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Cystometry: Its Value and Limitations1
CYSTOMETRY: ITS VALUE A:'\D LIMITATIONS 1 ::VIICHAEL KI_'.\KEY O'HEERO~ From the Thompson Urological Fund, Rush Medical College, and The Urological Service of The Presbyterian Hospital, Chicago
Is the cystometer essential to the making of a diagnosis in the fields of urology and neurology? Is it of assistance in the making of a diagnosis, and is it of value to the student of physiology? These questions can be asked because upon their answer hangs the future of this procedure. In this study the cystometric diagnosis has been compared to the diagnosis made by the usual methods; that is, urinalysis, residual urine determinations, rectal examination of the prostate, cystoscopy, neurological examination, history, blood Wasserman, and spinal fluid studies when indicated, and when possible. The cystometer is of possible value in 2 fields: (1) the fields of diagnosis and (2) physiology. To all it serves as a function test to that part of the nervous system that is distributed to the urinary bladder, and posterior urethra. vVorkers in this field have made many claims regarding the value of the procedure, but undoubtedly some of these were overstatements, as they were later withdrawn. If the clinician is interested in cystometry, it is because of its value as a diagnostic procedure, and it is in this field that a careful analysis of its real value is needed. In the field of physiology much has been contributed to our knowledge of bladder function by Rose, Simons, Langworthy, Dees, Muschat and many others. Modern cystometry is the direct outgrowth of the work of D. K. Rose who published his first paper in 1927. Rose early demonstrated the accuracy of the procedure in the diagnosis of certain urological and neurological conditions. The study was taken up by others who have made many contributions to this subject. The majority of workers have preferred to model their own instrun1ent, so that many different instruments are on the market. These instruments fall into 2 general classes: (1) Those with a water manometer and (2) those with a mercury manometer. Some of the instruments have been made with an air drum which has the advantage of compactness, portability, accuracy and sensitivity. Both the water and mercury types are accurate, but the water type is 13½ times as sensitive as the mercury type because the specific gravity of mercury is 13.5. This added sensitivity is of no value when using the instrument for diagnostic studies. The minor fluctuations due to respirations, slight movements of the patient's body while lying on the table, and other extraneous factors are recorded; and only add to the confusion when reading the curve. Some instruments make a continuous tracing, while others have to be read and recorded at the end of each addition of water. I do not think the continuous tracing adds to the test any information of diagnostic 1 Read before Section on Urology, at annual meeting of American Medical Association, Cleveland, on June 3, 1941. 824
CYSTOMETRY: ITS VALUE AND LIMITATIONS
825
value, that cannot be obtained by interrupted readings. The type of instrument used is of no importance so long as the operator understands it and uses it correctly. The instrument used in these studies is an apparatus of my own design (fig. 1). It merely offers the simplest and shortest connections between the bladder and a manometer which is the ordinary blood pressure apparatus. It has a simple arrangement of tubes with which to fill the bladder. A 100 cc syringe is used for the filling procedure. The technique is simple. The apparatus is filled with water to empty it of air. The level of the water in the inverted bottle is made to correspond to the floor of the bladder, and the apparatus is connected to the double eye catheter in the bladder. A rather large catheter is used to reduce the "stretch reflex" which is simply resistance in the system. I prefer a No. 20-22 F. double eye catheter. At times a smaller one is used, and it is satisfactory if one allows time for the "stretch reflex" to disappear before taking the reading. Twenty cubic centi-
Fiy· Cy5fometer .f>reS:.(.(re
IJ1>ft!e-----
Water--··
meters of water, at room temperature, is injected at a time, and a reading is taken at the end of each injection. The sensation of desire to urinate, urgent desire to urinate, pain, and severe pain are also recorded. Two curves are made during each examination, because the second curve frequently gives information not obtained in the first curve. This point was first stressed by D. K. Rose. A comparison of the 2 curves is also of value as the second curve always shows the effect of the first curve. (This effect may be to partially decompensate the bladder, in normal or hypotonic bladders, and to a lesser extent in hypertonic bladders that are not infected. In infected bladders the irritability is increased, unless muscular hypotonicity be so marked that the increased irritation fails to induce a motor response.) The point I wish to make here is that the second curve is always lower and longer than the first, unless the bladder is infected; of course, this is dependent upon the first curve having been carried far enough to fully dilate the bladder. I make a practice of carrying both curves to the point of pain.
826
MICHAEL KINNEY o'HEEROX
The theoretical explanation of cystometry is essentially the physiology of micturition, and much has been written about it by others. Although it has been presented to the profession many times in the last few years, it may not be amiss to discuss it in brief here. If one looks upon the bladder as being composed of 2 elements, muscle and nerve, that affect its function, it will be much easier to understand its variations in function. The nervous elements of the bladder consist of the sacral autonomics which act as the detrusor nerve and contain sensory fibers, mostly pain fibers. The thoracolumbar nerves which act as the filling nerves of the bladder; and also contain sensory fibers, chiefly those of sensation of fullness. The pudic nerve which is also both motor and sensory and distributed to the posterior urethra and external sphincter. The internal sphincter is dilated by the sacral autonomics and is closed by the thoracolumbar autonomics. Each of these sets of nerves consists of a primary reflex arc, which is inhibited by an upper neurone, and therefore affected by lesions of the central nervous system. TABLE NO.
TYPE
1.
