Researches upon the of Idiopathic Epilepsy. A Preliminary Communication. C. A. HERTER, M. D., BT Lecturer on the Anatomy and Pathology of the Nervous System, New York Polyclinic, E. E. SMITH, Ph. I>. AMD Weto Yorlt f&efcfcal “Journal REPRINTED PROM THE for August 20 and 27, and September 3, 1892. Reprinted from the Few York Medical Journal for August 20 and 27, and September 3, 1892. RESEARCHES UPON THE AETIOLOGY OF IDIOPATHIC EPILEPSY. A PRELIMINARY COMMUNICATION* LECTURER ON THE ANATOMY AND PATHOLOGY OF THE NERVOUS SYSTEM. NEW YORK POLYCLINIC, C. A. HERTER, M. D., and E. E. SMITH, Pn. I). It is the aim of this paper to present the results of a research upon epilepsy that has been in progress during the past winter. This research ivas originally undertaken with a view to studying the relation of uric-acid excre- tion to the epileptic paroxysm—a line of inquiry brought to our notice by the recent publications of an English writer, Haig.f According to this author, the grand mal seizure is determined by an excessive accumulation of uric acid in the blood. In the study of this question our results were not confirmatory of the view of Haig. Certain obser- vations, however, of another kind, suggested to us the pos- sibility of a causal relationship in some cases between putre- factive processes in the intestine and epileptic seizures. As a consequence we were led to undertake the research that •)■ Uric Acid as a Factor in the Causation of Disease, 1892. * Read before the American Neurological Association. Copyright, 1892, by I). Appleton and Company. RESEARCHES UPON THE is here recorded and with which the greater part of this pa- per is concerned. Evidently the planning of a study of this character involves the assumption that the discharge of nerve force from the cortex which constitutes the epileptic seizure may be in some way conditioned by the quality of the blood by which the cerebral elements are nourished. The idea that epileptic paroxysms may be related to toxic substances in the blood is not a new one, the clinical aspects of epilepsy being such that they have suggested a depend- ence of this kind to some authors who have not been satis- fied with the purely mechanical explanation of the epileptic seizure. Thus Flint * says : “In a large proportion of the cases of epilepsy no sources of centric or of eccentric irri- tation are apparent. That under these circumstances the epileptic paroxysms are due to the action of an internal and at present unknown toxical agent seems to me the most ra- tional hypothesis.” That toxic substances produced in the intestine may sometimes determine the occurrence of epi- leptic seizures is a possibility that occurs to one on consid- ering the cases of epilepsy in which the symptoms of disor- dered digestion, often from an error in diet, are associated with an unusual frequency of the seizures. The observations which we have made upon intestinal putrefactive processes in epileptics are based upon a study of the urine of such cases. As we shall explain further on at greater length, cer- tain substances in the urine—namely, the ethereal sulphates —have been shown to be derived from putrefaction in the in- testine, and the extent to which such putrefaction occurs may be inferred, bearing in mind certain precautions, from the quantity of these substances in the urine. These substances have been studied by us in thirty-one different cases of epi- lepsy, most of the cases being unquestionably idiopathic in nature, according to the generally accepted meaning of this * Practice of Medicine. Sixth edition, p. 825. -ETIOLOGY OF IDIOPATHIC EPILEPSY. 3 term. In the majority of these cases the uric-acid excre- tion also has been studied. The results that have been de- rived from this inquiry may be presented under the follow- ing- titles : First. Synopses of the clinical histories of the cases of epilepsy that form the basis of this paper, together with the tabulated results obtained from analysis of the urine. Second. Conclusions relating to the excretion of uric acid in epilepsy. Third. Conclusions relating to the occurrence of intes- tinal putrefaction in epilepsy. Case I.— J. V. S., aged fifty-two; weight, one hundred and seventy pounds. First grand mol seizure occurred during night in patient’s forty-third year. Consisted of a general convulsion without aura, biting of tongue, or passage of urine, followed by active delirium and deep sleep. Grand mol seizures increased gradually in frequency; they now recur three or four times a month. Two years after first seizure developed petit mal at- tacks, of which there are several a week. Slight loss of mental power. General health fair. Has always been predisposed to diarrhoea and dyspepsia. Case lI.—M. E., female, aged twenty-four; weight, one hun- dred pounds. Has had typical grand mod paroxysms for four years, two to three every month. No known cause. Parox- ysms have been diminished in frequency (one to two months) under bromide treatment. Seizures usually occur just before, during, or after menstrual period. General health feeble. Marked anaemia. Intercostal neuralgia. Frequent attacks of gastric pain after food. Occasional constipation. Case HI.—M. M., aged twenty-six. Grand mal seizures for several years. Developed without known cause. At first bad only three or four seizures a year; now has about one a month, usually during or just after menstrual period. Epigas- tric aura. Bites tongue. Clonic spasm general. Seizure fol- lowed by stupor. No appreciable mental impairment. General health good. Digestion usually good. Seldom constipated. 4 RESEARCHES UPON THE Case IV.—E. E., aged twenty-six; weight, one hundred and sixty (?) pounds. Good health until two years ago. At the time was struck upon the right side of the head by the falling of a brick. No loss of consciousness resulted, but a scalp wound was made. About two months later had the first epileptic seizure. Since that time there have been many seizures, and at the present time there are many seizures weekly. Frequently there are many seizures in succession. The convulsions are general. Much mental impairment. General health good. No constipation or digestive disorder. Case V.—O.C. P., male, aged sixteen; weight, one hundred and thirty-five pounds. Epileptic convulsions since third year. Early history obscure. Paroxysms said to have come on with- out cause. Much mental impairment. Seizures two to four a week; uncontrolled by bromides. No aura. Deviation of eyes to right; clonic spasm more marked on right side. General health excellent. No evidences of indigestion. No constipation. Suspicion that the disease may have been of organic origin. Case Vl.—o. T. 8., male, aged thirty-four; weight, one hundred and fifty pounds. Seizures commenced during early childhood without known cause. Have continued without change in frequency or character. Much mental impairment. Seizures, five or six a month; uncontrolled by bromides. Typical grand mal seizures. Clonic spasm general. Sensory aura in small proportion of seizures (one in ten). General health robust. Case VII.—F. G. S., aged thirty. First grand mal seizure at age of ten (without known cause?). Now has two or three seizures a month. Often these are followed by maniacal excite- ment. General health good. Great mental enfeeblement. Is apt to become constipated. Two months ago became consti- pated, and the grand mal seizures became more frequent and severe during this time than usual. Does not suffer from dyspepsia. Case VIII.—E. M. 8., aged fifty. For more than twenty years has had infrequent typical grand mal seizures, which de- veloped without known cause. Considerable mental excitement before and after seizures. Has been free from seizures as long .ETIOLOGY OK IDIOPATHIC EPILEPSY. 5 as three years. At present has two or three seizures every fort- night. Great mental enfeeblement. General health excellent. Does not suffer from dyspepsia or constipation. Has a uterine fibroid. This began to grow rapidly five years ago, and the seizures have been more frequent ever since. CaselX.--P. S., male, aged sixty-three; weight, one hundred and sixty pounds. One uncle epileptic. Rugged health until eighteen years ago. Then a sudden mental shock was followed by first petit mal seizure. Petit mal seizures increased gradu- ally in frequency from one a month to five a day in 1888. Then first grand mal seizure. Grand mal seizures of typical character at night; loss of consciousness, with falling, but with- out true convulsive movements, during day. Falling seizures about one a day. On bromides since first petit mal seizure. Seizures much more frequent when bromides discontinued. Gas- tric dyspepsia since bromides begun. Transient glycosuria at times. General health excellent. Very little mental impair- ment. Bowels regular usually. Case X.—S. S., aged twenty-nine; weight, one hundred and fifteen (?) pounds. First epileptic seizure occurred at age of eighteen, without known cause. The first seizure coincided with the menstrual period. Since then seizures have been fre- quent. Several typical grand mal seizures occur at present in the course of a week. Patient has a vague epigastric aura. Always cries out. Has occasional petit mal seizures. Mental condition good. General health good. Bowels regular. Case XL—E. 8., aged forty-five; weight, one hundred and forty (?) pounds. Patient had the first grand mal seizure fifteen years ago. Came on without known cause. Received a severe burn of the right hand in the first seizure. Has had ever since many grand mal seizures monthly, and usually several petit mal seizures. No relation of the seizures to menstruation. During past year seizures have been somewhat less frequent than for- merly. Little or no mental impairment. General health ex- cellent. Xeither indigestion nor constipation. Case XII.—K. S., aged forty-three ; weight, one hundred and ten pounds. First seizure at age of seventeen, without known cause. Now has about one seizure a week, and several petit RESEARCHES UPON THE mal seizures daily. No aura. No relation of grand mad to menstrual periods. Much mental impairment. Genera! health fair. Is not dyspeptic. Case XIII.