course of certain insanities emphasized. He was 
unable to agree entirely with Dr. Hamilton, that nearly 
all the rapidly developing manias and insanities, with 
hallucinations or acute mental confusion, were of auto- 
toxic origin. In many such cases quite other and ade- 
quate causes could he easily ascertained; though errors 
of diet and digestion, neglect of the bowels, and conse- 
quent auto-intoxication from the intestines, might play 
a minor part. He was chiefly impressed with the fre- 
quency with which such autotoxis might occur, and 
thus aggravate the symptoms in already established in- 
sanities, such as general paralytic, epileptic, alcoholic, 
and slowly developing delusional insanity. The clinical 
phenomena in these cases were a slight subacute de- 
lirium with restlessness, the patient stumbling and fum- 
bling about in his room, with insomnia, which did not re- 
act to the usual sedatives and hypnotics, and where the 
temperature was slightly raised, the tongue furred, the 
breath offensive, and the skin and flesh peculiarly liable 
to undue markings like bruisings, even from mere rest- 32 
INTESTINAL AUTOTOXIS AND INSANITY. 
lessness and the pressure of garments alone. Where he 
had examined the urines in such cases (about nine or 
ten cases) he had noticed considerable excess of indican, 
as compared with the same case after such a delirious 
episode in the course of the insanity was over. Sucli 
cases reacted well to brisk purgation and enemata with 
a predominantly farinaceous and milk diet: calomel was 
excellent for the former, and it could with advantage be 
administered with a capsule of naphthol. Personally he 
had great faith also in capsules containing pure carbolic 
acid, given between meals if gastric fermentation co- 
existed. He referred to an important class—what he 
would call a diathetic class—of the insanities which 
the text-books as yet had not recognized, lie did not 
refer to the so-called gouty or rheumatismal insanities, 
but to those associated with and growing in the soil of 
myxoedema and acromegaly, with a very constant and 
distinct physiognomy of their own, and with a patho- 
genesis that could be harmonized and well explained 
by the morbid changes present, changes which lay at the 
root of the mental as well as the bodily conditions. In 
the one case (myxoedema), a morbid process starting from 
the thyreoid gland affected the whole capacity of the 
blood in regard to its power of taking up oxygen from 
the air. On examining the blood with the mercurial 
pump it was found that its gases 0 and C02 were much 
diminished, and by placing the individual in the ap- 
paratus for examining the gases of respiration, it was 
found out that he took in but little oxygen and corre- 
spondingly gave out but little C02 during life. Thus 
he suffered from weakness and dullness, from subnor- 
mal temperature, and from a tendency to the accumula- 
tion of incompletely oxidized bodies (fat, etc.) in his 
tissues. Similarly in the insanity of acromegaly pituita- 
ry feeding gave corresponding benefit, and for those 
who cared to follow the function of this gland and its 
special relation to the brain and nervous system he 
would refer to his paper on the pituitary, published 
in the British Medical Journal, January, 1894. Finally, INTESTINAL AUTOTOXIS AND INSANITY. 
33 
as to toxines formed in the central nervous organs, this 
possibility must not be overlooked. Toxines may form 
in muscle and gland from the chemical products gener- 
ated during the activity of such tissues—e. g., C02, lactic 
acid, creatine, etc. Now, in the central nervous system 
there was a very complex lymph apparatus for the ab- 
sorption, carrying off, and elimination of these metabolic 
waste products. The whole nervous tissue of brain and 
spinal cord and the sheaths of the cranial and spinal 
nerves were perforated by a system of lymph channels, 
which in the brain cortex itself formed a special pro- 
longation around each of the larger nerve cells (peri- 
cellular lymph sacs), and which had peculiar relation- 
ships with the adventitial sheaths of the pia-arachnoid 
and intracerebral blood-vessels. In the general paralytic 
and in the chronic alcoholic these lymphatic structures 
were affected in a special and peculiar way, producing 
in places blockages of the lymph streams and overgrowth 
of these lymphatic (lymph-secreting and lymph-absorb- 
ing) cells, which, according to their local incidence and 
preponderance, affected different spots, centres, and 
tracts of the central nervous system. An associated 
paresis of the muscular coats of the blood-vessels fol- 
lowed by fusiform and ampullary dilatations of the vas- 
cular and lymphatic channels also coexisted and added 
to the complexity of the morbid involvement, and this 
apart from changes which took place in the dynamic 
connections of nerve cells (dynamic changes) and in the 
internal nutrition of the cells, bodies and protoplasm 
(nutritive changes). The products of metabolism of the 
nerve cells would thus he in places retained in the dilated 
or obstructed sacs and lymphatic channels, producing 
from time to time—i. e., continuously or cumulatively— 
various symptoms of toxis; the toxine being in such 
cases the unescaped, uneliminated products of cell ac- 
tivity. He concluded by stating that more often than 
not toxic agencies played a part in the course of an in- 
sanity which was already established; in a small number 
they played a truly causal part, hut that in any case they 34 
INTESTINAL AUTOTOXIS AND INSANITY. 
should be vigorously treated when indications of their 
presence existed, the treatment being lavage or enemata, 
purgation with calomel, and antiseptic drugs taken in- 
ternally; while to aid the convalescent stage and its as- 
sociated ansemia iron, extract of bone marrow, etc., were 
indicated. 