Classification of cystornetrugrams
LOCATION OF LESION
I
COMMON CAUSES
-~-~,---1-------.--------~
I
II
III
IV
V
Hypotonic Decreased tone of muscle m I Obstruction in lower urinary tract myogenic bladder wall I of long duration Hypertonic Increased tone of muscle in Lower tract obstruction, elusive myogenic bladder wall ulcer, bladder stone, tumors, cystitis, etc. ~ormal Hypotonic Involves primarily the sensory Tabes, some cases of pernicous side of the primary reflex arc anemia and pellegra, congenital ncuroabsence of the detursor nerve, genic of the sacral autonomics etc. Hypertonic Involves the upper neurone Cord tumor, fra.cturc of spine, neurocerebral accidents, mental degenic ficiency, spina bcfida, etc. II
The bladder muscle may undergo changes which affect the physiology of the bladder. These changes may be in the form of hypertrophy, atony, fibrosis, edema or even masses outside of the bladder; all of which alter the intra vesicular pressure. As the bladder is filled with water it approaches the same physiological condition as when filled with urine; though, of course, the artificial filling is more rapid. At each addition to the volume of fluid in the bladder, the volume, pressure, sensory relationship is determined and compared to the accepted normal relationship. Most workers in this field have 5 general classes into which all cystometrograms fall (table 1). These are: 1. Hypotonic myogenic-in which there is muscular decompensation and increased resistance at the bladder neck, but 'with a normal nervous mechanism. I say normal nervous mechanism, but there is an exception; that is, "the physiological anesthesia" in decompensated bladders carrying residuals. This is probably a peripherial lesion resulting from the pressure of the residual urine. 2. Hypertonic myogenic-in which the bladder capacity is small due to
827
CYSTOMETRY: ITS VALUE A?\D LIMITATIONS
increased detrusor activity of the bladder ,vall, and with a. normal nervous mechanism. 3. Normal-in which there i1:, the normal balance between the :-;phincteric resistance, and muscular detrusor activity; and betvveen the sacral, and thoracolumbar autonomies. 4. Hypotonic neurogenic-in which there is also muscular decompensation hnt on the basis of a lesion of the afferent branch of the sacral autonomics. 5. Hypertonic neurogenic--in which the ;;ame condition prevails hut in which the fault is with an increased tone of the efferent branch of the sacral autonomics. In this study are included 100 cystometrograms from the service of Dr. H. L Kretschmer, at the Central Free Dispensary of the Rush Medical School and the Presbyterian Hospital of Chicago. These cases are grouped in the usual 5 classes based on the cystometric findings and compared with the results of the other diagnostic procedures (table 2). The cystometric and clinical diagnose:" corresponded in the members of all the groups except the hypotonic neurogenic group, and in this group only 3 membern (14 per cent) of the group fail to correTABLE
2.
Comparison of 100 cases I DIVISION OF CASES INTO CLASSES
Ii 1
I
CLASSIFIC/1TlON
'
CASES 'l~'lTH Tfl E SAME CLINICAL AND CYSTOlVrETRIC DIAGNOSIS
Per cent of cases
No. of cases
13 :36 16 23 12
13 36 16 23 12
13 :36 16 20 12
100
100
No. of cases
Per
Totals ..
100 100 100
I I
0 ()
I,___Per cent of cas_c5_ __ 0 0
14
100
0 ::l 0
D7
:3
3
86
---, 97
of ~~~-1 _ No. cases
of cases
--1--··
Hypo tonic rnyogenic. Hypertonic rnyogcnic. N orrnal. ... Hypotonic ncurogcnic. Hvpertonic neurogcnic.
CASES WHERE THE CLINICAL AND C\'STO· l\JETRIC DIAGNOSIS DJ.F"FER
0 ()
~pond. This is 3 per crnt of the total number of patients studied. In these 3 patients the cystometcr has been of value in arriving at a diagnosis. A brief analysis has been made of 2 of these patients; the third haR bern lost, and poRsibly had he returned for additional study as he was instructed to do, the clinical diagnosis and the cystometric diagnosis might have been the ,.;ame. In Case 1, :\1r. P. V., aged 62, the clinical diagnosis made by phy:oical examination, rectal examination and cystoscopy, was benign hypertrophy of the prostate gland. There was no residual urine present. The blood vVasscrman test was negative, and the neurological examination was normal. The cy1,tometrogram iR as shown in figure 2, and the cystometric diagnosir:, is tabetic bladder. Comment: There may be those who wish to question the eystometric diagnosis, but I wish to call attention to the fact that the pressme is low, the volume great, and the sensory points shifted to the right. This makes the diagnosis of early tabetic bladder probable. This cannot be confirmed until Rcwcral years from now when the cmir,,e of his illness can be obserTed. Case l!. The next case in which the cystometric diagnosis did not fit the
828 clinical diagnosis is that of Mr. J. R., aged 57. His cystometrogram is shmn1 in figure 8. His general physical examination was negative. The blood Was:oerman test was negative. The neurological examination was normaL Rectai examination of the prostate revealed a slight enlargement. Residual urine 5 cc and it wafs not infected. The cystoscopic diagnosis was normal bladder There was no evidence of obstruction at the bladder neck. The diagnosi10 was early tabetic bladder. Comnwnt: Here again one is confronted ·with a curve of an early tabetic bladder in the fact> of a normal neurological examination and a normal blood serology. Only time will tell whether or not the cystometric diagno,.;is correct. I regret that neither of these patients would ,mbmit to spinal puncture. The question is, in these 2 cases, has the cyRtometer given information not
tained by the usual clinical examination; or, arc the cystonwtric findings This question cannot be ans,vered at this time and will have to wait until thc:-;c patient" can be examined at some future time. In this connection attention shonld be drawn to the work of Brodie and Phifer. In a review of 24 ca,ws, in their preliminary report, they came to the conclusion that eystometry is more valuable than cystoscopy in demonstrating early neurogenic bladders in case::of neuroNyphilis. They emphasized the fact that cystometry ·will demonstrate neurogcnic lesions before frank decompcnsation of the bladder has taken vVith this statement I am in accord; but I wish to go further and state that m most the same diagnosis can be made with the aid of a good a neurological examination, a cystoseopic examination and without the aid of eystometry.