—K. M., aged twenty-four; weight, one hundred and sixty (?) pounds. Has had typical grand mal seizures since her eleventh year. These came on without known cause. Seizures were very frequent from the beginning (several a week). At present patient is having from six to twelve seizures daily. Often one seizure occurs directly after another. Both clonic and tonic spasm are usually rather more marked upon the right side. Stupor lasts long after seizures. Great mental im- pairment and continuous dullness. No relation of seizures to menstruation. General nutrition good. Case XIY.—B. F,, aged nineteen. First grand mal seizure at the age of ten without known cause. Seizures frequent from the first. Menstruation at thirteen. Seizures especially fre- quent about menstrual period. Now has several seizures daily (three to five), sometimes as many as twelve. No distinct aura. Patient utters a cry and falls. A short period of general rigidi- ty is followed by clonic spasm, chiefiy of left arm. After this, patient grows violent and abusive for a short time. Seizures vary much in severity and duration. Mental power not greatly impaired. General health good. Chronic constipation. Case XV.—K. A., aged twenty-five. First grand mad seiz- ure at age of thirteen, without known cause. First menstrual period about a month after first seizure. Seizures from two to twelve a month ; severe and typical grand mal. More frequent at menstrual period; less frequent now than formerly. Con- siderable mental impairment. General health good. Usually constipated. Case XVI.—S. 0., aged thirty-one; weight, one hundred and twenty-five pounds. First grand mal seizure at fifteen, without known cause. Seizures increased gradually in fre- quency ; now has eight to ten seizures a month. Seizures are rather more frequent about the menstrual period. General health good, with the exception that patient suffers from dys- menorrhcea. Slight mental failure. Is not troubled with con- stipation or indigestion. .ETIOLOGY OF IDIOPATHIC EPILEPSY. 7 Cask XVII.—K. M., aged twenty-two; weight, one hundred and thirty (?) pounds. Has had grand, mal seizures since her thirteenth year. Seizures average one or two a month. They usually occur just before or during a menstrual period. No aura. No petit mal seizures. Mental condition apparently little impaired. General health excellent. Is usually consti- pated. Case XVIII.—M. D., aged thirty-five; weight, one hundred and thirty pounds. First grand mal seizure in seventeenth year, without known cause. At one time had ten to twelve seizures a month ; now has about seven seizures a month. Seizures are a little more frequent at menstrual periods. Has two or three petit mal seizures a month. General health good. Considera- ble mental failure. Is not troubled with constipation or indi- gestion. Case XIX.—R. M., aged seventeen. First grand mal seiz- ure at age of thirteen, without known cause. Seizures have been frequent ever since this time, and now occur from three to five times a week. Menstruation began at the age of fourteen, and has always been scanty and irregular. Now suffers from amenorrhoea. Mental condition good. General health good. Does not suffer from indigestion or constipation. Case XX.—M. J., aged thirty-three; weight, about one hun- dred and forty pounds. First seizure occurred during eleventh year without knowm cause. Since then has had many grand mal seizures monthly until recently. Has had as many as six- teen seizures a day ; now has one or two in the month. Gen- eral health good. Intelligence somewhat impaired. Is troubled with constipation, but seldom has indigestion. Case XXL—D. K., aged thirty-seven; weight, about one hun- dred and thirty pounds. At age of fourteen had the first grand-, mal seizure, which came on without known cause. Since that time has been naving from six to ten severe grand mal seizures, with prolonged loss of consciousness, in the month. Seizures are rather less frequent now than formerly. They occur with especial frequency at the beginning of the menstrual period. Is much troubled with constipation. Is not troubled with indi- gestion. 8 RESEARCHES UPON THE Case XXL—A. W., female, aged thirty-seven. Grand mal seizures since age of thirteen. First seizure occurred about time of first menstruation, but referred to fright. Four or five paroxysms monthly, three or four of them usually within a few days of period. Considerable mental impairment. General health good. No digestive disorders. No constipation. Bro- mide treatment. Case XXIII.—F. K., female, aged thirty-four. Seizures commenced at the age of eighteen without known cause. Has both grand and petit mal paroxysms, the former especially at the menstrual period. Three to four grand mal seizures a month. Three to five petit mal seizures a week. Grand mal seizures formerly more frequent than now ; appear to be partly controlled by bromides. General health good. Does not suffer from indigestion or constipation. Case XXIV.—A. D., female, aged thirty-nine; weight, one hundred and eighty (?) pounds. Severe typical grand mal seiz- ures began nine years ago at a time of grief and anxiety. Seiz- ures especially apt to occur at menstrual period ; three or four a month ; formerly one or two a month. (Constipation and in- digestion marked.) Mental state good. General health robust. No bromides for five months. Case XXV.—B., female, aged thirty-one. Grand mal par- oxysms began twelve years ago without known cause. Three or four seizures a month; formerly less frequent. Seizures especially apt to occur during the week after menstruation. Mental condition good. General health robust. Suffers from constipation and indigestion. Case XXVI.—M. H., aged thirty; weight, one hundred and ten pounds. Seizures of typical grand mal coming about three years before without known cause. Second seizure about one year after first; third, about six months after second. Now has one seizure about every month. Non-menstrual. Aura and cx-y before seizure. Tonic followed by general clonic con- vulsions. Mental condition good. General health good. Does not suffer from constipation or indigestion. Severe bromism at one time. Case XXVll.—Julia Hackett, aged fifty-nine; weight, one ETIOLOGY OF IDIOPATHIC EPILEPSY. 9 hundred and sixty-five (?) pounds. Severe and typical grand mal seizures since her ninth year. First seizure occurred about two weeks after a fright received from falling from an apple tree. Slight scalp wound at this time. Has about one seizure a month at present; formerly had several a month. No aura. Onset of seizures very sudden. Period of tonic spasm very short; spasm clonic almost from first. Duration, two to three minutes. Mental condition apparently unimpaired. General health robust. Bowels regular. No symptoms of dyspepsia. Case XXYIII.—M. R., aged twenty-four; weight, one hun- dred and ten (?) pounds. Severe grand mal seizures began at age of five, without known cause, but early history is obscure. During past four years has had from five to ten severe grand mal seizures a month. Especially frequent just before or dur- ing menstrual period. No aura; screams and falls suddenly; long period of rigidity (two minutes) before general clonic spasm comes on. Great mental enfeeblement. General health good. Appetite good. Frequent constipation. No dyspeptic symptoms. Case XXIX.—I). If., aged twenty-seven; weight, one hun- dred and three pounds. When seven years of age began to have 'petit mal seizures, which developed without known cause. Seizures continued for several years, ceased spontaneously, and then recurred. Has from three to ten seizures a week. Usu- ally a painful epigastric aura an appreciable time before the seizure, which consists of temporary loss of consciousness, during which there are automatic movements. After seizure, patient is pugnacious. Seizures diminished in frequency under influ- ence of bromides. Slight mental weakness. General health fair. Case XXX.—R. K., female, aged thirty-six; weight, ninety- nine pounds. Good health until twelfth year. Then first petit mal seizure without apparent cause. Several petit mal seizures daily. Aura of general painful sensation all over her, with ac- cumulation of gas in intestines, arrested by inhaling amyl nitrite. Great increase of attacks on removal of bromides. Seizures most frequent at menstrual period. Rarely grand mal seizure. General health fair; suffers from constipation. 10 RESEARCHES UPON THE Cask XXXI.—J. K. S., aged thirty-three; weight, one hun- dred and thirty-eight pounds. Was in good health until two years ago, when he had a slight petit mal seizure ; sudden loss of consciousness, with pallor, while in sitting posture and talking. Duration of first seizure, a few seconds only. Second seizure, six- months after first and slight. Since then seizures much more frequent and more severe. Loss of consciousness and pallor, followed by temporary mental confusion. One hundred and fifty-one seizures in first three months of 1892. Mental power considerably impaired. General health good. Bowels regular. SYNOPSES OP THE HISTORIES, TOGETHER WITH THE TABULATED RESULTS OBTAINED FROM ANALYSIS OF THE URINE. In selecting the foregoing cases for study an effort was made to include only cases of idiopathic epilepsy. In three of the cases (IV, V, and VI) there is, however, reason to believe that the seizures may have been dependent on organic disease. In two of these three cases the seizures date from early childhood; in the other case they date from a severe injury to one side of the head. Of the thirty-two cases of epilepsy, grand mal seizures were the distinctive features in twenty-nine. In the three remaining cases (XXIX, XXX, and XXXI) there were very frequent petit mal seizures. In one of these three cases there was no history of the occurrence of any grand mal paroxysms, but in the two others such paroxysms were said to occur at irregular and usually long intervals. Eighteen of the thirty-one patients were inmates of the Hospital for Nervous Diseases, and we are indebted to Dr. E. D. Fisher and Dr. Frederick Peterson for their courtesy in placing these patients at our disposal for study. Case and Date. Volume. Specific gravity. Urea. Uric acid. Ratio of uric acid and urea. Preformed sulphates. j Ratio of Combined sulphates. jCed sul- phates. Ratio of total sul- phates and urea. Indigo- blue. Remarks. Case I. C. c. Grammes. Grammes. Grammes. Grammes. Grammes. October 26, 1891 ... . 