Dr. Hare said that, in listening to the paper, he had 
been struck by the fact of the large amount of knowl- 
edge the ancients possessed on the subject-matter dis- 
cussed by the author. The central point insisted upon 
was that of self-poisoning in relation to mental condi- 
tions; in other words, the connection between such states 
of the mind and of the nervous system and the processes 
of disintegration and disease within the body. But the 
physicians of two thousand years ago were well ac- 
quainted with these facts, and they used such terms as 
“ melancholia ” and “ hypochondriasis,” “ black bile,” 
and “ under the cartilages,” showing that the Greeks 
well knew the relation between mental disturbances and 
affections of the liver. But the physicians of the pres- 
ent day had demonstrated what was previously only 
known as the result of clinical observation. There was 
nothing of which he was more sure than this self-poison- 
ing, not only in insanity, but in many other conditions; 
and doubtless they would sadly neglect the treatment of 
many cases of insanity if they did not pay attention to 
the condition of the digestive organs. He was glad to 
hear the author insist upon the value of calomel and 
purgatives. 
Dr. Theodore Williams observed that in this coun- 
try one ought not to suffer so much from mental and 
other diseases due to defective excretion, because great 
attention was usually paid to regularity of bowels and 
the proper function of the skin. On this ground, if the 
author’s hypotheses were correct, such mental disturb- 
ances ought to be much more common in countries where 
it was quite common for persons to have an action of the 
bowels only once a week, and then only from purgation, 
and it was well known that the skin was not so well 
looked after there as here. INTESTINAL AUTOTOXIS AND INSANITY. 
35 
Dr. Bower suggested that probably the intestinal 
trouble was more often the result of the nervous trouble 
than the cause. In respect of alcoholic insanity, it was 
said that the neuroses made the patient drink, and the 
drink reacted on the neuroses. lie thought that wash- 
ing out the stomach and intestines was of the greatest 
possible advantage. 
Dr. Forbes Winslow observed that the subject was 
a very difficult one unless one had practical experience 
in a large institution. Patients in private practice did 
not afford sufficient opportunities to justify them in 
•coming to any conclusion on the subject. As, however, 
the question was being raised in the House of Commons 
us to the increase in the prevalence of insanity and its 
causes, it was a great thing to have a paper like the one 
to which they had just listened. The mention of the 
influence of uric acid in the system reminded him of a 
case of a man suffering from gout who had melancholia 
with monomania. After a time the presence of a stone 
in the bladder was made out, and on its removal all his 
delusions disappeared. 
Dr. Hamilton, in replying, thanked the president 
for his kind words of welcome and wished to say that his 
paper was simply suggestive of the vast possibilities of 
the subject. He had recognized the conditions so clearly 
enumerated by Sir Crichton Browne, which all played 
an important part in the causation of mental disease, and 
he proposed at a future time to publish further details 
of his investigations. The speaker was disposed to re- 
gard the conclusion of Dr. Haig, whose views of gout are 
:SO well known, as extreme in the present instance, and 
while he recognized the fact that increased uric-acid ex- 
cretion was found in many nervous disorders, he regard- 
ed these phenomena as the result of intestinal derange- 
ment such as he, the speaker, had demonstrated, rather 
than the initial cause, and he referred to Dr. Haig’s own 
writings in regard to the transferral of cerebral and joint 
symptoms as an illustration. While he recognized the 
importance of the study of insanities associated with 36 
INTESTINAL AUTOTOXIS AND INSANITY. 
myxoedema and acromegaly, and the formation of cer- 
tain alkaloids in the nervous system, he did not feel that 
the scope of the paper permitted him to go into this ques- 
tion, which seemed to have been so diligently studied 
by Dr. Andriezen. As to the query of his friend, Dr. 
Theodore Williams, regarding the antipathy of the 
French to water and to the carelessness regarding the 
ordinary functions of Nature and their relation with 
Gallic insanity as compared with the better habits of 
their Anglo-Saxon neighbors, he had his own views. 
In conclusion, while disclaiming any dogmatism, he still 
would insist that in most cases of suddenly developing 
acute mania, and especially such forms as the puerperal 
and periodic varieties, the existence of intestinal auto- 
toxis could be very often found. The New York Medical Journal. 
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