CYSTOMETRY: ITS VALUE AND LIMITATIO?\S
829
Eleven patients out of the total group of 100 fall into this class. That is, the cystometric diagnosis ,vas hypotonic neurogenic bladder; and none of the patients in this group carried residual urine of over 30 cc. That is, these bladders were all well compensated from the standpoint of their ability to empty. In 8 of these cases the same diagnosis of "tabetic" bladder was made as the result of the clinical examination. In the other 3 the diagnosis was made with the cystometer only. These 3 cases have been discussed above. In this connection the etiology is interesting. Five of the patientA had lues of the central nervous system. In 3 of the patients advanced arterioAclerosis was thought to be the cause, and in the remaining 3 no cause was found. In these 3 the blood serology was negative, and the neurological examination,, ,vere normal. In ] the 8pinal fluid examination was also negative. The other two
ere
,n
refused to submit to a spinal tap. The following case is representative of this group of three patients with early "tabetic" bladders of unknmvn etiology. this is the only case that can be accepted as being of unknown etiology, because it is the only one in which a lumbar puncture was made. Case 8. ::VIiss B. L., aged 20, was seen on ":\fay 5, 1939, complaining of urinary incontinence on and off for the past week. At times she suddenly became aware of the fact that urine was running down her leg. She had no sensation of voiding at such times, but at other times she was able to hold her urine quite well. During her childhood she had had 8 operations; 5 were for growths on the right side of her body including the right arm and leg; one was a tonsillectomy, and one was the removal of a large lipoma from the right flank. Thi;, was perClinic 11 years a.go, and the microscopic diagnosis was formed at the
830
MICHAEL KINKEY 0 1HEERON
obtained. At the same time she also had an anastomosis of the lympathatics of the right thigh by incision of the "facia lata." Examination of the patient revealed an asymetry of the body. The right arm, shoulder and chest were smaller than the left; but the right thigh and leg were swollen by lymphedema. The big toe and the tip of the second toe of the right foot had been amputated. The rest of the examination was normal, and the neurological examination, both motor and sensory, was normal. Particular emphasis was give to toensation below lumbar I, and this was normal. The blood Wasserman ·was negative. Spinal fluid was obtained and the follo-wing tests were negative or normal: '\Vasserman, Nonne, Ross-Jones, Lange, sugar and total protein. The urine was also negative. Cystoscopic examination revealed a large bladder with a capacity of 800 cc but otherwise normal. No
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obstruction was found either at the bladder neck or in the urethra. There was no residual urine present. The cystometrogram showed a hypotonic neurogenic type of curve. The volume was large, pressure low, and sensation delayed (fig. 4). She was then put on mecholyl, mg. 400-600, daily for 3 weeks. Since the beginning of treatment, she has been symptom-free. A cystometrogram done on September 15, 1939 shows slight improvement by a decrease in capacity, increased pressure, and improved sensations (fig. 5). Comment: This is a case of "tabetic" bladder of unexplained etiology. The diagnosis was easily made by the usual clinical methods, and in this case cystometry has been of no additional value. The patient's improvement was noted clinically, and confirmed by a cystometrogram. This case cannot be passed without a ·word concerning the possible etiology. I wish to reemphasize the fact that a careful examination failed to disclose the true diagnosis.
CYSTOMETHY: ITS V.\Ll:E ,\ND LIJ\ll.TATIO?\S
This case should he placed in the group reported by Entz and HaymomL They ,;uggested that the lesion may be congenital absence of a part of the detnrnor (Sacral) ne1Tes. I haw no explanation to offer. In the group of 2;3 hypotonic neurogenic patients, -± ,Yere of unknown etiology. Three of these had no residual mine, and 1 carried 200 cc of residual urine. The patient prec,entcd ahoYe ,Yas the only one that submitted to a spinal tap, and I am not ,Yilling to placP a patient in thi;-: idiopathetir group unless spinal fluid studies were made and ·were normal. In order to show the role played by the cystometer in arriYing at a diagnosici, I 11-ill select 1 case from ead1 of the 5 groups: Case 4- .l\Ir . .J. G., aged 72, at his first vi,;it complained of noctmia 5 to 6 times, dysuria, slmYing of the stream, poor force of the stream and a feeling that
he ,rns not emptying his bladder. On physical examination he ,ms found tu haYe advanced generalized arterio,;clcrosis and arterioc1clerotic heart disea:-,c. A neurological consultant reported the presence of cord changes :-;econdary to the arterio;;elcrosis. He ruled out Ryphilis by blood and spinal fluid studie,-;. His opinion ,rns that the neurological findings ,vere not sufficient to explain the hladder di:sturbanees. On admission the bladder was found to be Llp to the xiphoid process. The prostate ,rns greatly enlarged by rectal examination. This patient ,ms found to have a bilateral hydronephrosis and a badly infected mine. A tranc1methral resection was done, follmving which he was unable to empty his bladder, and carried a residual urine of fi50 ec. At this time a cycltomctrogram was made and the diagnosis waR hypotonic myogenic bladder (fig. G) The patient ,rns then rut on mecholyl, mg. 800, daily hy mouth, and over a period of 3 months the residual mine gradually cli:sappearcd until none wa;:;
832
MICHAEL KINNEY O'HEERON
present. He had 2 urethroscopic examinations to rule out the possibility of prostatic obstruction. The opinion was that he had an atonic bladder from the long-standing residual urine and that after the obstruction was removed proper compensation resulted. A cystometrogram performed after the residual disappeared showed marked improvement in sensation, pressure, and volume. Comment: This is a clear-cut case of bladder atony secondary to prostatic obstruction. The cystometrogram confirmed the diagnosis. Case 5. Mr. A. C., aged 26, had had frequency every 5 to 10 minutes for the past 2 years. This was present both day and night and was accompanied with severe pain. The pain was constantly present but was relieved somewhat by urination. He never passed very much urine at a time. During the past 2 years he had seen many physicians and had had as many different kinds of treat-
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P~ r,a.111 Pr= .severe pain mVI?= m«nn11Am
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ments; that is, prostatic massages, sounds, bladder lavages, and sulfanilamide. The physical examination was essentially negative. The prostate was normal and the strippings were free of pus. Urinanalysis was negative. There was no residual urine present. Neurological examination was normal and the blood Wasserman was negative. A cystometrogram (fig. 7) was made and the diagnosis was hypertonic myogenic bladder. Cystoscopy revealed the presence of several areas of submucous fibrosis (elusive ulcer). The bladder capacity was less than 1 ounce. Under ether anesthesia, the bladder was dilated with water to 500 cc, and the areas of elusive ulcer were thoroughly fulgurated ,,vith a bipolar current. The following day the patient left the hospital and stated that his pain was gone and his frequency of urination had decreased from every 5 to 10 minutes to every two hours.
CYSTOMETRY: ITS VALUE AND LIMfi'ATIONS
838
Comment: This is a clear-cut case of a hypertonic myogenic bladder secondary to elusive ulcer. In this type of case, as in the hypotonic myogenic bladder secondary to bladder neck obstruction, the diagnosis can easily be made the usual urological procedures. In this case cystometry did not add any information. Case 6. Mr. M. G., aged 24, was a medical student who was seen because he was nervous and wanted an examination to make sure that he had no disease of the bladder. At times he had some slight frequency but this was never very marked. He insisted on a complete urological check-up for his own peace of mind. The physical examination was normal. The urinalysis was normal. The prostate was normal on rectal palpation, and the prostatic secretion was normal. Cystoscopy and urethroscopy revealed a normal bladder and posterior
r IJ1a;r;,rnu
1)1
fi
urethra. The blood 1Vasserman vrns negative and neurological examination was normal. The eystometric findings are shown in figure 8. Comment: These curves may be cornidered normal except that the terminal pressures are rather low. This is frequently seen in nervous individuals and has been considered to be due to psychic inhibition, the important points being tlw sensory findings and these were normal. Diagnosis: X ormaI bladder. Case 7. :VIiss 0. S., aged 21, was an unmarried girl who was seen in cornmitation because of complete retention of urine which came on 2 weeks before, following a few days of rapidly increasing frequency and ::,lowing of the stream. At the time of the first admission she was catheterized for relief of complete urinary retention. The following day she wa:-, again catheterized and found to ha-ve 500 cc residual urine. Two days later ,vhen I saw her she had a r12ridual
834
MICHAEL KINNEY O'HEERON
urine of 200 cc. The physical and neurological examinations were negative. The pelvic examination revealed a third degree retrodisplacement of the uterus, and
2111
l/o}.
