ON THE RELATION OF UREA TO EPILEPSY. BY J. Nelson Teeter, M. D. Assistant Physician Utica State Hospital, Utica. N. Y Reprinted from the American Journal of Insanity, for January, 1895. BAND, MC NALLY A CO., PRINTERS, CHICAGO. ON THE RELATION OF UREA TO EPILEPSY. BY J. NELSON TEETER, M. D. Assistant Physician Utica State Hospital, Utica, N. Y. So much has been written upon epilepsy, its etiology, pathology, and treatment, that it is with great reluctance and hesitation these observations are presented to the medical profession, but in view of the fact that idiopathic epilepsy is one of the most obscure and therefore intensely interesting diseases we have to deal with, any research referring to its causation may be acceptable. Most observers, especially those of the present day, have dealt not so much with the etiology of this disease as with the treatment, and the whole pharmacopoeia has been exhausted, from the old-time remedies down to the newer agents, in the extensive search for a specific. From time to time articles appear in our medical journals praising the efficacy of certain agents to the exclusion usually of others; but they all lack the proof of time, for the majority of these observations extend only over a few months, or a year at most. We have all noticed an improvement in our cases upon the exhibition of a newly vaunted remedy, and are inclined to be enthusiastic over its efficacy as an anti-epileptic, but further experience and careful observation bring disappointment, and we pass on to other drugs. Thus, the bromides, belladonna, nitrate of silver, anti-febrine, beta naphthol, sodium borate, and opium, which has been revived, have all proved unsatisfactory. Is it not time to commence the study of epilepsy A, priori instead of heroically treating the great result - the convulsion - as if this were the root of the whole evil? 'Why should the convulsion be considered so much more important than other symptoms usually present-for example, the gradual mental enfee- blement which accompanies the progress of this disease? Regis, in an article read before the congress of psychological medicine, incidentally speaks of the probable cause of epilepsy as an auto-intoxication, in proof of which he finds an increase in the toxicity of the urine subsequent to an epileptic paroxysm, and quotes similar results obtained by MM. Fer£, A. P^rou, Chouppe, and Jules Voisin. This theory seems to be a very tenable one when we remember noticing in many of our cases considerable improvement for a time after thorough purgation or the exhibition of diuretics and exercise. Keeping in mind these facts, T was led to 2 believe that some definite constituent of the excretions of the body might be the cause of this auto-intoxication; that a continued and careful analysis of excrementitious materials would show a variation in amount before and after convulsions, and, perhaps, a lessening of the special poison during the whole course of the disease. Urea, it is well known, when not excreted by the kidneys in sufficient quantity, will give rise to great mental disturbance, often ending in severe convulsions, and finally bringing on coma and death. The convulsions in uraemia are very similar to those observed in epi- lepsy, so much so that they have been described as epileptiform in character. The peculiar epileptic cry, the fixation of the eyes, dilatation of the pupils, rigid features, congested countenance, and the tonic, followed by the clonic convulsion, have all been seen in the uraemic paroxysm. Upon examination of the urine, we find a lessened amount of urea excreted, and it is only after the accumu- lation of this special poison is gotten rid of by vicarious methods that the normal processes of the organism are again established. Uraemia is an auto-intoxication, and the special poison is urea. We notice in cases of status epilepticus convulsion following convulsion in rapid succession, bearing, as is often remarked, a close resem- blance to the uraemic state. The fact that the most efficacious treatment is very similar in both cases - the administration of chloro- form and the re-establishment of the functions of the excrementi- tious organs - suggested to me the strong presumption of a common origin of the two conditions. One need not necessarily assume for the production of uraemic convulsions a parenchymatous change in the kidney itself - might there not be a nervous origin for the impairment of its function? We notice in paralysis of muscles two origins, peripheral and central. In the peripheral there may be injury of the muscle itself, producing a temporary loss of power or disease of its parenchymatous substance, producing complete or partial destruction of the muscle, with a corresponding loss of func- tion. To this I would liken the condition of the kidney substance in pure Bright's disease, uraemia being too comprehensive a term. On the other hand, a central origin may account for the muscular