No. 4198.

FEBRUARY 13, 1904.

A Clinical LectureON

A CASE OF ADAMS-STOKESDISEASE

(PERSISTENT SLOW PULSE WITH EPILEPTIFORM FITS).

Delivered at the London Hospital on Oct. 28th, 1903,

BY PERCY KIDD, M.A., M.D. OXON.,F.R C.P. LOND.,

PHYSICIAN AND LECTURER ON MEDICINE TO THE LONDON HOSPITAL.

GENTLEMEN,-The patient, a woman, aged 58 years, hasbeen ill for about four years and complains of symptomswhich may be briefly summarised as follows: weakness,fainting fits, vomiting, swelling of the feet and legs, head-ache, sharp pain round the heart, slight hacking cough,occasional night sweats, swelling of the abdomen at times,and increasing stoutness. She has not had rheumatic feverbut she had scarlet fever when a child. Fifteen yearsago she had influenza very badly ; she has had it four timessince but mildly. She had small-pox 30 years ago. The

patient is a stout, flabby-looking woman and is very pale.She complains of dyspnoea, especially on exertion, and offainting fits usually brought on by exertion or excitement.The first fit occurred five years ago and since then she hasbeen unable to go out alone in consequence.The following is a description of the fits. There is no

warning ; they have always the same character ; the dura-tion varies from two or three minutes to half an hour. Shehas had from five to six fits in a day at times, though theymay be absent for weeks. Sometimes on recovering fromone fit she immediately has another. She also complains ofpain in the region of the heart which is described as sharpbut the pain does not radiate. She often has the pain with-out the fits, though at times the pain comes on as the fit is

passing off. The pulse on admission varied from 25 to 28.The tension was moderate and the artery was not thickened.The heart’s impulse was not felt. The apex beat was

apparently in the nipple line in the fifth space. Cardiacdulness was slightly increased outwards but not in otherdirections. On aucultation a faint systolic murmur washeard replacing the first sound in all areas ; it was loudestat the mid-sternum, about the level of the third rib. Thesecond sound was present in all areas, occasionally redupli-cated. Vomiting occurred occasionally, uual1y after foodbut often on rising in the morning ; it sometimes occurred asthe fit was passing off. The vomit was watery, sometimescoloured yellow with bile. The urine was healthy. The

menopause occurred nine years ago.The patient’s general condition did not vary much at first

but a few days after admission a fit occurred and wasobserved by the clinical clerk, Mr. M. Wyler, whom I have tothank for his careful notes. The patient suddenly cried out,her head was retracted, the pupils were widely diluted, theface was cyanosed, and the pulse was imperceptible for 40seconds. She was quite unconscious, her whole body beingrigid and extended Incontinence of urine occurred and asshe gradually recovered retchifg took place. On recoverythe pulse rose to 52. The whole fit lasted for five minute.In another fit a few days later the pulse ceased for 90seconds and this fit lasted for three minutes.At first the patient was treated with strychnine, ether,

and ammonia. Later, iaath of a grain of trinitrine wassubstituted three times a day and occasional inhalations ofamyl nitrite. After this gath of a grain of strychnine wasgiven hypodermically three times a day. Latterly she wasgiven thyroid extract, three grains in the day, which wasgradually increased to 15 grains daily. Two ounces of

whisky were allowed and the patient was put on light soliddiet. She has improved in all respects since her admission.There are less dyspncea and cardiac pain aad she has onlyhad one slight attack subsequently to the two previously- described. The thyroid extract was given at the suggestion ofDr. 0. F. F. Gruabaum. our medical registrar who had seenit recommended by a French observer, Dr. G4utier. It is- doubtful whether the improvement can be attributed to the

use of thyroid extract as nitro-glycerine and str) chnine werebeing administered at the same time. Subsequently thepatient was for a time put on thyroid extract and nitro-glycerine separately and continued to improve steadily.She now takes an occasional trinitrine tabloid and has hadno epileptiform attack for over two months. At times sheexperiences a slight pain in the cardiac region.The foregoing curious group of symptoms was first de-