Jn 111
cc.
the uterus was enlarged and tender. Blood vVasserman was negative, and the urine was free of pus, albumin, blood, and organisms. Cystometry was performed and the cystometric diagnosis was tabetic bladder (fig. 9). Cystoscopic exami-
CYSTOMETRY: ITS V.U,UE AND "'LIJVIITATIO~S
835
nation showed that the bladder ,va;-; normal, both ureters were catheterized and the differential urinalysis was normal in every respect. A plain urogram was normal, and retrograde pyelograms were normal. A gynecologist was called in consultation. He brought the uterus forward and held it there with a pessary. This resulted in disappearance of her urinary symptoms and the residual urine, within a couple of days. Comment: This i8 a case of a hypotonic neurogenic bladder on the basis of a peripheral lesion; that a break in the detrusor nerve produced by pressnre from the diRplaced uterus. In this case the cystometer was able to make the diagnosis of the neurogenic bladder hut was not nccesRary. Case 8. D. S., a 9-year-old boy, had been incontinent of urine and feces since birth. This incontinence was more of an uncontrollable urgency than a con-
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h1'1.Jf ;mun
tinual dripping. He felt the desire to urinate or defecate but unless he had a receptacle at hand, he c1oiled himself. At the age of 2 years a small peduneulated lipoma was removed from the sacral region. This did not contain ncITe fo,sue, according to the pathological report. Physical examination revealed the absence of the right wing of the sacrum, poor rectal sphincter tone, and sluggish reflexes throughout; but they were more active on the left than on the righL Over the right buttock was a small area of diminished sensation. He had a reRidual urine of from 60-100 cc. The urinalysis ,vaR normal. An x-ray of the spine revealed an absence of the right side of the sacrum and incomplete fusion of the spinous processes. The neurosurgeon made a diagnosis of cord tumor, and requested a cystometrogram to confirm his diagnosis (fig. 10). The cystometric diagnosis was hypertonic neurogenic bladder, secondary to a lesion of the upper
836
MICHAEL KINNEY O'HEERON
neurone. The lower reflex arc was intact. The important points in the curve are (1) the high pressures, (2) the fluctuations, (3) the low volume and (4) the diminished sensation. A laminectomy was performed by Dr. Adrain Verbruggern, and a lipoma was removed from the lower part of the cord. Following the operation, complete retention developed and the patient had to be catheterized. The catheter was left indwelling for 12 days, and when it was removed the patient was put on a schedule of voiding every hour. At each voiding he passed 50-100 cc of urine and was seldom wet. At night he did wet the bed. The fecal incontinence was still present at times, but was much better. On the twenty-fifth post operative day, another cystometrogram was performed (fig. 11). This showed an improvement in sensation, marked hypertonia, but absence of the spasms, so the hypertonia was better. )'."#"]
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Comment: This is a case of cord tumor with bladder symptoms. The diagnosis of the cord tumor was made by the neurological examination performed by the consulting neurosurgeon. The surgeon stated t hat the cystometric studies were of value in confirming his diagnosis but that he would have handled the case in exactly the same way had none been made. CONCLUSIONS
One hundred cystometrograms have been performed and have been matched and compared with the clinical diagnosis made by the usual diagnostic procedures. In 97 of these cases the diagnosis arrived at was the same with both methods. In 3 of the cases t he cystometrogram has given information not obtained by t he usual procedures. This may be additional information that will be of value to the Urologist in handling these cases, but follow-up studies will
CYSTOMETRY: ITS V_-\.LCE AND LIMITXl'lOXS
have to be made on these patients to determine of just what value the eystometric studies have been, Cystometry has a limited value as a diagnostic procedure in the field of Urology, because the information obtained is usually obtained just as easily by the other diagnostic procedures, In some instances is of definite harm to the patient, I have 1 instance of epididymiti,; following a cystometric determination, This wa:;; in a young boy, who had a neurogenic bladder secondary to a fractured :;;pine, The diagnosis -was obvious before cystometry was performed, The test yielded no additional information and the boy got epididymitis. There may be cases in which a test that can confirm a diagnosis already established would be of value; such was the case in Case 8 where the neurosurgeon admitted that the cystometrngram strengthened his opinion and was a valuable adjunct. It may also be of some value as a follow-up; that is, a quantitative test to determine the value of certain therapeutic procedures, as is seen in CaseR 3 and 8, To the physiologists it is of great value in :;;tudies on the urinary bladder, This has been proven by many -workers, such as Langworthy, Dees, and others, and is outside the scope of this study, Cystometry should never replace any of the usually performed diagnostic procedures. SUMMARY
One hundred cystometrograms have been performed and the results compared to the results of the usual tests performed on the same patients, Cystometry is a test of limited value, and in most instanccR adds nothing to the information on any given case. In some instances cystometry may be of value as a confirmatory test. Cystometry should never surplant any of the usual diagnostic tests. Cystometry may be of value in the early diagnosis of some cases of "tabetictype bladder." Time will have to prove or disprove this statement. Jfedical Arts Bldg., Houston, Texas. REFEREXCES BRoun;, ERNEST L, AND P1-nF1rn, L A.: Cystometric observations in asymptomatic ncw·osyphilis, ,L UroL, 38: 412-419, 1937, - - - , H~:LFERT, L AKD PHIFER, L A,: Cystometric observations in neurosyphilis, Urn!. and Cutan. Rev,, 43: 51-56, 1939, ENTZ AND HAYMOND: Atony of urinary bladder of undetermined "tiology, .J. l;roI., 27: 201-205, 1932, GRAHA:i.r, E, A,: Surgical Diagnosis, Vol. 3, 1930, Philadelphia and London: W I:L Saunders Co, Rorrn, D. K,: Determination of bladder pressure 1Yith cystometer; new principle in diagnosis. J. A, M, A., 88: 151-156, 1927, - - - : Cystometric bladder pressure determination: Their clinical importance, J, Urol., 17: 487-.501, 1927,