palsy. A degeneration, an injury of the motor area, or a tumor compressing it, may cause the trouble, and so it appears to me is the state in idiopathic epilepsy. There is a slowly progressing dis- ease of some center or brain area not yet demonstrated, commencing often in early life and gradually extending to the rest of the brain substance, producing atrophy and sclerosis of important structures, 3 and finally ending in imbecility and terminal dementia. In epilepsy we have an actual disease of brain substance; no other process could bring about the pitable state of utter helplessness, such as some of the cases in our institution present. I have not had an opportunity for an examination of the epileptic brain, but the researches of Doctor Worcester, showing such changes as atrophy, with sclerosis of the hippocampus major; those of Barthez and Rilliet, finding sclerosis of the gray matter of the cortex; those of Bevan Lewis, showing degenerative changes in the second layer of the cortex, and of Eccheveria, describing changes in the sympathetic ganglia, as well as of Ziegler, revealing in some cases heterotopia, and of many other observers reporting various changes, warrant the belief that important alterations exist, although we have no exact data as to their special nature in all cases. Treatment. Date. Reaction. Specific Gravity. Albumen. Sugar. Drea in Grammes per C. C. Quantity of Urine in C. C. Total Urea in Grammes. None. July 19 Slightly alk. 1015 None. 4 4 None. 4 4 005 1184 0 5 920 "" 20 Acid 1023 01 1186 0 11 860 <c " 21 4 4 1022 4 4 44 015 947 2 14 208 < ( " 22 4 4 1010 4 4 4 4 004 1420 8 5 683 ( c " 23 1020 4 4 4 4 Oil 660 4 7 264 (I " 24 Slightly alk. 44 1022 44 4 4 '015 1032.0 15.480 < ( " 25 1010 44 4 4 006 1420 8 8 595 < < " 26 44 1017 4 4 4 4 008 1184 0 9 472 < c " 27 Acid 1020 4 < 4 4 01 1006 4 10 064 < < " 28 4 4 1024 44 4 4 01 948 4 9 484 c < " 29 4 4 1025 C 4 4 4 012 1000 0 12 000 ( 4 " 30 4 4 1024 C i 4 4 02 592 0 11 840 C " 31 44 1030 4 4 4 4 019 710 4 13 498 ( 4 Aug. 1 4 4 1014 4 4 44 Oil 1539 2 16 931 C C 2 4 4 1025 4 4 4 4 015 950 0 14 250 « C " 3 4 4 1015 4 4 4 4 015 651 2 9 768 4 4 " 4 4 4 1030 4 4 4 4 022 473 6 10 419 4 4 " 5 k 4 1022 44 4 4 02 540 0 10 800 4 4 " 6 4 4 1023 4 4 4 4 02 592 0 11 840 4 4 " 7 44 1025 4 4 4 4 028 651 2 18 234 4 4 " 8 4 4 1025 4 4 4 4 026 532 8 13 853 4 4 " 9 4 4 1023 4 . 4 4 .019 562 4 10 6>-6 4 4 " 10 4 4 1015 4 4 4 4 018 1716 8 30 903 4 4 '■ 11 44 1025 4 4 4 4 024 710 4 17 049 It " 12 4 4 1025 4 4 4 4 025 478 0 11 950 4 4 " 13 4 4 1024 4 4 if 02 680 8 13 616 4 4 " 14......... 4 4 1015 4 4 4 4 008 1184 0 9 472 < 4 " 15 4 4 1020 4 4 4 4 02 740 0 14 800 44 " 16 4 4 1015 4 4 4 4 Oil 888 0 9 768 44 " 17 4 4 1015 4 4 4 4 Oil 621 6 6 838 44 " 18 4 4 1012 4 4 4 4 007 835 0 5 845 4 4 " 19 4 4 1015 4 4 44 .01 946.4 9^464 4 I wish to present the final result of some observations extending over a period of about six months upon two cases of idiopathic epilepsy - one of the grand mal and one of the petit type. The first case, J. H., twenty-five years old, male, in good physical condition, has had attacks of major epilepsy since childhood. Family history negative. He came to the hospital in April, 1894, previous to which time he had been confined in two other State hospitals as a confirmed epileptic. He was very much demented upon admis- sion, and subsequently had about three or four convulsions a week. Owing to the patient's greatly demented condition, considerable difficulty was experienced in collecting the urine, and it was finally necessary to confine him in a separate room before all the urine passed could be obtained. An examination of the urine of twenty- four hours, without treatment and with the ordinary hospital diet, for the first month, and without particular reference to convulsions, showed a large decrease in the total amount of urea from the normal, as is shown in the tabulated record on preceding page. From this it will be seen that the amount of urea excreted is far below the normal average of 33.19 grammes per twenty-four hours - the average here being only 11.93 grammes. This is contrary to the results of Regis, who finds 25.17 grammes, which he says exceeds the normal by about two grammes. Observations were continued in this case, and particular attention was paid to the amount of urea excreted before and after the epileptic convulsions. All the urine passed by patient until the time of fit was considered to be before the convulsion - that excreted for eight hours after each attack was BEFORE. 1020 1020 1022 1006 1004 1012 1020 1010 1020 Specific Gravity. .007 .007 .02 .002 .001 .003 .019 .004 .016 Urea in Grammes per C. C. 473.6 428.0 458.8 976.8 1045.0 478.0 450.0 505.0 425.0 Quantity of Urine in C. C. 3.315 2.996 9.176 1.954 1.045 1.434 8.550 2.020 6.860 Total Urea in Grammes. OOOOOOOOO to - Z O J O ; c IC tcc3M<;a>cciS.t>5 Specific Gravity. AFTER. .014 .015 .019 .008 .015 .01 .02 .007 .02 Urea in Grammes per C. C. ojwo^jwqowwm ooiCtoo!Qo®a<i oohuooooooci Quantity of Urine in C.C. 2.486 4.875 4.499 7.104 3.375 4.720 4.008 5.985 9.000 Total Urea in Grammes. QDCOCICOtOQOCSKias *josoto<»ja(owoi oo^ooooook Total Urine in C. C. for 24 hours. TOTAL. ccouT^itoc'. act C: O Ct O1 W Ci o -7 O c i, a o. o a w r- « Total Urea in Grammes Ibr 24 hours. 