2,170 1,780 1-018J 21-49 0-590 36-4 0-0411 “ 28 1-015 22-59 0-520 43-4 “ 30 1,230 1017* 19-51 (Lost.) 0-422 0-0458 1,580 1-015* 19-64 46-5 Grand mal seizure, night, November 2. “ 4 1,650 1,500 1-01U 19-98 “ 6 1*019' 28-70 0" 666 43-1 Begins use of highly nitrogenous food. “ 9 2,100 1,320 1,650 1-014 29-07 0-643 45-2 j a ii 1-012* 19-79 29-35 0-875 52-8 “ 13 1-016J 1-023 0" 553 53-0 i .... “ 19 1,425 1,420 37-26 (Lost.) 0-637 i .... 0'0544 “ 20 1 ■ 023 39-73 63-9 0-0552 Seizm-e at 3 a. m. “ 21 1,525 l-020i 41-20 0-534 77-1 0-0615 “ 22 1,690 1-020J 39-16 0-358 109-3 0-0824 “ 23 1,555 1-022 38-12 0-686 55'5 0-0636 “ 24 1,750 1,535 ? 1 • 020 41-39 0-749 55-2 0-0516 1-019* 36-60 0-648 56 "4 — 0-0517 2,190 1-013 27-79 0-627 44-3 2-196 0-167 13-0 ii-6 “ 7 2,300 ? 1,860 1-014* 1 016 29-19 0-554 52-7 “ 8 24-14 0-379 63-7 1 From December 1-8, 15 grammes sodi- um salicylate t. i, d. Table showing the Excretion of Uric Acid and Urea and of the Sulphates and Indigo-Blue. Case and Date. Volume. Specific gravity. Urea. Uric acid. Ratio of uric acid and urea. Preformed sulphates. Combined sulphates. Ratio of R ti f preformed “o0 and com- hinprl «nl Pnates phis Indigo- blue. Remarks. C. c. Grammes. Grammes. Grammes. Grammes. Grammes. December 9 2,120 1-014 23-03 0 • 367 66-3 1 • 745 0-237 7-3 11-6 0 009 “ 10 1,550 1-0171, 24 29 0-462 52 • 5 “ 11 1,560 1-021“ 26 • 54 0-513 51-7 u 1,380 i-oiH 25-08 0-400 62-7 1 • 740 0 • 285 6-1 12-2 0-0392 “ 28. 2,115 1-014 23-15 0-596 38-8 1 • 695 0-225 7-3 12-4 0-0171 Blurred vision to-day. “ 29 1,945 1’016J 24 • 90 0-486 51-2 1-915 0-235 8-1 11-1 0-0318 “ 80 1,315 1-017 22-36 0-379 59-2 1-780 0 • 087 20-4 11-9 0-0163 “ 31 1,505 1-015^ 26-47 0-408 64-9 1-964 0-173 11-3 12-4 0-0312 January 1, 1892 1,610 1-019| 31-15 0-557 55-9 2-077 0 ’ 262 7-9 13-3 0-0573 Ate and smoked to excess to-day. “ 2, I.. . . 845 1-017 14 • 78 0-258 57-2 a. m., January 2. “ 2, II 435 ? 1-0161- 5'65 0-096 58-8 “ 2, III 1-009| 5-24 0-103 50-9 “ 2 (total) 2,015 25-68 0-457 56-1 2-045 0-318 6-4 0-0453 “ 3..', . / l'l75 1-019 21-47 0-467 46-0 1-698 0-231 7-3 0-032 “ 4 1,925 1-015 25-39 0-429 59-2 1 • 505 0-383 3-9 0-039 “ 5 1,400 1-020 21-34 0-426 50-1 1-765 0-256 6-9 0-0379 “ 21 1,460 1-015 26-11 0-500 52-2 1-437 0 • 533 2-7 0 • 569 “ 23, II 705 1-015 5-44 0-172 31-6 “ 23, III 335 1-012 8-64 0 • 143 60-4 “ 23,11,111 1,040 14-08 0-315 44-7 0-772 0-124 4-4 “ 24:'...'. 1,185 1-013J 15-63 0-586 26-6 1-327. 0-174 7-6 0-0207 January 31 1,540 1 020| 29-87 0 764 39-1 2 428 1 0 331 7 3 0-0564 1,270 1 017 19-68 0 441 44" 6 1 300 0 208 0 a t> l'390 1 016£ 20-85 0 401 50-0 i 638 0 223 7 0 “ 3, I l'070 1 02l| 19-58 0 426 “ 3, II 320 1 0164 4-60 0 085 53-8 “ 3, III . . . 520 1 0144 6-39 0 169 37-8 “ 3 (total).... 1,910 30-58 0 680 44-9 3 415 0 373 9 1 0-0695 “ 4 1,090 1 020 23-87 0 563 42-4 2 034 0 194 10 3 i;455 1 020 26 • 83 0 604 43-6 2 175 0 216 10 0 “ 8, 9 \ 1,420 ) 1 017 3 597 0 507 7 0 0-0697 ’ i 1,520 ) “ 10 1,365 1 0204 928 0 275 7 0 825 1 017 14-93 0 212 70-4 “ 10, II 780 1 019* 12-55 0 481 26-1 • 1,605 27-49 0 693 39-6 ... i “ 31...... . . . 1^20 1 018 34-94 0 545 61-1 4 022 | 0 237 17 0 Milk diet commenc’d. April 27 l^SS 1 018 33-49 0 561 2 77 0 232 11 0 *“ 27, 28, I 850 1 010 8-92 0 136 0 717 0 052 13 8 “ 27, 28 II 530 1 017 7-82 0 no 71-1 0 493 | 0 046 10 7 One seizure, 6.45 a. >1. “ 27, 28 III. 610 1 012 7-61 0 176 43-2 0 521 0 050 10 4 “ 27 28 I II III 1 990 24-36 0 422 57’7 1 730 0 149 11 6 “ 28, 29' 1,670 1 015 30-39 0 518 58-6 2 439 j 0 226 10 8 Mav 6 i:855 1 015 30-48 0 528 57-7 2 306 0 217 10 6 Almost negative. “ 9 . 1,715 1 012 24-07 0 419 57’4 Strong. “ 10, I 0520 1 012 20-07 0 364 55-1 Strong. “ 10' II ' 225 1 015 3-32 0 054 61-0 Seizure at 7.45 a. m. “ 10' III. 705 1 on 7-40 0 223 33-2 Ate asparagus on night of Mav 9. “ 10, I, II, III 2,450 30 • 80 0 679 45-2 < Case and Date. Volume. Specific gravity. Urea. Uric acid. Ratio of uric acid and urea. Preformed, Combined sulphates.1 sulphates. Ratio of preformed and com- bined sul- phates. Indigo- blue. Remarks. C. c. Grammes. Grammes. Grammes. Grammes. May 11 1,250 1-013 19-24 0-402 47-8 “ 14,15 1,980 1-011 26-56 0-464 57-2 “ 15,1 1,080 1-011 11-90 0 • 203 58-6 “ 15, II 570 1-015 8-18 0 ■ 143 57-2 “ 15, III 320 1-021 6-98 0-215 32-5 “ 15; i, ii, in 1,970 27-07 0-561 48 • 2 “ 16, iV 700 1-018 16-38 0 • 340 48-1 .... Seizure at 6.30 a. m., May 16. June 4 1,440 1 -oio 15-64 1-178 0-254 4-6 strong. Case II. October 8, 1891 920 1-014 9-377 0-389 23-4 “ 20 1,340 1-011 13-780 0-440 31-3 ■ j 0-0095 “ 20 196 1-019 0-135 u 2 7 1,160 1016 16"955 0-529 32-0 Traces. November 2 1,200 1-019$ 22-155 0-635 34-9 590 1-021$ 20-529 -0-639 32-1 only. January 5, 1892 530 1 -019 9-064 0-380 23-8 0-525 0-162 3-2 One seizure. “ 12 1,005 1-020 24-360 0*532 45-8 1 387 0-233 4-9 6-0113 “ 15.... 340 1-0294 12-295 0-321 38-3 0-839 0-108 7-8 24 hours following seizure. “ 18 800 1-025$ 23•142 0-565 40-9 1-381 0-206 6 * 7 rp,,_ JLI diCCo only. “ 25 995 1-012$ 12-390 0-375 32-9 0-679 j 0-191 3-5 0-0136 “ 28 2,095 1-014$ 31-120 0-806 38-6 2-019 0-393 5-1 0-0158 I' wo seizures on June 30. 765 1-0234 J -312 0-136 8 * 6 One seizure. \TnrnVi R 835 1-026“ .... 2-263 0-273 8-2 « 19 1,910 1 -018 2-086 0-221 6-5 Case III. 745 1 • 09,9. 16'69 January 29, 1892 .... 705 1-009 6-95 0-228 30" 5 0 • 330 0 • 079 4-1 825 1 • 022 1-270 ()■ 185 Case IV. 900 1 -021 24-12 0 • 386 62-4 0-229 a 4 820 1-016 19-27 0-329 58-5 After live grand mol seizures. U 815 1 -023 26-97 0-456 59-1 Two seizures. a 1,635 46-24 0-785 58-9 6-212 u 6 l’l95 1-014 16-01 0-265 62-8 I One seizure. u 6 *7 990 1-018 19-00 0-231 82-2 a 6, 7 2,185 35-02 0-486 72-0 1-683 0-139 12-1 ■ U 10 l'020 1-026 34-37 0-442 77-7 u 15 1,013 0-985 1-478 6-088 15-8 Case Y. February 9. 10, 1892.. 690 1-024 17-319 0-451 38-41 U ‘ 10, 11 400 1-026 14-360 0-388 37-0 9 • 085 0-868 10-4 Traces 12 hours following seizure. “ 11, 12 635 1-025 19-749 0-474 41-6 only. “ 14, 15 590 1-027 26-373 0-419 62-91 a 15, I 330 1-029 15-972 0-273 50-5 44 15, 16, II. . . 260 1-025 10-140 0-176 56" 6 I 3-757 0 ■ 422 8-9 Traces Seizure between 1 and 11. 44 15, 16, I, II.. 590 26-112 0-449 58-1 only. 44 i6, n 520 1 027 22-860 0-476 47-0 “ 20, 21 770 1-023 19-481 0-446 43-61 “ 21, 22 660 1-023 18-216 0-448 40-6 V 5-729 0-431 13-3 0-0080 “ 22, 23 630 1-025 20-160 0-648 31-1 1 Case and Date. Volume. Specific gravity. Urea. Uric acid. Ratio of uric acid and urea. Preformed sulphates. Combined sulphates. Ratio of preformed and com- bined sul- phates. Indigo- blue. Remarks. Case YI. Grammes. Grammes. Grammes. G raimnes. February, 1892 785 1-019 25-512 0-439 58-1 I 265 1-019 9 ■ 805 0-135 72 • 6 II 165 1 • 028 6" 501 0-150 43-3 3-493 0-436 8-0 Traces only. I, II 430 16-306 0-285 57' Seizure between I and II. 390 1-027 16-497 0'304 54-2 February 29 925 1-025 27-935 0-768 36-3 March 1, 2, I 375 1-012 7" 65 0-144 53-1 .... “ 2, II 310 1-023 10-57 0 • 220 48-0 5'590 0-798 7-0 0-0018 Seizure between I and II, “ 2, I, II 685 18-22 0-364 50" 0 “ 2, 3 835 1 • 025 26-14 0-631 41-4 Case YU. February IS, 1892... . 875 1-020 19-16 0 ‘ 348 55" 0 “ 16 1,425 1-023 35-48 0-769 46-1 5"278 0-524 10-0 One grand mal seizure. “ 17 545 1-027 19-78 0-578 34-2 “ 26 2,070 1-022 47-40 1-002 47.3 3 • 920 0-310 12-6 “ 26 2,115 1-014 36" 37 0-852 42-7 3-059 0-281 10-8 One grand mal seizure. “ 26 2,080 1-018 38 • 68 0-733 52-7 2-938 0-383 7*7 Case VIII. February 22, 1892... . 660 1-023 17-88 0-418 40-3 ) u 23 985 1-013 18-71 0-570 32 • 8 ) 2*4/0 0-311 7 ■ 9 On e grand mal seizure. Case IX. March 13, 1892 900 1 -015 10-53 0-206 51-1 ) 1-714 0-332 Sample of 24 hours’ urine. CO “ 14 950 1 -015 11-30 0-249 45-4 \ 5-1 May 24, 25 1,245 840 1-015 16-710 1-415 0-260 5-4 25, 26 1 -024 17-170 1-567 1-763 0-198 7-9 4.7 “ 26' 27 1,360 1-020 22-843 0-375 Case X. March 9, 1892 1,160 1-018 25-40 0-504 50-4 2*375 0-241 9-8 One grand mol seizure at night. “ 10 1,975 835 1-010 22-31 0-311 0-392 71-7 57-5 68-1 1-652 1-984 0-231 0-211 7-1 9-3 “ 11 1-025 22-54 “ 12 1,305 825 1-009 15-00 0-220 0-494 0-337 0-328 “ 13 1-022 23-01 46-6 ) 52-7 I 54-9 ) “ 14 1,040 1,140 755 1-014 17- 18- 4-614 0-617 7*5 “ 15 1-013 “ 16 1-022 19-63 0-281 69-8 / 2-893 0-432 One grand mat seizure. “ 17 1,700 1,150 1-010 20-40 0 • 399 51-1 \ 6-7 May 19, 20 1-019 28-61 3-711 0 • 242 15-3 One seizure; sod. sal., gr. x,t.i.d. U U 20' 21 M70 1,250 1-010 17-86 31-50 1- 2- 0-183 8-8 9-6 7-4 “ 2l' 22 1-020 0 • 306 u u “ 22' 23 l'090 1,076 1-015 22-45 1-703 0-231 u « “ 23, 24 1-020 26-24 1-706 0-217 7-8 Two seizures. “ 24, 25 1,610 1-008 18-61 1-330 0-248 5-3 Sod. sal., gr. x, t. i. d. “ 25, 26 1,455 i-oio 24 • 63 1-847 0-251 7-3 1 .... Case and Date. Volume. Specific gravity. Urea. Uric acid. Eatio of uric acid and urea. Preformed sulphates. Combined sulphates. Eatio of preformed and com- bined sul- phates Indigo- blue. Eemabks. Case XI. March 10, 1892 C. c. 1,225 1-012 Grammes, 15-80 Grammes. 0-387 40-8 Grammes. 1- 2- Grammes. 0-265 4-2 Grammes. “ 19/ 1,525 1-014 22-41 0-482 46-5 } 49-4 J 5-0 “ 13 920 1-014 14-44 0-292 0 • 508 “ 14 1,960 1-014 25-48 0-625 40-7 1-850 3 • 227 0-363 5-1 One grand mol seizure. “ 15.:.::::::.: 910 1-018 18-38 0"353 52-0 } 59-7 y 49-6 “ 16 840 1-019 22-09 0-370 0-549 5-8 One grand mal seizure. “ 17 1,220 1-011 15-25 0-307 1-063 0-188 5-6 One grand mal seizure. Case XII. March 22, 23, 1892... “ 23, 24....... . 990 780 1-013 1-013 15-93 14-74 0-192 0-230 83-0 ) 64-0 V 3-344 0-536 6-2 “ 24, 25 585 1-019 16-16 0-228 70-8 ) “ 26: 27 580 1-017 16-41 0-209 78-5 1 • 090 0-165 6-6 “ 28: 29 1,550 1-015 27-43 0-273 100-4 2-143 0-251 8-3 One grand mal paroxysm. Case XIII. March 22, 23, 1892... “ 23, 24 480 210 1-020 1-015 4-88 1-688 0-166 0-072 25-4 23-2 1 • 699 0-152 11-2 Eight seizures. Partial sample for 24 hours; nine seizures. Twelve seizures. “ 28, 29 770 1-010 7-909 0-116 68-1 I 1-559 0-179 8-7 ( “ 30: 31 910 1-008 10-62 0-212 50-0 \ .... Ten seizures. Case XIV. March 29, 30, 1892... 1,800 1-009 20-34 0-263 77-3 t ( Six seizures. “ 30, 31 2,035 1-007 14-24 0-394 36-1 4* i • • • ' ( Nine seizures. “ 31 to April 7.. 1,900 1-011 26-03 0-550 47-3 ■ s Twelve'seizures. April 1, 2 1,720 1-015 31-30 0-495 65-0 ■■■■} Seven seizures. May 19, 20 1,560 1-013 19-92 1-500 0-243 6-2 20* 21 2,000 1-012 25-95 2-203 0-233 9-4 “ 21, 22 1,460 1-012 25-06 1-904 0-219 8-7 “ 22' 23 785 1-014 15-22 1-060 0-144 7-3 “ 23' 24 1,555 1-009 19-72 1-572 0 • 140 11-2 “ 25, 26 1,530 1-012 25-69 2-008 0-293 6-8 Six “ “ “ 1,870 1-009 22-82 1-746 0-343 5-1 “ 3,4 1,830 1-007 8-54 0-648 0-272 2-4 Three “ “ “ 4, 5 1,845 1-008 9-95 0-866 0-237 3-6 “ 5! 