Is the cystometer essential to the making of a diagnosis in the fields of urology and neurology? Is it of assistance in the making of a diagnosis, and is it of value to the student of physiology? These questions can be asked because upon their answer hangs the future of this procedure. In this study the cystometric diagnosis has been compared to the diagnosis made by the usual methods; that is, urinalysis, residual urine determinations, rectal examination of the prostate, cystoscopy, neurological examination, history, blood Wasserman, and spinal fluid studies when indicated, and when possible. The cystometer is of possible value in 2 fields: (1) the fields of diagnosis and (2) physiology. To all it serves as a function test to that part of the nervous system that is distributed to the urinary bladder, and posterior urethra. vVorkers in this field have made many claims regarding the value of the procedure, but undoubtedly some of these were overstatements, as they were later withdrawn. If the clinician is interested in cystometry, it is because of its value as a diagnostic procedure, and it is in this field that a careful analysis of its real value is needed. In the field of physiology much has been contributed to our knowledge of bladder function by Rose, Simons, Langworthy, Dees, Muschat and many others. Modern cystometry is the direct outgrowth of the work of D. K. Rose who published his first paper in 1927. Rose early demonstrated the accuracy of the procedure in the diagnosis of certain urological and neurological conditions. The study was taken up by others who have made many contributions to this subject. The majority of workers have preferred to model their own instrun1ent, so that many different instruments are on the market. These instruments fall into 2 general classes: (1) Those with a water manometer and (2) those with a mercury manometer. Some of the instruments have been made with an air drum which has the advantage of compactness, portability, accuracy and sensitivity. Both the water and mercury types are accurate, but the water type is 13½ times as sensitive as the mercury type because the specific gravity of mercury is 13.5. This added sensitivity is of no value when using the instrument for diagnostic studies. The minor fluctuations due to respirations, slight movements of the patient's body while lying on the table, and other extraneous factors are recorded; and only add to the confusion when reading the curve. Some instruments make a continuous tracing, while others have to be read and recorded at the end of each addition of water. I do not think the continuous tracing adds to the test any information of diagnostic 1 Read before Section on Urology, at annual meeting of American Medical Association, Cleveland, on June 3, 1941. 824
CYSTOMETRY: ITS VALUE AND LIMITATIONS
825
value, that cannot be obtained by interrupted readings. The type of instrument used is of no importance so long as the operator understands it and uses it correctly. The instrument used in these studies is an apparatus of my own design (fig. 1). It merely offers the simplest and shortest connections between the bladder and a manometer which is the ordinary blood pressure apparatus. It has a simple arrangement of tubes with which to fill the bladder. A 100 cc syringe is used for the filling procedure. The technique is simple. The apparatus is filled with water to empty it of air. The level of the water in the inverted bottle is made to correspond to the floor of the bladder, and the apparatus is connected to the double eye catheter in the bladder. A rather large catheter is used to reduce the "stretch reflex" which is simply resistance in the system. I prefer a No. 20-22 F. double eye catheter. At times a smaller one is used, and it is satisfactory if one allows time for the "stretch reflex" to disappear before taking the reading. Twenty cubic centi-
Fiy· Cy5fometer .f>reS:.(.(re
IJ1>ft!e-----
Water--··
meters of water, at room temperature, is injected at a time, and a reading is taken at the end of each injection. The sensation of desire to urinate, urgent desire to urinate, pain, and severe pain are also recorded. Two curves are made during each examination, because the second curve frequently gives information not obtained in the first curve. This point was first stressed by D. K. Rose. A comparison of the 2 curves is also of value as the second curve always shows the effect of the first curve. (This effect may be to partially decompensate the bladder, in normal or hypotonic bladders, and to a lesser extent in hypertonic bladders that are not infected. In infected bladders the irritability is increased, unless muscular hypotonicity be so marked that the increased irritation fails to induce a motor response.) The point I wish to make here is that the second curve is always lower and longer than the first, unless the bladder is infected; of course, this is dependent upon the first curve having been carried far enough to fully dilate the bladder. I make a practice of carrying both curves to the point of pain.
826
MICHAEL KINNEY o'HEEROX
The theoretical explanation of cystometry is essentially the physiology of micturition, and much has been written about it by others. Although it has been presented to the profession many times in the last few years, it may not be amiss to discuss it in brief here. If one looks upon the bladder as being composed of 2 elements, muscle and nerve, that affect its function, it will be much easier to understand its variations in function. The nervous elements of the bladder consist of the sacral autonomics which act as the detrusor nerve and contain sensory fibers, mostly pain fibers. The thoracolumbar nerves which act as the filling nerves of the bladder; and also contain sensory fibers, chiefly those of sensation of fullness. The pudic nerve which is also both motor and sensory and distributed to the posterior urethra and external sphincter. The internal sphincter is dilated by the sacral autonomics and is closed by the thoracolumbar autonomics. Each of these sets of nerves consists of a primary reflex arc, which is inhibited by an upper neurone, and therefore affected by lesions of the central nervous system. TABLE NO.
TYPE
1.