scribed by Robert Adams in the Dublin Hospital Reports 1.in 1827. Adams described the following case. A man,aged 68 years, of full habit, had for a long time been in-capable of exercise and subject to oppression of breathingand cough. The patient was seen as he was recoveringfrom an apoplectic attack which had seized him three dayspreviously. At this time he was able to go about the housebut was still oppressed by stupor, a constant dispositionto sleep, and troublesome cough. Adams says: "Whatmost attracted my attention was the irregularity ofhis breathing and the remarkable slowness of the pulse,which generally ranged at the rate of 30 a minute."The patient’s medical attendant, Mr. Duggan, gave Adamsthe following history. "The patient had had at least20 apoplectic attacks in the last seven year.3, pre-ceded for a day or two by vertigo and loss of memory.During the fits the pulse would become even slower thanusual." (No statement as to the frequency is given here.)Death occurred in a fit six months after he was first seenby Adams. At the necropsy fatty degeneration of the heartwas found. In his comments on the case Adams says:"When the heart is slow in transmitting the blood itreceives we find, I imagine, even in thi a means ofaccounting for the lethargy, loss of memory, and vertigowhich attend these cases."The next reference to this disease appears to have been by

W. Stokes,2 where he published a paper on Observations onSome Ca-es of Permanently Slow Pulse. The first case wasthus described. 11 repeated pse?ido-apop7ectic attacks notfollowed by paralysis; slo7v pulse, with valvular murlltur.-Aman, aged 68. had a fainting fit three y(ars previously andsince then many similar attacks had occurred, at least 50 in all.These varied much in duration and intensity, being inducedby sudden exertion, distended stomach, or constipation. Thepatient had a sight warning in the form of a sensation of alump in the stomach, passing up through the right side ofthe neck into the head where it seems to explode and passaway with a loud noise resembling thunder, by which he isstupefied.’ This is often accompamed by a fluttering sensa-tion of the heart. No convulsions or frothing at the mouthduring the fit, but he has occasionally injured his tongue.Fit seldom lasts more than four or five minutes Duringthe fit the patient is entirely unconscious ; but he has noparalysis after any fit. He never heard that his pulse orheart was affected. He had found that spirits were thebest restoratives but he had not used them latterly,being afraid to die with spirits in his belly.’ He alwaysfeels cold unless he is near the fire. On admission therewas slight cough and expectoration, and large mucous

rates over the lungs. The heart’s impulse was slow, dull,prolonged, and heaving, giving the idea of painful as wellas slow action. The first sound was accompanied by ablowing murmur heard very distinctly up along the sternumand even into the carotid arteries ; second sound also im-perfect, though very slightly so. Pulse 28. prolonged, andsluggish. Ar eries pulsate visibly all over the body andappear to be in a state. of permamnt distention. Urinesp. gr. 1010 ; free from albumin " The pulse varied from28 to 30, at times rising to 36 The patient had two

threatenings of a fit after admission but the attacks werewarded off by turning on his hands and knees and keepinghis head low. This often averts a fit Stakes says thatoccasionally "some of the beats" occurred between theregular contractions unattended with impulse or pulse.Stokes did not observe any of the fits himself and thepatent had no fits after admission. He was dischargedimproved and was lot sight of.

Stokes described briefly another case which was sum-marised thus : "Ansem’a. very slow pul..e, valvular murmur,death apparently from syncope. Pst mortem, aortic stenosiswas found." No further details. A third onse was com-municated to Stokes by Dr. Law. The patient, a man,

aged 44 years, had a pulse of from 24 to 30 and suffered

1 Vol iv , p. 396.2 Dublin Quarterly Journal of Medical Science, 1846.

412

from apoplectic attacks, in one of which he died. No bu

necropsy was made. m(

Very little attention seems to have been directed to this fo]disease subsequently, as shown by the fact that the late Dr. toJ. S. Bristowe in his presidential address to the Medical th