6 1,840 1-011 17-05 1097 0-333 3-3 “ 6, 7. 1,675 1-007 15-68 0-895 0 • 293 3-0 “ 7' 8 1,770 1-005 11-91 0-721 0-241 3-0 “ 8, 9 1,060 1-003 5-20 0-284 0-106 2-7 “ 10,11 1,475 1-009 12-62 0-895 0-303 2-9 “ ll' 12 1,980 1-015 11-88 0-873 0-205 4-2 “ 12’ 13 1,780 1-008 20-71 1-458 0-310 4'7 Three seizures. Case XY. April 2-4, 1892 3,825 1-002 12-34 1-024 0-147 7-0 “ 4, 5 1,960 1-004 11-97 0-328 36-4 “ 6 2,065 1-007 16-89 0-374 45-1 2-253 0-386 5-8 One seizure. Case and Date. Yolume. Specific gravity. Urea. Uric acid. Ratio of uric acid and urea. Preformed sulphates. Combined sulphates. Ratio of preformed and com- bined sul- phates. Indigo- blue. Rbmaeks. Case XVI. April 16, 17 C. c. 1,880 1-009 Grammes. 15-98 Grammes. 0-238 67-1 Grammes. 1-206 Grammes. 0-169 7-1 Grammes. “ 17, 18 1,380 1-009 14-90 0 • 298 50-0 1-065 0-161 6-1 One grand mal seizure. “ 18, 19 1,355 1-012 16'66 0 • 305 54-6 1-232 0-152 8-1 .... Two grand mal seizures. “ 23, 24 1,885 1-006 15-32 0-234 65-5 1-160 0-130 8-9 u u u “ 24, 25 May 19, 20 1,150 1,675 1-008 1-009 8-56 13-83 0-121 70-7 1-001 0-173 5-7 .... Oneseiz.; sod.bicarb.,gr.x,t.i.d. u a “ 20, 21 2,070 1-006 11-98 0-950 0-190 5 •(} “ 21, 22 1,905 1-005 10-10 0-637 0-185 3-4 Three “ “ “ “ 22, 23 1,820 1-007 8-76 0-515 0-300 1-7 Two “ “ “ “ 23, 24 1,935 1,740 1'004 5-49 0-358 0-116 3-1 Two “ “ “ “ 27, 28 1-005 8-89 0-631 0-192 3-3 “ gr. xx, ti.d. “ 28, 29 905 1-007 5-35 0-387 0-095 4-0 u a “ 29, 30 1,100 1-007 7-36 0-415 0-140 2-9 u u “ 30, 31 1,045 1-005 5-51 0-392 0-070 5-6 u a “ 31 to June 1.... 1,775 1-005 9-71 0-551 0-179 3-0 Two seiz.; “ “ Case XVII. April 22, 23 1,430 1-012 15-73 0-315 49-9 1-354 0-153 8-8 “ 28, 29 “ 29, 30 1,355 1,455 990 1-012 1-013 23-81 26 • 63 0-402 66-2 1- 2- 0-109 0-170 17-7 13-3 One seizure. “ 30 to May 1... . 1-013 14-41 0-164 87-8 1-349 0-143 9-4 Cask XVIII. May 6, 7 1,505 1-012 22-85 0-349 65-5 1-519 0-221 6-7 “ 8,9 1,965 1-006 18-69 0-398 47-0 1-316 0-139 9-4 One seizure. “ 9, 10 1,400 1-005 13-10 0-924 0-198 4-6 One seizure, May 10, 11 Case XIX. May 8, 9 1,710 1-008 17 • 78 1-296 0-151 8-5 “ 9, 10 l'835 1-011 21-56 1-761 0-208 8’4 Two seizures. “ 10, 11 1,816 1-007 18-02 1-535 0-162 9-4 Case XX. May 12, 13 1,515 1-011 32-81 1-961 0-148 13-9, One seizure. 13' 14 2,025 1-010 28-44 1-599 0-165 9-6 “ 15' 16 1,485 1-015 2-494 0-272 9-1 Case XXI. May 14, 15 1,155 1-013 24-08 1-607 0-254 5-9 15' 16 940 1-015 19-64 1-351 0-240 5-6 One seizure. “ 16, 17 1,285 1-014 20-35 1-806 0-227 7-9 Case XXII. May 17, 18 1,480 1-008 9-64 0 812 0-082 9-9 18, 19 l'730 1-006 8-61 0-649 0-109 5-9 “ 19' 20 i'soo 1-005 10-86 0-777 0-108 6-5 Case XXIII. May 20, 21 1,780 1-009 15-90 1-350 0-204 6-6 2l' 22 l'350 1-012 14-32 1-135 0-170 6-6 One seizure. “ 22, 23 L050 1-013 13-26 0-993 0-146 6-8 Case and Date. Volume. Specific gravity. Urea. Uric acid. Ratio of uric acid and urea. Preformed sulphates. Combined sulphates. Ratio of preformed and com- Indigo- blue. Remarks. phates. Case XXIY. May 27, 28 C. c. 1,620 1,735 1,235 1-012 Grammes. 19-88 Grammes. Grammes. Grammes. •6 Grammes. “ 28, 29 1-013 22-85 •018 •884 0 0 •460 165 6 One “ 29, 30 1-013 25-05 4 *4 severe seizure. 11 *4 Case XXV, May 30, 31 1,520 1,440 1,045 1-014 1-013 1-016 1-011 1-013 1-016 1-018 1-009 1-003 1-010 1-022 1-015 1-024 1-020 27- 21-48 25-20 17- 19- 28- 23-68 20- 31-87 16-37 20-67 9-88 18- 25-40 I 2 1 1 1 1 2 1 9 8 May 31 to June 1.... June 2, 3 102 666 0 0 199 3 3 One seizure. “ 3,4 1,595 1,620 955 0 215 9 0 Sod. bicarb., gr. xx, t. i. d. U U “ 4, 6 573 0 213 7 4 “ 5, 6 1^725 1,110 640 0 204 8 9 0 8 u u “ 6, 7 442 0 248 < << “ 7, 8 1,855 2,030 1,450 930 0 231 8 3 “ “ “ 8, 9 1 678 0 220 7 6 One seizure. “ 10, 11 1 443 0 275 8 9 U a “ 11, 12 '835 516 955 844 639 077 1 0 137 11 0 “ 12, 13. . . 580 0 1 0 212 9 2 “ 13, 14 565 j ■ • • • • 0 096 8 8 “ 14, 15 1,080 ! | — 0 163 10 5 * o- 201 10 3 Case XXVI. 520 510 1*030 14*45 0-422 34*2 “ 2! 3 1*028 13*87 1030 0-147 7*0 “ 3,4 620 1*025 16*54 0-462 35*8 1*258 0*167 7-5 Case XXVII. 1,160 1,550 990 1,460 1*016 20*79 .... 1-473 Ethereal sulphates. 0*344 4*2 One seizure. “ 3 4 1*009 14*01 .... 1*013 0*275 3-6 “ 6 7 1*007 17*74 1 490 0*280 5*3 One seizure. “ 7 8 1*011 18*86 1*531 0*303 5-0 '* 8 9 1,880 1,845 1*008 13*78 1*230 0*226 5*4 “ 9 10 1*009 20*43 1-434 0*334 4-3 One seizure. “ in n 1,865 395 1-007 1*023 16*55 1*026 0-361 2*8 “ 13 14 14*58 1*246 0*221 5*6 “ 14 IK 885 1-017 21*53 1*880 0*306 6*1 Case XXVIII. 1,775 1,770 1,760 850 1,290 1,255 1-010 12-86 1*003 0*237 4*2 “ 3 4 1*008 11-40 0*996 0*192 5*0 One grand mal seizure to day. “ 45 1*011 16*28 1-523 0*258 5*9 Case XXIX. December 29, 1891... January 11, 1892 ... . “ " 17 1*017 1*021 1*019 19*60 26 * 60 34-83 0*594 0-494 0*577 33*0 Combined sulphates. 0 0044 Several petit mal seizures week ly. 53*8 60*3 2-876 0*164 0-200 13*7 0*0164 Traces “ 20 155 1*017 3*34 only. u 20 1,875 2,030 1*014 30*42 0*435 70*0 “ 20 35*96 2*456 0-234 10-5 Traces only. Case and Date. Volume. Specific gravity. Urea. Uric acid. Ratio of uric acid and urea. Preformed sulphates. Combined sulphates. Ratio of performed and com- bined sul- phates. Indigo- blue. Rbmaeks. C. c. Grammes. Grammes. Grammes. Grammes. Grammes. January 27 1,260 1'012 14-28 0-352 40-5 1-207 0-128 9-4 “ ' 28 134 1-019 2-69 0-048 56-2 “ 28 1,210 1-012 17-97 0-347 52-1 “ 28 1,344 20-67 0'395 52-3 1-632 0-207 7-9 Traces only. “ 29 1,520 1-012 19-16 0-386 49-1 1-738 0-221 7-8 “ “ 30 910 1-012 14-58 0-238 61-2 “ 30 460 1-018 8-58 0-217 39-5 . “ 30 1,370 23-17 0-455 50-9 2-081 0-184 11-3 Traces only. “ 31 1,015 1-017 20'73 0-447 46-3 “ 31 400 1-013 5-35 0-123 43-5 “ 81 1,415 26-08 0-570 45-7 2-327 0-209 11-] Traces only. U February 2 2,040 1-014 29-17 0-706 41-3 2 • 643 0-261 10-1 “ 3 1,750 1-013 20-47 0-489 41-9 1-813 0-253 7-1 “ “ 10 1,345 1-013 20-71 0-460 45-0 2-202 0-109 20-2 April 9 '805 1-018 18-99 0-346 54-9 1-701 0-093 17-3 Case XXX. 1 March 3, 1892 600 1-020 “ 4 830 1-020 15-53 0'478 32-5 “ 4, 5 910 1-023 20-01 0-544 36-8 ) “ 5, 6 890 1 -023 20-64 0-526 39-2 V 4-867 0-238 20-4 “ 6,? 775 1-025 17-96 0-415 43-2 ) “ 7,8 830 1-023 16-46 0-419 39-2 “ 9, 10 950 1-012 11-93 0-194 61-4 “ 10,11 945 1-012 14-97 0-226 66-1 “ 11,12 “ 12 13 960 9QO 1-014 1 *^12 17-30 17 - 50 0*226 0 * 204 76-5 \ 2-751 o-no 25-0 May 4 1,680 1-021 • “ 5, 6 950 1-015 Case XXXI. March 9, 1892 855 1-031 24-54 0-593 41-3 2 • 208 0-137 16-1 April 25 935 1-031 34-59 0-521 66-4 2-565 0-148 17-3 26 RESEARCHES UPON THE Conclusions relating to the Excretion of Uric Acid in Epilepsy.—ls the epileptic paroxysm associated with any peculiarities in the excretion of uric acid ? According to Haig, there is a great diminution in uric-acid excretion be- fore the paroxysm, and an equally considerable increase in the uric acid excreted at the time of the paroxysm. Look- ing at those of our figures that relate to the elimination of uric acid before the seizure, we find that the excretion has only in rare instances varied from the limits of health. This is true both of the cases where the urine just before the paroxysm was examined, and of the instances where only the urine for the twenty-four hours preceding the day of the seizure was studied.* In a few instances the uric-acid content has been higher than is seen in health, but this has been in cases where high uric acids were frequent without respect to the time of the seizures, f The general statement * In studying the relation of uric-acid excretion to the epileptic seizure we have to look both at the results obtained from the estima- tion of uric acid in the twenty-four hours’ urine immediately preceding, in that of, and in that immediately following the seizure, and at the re- sults obtained from the estimation of uric acid in divided portions of the urine of the twenty-four hours in which the paroxysm has occurred. The latter method is followed in some instances because there is the possibility that abnormities in separate portions may neutralize one another in the total twenty-four hours’ urine and thus escape detection. For instance, the urine before the seizure might contain abnormally little uric acid, and that at the time of or after the seizure a large excess ; but a mixture of the two portions might show no departure from the normal limits. f One of the first things that one notices in looking over the tables is that in nearly every case some of the twenty-four hours’ urines show deviations from the normal ratios (1:46 to 1; 65). In sixteen of the twenty-one cases where uric acid was studied, the uric acid varies from the limits of health, most of them showing a considerable proportion of urines in which the ratio to urea is distinctly high. The same cases and some of the others show also a deviation of another character. AETIOLOGY OF IDIOPATHIC EPILEPSY. 27 may safely be made that there is nothing distinctive about the uric-acid content of the urine just before a paroxysm. The urines passed on the days of paroxysms (total twenty- four hours) and the urine passed immediately after seizures have also shown nothing distinctive. The latter are apt to show a higher uric-acid ratio than the urines passed just before seizures; very often, however, the ratio is one that belongs within the limits observed in health. In general, it may be said that the urine passed after a seizure is apt to have a higher uric-acid ratio than the urine before or about the time of the seizure (including that passed immediately after). The difficulty in getting the conditions in the collection of urine the same in different cases makes numerical comparisons difficult. Of fifteen seizures where a comparison may be made of the uric-acid content of the urines after seizures (either immediately or the day after) with the uric-acid content on the day of the seizures, the urines in nine cases showed an increase in the uric-acid con- tent after the seizures, and in six of these cases the uric- acid ratio was higher than Ito 45.