Classification of cystornetrugrams
LOCATION OF LESION
I
COMMON CAUSES
-~-~,---1-------.--------~
I
II
III
IV
V
Hypotonic Decreased tone of muscle m I Obstruction in lower urinary tract myogenic bladder wall I of long duration Hypertonic Increased tone of muscle in Lower tract obstruction, elusive myogenic bladder wall ulcer, bladder stone, tumors, cystitis, etc. ~ormal Hypotonic Involves primarily the sensory Tabes, some cases of pernicous side of the primary reflex arc anemia and pellegra, congenital ncuroabsence of the detursor nerve, genic of the sacral autonomics etc. Hypertonic Involves the upper neurone Cord tumor, fra.cturc of spine, neurocerebral accidents, mental degenic ficiency, spina bcfida, etc. II
The bladder muscle may undergo changes which affect the physiology of the bladder. These changes may be in the form of hypertrophy, atony, fibrosis, edema or even masses outside of the bladder; all of which alter the intra vesicular pressure. As the bladder is filled with water it approaches the same physiological condition as when filled with urine; though, of course, the artificial filling is more rapid. At each addition to the volume of fluid in the bladder, the volume, pressure, sensory relationship is determined and compared to the accepted normal relationship. Most workers in this field have 5 general classes into which all cystometrograms fall (table 1). These are: 1. Hypotonic myogenic-in which there is muscular decompensation and increased resistance at the bladder neck, but 'with a normal nervous mechanism. I say normal nervous mechanism, but there is an exception; that is, "the physiological anesthesia" in decompensated bladders carrying residuals. This is probably a peripherial lesion resulting from the pressure of the residual urine. 2. Hypertonic myogenic-in which the bladder capacity is small due to
827
CYSTOMETRY: ITS VALUE A?\D LIMITATIONS
increased detrusor activity of the bladder ,vall, and with a. normal nervous mechanism. 3. Normal-in which there i1:, the normal balance between the :-;phincteric resistance, and muscular detrusor activity; and betvveen the sacral, and thoracolumbar autonomies. 4. Hypotonic neurogenic-in which there is also muscular decompensation hnt on the basis of a lesion of the afferent branch of the sacral autonomics. 5. Hypertonic neurogenic--in which the ;;ame condition prevails hut in which the fault is with an increased tone of the efferent branch of the sacral autonomics. In this study are included 100 cystometrograms from the service of Dr. H. L Kretschmer, at the Central Free Dispensary of the Rush Medical School and the Presbyterian Hospital of Chicago. These cases are grouped in the usual 5 classes based on the cystometric findings and compared with the results of the other diagnostic procedures (table 2). The cystometric and clinical diagnose:" corresponded in the members of all the groups except the hypotonic neurogenic group, and in this group only 3 membern (14 per cent) of the group fail to correTABLE
2.
Comparison of 100 cases I DIVISION OF CASES INTO CLASSES
Ii 1
I
CLASSIFIC/1TlON
'
CASES 'l~'lTH Tfl E SAME CLINICAL AND CYSTOlVrETRIC DIAGNOSIS
Per cent of cases
No. of cases
13 :36 16 23 12
13 36 16 23 12
13 :36 16 20 12
100
100
No. of cases
Per
Totals ..
100 100 100
I I
0 ()
I,___Per cent of cas_c5_ __ 0 0
14
100
0 ::l 0
D7
:3
3
86
---, 97
of ~~~-1 _ No. cases
of cases
--1--··
Hypo tonic rnyogenic. Hypertonic rnyogcnic. N orrnal. ... Hypotonic ncurogcnic. Hvpertonic neurogcnic.
CASES WHERE THE CLINICAL AND C\'STO· l\JETRIC DIAGNOSIS DJ.F"FER
0 ()
~pond. This is 3 per crnt of the total number of patients studied. In these 3 patients the cystometcr has been of value in arriving at a diagnosis. A brief analysis has been made of 2 of these patients; the third haR bern lost, and poRsibly had he returned for additional study as he was instructed to do, the clinical diagnosis and the cystometric diagnosis might have been the ,.;ame. In Case 1, :\1r. P. V., aged 62, the clinical diagnosis made by phy:oical examination, rectal examination and cystoscopy, was benign hypertrophy of the prostate gland. There was no residual urine present. The blood vVasscrman test was negative, and the neurological examination was normal. The cy1,tometrogram iR as shown in figure 2, and the cystometric diagnosir:, is tabetic bladder. Comment: There may be those who wish to question the eystometric diagnosis, but I wish to call attention to the fact that the pressme is low, the volume great, and the sensory points shifted to the right. This makes the diagnosis of early tabetic bladder probable. This cannot be confirmed until Rcwcral years from now when the cmir,,e of his illness can be obserTed. Case l!. The next case in which the cystometric diagnosis did not fit the
828 clinical diagnosis is that of Mr. J. R., aged 57. His cystometrogram is shmn1 in figure 8. His general physical examination was negative. The blood Was:oerman test was negative. The neurological examination was normaL Rectai examination of the prostate revealed a slight enlargement. Residual urine 5 cc and it wafs not infected. The cystoscopic diagnosis was normal bladder There was no evidence of obstruction at the bladder neck. The diagnosi10 was early tabetic bladder. Comnwnt: Here again one is confronted ·with a curve of an early tabetic bladder in the fact> of a normal neurological examination and a normal blood serology. Only time will tell whether or not the cystometric diagno,.;is correct. I regret that neither of these patients would ,mbmit to spinal puncture. The question is, in these 2 cases, has the cyRtometer given information not
tained by the usual clinical examination; or, arc the cystonwtric findings This question cannot be ans,vered at this time and will have to wait until thc:-;c patient" can be examined at some future time. In this connection attention shonld be drawn to the work of Brodie and Phifer. In a review of 24 ca,ws, in their preliminary report, they came to the conclusion that eystometry is more valuable than cystoscopy in demonstrating early neurogenic bladders in case::of neuroNyphilis. They emphasized the fact that cystometry ·will demonstrate neurogcnic lesions before frank decompcnsation of the bladder has taken vVith this statement I am in accord; but I wish to go further and state that m most the same diagnosis can be made with the aid of a good a neurological examination, a cystoseopic examination and without the aid of eystometry.
CYSTOMETRY: ITS VALUE AND LIMITATIO?\S
829
Eleven patients out of the total group of 100 fall into this class. That is, the cystometric diagnosis ,vas hypotonic neurogenic bladder; and none of the patients in this group carried residual urine of over 30 cc. That is, these bladders were all well compensated from the standpoint of their ability to empty. In 8 of these cases the same diagnosis of "tabetic" bladder was made as the result of the clinical examination. In the other 3 the diagnosis was made with the cystometer only. These 3 cases have been discussed above. In this connection the etiology is interesting. Five of the patientA had lues of the central nervous system. In 3 of the patients advanced arterioAclerosis was thought to be the cause, and in the remaining 3 no cause was found. In these 3 the blood serology was negative, and the neurological examination,, ,vere normal. In ] the 8pinal fluid examination was also negative. The other two
ere
,n
refused to submit to a spinal tap. The following case is representative of this group of three patients with early "tabetic" bladders of unknmvn etiology. this is the only case that can be accepted as being of unknown etiology, because it is the only one in which a lumbar puncture was made. Case 8. ::VIiss B. L., aged 20, was seen on ":\fay 5, 1939, complaining of urinary incontinence on and off for the past week. At times she suddenly became aware of the fact that urine was running down her leg. She had no sensation of voiding at such times, but at other times she was able to hold her urine quite well. During her childhood she had had 8 operations; 5 were for growths on the right side of her body including the right arm and leg; one was a tonsillectomy, and one was the removal of a large lipoma from the right flank. Thi;, was perClinic 11 years a.go, and the microscopic diagnosis was formed at the
830
MICHAEL KINKEY 0 1HEERON
obtained. At the same time she also had an anastomosis of the lympathatics of the right thigh by incision of the "facia lata." Examination of the patient revealed an asymetry of the body. The right arm, shoulder and chest were smaller than the left; but the right thigh and leg were swollen by lymphedema. The big toe and the tip of the second toe of the right foot had been amputated. The rest of the examination was normal, and the neurological examination, both motor and sensory, was normal. Particular emphasis was give to toensation below lumbar I, and this was normal. The blood Wasserman ·was negative. Spinal fluid was obtained and the follo-wing tests were negative or normal: '\Vasserman, Nonne, Ross-Jones, Lange, sugar and total protein. The urine was also negative. Cystoscopic examination revealed a large bladder with a capacity of 800 cc but otherwise normal. No
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obstruction was found either at the bladder neck or in the urethra. There was no residual urine present. The cystometrogram showed a hypotonic neurogenic type of curve. The volume was large, pressure low, and sensation delayed (fig. 4). She was then put on mecholyl, mg. 400-600, daily for 3 weeks. Since the beginning of treatment, she has been symptom-free. A cystometrogram done on September 15, 1939 shows slight improvement by a decrease in capacity, increased pressure, and improved sensations (fig. 5). Comment: This is a case of "tabetic" bladder of unexplained etiology. The diagnosis was easily made by the usual clinical methods, and in this case cystometry has been of no additional value. The patient's improvement was noted clinically, and confirmed by a cystometrogram. This case cannot be passed without a ·word concerning the possible etiology. I wish to reemphasize the fact that a careful examination failed to disclose the true diagnosis.