Society of London in October, 1893, On the Influence of TlExtreme Slowness of Pulse in the Causation of Epilepti- puform Convulsions,3 stated that the earlie-t recorded case was va

-published in THE LANCET of 1885 by Mr. F. St. George AiMivart.4 A man, aged 61 years, had been subject to ou

epileptic seizures for six years and the pulse varied from 20 dito 26. There were a slight systolic murmur at the base cc

and a prolonged first sound at the apex. The urine tocontained a trace of albumin. Mr. Mivart regardedthese symptoms as "simple slowness modified by the af

patient’s epileptic tendency." The next case Dr. Bris- Atowe mentions is to -be found in THE LANCET of the in

same year by Dr. A. T. Gibbings.5 The patient, a man, A

aged 66 years, stated that his pulse had been intermittent as oj

long as he could remember. He was first seen in 1882, d,

suffering from weakness, dyspnoea on exertion and occurring s(

spontaneously at night, and cough. The pulse was 60 and ej

intermittent and the heart was free from murmur. Ten smonths later the pulse was 44 but regular. Subsequently E

dyspnaea and faintness appeared and the pulse fell to 34. SConsultations were held with Sir Andrew Clark and with Dr. hWalter Moxon. Fainting and epileptiform attacks recurred, t]

During each attack the pulse became very slow, at times r

falling to 12. Towards the end it varied from 15 to 31. r

The first indication of an attack was the non-occurrence of a

the usual pulse beat. The patient died in a fainting fit ten a

months after he was first seen. A post-mortem examination din the presence of Dr. Moxon showed that the heart and tother organs were all healthy. Dr. Gibbings attributed the s

epileptiform seizures to acsemia of the brain and suggested tthat the slow action of the heart was due to an irritative clesion of the vagus or degeneration of the cardiac ganglia. e

The next case was recorded by Dr. Bristowe also in 2

THE LANCET of the same year. 6 A man, aged 31 years. fformerly a soldier, had had syphilis, fever, and ague inIndia. He was discharged after 12 years’ service for i"weakness of the constitution." " He bad never had 1rheumatism nor had he suffered previously from dyspnoea. <

Two weeks before admission into St. Thomas’s Hospital he 1

had an attack of faintness after mental excitement and the J

next morning he had heavy breathing. On the following 1evening he had shortness of breath and he lost consciousness.Since then similar attacks had recurred frequently, bothnight and day. The fits were preceded by faintness andfollowed by flushings and insensibility. He once bithis tongue. There was no pain in the chest. Duringhis stay in the hospital fits occurred frequently andseemed to come on always after long periods of cardiacintermission, the pulse rate being 26 or slightly more as arule. When intermissicn was prolonged to five seconds afit generally followed. A loud, roaring, systolic murmurwas heard above and to the right of the apex of the heartand was prolonged to the base. The fits recurred frequently.Their duration varied much but unconsciousness only lasteda few seconds. The pulse became more frequent, risingonce to 80, sometimes regular, at other times very irregular.The patient lost his palpitation, dyspnoea, and fits and wasdischarged and lost sight of.The fourth case was seen by Dr. Bristowe with Dr. John C.

Ferrier. A widow, aged 54 years, had had acute rheumatism,followed by cardiac uneasineas one year previously. In

September, 1891, she bad an attack of giddiness, and similarattacks followed in which she lost consciousness. Theattacks lasted a few seconds and were attended with pallor,a cessation of respiration, unconsciousness, and slight con-vulsions. During the attack the pulse was about 30. Theattacks became more frequent and the pulse fell to 17. Theurine became slightly albumimus. On the day before deaththe pulse became regular, from 108 to 120, but then it fellto 20 and later to 18. Occasionally a soft systolic murmurwas heard at the apex, but nothing further was detected.Death occurred quietly about three months after the first fitand was preceded by a disappearance of fits for the last threeand a half hours.The fifth case was not seen by Dr. Bristowe during life