5 labeled as after the fit. A uniform variation in specific gravity and the amount of the urea present in the two specimens was invari- able during a period of about four months' examination-the urine passed after the fit, having a higher specific gravity and a larger amount of urea per C. C., as shown in the foregoing table. It will be seen by this table that, with one exception (Observation No. 3), the specific gravity and amount of urea was increased after each convulsion. Case No. 2-L. F., a strong, healthy man, thirty-eight years old has had attacks of petit mal since the age of fifteen, which he believes were brought on by masturbation. The attacks occurred daily and were usually light, accompanied by the peculiar epileptic cry, but no convulsion occurred. At rare intervals he had convul- sions of the grand-mal type. This patient was intelligent, and no difficulty was experienced in collecting all the urine, and the vari- ation in amount of urea before and after the fit was more marked than in the previous case. The average amount of urea excreted was 11.57 grammes per twenty-four hours. The following table shows the variation in amount of urea before and after convulsion : BEFORE. • 1012 1007 1010 1010 1011 1008 1011 1010 1010 1010 Specific Gravity. .003 .004 .005 .004 .004 .003 .004 .004 .006 .006 Urea in Grammes per C. C. 1243.2 828.8 888.0 1657.6 1420.8 1685.2 925.4 940.2 1110.0 1460.2 Quantity of Urine in C. C. 3.630 3.315 4.440 6.730 5.683 5.056 3.702 3.761 6.660 8.761 Total Urea in Grammes. 1013 1017 1011 1013 1012 1010 1012 1012 1014 1010 Specific Gravity. AFTER. .005 .007 .007 .006 .007 .008 .006 .008 .01 .008 Urea in Grammes per C. C. 769.6 3.848 505.6 3.539 562.4 3.937 296.0 1.776 769.6 5.787 450.3 3.602 650.3 3.902 1300.410.403 675.0 6.750 620.0 4,960 Quantity of Urine in C. C. Total Urea in Grammes. 2012.8 1334.4 1450.4 1835.2 1690.4 2135.5 1575.7 2240.6 1785.0 2082.0 Total Urine in C. C. for 24 hours. TOTAL. HO^WGCQa«Q^CO Total Urea in Grammes for 24 hours. These results led to the proposition that agents eliminating urea would have an influence upon the disease, and, with this idea in view, certain drugs were tried, combined with exercise. Particular atten- tion was paid to digitalis, which was given in the form of the infu- sion, commencing with 3 i and increasing to § ss. Under this drug the 6 urine showed but little change -in Case No. 1 the urea fell below the average without drugs, being 9.30 grammes per twenty-four hours. Tn Case No. 2 the average was about the same as when no medica- tion was used, being 11.32 grammes per diem. No decrease in the number of convulsions was noticed. Under the influence of the bromides the urea fell below the usual average in the first case, being 9.50 grammes per twenty-four hours. The convulsions were decreased in frequency, being six to nine of the previous month. Sod. borate, used after the popular method of increasing the dose from time to time, caused in Case 1 no noticeable effect, either on convulsions or amount of urea excreted; in Case 2 it caused great loss of memory, anxiety, erotic dreams, and an alarming increase in frequency of the convulsions, and no effect on urea elimination; in two other epileptics marked eczema occurred, and in a fifth case catalepsy. In no case did the dose exceed gr. xxx T. i. d. Beta naphthol and belladonna showed but little influence over the dis- ease. Opium in increasing doses is now being tried, and a decrease in the number of convulsions has been noticed, but no effect on urea has occurred, except to diminish it somewhat. The purpose of these observations is, as I said in the beginning of my paper, to look more closely into the etiology of this interest- ing disease, idiopathic epilepsy. When we know the cause, then, and only then, can a rational treatment be advanced. Is the dis- ease an auto-intoxication or one of central origin? Is it primarily an auto-intoxication with a poison which has a particular elective affinity for the brain structure, producing a gradual atrophy and deterioration of the latter? This latter theory seems to me the most tenable one, and the one toward which we should direct our observations - it is a cause of tangible origin, and gives to the eti- ology of epilepsy a rational and practical basis. Whether urea exercises a special influence in producing this auto-intoxication can not be stated from the above researches, but the fact remains that it is insufficiently eliminated, and this truth opens to us a new field - the study of the influence of toxic substances in the produc- tion not only of epilepsy, but all diseases of nervous origin.