* This tendency to a high uric-acid ratio after paroxysms is to be regarded as a consequence of conditions which determine the seizures, or possibly of the seizure itself. The excess of uric acid that is observed in epilepsy can not reasonably be construed as the cause of seizures.f The foregoing remarks apply to cases of grand mol. In petit mol cases we have observed a continuously high uric-acid excretion which appeared to be related in some way to the cause of the seizures. It was While many of the ratios are such as are met with in health among dif- ferent individuals, the variations are certainly wider from day to day than those of individuals in health and on a reasonably constant diet. f See also Herter and Smith. Observations on the Excretion of Uric Acid in Health and Disease. N. Y. Medical Journal, June 4, 1892. * These ratios are as follows: 50, 43, 38, 3V, 31, 43, 48, 34, and 51. 28 RESEARCHES UPON THE found in two out of three petit mal cases that when the ex- cretion of uric acid was reduced to normal by the use of a milk diet, the seizures were greatly reduced in frequency. This etfect upon the seizures of reducing the uric-acid ex- cretion has been of considerable duration in these cases and may prove to be permanent. Conclusions relating to the Occurrence of Intestinal Pu- trefaction in Epilepsy.—Before we undertake to point out the conclusions of be drawn from a study of the facts relat- ing to intestinal putrefaction in the cases of epilepsy that are here presented, it is desirable to indicate the nature of the evidence on which these conclusions are based. Before the use of scientific methods in medicine diges- tion was regarded wholly as a putrefactive process. Early observers, however, pointed out the error of this view. As wras shown by recent investigations of Harris and Tooth,* normal digestion in the stomach is always free from bac- terial action. But in the intestine, while the ferments of the various secretions are giving rise to those changes that are essential for the absorption of food, putrefactive pro- cesses always occur and possibly aid in digestion. The bac- teria which are the immediate cause of this putrefaction are introduced with the food and escape the destructive action of the gastric juice. This intestinal putrefaction is kept within normal limits by certain natural antiseptic conditions. The action of the bile in this direction is well known. Its power of dimin- ishing putrescence is due chiefly to the fact that by increas- ing peristalsis it hastens the passage of its contents through the intestine.f The acid of the gastric juice has an anti- * Journal of Physiology, ix, p. 220; see also in this connection Straus and Wurtz (Archives de mid. experimentale, 1890). f Ueber den Einfluss von Magengahrung auf die Faulnissvorgange im Darmkanal. Archiv f. experim. Pathologic u. Pharmakol., Bd. 26, S. 133-138. OF IDIOPATHIC EPILEPSY. 29 septic action on the contents of the small intestine, as has been recently shown by Wasbutzki.* The tendency of mi- cro-organisms to produce compounds which, if allowed to accumulate, would ultimately destroy their own life, is of interest in this connection. Thus we hnd in the intestine, under perfectly normal conditions, two distinct kinds of ferment action by two widely different orders of ferments, which give rise to the formation of products of entirely different nature. On the one hand the unorganized digestive ferments produce changes in the food preparatory to absorption. They form from albumin, aided by the alkaline medium in which they act, successively an albuminate (alkali-albumin), albumoses, and true peptones, which latter may yield in part leucine, tyrosine, asparaginic acid, ammonia, and proteincromogen. On the other hand, the organized ferments—the bacteria— yield by their action on proteids, or on the products into which the proteids have already been transformed by the digestive action of the unorganized ferments, the following- substances or classes of substances : ammonia, sulphureted * Wasbutzki found that the excretion of ethereal sulphates was increased when the secretion of hydrochloric acid in the stomach- was diminished in consequence of gastric disease. He found further that in cases of hyperacidity of the stomach the excretion of ethereal sulphates was diminished. This he attributes to the action of lactic and butyric acids. See also in this connection Bierfiacki (Leber die Darmfaulniss bei X ierenentzii uduug und Icterus nebst Bemerkungen iiber die normale Darmfaulniss. Deutsches Archiv fur klinische Medicin, Band 49, 1. Heft, 1891). This author found that in cases of Bright’s disease (chronic diffuse nephritis) in which the secretion of hydrochloric acid is diminished there is a corresponding increase of the ethereal sulphates in the urine. In cases of catarrhal Jaundice with complete occlusion of the bile- duct he found a similar increase in ethereal sulphates, and he regards this fact as evidence that the bile has an antiseptic action. 30 RESEARCHES UPON THE hydrogen, ammonium sulphide, volatile and fatty acids, amines and amido-acids, especially leucine and tyrosine ; indol, skatol, phenol, cresol, phenyl-propionic and phenyl- acetic acids, and the aromatic oxyacids hydroparacumaric acid and parahydroxyphenylacetic acid.* The presence of these numerous acid compounds, espe- cially of lactic acid, gives the contents of the large intes- tine, as a rule, an acid reaction. Further, intestinal bacteria have a fat-splitting action similar to that of the steapsin of the pancreatic juice, giving rise, however, in addition, to lower acids of the fatty series. Likewise lecithin is decom- posed into glycero-phosphoric acid and the ptomaine cho- line, which further breaks up into carbonic acid, marsh gas, and ammonia. Besides this long and varied list there are doubtless other substances which may result from bacterial activity in the alimentary canal, of which nothing is directly known, but which may nevertheless play an important part in the condition of the subject. It is held by some observers that the production of poisonous alkaloids in the intestine is a normal process and that these are absorbed, and, if excessive in amount, may lead to auto-intoxication. There is some evidence that this is the case in certain forms of disease. That many of the products of intestinal putrefaction are absorbed is well known. They are, however, rapidly ex- creted by the kidneys, so that the individual generally es- capes their poisonous action. In the urine these substances appear in but slightly modified forms, and their amount and nature may reveal the condition in the intestine. Several methods are available for estimating putrefactive changes from a study of the urine. Thus Brieger f estimated the * See Haliburton, Text-hook of Chemical Physiology and Pathology, 1891, p. 694. f Zeitschrift f. physiolog. Chemie, Bd. 11, S. 221. .ETIOLOGY OF IDIOPATHIC EPILEPSY. 31 quantity of phenol from the distillate of acid urine. The quantity of indigo-blue * which the urine yields may also serve as an index to these changes. These methods, however, are open to objection, since they take into account only one of the many possible prod- ucts of putrefaction which may be present. These prod- ucts exist in the urine in combination with sulphuric acid as ethereal potassium sulphates. Thus phenol, cresol, cate- chol, indol, skatol, etc., which are formed in the intestine appear in the urine as phenolsulphate of potassium, cresol- sulphate of potassium, catecholsulphate of potassium, in- doxylsulphate of potassium, skatoxylsulphate of potassium, etc. An estimation of the amount of sulphuric acid in this ethereal combination gives, therefore, a more nearly correct indication of the amount of these substances present, and hence of the putrefaction in the intestine. Putrefactive processes outside the alimentary canal, putrid cystitis, putrid abscesses, putrid peritonitis, etc., have the same result as putrefactive processes within the intestine. The amount of the ethereal sulphates is in a general way pro- portional to the degree and extent of the putrefactive processes. We may now indicate a little more fully the character * This is often a very unreliable index to the degree of intestinal putrefaction, for there is no necessary relation between the amount of indican in the urine and the quantity of the ethereal sulphates. Only a small number of our cases of epilepsy in which the sulphates were in marked excess showed an excess of indican. In our experience, a large excess of indican (30 to 80 milligrammes) has been met with chiefly in cases which showed symptoms of chronic intestinal catarrh. Regarding the occurrence of indican see the following : Jaffe {Arch, f gemmmte Physiologic, Bd. 30, S. 483), Senator {Ctrlbl.f. d. medicinische Wissen- schaften, No. 20-22, 1877), De Yreis (Ueber Indican in Harn, Kiel, 1879), Henninga (Deutsch. Arch. f. Min. Med., Bd. 23, S. 271-287), Filati (Oazzetta chhnica italiana, vol. xiii, p. 378). 32 RESEARCHES UPON THE of the evidence on which this relation between ethereal sul- phates in the urine and putrefaction within the intestine is based. It was at one time held that the aromatic substances in combination with the sulphate were derived directly from aromatic constituents of the food. But while this may in exceptional instances and to a limited extent be true, espe- cially in herbivora, in the case of animals like dogs and man, who live on a mixed diet containing little or nothing of an aromatic nature, this possible origin has failed to explain the regular presence of these aromatic substances in the urine. Next, the various tissues themselves came to be re- garded as the seat of their formation, and there seemed to be considerable support for this view. In starving dogs Salkowskl * found considerable quantities of indoxyl potas- sium sulphate (indican) present in the urine. Likewise, R. van der Velden ■(• found the ethereal sulphates reduced only one half when the animal was kept entirely without food for five or six days. Both Ewald J and Baumann,* however, working upon cases of intestinal fistula in man, found that when the intestinal contents were withdrawn through the fistula the aromatic substances almost entirely disappeared from the urine. They further found that when the fistulous opening was closed and the intestinal contents were made to pass through the entire length of the intestine these sub- stances reappeared in the urine in the usual amounts. Kiihne and Nenki have shown that these aromatic bodies, especially indol, come from the putrefaction of proteids. Artificial pancreatic digestions of albumin were found to * Berichte der deutsch. chem. Gesellschaft, Bd. ix, S. 408. f Ueber die Ausscheidung der gepaarten Schwefelsauren im Harn. Virchow’s Archiv, Bd. *7O, 1872. £ Arch. f. pathol. An at.. Bd. 75. # Zeit. f. physiolog. Chemie, Bd. x, 1886. .ETIOLOGY OF IDIOPATHIC EPILEPSY. 