3 Transactions of the Medical Society of London, vol. xvii.4 THE LANCET, Jan. 3rd, 1885. p. 10.5 THE LANCET, Feb. 14th, 1885, p. 288.6THE LANCET, March-7th, 1885, p. 447.

ut the history was obtained subsequently to the post-iortem examination. The patient had had fits off and on3r about two years. On admission the pulse varied from 25J 30, the cardiac dulness was abolished, the first sound athe apex was blowing, and the sounds at the base were weak.’he pulse at times rose to 72. The fits came on when thernlse became very infrequent (from 20 to 25), but not in-ariably. Death occurred in a fit one month after admission.t the post-mortem examination the heart weighed 154ounces. The le&Iacute;G ventricle was bypertrophied, but notlilated. There was slight atheroma of the aorta and

ioronary arteries and of the mitral and aortic valves. Big,oe-joints contained urate of soda.Although this affection received little attenticn in England

tfter Stokes’s paper above referred to continental andAmerican authors were well aware of its existence. Huchard,n his work on cardiac disease speaks of it as the "Stokes-!B.dams syndrome." He regards the slow pulse as the result:)f changes in the vagus centre due to arterial disease anddescribes the affection as ’’ the cardio-bulbar form of arterio-sclerosis. " He mentions the fact that Stackler and Lannoiseach published a case of permanently slow pulse with

syncopal attacks due to compression of the vagus nerve.Dr. W. Osler in his lectures on "Angina Pectoris and AlliedStates" in 1897 refers to this disease which he regards ashaving close connexion with angina. Dr. Osler considersthat transient disturbances of the cerebral circulation areresponsible for the syncope and apoplectiform attacks whichremind one of the transient hemiplegia, monoplegia,aphasia, and paraplegia to which the subjects of advancedarterio-sclerosis are liable. He mentions a case fullydescribed by Prentis of Washington of a man, aged 53 years,the subject of arterio-sclerosis who had innumerable faintingspells and a slow pulse which for two years varied from 11to 40. The patient was delirious for some days before hisdeath. At the post-mortem examination the heart was

enlarged but there was no atheroma of the aorta or coronaryarteries. Sections of the medulla oblongata showed con-gestion only.

Dr. Osler describes one case himself. A man, aged 46 years,who had never had rheumatism, chorea, or syphilis, had notbeen alcoholic, and had not been subjected to hard labour,complained of pr2ecordial uneasiness on waking which hadbeen coming on for two years. The patient could not lieflat on his back but could lie on either side with his headraised. There was no sharp pain in the chest but he had anuneasy sensation and a feeling of suffocation. There was no

agonising sensation or palpitation. At times severe vertigowas present but not loss of consciousness. A year previouslyhe noticed that his pulse was very slow and in the earlymorning it had been as low as 20 per minute. When seen

by Dr. Osler his pulse was 34, the tension was increased,the up-stroke was laboured, and the wave was well sustained.Cardiac dulness was normal, impulse was not visible, andthere was no abnormal pulsation. Hypertrophy was notevident. There was a systolic murmur at the aortic carti-lage but no accentuation of the aortic or pulmonary secondsound. The patient was relieved somewhat as regards thevertigo but his slow pulse persisted.Huchard gives a useful classification of "bradycardia" " as

follows : (1) physiological (an idiosyncrasy seen in some

healthy persons, for instance, Napoleon, whose pulse wassaid to be 44) ; (2) convalescence from typhoid fever,pneumonia, and other acute diseases ; (3) toxic (digitalis,aconite, colchicum, opium, tobacco, tea, coffee, and uraemia) ;(4) reflex from the digestive organs ; (5) nervous (menin-gitis, insanity, melancholia, neurasthenia, hysteria, epilepsy,cerebral disturbances of various sorts, lesions of the spinalcord and vagus trunks) ; and (6) cardiac (fatty heart,aortic stenosis, coronary sclerosis, and cardio-bulbar arterio-sclerosis).