CYSTOMETHY: ITS V.\Ll:E ,\ND LIJ\ll.TATIO?\S
This case should he placed in the group reported by Entz and HaymomL They ,;uggested that the lesion may be congenital absence of a part of the detnrnor (Sacral) ne1Tes. I haw no explanation to offer. In the group of 2;3 hypotonic neurogenic patients, -± ,Yere of unknown etiology. Three of these had no residual mine, and 1 carried 200 cc of residual urine. The patient prec,entcd ahoYe ,Yas the only one that submitted to a spinal tap, and I am not ,Yilling to placP a patient in thi;-: idiopathetir group unless spinal fluid studies were made and ·were normal. In order to show the role played by the cystometer in arriYing at a diagnosici, I 11-ill select 1 case from ead1 of the 5 groups: Case 4- .l\Ir . .J. G., aged 72, at his first vi,;it complained of noctmia 5 to 6 times, dysuria, slmYing of the stream, poor force of the stream and a feeling that
he ,rns not emptying his bladder. On physical examination he ,ms found tu haYe advanced generalized arterio,;clcrosis and arterioc1clerotic heart disea:-,c. A neurological consultant reported the presence of cord changes :-;econdary to the arterio;;elcrosis. He ruled out Ryphilis by blood and spinal fluid studie,-;. His opinion ,rns that the neurological findings ,vere not sufficient to explain the hladder di:sturbanees. On admission the bladder was found to be Llp to the xiphoid process. The prostate ,rns greatly enlarged by rectal examination. This patient ,ms found to have a bilateral hydronephrosis and a badly infected mine. A tranc1methral resection was done, follmving which he was unable to empty his bladder, and carried a residual urine of fi50 ec. At this time a cycltomctrogram was made and the diagnosis waR hypotonic myogenic bladder (fig. G) The patient ,rns then rut on mecholyl, mg. 800, daily hy mouth, and over a period of 3 months the residual mine gradually cli:sappearcd until none wa;:;
832
MICHAEL KINNEY O'HEERON
present. He had 2 urethroscopic examinations to rule out the possibility of prostatic obstruction. The opinion was that he had an atonic bladder from the long-standing residual urine and that after the obstruction was removed proper compensation resulted. A cystometrogram performed after the residual disappeared showed marked improvement in sensation, pressure, and volume. Comment: This is a clear-cut case of bladder atony secondary to prostatic obstruction. The cystometrogram confirmed the diagnosis. Case 5. Mr. A. C., aged 26, had had frequency every 5 to 10 minutes for the past 2 years. This was present both day and night and was accompanied with severe pain. The pain was constantly present but was relieved somewhat by urination. He never passed very much urine at a time. During the past 2 years he had seen many physicians and had had as many different kinds of treat-
u "J e
P~ r,a.111 Pr= .severe pain mVI?= m«nn11Am
_va2to,f"?
;oressur1:;;
rn. v: P.
ments; that is, prostatic massages, sounds, bladder lavages, and sulfanilamide. The physical examination was essentially negative. The prostate was normal and the strippings were free of pus. Urinanalysis was negative. There was no residual urine present. Neurological examination was normal and the blood Wasserman was negative. A cystometrogram (fig. 7) was made and the diagnosis was hypertonic myogenic bladder. Cystoscopy revealed the presence of several areas of submucous fibrosis (elusive ulcer). The bladder capacity was less than 1 ounce. Under ether anesthesia, the bladder was dilated with water to 500 cc, and the areas of elusive ulcer were thoroughly fulgurated ,,vith a bipolar current. The following day the patient left the hospital and stated that his pain was gone and his frequency of urination had decreased from every 5 to 10 minutes to every two hours.
CYSTOMETRY: ITS VALUE AND LIMfi'ATIONS
838
Comment: This is a clear-cut case of a hypertonic myogenic bladder secondary to elusive ulcer. In this type of case, as in the hypotonic myogenic bladder secondary to bladder neck obstruction, the diagnosis can easily be made the usual urological procedures. In this case cystometry did not add any information. Case 6. Mr. M. G., aged 24, was a medical student who was seen because he was nervous and wanted an examination to make sure that he had no disease of the bladder. At times he had some slight frequency but this was never very marked. He insisted on a complete urological check-up for his own peace of mind. The physical examination was normal. The urinalysis was normal. The prostate was normal on rectal palpation, and the prostatic secretion was normal. Cystoscopy and urethroscopy revealed a normal bladder and posterior
r IJ1a;r;,rnu
1)1
fi
urethra. The blood 1Vasserman vrns negative and neurological examination was normal. The eystometric findings are shown in figure 8. Comment: These curves may be cornidered normal except that the terminal pressures are rather low. This is frequently seen in nervous individuals and has been considered to be due to psychic inhibition, the important points being tlw sensory findings and these were normal. Diagnosis: X ormaI bladder. Case 7. :VIiss 0. S., aged 21, was an unmarried girl who was seen in cornmitation because of complete retention of urine which came on 2 weeks before, following a few days of rapidly increasing frequency and ::,lowing of the stream. At the time of the first admission she was catheterized for relief of complete urinary retention. The following day she wa:-, again catheterized and found to ha-ve 500 cc residual urine. Two days later ,vhen I saw her she had a r12ridual
834
MICHAEL KINNEY O'HEERON
urine of 200 cc. The physical and neurological examinations were negative. The pelvic examination revealed a third degree retrodisplacement of the uterus, and
2111
l/o}.