33 yield considerable quantities of indol, but when bacterial action was prevented by thymolization, indol and other aromatic putrefactive products were entirely absent. Thus there is satisfactory evidence that these products, which are formed from the decomposition of proteids in the intestinal canal by the activity of micro-organisms, are ab- sorbed, and are idtirnately excreted by the urine. In con- lirmation of this is the influence on the separation of ethe- real sulphates which is exerted by antiseptics when intro- duced into tjie intestine. As shown by Baumann * and Morax,f putrefaction can be checked in the intestine of the dog by inanition together with the administration of large doses of calomel or iodoform. Under these circumstances a concomitant disappearance of ethereal sulphates in the urine was noted. In man it is not possible to administer sufficiently large doses of these drugs to produce this result. Rovighi,| working in the laboratory of Baumann, has recently shown that the administration of terpenes and camphors,* in the case both of men and dogs, diminished the separa- tion of ethereal sulphates to only a moderate extent in men,, but considerably in dogs. It is interesting to note in this connection that, as pointed out by Rovighi, there are varia- tions in the separation of the ethereal sulphates at different * Baumann and Wassilieff. Zeitsch. f. physiolog. Chemie, Bd. 6, S. 112. f Bestimmungen der Darmfaulniss durch Aetherschwefelsauren im Harn. Zeitsch. f. physiolog. Chemie, Bd. x, S. 318, 1886. \ Die Aetherschwefelsauren im Harn und die Darmdisinfection. Zeitsch. f. physiolog. Chemie, Bd. xvi. * Rovighi (loc. cit.) experimented also with kumyss. He found that by taking 15 litres of kumyss daily for five days the ratio of his sul- phates was reduced from 10A to 20. He does not state whether he took other food at this time, but it is presumed that he did.' The de- cided influence of the kumyss is probably to be referred to the lactic acid it contains. RESEARCHES UPON THE hours of the day. Their separation is greatest during the day, more especially after meals. This fact illustrates the importance of drawing conclusions only from the examina- tion of the twenty-four hours’ urine. The amount of putrefactive products in the urine is di- rectly related to the amount of proteid food ingested, and it is important to consider this factor in drawing conclu- sions as to the degree of putrefaction that is going on. The total sulphates of the urine run parallel to the elimina- tion of nitrogen.* Hence they indicate in general way the extent of nitrogenous metabolism, which is directly de- pendent on the amount of nitrogenous food absorbed. Thus, by a comparison of the sulphates in ethereal combi- nation with the other (so-called preformed sulphates) sul- phates of the urine, we have an index of the degree of in- testinal putrefaction, without further consideration of the amount of proteid food ingested. It is usually stated that under normal conditions the relation between the ethereal and preformed sulphates is about one to ten.f But, while this may represent in general terms the normal relation, it is liable to fluctuation with the nature of the food. On a diet composed of vegetable proteids the proportion of ethe- real sulphates may be somewhat increased (one to eight), while on a milk diet the ratio normally falls very much (one to twenty or less). We may now pass to the consideration of the results obtained from the study of the products of intestinal pu- trefaction in our cases of epilepsy. We may begin with * We have found in a large number of cases, both epileptics and non- epileptics, that the ratio of the total sulphates to the urea is singularly constant, being usually from 1:10 to 1:13. f Hoppe-Seyler. Ueber die Ausscheidung der Aetherschwefelsaiiren im Urin bei Krankheiten. Zeitschr. f. physiol. Chemie. Also R. van der Yelden, loc. cit., Bd. xii, S. 1, 1888. ETIOLOGY OF IDIOPATHIC EPILEPSY. the examination of the grand mal cases, for these are greatly in the majority, and show the most pronounced de- viations from the normal. Taking first the sulphates (since, as we have seen, they are the safest general indication of the degree of intestinal pu- trefaction), we observe that a very large proportion of our cases show a higher ratio of the ethereal to the preformed sulphates than is observed in health. It is convenient to group the cases of grand mal according to the degree to which the sulphates deviate from the normal. Of the twenty-nine cases, only two (Y and XX) can be called dis- tinctly negative; six (Cases IV, VI, YII, XIII, XVII, and XXIV) are classified as doubtful, because the results are not sufficiently distinctive, either of health or disease, to enable us safely to interpret them ; three (Cases VIII, XVI, and XXV) are classified as giving decided results, and all the rest, nineteen in number, as giving results that are very marked. It is important to note that on some of the days on which the ratio of the sulphates is excessively high the total amount of ethereal sulphates is distinctly high, while in other cases it is low. Thus, in Case I, on January 21st, the ratio of sulphates is 2’7, and in Case 11, on January sth, it is 3*2. Both these ratios are very high and nearly equal, but in Case I the total ethereal sulphates are 53’3 milligrammes, while in Case II they are 16’2 milligrammes. That is, in Case I the ethereal sulphates are present in more than three times the quantity than in Case 11. Is the significance of these ratios (2-7 and 3*2) approximately the same notwithstanding the great difference in the total quantities of the ethereal sulphates ? In interpreting our results are we to give most weight to the ratios of the sul- phates or to the total ethereal sulphates ? While we ought to be guided mainly by the ratios, we must in some cases 36 RESEARCHES UPON THE take into consideration also the totals.* in the instances that have been cited the ratios are so high that we can not doubt that they were caused by excessive intestinal putre- faction in both cases, for, though in Case II the total ethe- real sulphates were only 16’2 milligrammes—an amount usually quite within the limits of health—we must regard this as excessively high in the presence of so small an amount of the preformed sulphates as is here present (52‘5 milligrammes). This amount (52‘5 milligrammes) of pre- formed sulphates is less than is usually observed in health, and depends on the fact that only a small amount of nitro- genous food has been assimilated. We know, however, that when the preformed sulphates are reduced to this amount in health, the combined sulphates are correspond- ingly reduced, a relation of about 1 to 10 being main- tained. When, therefore, we find that the ethereal sulphates are not correspondingly reduced, as in Case 11, we have no hesitation in pronouncing the figures distinctly abnormal. There are many instances, however, in which it is al- most impossible to decide whether or not a case deviates from the normal. Thus, inCase XIII we find two ratios— 11-2 and 8‘7—the former certainly normal, the latter a lit- tle high, but not positively outside the limits of health. In this case the ethereal sulphates are small in amount (IV-9 milligrammes for two days), and this leads one to question whether the ratio of 8-V is to be regarded as dis- tinctly abnormal. The case has therefore been classed with the doubtful ones. * The totals vary so enormously in heathy adults (100 milligrammes to 300 milligrammes in the day) that the importance of relying on the ratios is especially impressed upon us. The establishment of a stand- ard in health for the ethereal sulphates involves considerations very similar to those that apply to the establishment of a criterion of uric- acid excretion. See N. Y. Med. Jour., June 4, 1892. ETIOLOGY OF IDIOPATHIC EPILEPSY. 37 Having established the fact that a majority of our cases give unmistakable evidence of an excessive formation of putrefactive products in the intestine, it remains to consider whether the excess of these products is or is not to be regard- ed as bearing a relation to the occurrence of the epileptic seizures. If in any given case in which there are evidences of excessive intestinal putrefaction a more or less constant relation exists between the degree of this excess and the frequency or character of the seizures, such a relation may reasonably be considered evidence of something more than coincidence, and the more constant the relation the more strongly does it suggest a dependence of the seizures on toxic substances produced by the excessive putrefaction in question. Before attempting any generalizations, we may advantageously take up certain cases with a view to seeing what they teach regarding such a relation. One of the first seizures that is available for the present inquiry is that which occurred in Case I, on January 25th. On January 21st the ratio of the sulphates was higher than at any period recorded in this case—namely, 2*7 ; on the day of the seizure it was 4-4, and on the day after it was 7-6. The ratio on the 22d, immediately before the seizure, is unfortunately unknown. Between December 9, 1891, and January 21, 1892, there are nine estimations of the sulphates, which for this period give a ratio much nearer the normal than for the period just before and at the time of the seizure. In the six weeks mentioned there was one paroxysm only (January 2d). It is to be noted that on January 21st the amount of indican (which is regularly present greatly in excess) was 56'9 milligrammes—that is, higher than at any time between December 5, 1891, and January 23, 1892, with one exception (January 1, 1892), when the indican reached 57'3 milligrammes, but when the sulphates give a less abnormal ratio (7-9) than those above 38 RESEARCHES UPON THE noted. On December Ist the patient began to take sodium salicylate. Between December Ist and December Bth he took fifteen grains three times daily. From December Bth until January 27tb he