Robert Adams who first described this affection clearlyregarded the slow action of the heart as the primary factor.This view was more precisely stated by Dr. Gibbings.Huchard boldly stamps the complaint as the cardio-bulbarform of arterio-sclerosis. Dr. Osler is more cautious and

. would explain the syncope and other cerebral symptoms asi the result of transient disturbances of the cerebral circula-

tion analogous to the temporary paralyses that occur inI arterio-selerosis. Cases like those of Gibbings and Prentis

make one heitate to accept Huchard’s view that theaffection is due to organic disease of the bulbar arteries asuniversally true. The cases that have been describedillustrate the fact pointed out by Osler that slowness of

413

the heart’s action may cause different grades of cerebraldisorder, vertigo, syncope, or epileptiform attacks. Thecase that I have brought forward is an instance of theseverest form and it is interesting to note the length oftime during which in two attacks the pulse disappearedat the wrist-viz, 40 and 90 seconds. Unfortunately theheart was not examined during this period. But I repeatedlyexamined the heart myself when the pulse was 30 and I

always found that the pulse and heart sounds exactly corre-sponded. This patient shows no sign of general arterial

degeneration though lesions of the coronary arteries cannotbe excluded. It is probable that she is uffering from aorticstenosis.

_________ _____

THE SIGNIFICANCE OF THE ZOOLOGICAL

DISTRIBUTION, THE NATURE OFTHE MITOSES, AND THETRANSMISSIBILITY OF

CANCER.1BY E. F. BASHFORD, M.D. EDIN.,

GENERAL SUPERINTENDENT AND DIRECTOR, CENTRAL LABORATORY OFCANCER RESEARCH FUND OF THE ROYAL COLLEGE OF PHYSICIANS

OF LONDON AND SURGEONS OF ENGLAND;AND

J. A. MURRAY, M.B., B.SC. EDIN.

[ We are informed by the assistant-secretary and librarianof the Royal Society that excepting the summary which wassent to the " Times" the day after the paper was read anyversion which has already appeared in the press is anunauthorised version. We received permission to publish thepaper on Monday last, Feb. 8th.&mdash;Ed. L.]

THE object of this communication is to relate some

results of the work conducted under the immediate directionof the executive committee of the Cancer Research Fund

during the past year. We believe that these results will

convince others of the important practical assistance whichbiologists generally can give in the further elucidation ofcertain problems of cancer which must be settled beforescientific preventive and curative measures can be devised.It will also be made evident that the elucidation of canceris something more than a problem of human pathology only.We shall adduce evidence tending to show that the widezoological distribution, the character of the mitoses andthe transmissibility of cancer are nearly related phenomenawith a common basis. The fundamental significance of

ascertaining the extent of the zoological distribution ofcancer was recognised by the Cancer Research Fund fromthe first and determined the prosecution of definite lines ofinquiry with all the means at the disposal of the organisa-tion, not only with the object of eliciting new facts in regardto the zoological distribution itself, but also with the objectof discovering cancer in animals well adapted to cytologicaland experimental observations.

Zoologioal Distribution.Within the past year specimens of malignant new growths

have accumulated from all the domesticated animals andfrom many other vertebrates. The appended list shows theabundance of the material which has thus been examined.The list includes also specimens which we have been privi-leged to examine through the courtesy of investigatorsabroad, who, subsequently to the inauguration of the CancerResearch Fund, have published descriptions of malignanttumours in the lower vertebrates. It is noteworthy thatsuch growths have been obtained not only in domesticanimals but also in animals living in a state of nature-wild mouse, codfish, gurnard. The clinical, pathological,anatomical, and microscopical characters of these new

growths are identical with those found in man in allessential features, although the animals themselves aredrawn from the different classes of the vertebrate phylum.A detailed histological description of the various tumoursexamined will not be attempted here. Only the generalsignificance of the observations in relation to the incidenceof cancer in man will be emphasised.The great diversity of the habitat, food, and conditions of