Jn 111
cc.
the uterus was enlarged and tender. Blood vVasserman was negative, and the urine was free of pus, albumin, blood, and organisms. Cystometry was performed and the cystometric diagnosis was tabetic bladder (fig. 9). Cystoscopic exami-
CYSTOMETRY: ITS V.U,UE AND "'LIJVIITATIO~S
835
nation showed that the bladder ,va;-; normal, both ureters were catheterized and the differential urinalysis was normal in every respect. A plain urogram was normal, and retrograde pyelograms were normal. A gynecologist was called in consultation. He brought the uterus forward and held it there with a pessary. This resulted in disappearance of her urinary symptoms and the residual urine, within a couple of days. Comment: This i8 a case of a hypotonic neurogenic bladder on the basis of a peripheral lesion; that a break in the detrusor nerve produced by pressnre from the diRplaced uterus. In this case the cystometer was able to make the diagnosis of the neurogenic bladder hut was not nccesRary. Case 8. D. S., a 9-year-old boy, had been incontinent of urine and feces since birth. This incontinence was more of an uncontrollable urgency than a con-
!/
r"''n
;;:;
h1'1.Jf ;mun
tinual dripping. He felt the desire to urinate or defecate but unless he had a receptacle at hand, he c1oiled himself. At the age of 2 years a small peduneulated lipoma was removed from the sacral region. This did not contain ncITe fo,sue, according to the pathological report. Physical examination revealed the absence of the right wing of the sacrum, poor rectal sphincter tone, and sluggish reflexes throughout; but they were more active on the left than on the righL Over the right buttock was a small area of diminished sensation. He had a reRidual urine of from 60-100 cc. The urinalysis ,vaR normal. An x-ray of the spine revealed an absence of the right side of the sacrum and incomplete fusion of the spinous processes. The neurosurgeon made a diagnosis of cord tumor, and requested a cystometrogram to confirm his diagnosis (fig. 10). The cystometric diagnosis was hypertonic neurogenic bladder, secondary to a lesion of the upper
836
MICHAEL KINNEY O'HEERON
neurone. The lower reflex arc was intact. The important points in the curve are (1) the high pressures, (2) the fluctuations, (3) the low volume and (4) the diminished sensation. A laminectomy was performed by Dr. Adrain Verbruggern, and a lipoma was removed from the lower part of the cord. Following the operation, complete retention developed and the patient had to be catheterized. The catheter was left indwelling for 12 days, and when it was removed the patient was put on a schedule of voiding every hour. At each voiding he passed 50-100 cc of urine and was seldom wet. At night he did wet the bed. The fecal incontinence was still present at times, but was much better. On the twenty-fifth post operative day, another cystometrogram was performed (fig. 11). This showed an improvement in sensation, marked hypertonia, but absence of the spasms, so the hypertonia was better. )'."#"]
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Comment: This is a case of cord tumor with bladder symptoms. The diagnosis of the cord tumor was made by the neurological examination performed by the consulting neurosurgeon. The surgeon stated t hat the cystometric studies were of value in confirming his diagnosis but that he would have handled the case in exactly the same way had none been made. CONCLUSIONS
One hundred cystometrograms have been performed and have been matched and compared with the clinical diagnosis made by the usual diagnostic procedures. In 97 of these cases the diagnosis arrived at was the same with both methods. In 3 of the cases t he cystometrogram has given information not obtained by t he usual procedures. This may be additional information that will be of value to the Urologist in handling these cases, but follow-up studies will
CYSTOMETRY: ITS V_-\.LCE AND LIMITXl'lOXS
have to be made on these patients to determine of just what value the eystometric studies have been, Cystometry has a limited value as a diagnostic procedure in the field of Urology, because the information obtained is usually obtained just as easily by the other diagnostic procedures, In some instances is of definite harm to the patient, I have 1 instance of epididymiti,; following a cystometric determination, This wa:;; in a young boy, who had a neurogenic bladder secondary to a fractured :;;pine, The diagnosis -was obvious before cystometry was performed, The test yielded no additional information and the boy got epididymitis. There may be cases in which a test that can confirm a diagnosis already established would be of value; such was the case in Case 8 where the neurosurgeon admitted that the cystometrngram strengthened his opinion and was a valuable adjunct. It may also be of some value as a follow-up; that is, a quantitative test to determine the value of certain therapeutic procedures, as is seen in CaseR 3 and 8, To the physiologists it is of great value in :;;tudies on the urinary bladder, This has been proven by many -workers, such as Langworthy, Dees, and others, and is outside the scope of this study, Cystometry should never replace any of the usually performed diagnostic procedures. SUMMARY
One hundred cystometrograms have been performed and the results compared to the results of the usual tests performed on the same patients, Cystometry is a test of limited value, and in most instanccR adds nothing to the information on any given case. In some instances cystometry may be of value as a confirmatory test. Cystometry should never surplant any of the usual diagnostic tests. Cystometry may be of value in the early diagnosis of some cases of "tabetictype bladder." Time will have to prove or disprove this statement. Jfedical Arts Bldg., Houston, Texas. REFEREXCES BRoun;, ERNEST L, AND P1-nF1rn, L A.: Cystometric observations in asymptomatic ncw·osyphilis, ,L UroL, 38: 412-419, 1937, - - - , H~:LFERT, L AKD PHIFER, L A,: Cystometric observations in neurosyphilis, Urn!. and Cutan. Rev,, 43: 51-56, 1939, ENTZ AND HAYMOND: Atony of urinary bladder of undetermined "tiology, .J. l;roI., 27: 201-205, 1932, GRAHA:i.r, E, A,: Surgical Diagnosis, Vol. 3, 1930, Philadelphia and London: W I:L Saunders Co, Rorrn, D. K,: Determination of bladder pressure 1Yith cystometer; new principle in diagnosis. J. A, M, A., 88: 151-156, 1927, - - - : Cystometric bladder pressure determination: Their clinical importance, J, Urol., 17: 487-.501, 1927,