took ten grains three times daily, the bromides being continued. On December 6th the ratio of the sulphates was 13—i. e., within the normal. On Decem- ber 9th it was 7'3, but the quantity of indican was very low indeed (possibly within the normal), and much lower than during October and November, when the patient was hav- ing frequent seizures (about once a week). The quantity of indican remained relatively low (as compared with October and November) until January Ist, when it rose to 57‘3 milligrammes. The day following there was a mild seizure, but during the entire month of December there was not one. On the day before this seizure the sulphates gave a ratio of 7’9, a much higher ratio than the average of the days preceding. On the day of this seizure the ratio of sulphates was 6'4 and the indican 45-3 milligrammes. It is true that on January 4th there was a ratio of 3'9 and no seizure, but the indican was distinctly lower than on the days of the two seizures we have mentioned. The patient had another seizure on February 3d. On this day the ratio was 9T, but the ethereal sulphates were in large amount (373 milligrammes), and the indican was very high (69-5 milligrammes). On March 31st the patient went on an almost exclusively milk diet, which had the effect of greatly reducing the ratio of sulphates and of somewhat diminishing the frequency and severity of the seizures. The seizures during this period were but imperfectly studied, and we can not safely draw conclusions from them, but it is interesting to note that the ratio for the day of the seizure of the 28th of April was 11‘6. This ratio would ordinarily be regarded as be- longing to health, but it is much higher than should be ob- .ETIOLOGY OF IDIOPATHIC EPILEPSY. 39 served in an individual upon a milk diet (1 to 20). On May 6th the ratio was KP6, and for the first time in our knowl- edge of the case indican was almost wanting. On May 9th there was a strong indican reaction, and on May 10th there was a strong indican reaction and a seizure. In this case, therefore, there was a general correspond- ence between the seizures and the degree of putrefactive action in the intestine. When the salicylates were first given they exerted a check upon the products of intestinal putrefaction, and during this time seizures were absent. As soon as this antiseptic effect wore away (as shown by the reappearance of the products of putrefaction in excess) the seizures recommenced. In Case II there was a seizure on January sth, when the ratio of sulphates was high (3'2). On January 14th there was another seizure, and on January 12th the sulphates were again high (4-9), and a considerable amount of indican was present. On the day following the seizure the ratio of sulphates was considerably lower (7'B), and the total ethereal sulphates were less in amount than on either the Ist or 12th. Two seizures occurred on June 30th, hut, as observations were made only on the 25th and the 28th (when the ratios were high—3-5 and ST), we can not reach any conclusion in the case of these paroxysms. A seizure oc- curred on February 15th, when the sulphates were not very high relatively or absolutely. In general, however, we may say that the ratio of sulphates has run unusually high in this case about the time of seizures—i. e., just before or at the time of the seizures. But it is to be regretted that so few observations were made in the interparoxysmal periods. In Case XIX we have a ratio slightly higher on the day of the seizure than on the day before or after. The total amount of ethereal sulphates was considerably higher on the day of the paroxysm than on that before or after. 40 RESEARCHES UPON THE In Case XXI the ratio was 5*6 on the day of the seiz- ure, 5-9 on the day before, and 5*7 on the day after. The ethereal sulphates were slightly greater in amount on the day of the seizure and on the day before than on the day after. In Case XXII the ratio was 5'9 on the day of the seiz- ure, 9'9 on the day before, and 65 on the day after. On the day of the paroxysm the total ethereal sulphates were greater than on the day before, but about the same as the day after. The seizure in this case was a slight one, con- sisting of loss of consciousness and slight general tonic spasm, but without clonic spasm. In Case XXTII the ratio was 6*6 on the day of the seiz- ure and on the day before. On the day after it was 6*B. The ethereal sulphates were greatest in amount the day be- fore the seizure, and were greater on the day of the seizure than on that following it. But the differences in the ratios are so slight that the case is not conclusive as regards the particular point of our present inquiry. In Case XXIV the ratio was 4*4 on the day of the seiz- ure, 6*6 the day before, and 11*4 the day after. The ethereal sulphates were about twice as abundant on the day of the seizure as on the day before or the day after. In Case XXVIII the ratio was s*o on the day of the seizure, 4*2 on the day before, and 5*9 on the day after. The ethereal sulphates were greater in amount the day be- fore and the day after than on the day of the seizure. It is difficult to interpret the figures in this case. The cases of grand mol which have not been mentioned in the foregoing enumeration were not available for the in- quiry in point, either because the seizures were too numer- ous, because drugs were given which are thought to affect intestinal putrefaction, or because no individual seizure was carefully studied in its relations to the interparoxysmal period. AETIOLOGY OF IDIOPATHIC EPILEPSY. 41 In Cases X and XIV sodium salicylate was given in doses of ten grains three times daily (the bromides being- continued) for seven days, to see whether they diminished the products of intestinal putrefaction and concomitantly the number of epileptic seizures. In Case X the results were negative in that the drug failed to exert an appreciable effect upon either the products of putrefaction or the seizures. In Case XIV, however, there was a pronounced diminu- tion in the ratios of the sulphates at the time the drug was given and a distinct diminution in the number of seizures. But the ratio of sulphates was not brought inside the limits of the normal, and the seizures, though reduced in fre- quency, continued numerous. This observation, together with that made upon Case I, shows that a reduction of the products of putrefaction by means of sodium salicylate is likely to be associated with at least a temporary reduction of the number of seizures. It was determined to see whether it is possible to in- crease the products of putrefaction experimentally and con- comitantly the number of seizures. For this purpose it was decided to make use of considerable doses (twenty grains) of sodium bicarbonate, it having been shown by Stadel- mann * that in health the antiseptic action of the gastric juice may be diminished by alkalies, with a consequent in- crease of the products of intestinal putrefaction. The re- sults of our experiments were as follows : In Case XVI, ten grains of sodium bicarbonate, three times daily, were given for live days, and then twenty grains, three times daily, were given during live days more. During these ten days the patient had ten seizures, eight of them occurring during the first five days of the period. * Ueber den Einfluss der Alkalien auf den menschlichen Stoff- wechse!. Bericht iiber die Verh. des IX. Congresses. Abstract in Cen- frnlhlutt f. Min. Medicin, 1890, No. 21, RESEARCHES UPON THE During- the thirty days preceding this seizure the patient had eleven seizures only—i. e., she had about the average number for an entire month. Reference to the table shows that during the period when the soda was given the ratio of sulphates was very greatly increased as compared with the preceding days. The total ethereal suljahates were also markedly increased, but it is interesting to note that this increase is confined to the first period of five days when the seizures were most numerous. It should be noted also that the urea excreted was very small in amount while the soda was being taken, this being due, no doubt, to the loss of appetite caused by the administration of the salt. It is possible that this greatly diminished assimilation of nitro- genous food, as shown by the diminution in urea, had a tendency to diminish the number of seizures rather than to increase them. It would be interesting to know what would have been the effect of the sodium salt upon the seizures and upon the ethereal sulphates had the assimilation of nitrogen been maintained at the level of the days preceding the experiments. In Case XXV sodium bicarbonate was given in doses of fifteen grains, three times daily (with meals), for seven days. During this period there were two seizures—one on each of the last two days. Two consecutive seizures have not been noted before in this patient. During the period when these seizures occurred the ratios ran higher than usual, and the total ethereal sulphates were somewhat in- creased. In the week following the discontinuance of the sodium bicarbonate (perhaps longer) there was no seizure, and the ratios ran very nearly normal. In Case XIV twenty grains of sodium bicarbonate were given for five successive days, soon after the administration of sodium salicylate for six days. Putrefaction was un- questionably increased, as is shown both by the total AETIOLOGY OF IDIOPATHIC EPILEPSY. 