1 A paper communicated to the Royal Society by Dr. J. RoseBradford, F.R.S.

life generally of the forms in which malignant new growthsoccur relegates Euch external conditions to a subsidiary rolein determining the incidence cf the disease and shows thatthe essential factors must be sought in the potentialitieswhich reside in the cells constituting the living body. Thelist of specimens, while giving no safe basis ot deduction asto the relative incidence of cancer in the different classesof vertebrates, or of the comparative susceptibility of thedifferent sites of the body, is extremely suggestive. The

large number of epitheliomata obtained in the horse and dogindicates very clearly that malignant new growths are re-

cognised according to the ease with which animals can beexamined and the length of time they are kept underobservation. The larger ratio of malignant new growthsoccurring in the internal organs of cows have beendiscovered during meat inspection at abattoirs and form awelcome corollary to the other observations. Stated gene-rally, it may be said that malignant new growths are

frequent according as animals are carefully examined, andare unrecorded in forms which are difficult to examine or donot reach old age in considerable numbers. The figures arenot sufficiently extensive to determine accurately the ageincidence of the various types of new growths in differentanimals, but a relatively higher incidence in old age is

apparent.The Phenomena of Cell-division in Jlalignant New Growths.The progressive increase in size of malignant tumours is

due to the division and increase in size of their con-

stituent cells. The process of cell-division is usuallyindirect, mitotic division of the nuclei preceding thedivision of the protoplasm. The protoplasm division isfrequently omitted and multi-nucleated cells are formedand these may subsequently enter on mitosis, givingrise to pluripolar figures. Amitosis or direct nucleardivision also occurs, but its full significance has not

yet been determined. It is, however, evident that theoccurrence of amitosis does not signify degeneration. Theamount of chromatin entering into the equatorial plate ofthe mitoses of malignant new growths had long been reco-gnised as subject to variation (byperchromatosis, hypo-chromatosis of von Hansemann, 1893), but a new light hasbeen thrown on this phenomenon by a paper communicatedto the Royal Society on Dec. 10th, 1903, by J. B. Farmer,F.R.S., J. E. S. Moore, F.L.S., and C. E. Walker, entitled"Resemblances exhibited between the Cells of MalignantGrowth in Man and those of Normal Reproductive Tissues."These observers found that while the growing margin ofcarcinomata and sarcomata presented mitoses similar tothose found in other tissues in repair and inflammation,certain cells in the deeper layers, after a slight increasein size, entered on mitosis with ring chromosomes similarto those found in the heterotype division of spore-mothercells of plants and spermatocytes of animals, and likethese, with chromosomes in number only half that charac-teristic of the mitoses of somatic cells. Mitoses similarin character to the somatic divisions but with reducednumber of chromosomes were also seen (hcmotype) corre-sponding to the divisions in the sexual generation of plantsand the second ripening divisions of animals. From theseobservations the authors concluded that malignant newgrowths were virtually reproductive tissue arising inabnormal situations and possessed of an independence andpower of growth like that of the testis in the mammalianbody.

This striking sequence of characteristic mitoses had beenfound in all malignant tumours examined and was absent inthose of benign character. We at once determined to com-municate with the authors who with great courtesy affordedus an early opportunity to examine their preparations. Itwas then decided to determine how far similar phenomenawere characteristic of the malignant new growths occurringin animals. The result has been a complete confirmation ofFarmer, Moore, and Walker’s observations in tumours fromthe trout (Mr. Gilruth’s and Miss Plehn’s cases of adeno-

carcinoma), the mouse (two cases of adeno-carcinoma,Jensen’s epithelioma), and the dog (mixed cell sarcoma,round cell sarcoma, squamous cell carcinoma). In thecolumnar cell carcinoma of the trout the phenomena wereespecially distinct, the small number of chromosomes 2 (24,

2 The achromatic figure has always been carefully studied as a

control to the observations made on the chromatin of the mitosis.When the chromosomes have been counted, this has been done onsections 5&mdash;10 &micro; thick, mounted in series.