43 ethereal sulphates and by the ratios. The number of seiz- ures, however, continued small. This is in direct opposi- tion to what wre should have expected. No definite con- clusion can be drawn as to the effect upon seizures of the increased putrefaction induced by the administration of sodium bicarbonate, since the evidence from the three ex- periments is conflicting’. The study, therefore, of our twenty-nine cases of grand mol shows that in twenty-one cases there was present un- mistakable evidence of excessive intestinal putrefaction. Furthermore, a large proportion of the cases in which the observations were of such a character as to render a com- parison possible, showed at least a general correspondence between the seizures and the degree of intestinal putrefac- tion as gauged by the analysis of the urine. This corre- spondence has been sufficiently close, in our judgment, to warrant the suspicion that intestinal putrefaction may play an important part in determining the occurrence of epilep- tic seizures in some cases of epilepsy—perhaps in a consid- erable proportion of cases. More than this we are unable to say at present, for those of our observations that relate to the concomitant variations of seizures and products of putrefaction are too few in number to permit a statement regarding epileptic seizures in general, although they appear convincing as regards most of the cases that have been studied. We may conclude, then, that the excess in the products of intestinal putrefaction which we have noted is a charac- teristic of a considerable proportion of all cases of idio- pathic grand mal, for the number of our cases is sufficiently great to exclude the possibility that our results depend on the mere coincidence of intestinal derangement and epi- lepsy which one might expect occasionally to meet. Never- theless the question arises, How does it happen that so 44 RESEARCHES UPON THE many cases of epilepsy give evidence of this abnormal con- dition ? Is it not possible that there may be some pecul- iarity about the life of the epileptic which predisposes him to excessive intestinal putrefaction? Two possible sources of error in the interpretation of results suggest themselves in this connection: First, peculiarities in diet; and, second, the influence of bromides. As regards the possible dependence of our results upon any peculiarity in the diet of our patients, it may be said that no peculiarity existed such as would account for these results. It is possible that the use of a large proportion of nitrogenous food, such as readily undergoes putrefaction (especially vegetable nitrogenous food), might bring the ratios of the sulphates within the pathological limits, but none of our cases were known to be upon such a diet. These cases were, moreover, drawn from several different sources, and it is hardly to be thought of that the same unusual dietetic condition should have been operative in each of these groups of cases. Again, in several of our cases the dietary was one which included a minimum of nitrogenous food, and these cases are among those that show the greatest deviation from the normal in the products of putrefaction. We can not, therefore, seriously entertain the idea that the diet in our cases affords an explanation of the results. The possibility that our results may depend, in part at least, upon the influence of bromides is not so easily to be disposed of. Almost all of the cases of epilepsy were tak- ing bromides at the time of our study and for a consid- erable period before, and one might hold, with some plausi- bility, that this circumstance invalidates the interpretation of results, since there is reason to think that long-continued, large doses of the bromides may give rise to intestinal dis- order, and very possibly to excessive intestinal putrefac- .ETIOLOGY OF IDIOPATHIC EPILEPSY. 45 tion.* As we have been able to find few epileptics in whom this possible influence of the bromides can be ruled out, it is difficult for us to give direct proof that no such influence was exerted in the cases that have been under con- sideration. The question really resolves itself into one of probabilities, and it is believed that the following considera- tions render it in the highest degree improbable that the bromides are responsible for the evidences of putrefaction that have been dwelt upon : First. The quantity of the bromides taken in our cases was moderate (twenty to eighty grains per day—the “ mixed ” bromides being used in many cases), and there is no evidence that moderate doses of the drug give rise to in- testinal putrefaction, either directly or indirectly, whatever may be the case with very large doses f (three to four drachms in twenty-four hours). Second. As already stated, in the cases where compari- son was possible the evidences of intestinal putrefaction were distinctly greater about the time of the seizures than in the intervals, notwithstanding the fact that the bromides were given in equal doses from day to day. This increase in the products mentioned at the time of seizures could hardly be explained by any known effects of the bromides. Third. As already stated, seizures have been controlled by influences which coincidently controlled the products of putrefaction. It is impossible to explain this fact on any theory connected with the action of the bromides. Fourth. There are among our cases of epilepsy several (IV, XXIX, and XXX) in which bromides have been taken in moderate doses for a long period of time, but in which there is no evidence of excessive putrefaction in the * Fere. Bromuration et antisepsie intestinale. Nouvelle icono- graphie de la Salpetriere, 1890, p. 349. f See Fere (loc. eit.). 46 RESEARCHES UPON THE contents of the intestine. On the other hand, there are among- the cases two (VI, XXVI) in which the patient has had no bromides for many months, but in which the putrefactive processes nevertheless run high. In view of these facts, it must be admitted that we are unable at present to offer any explanation of the pathologi- cal conditions noted in our cases of epilepsy; we can not say why there should occur in epilepsy so considerable a proportion of cases in which there are evidences of ex- cessive intestinal putrefaction. It is possible that future research will determine the nature and significance of the relation. While we can not profess that we have proved that the epileptic seizure is ever the consequence of abnormal putre- factive processes in the intestine, we have at least obtained evidence which forcibly suggests that epileptic seizures are sometimes the consequence of toxic substances produced in the intestinal canal, and that the formation of these sub- stances is related to processes of a putrefactive nature. It is of course evident that no pretense is made to having dis- covered the cause of epilepsy. If, as we suspect, intestinal putrefaction plays a r6le in the causation of some cases of epilepsy, it is certainly operative only in determining seiz- ures, and probably acts in most cases, and perhaps in all, upon that predisposition to the excessive liberation of nerve force, either hereditary or acquired, which we must recognize as by far the most powerful factor in the causation of the disease. A very interesting question presents itself in connection with the facts we have brought forward. Do cases of epi- lepsy which rest on an organic basis differ in any way from idiopathic cases as regards the evidence that toxic sub- stances formed in the intestine may operate in determining- seizures ? Much more extended observation is necessary .ETIOLOGY OF IDIOPATHIC EPILEPSY. before this question can be answered. Yet it is of interest to note that of the three cases of grand mal in which there was some reason to suspect organic disease, one was nega- tive and two were doubtful as regards the evidences of ex- cessive intestinal putrefaction. Regarding the possibility of a difference between grand mal and 'petit mal there is little to be said. It should be noted that in two cases of petit mal where the seizures were very frequent (in one of these cases there were occasional grand mal seizures) there were no evidences of intestinal putrefaction, and that in a third case, in which the seizures were exclusively of the petit mal type, the indications were doubtful or negative. We have made no systematic study of the influence of intestinal antiseptics in diminishing the number or modify- ing the character of epileptic seizures. Judging from a limited experience with salicylate of sodium, there is some reason to think that we may exert a beneficial influence, at least temporarily, upon some cases of epilepsy, by the use of drugs that are thought to control bacterial activity in the intestine. But before anything further can be said about the possibility of thus modifying the course of epilepsy in even a limited proportion of cases, it is essential that there should be carried out an extended and carefully planned series of observations upon the action of the various drugs of the class mentioned.* Note.—lt is interesting to note the large number of cases in which dark (black) urines were obtained—i. e., urines which when voided ap- peared normal, but on becoming alkaline and on exposure to the air * Some work has been done upon the influence of drugs upon the excretion of the ethereal sulphates in human subjects. Thus Ortweiler (Physiolog. und patholog. Bedeutung des Harnindicans, Mittheil. d Wurzburger medic. Klin., Bd. 11, S. 153, 1888) found that in six cases of intestinal disease naphthaline had very little influence in checking putrefaction. R. Steiff (Ueber die Beeinflussung der Darmfaulniss 48 .ETIOLOGY OF IDIOPATHIC EPILEPSY. acquired a dark color, first forming a black zone at the exposed surface of the liquid. This appearance is known to be due to the presence of hydroquinone and pyrocatechin, two aromatic substances formed by intestinal putrefaction. Although no attempt has been made to study the urine in regard to this particular point, the formation of the dark color was noted in Cases XIV, XV, XVI, XVIII, XXI, and XXVIII. Several other cases, studied earlier, gave the same appearance, but no importance was then attached to the peculiarity. Sulphates were determined by the Salkowski-Baumann method ; urea by Pfliiger’s modification of Liebig’s method or from the total amount of nitrogen as estimated by the Kjeldahl method ; uric acid by the Ludwig-Salkowski method ; indigo-blue by Jaffe’s gravimetric method ; phenol after the method of Koppe-schaar; and oxy acids after the manner described by Baumann. durch Arzneimittel, Zeitsch. f. Min. Median, Bd. 16, S. 311-324) found that doses of 0-3 gramme of calomel, three times daily, did not diminish the ethereal sulphates. Equal doses of camphor caused a slight reduction in the excretion of the ethereal sulphates. Rovighi (loc. cit.) found that oil of turpentine and camphor exert a moderate ef- fect on intestinal putrefaction in man. Carlsbad salts at first increased the ethereal sulphates excreted, but subsequently diminished them. Kumyss he found to exert a very marked influence in the elimination of the ethereal sulphates. 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