0022-534 7/79/1223-0342$02.00/0 Vol. 122, September
THE JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
Printed in U.S.A.
Urological Neurology and Urodynamics VESICOURETHRAL DYSFUNCTION IN MULTIPLE SCLEROSIS JERRY G. BLAIVAS,* GULAM BHIMANI
AND
KAMAL B. LABIB
From the Departments of Urology, and Physical Medicine and Rehabilitation, Tufts-New England Medical Center Hospital and the Tufts University School of Medicine, Boston, Massachusetts
ABSTRACT
Urodynamic evaluation was done 45 times on 41 consecutive patients with multiple sclerosis. Bladder symptoms correlated poorly with any single urodynamic finding and, accordingly, a comprehensive evaluation was necessary to define the underlying pathophysiology. Only 63 per cent of the patients with symptoms of urgency, frequency and urge incontinence actually were found to have uninhibited bladder contractions, while 73 per cent of the patients with obstructive symptoms had detrusor areflexia. Six patients (15 per cent) had a marked change in urodynamic findings upon repeat examination either because of a change in symptomatology or poor response to treatment. An additional 6 patients had vesicoureteral reflux. Bladder symptoms in multiple sclerosis patients should serve more to alert the clinician to the need for urodynamic testing than to mandate specific treatment. Vesicourethral dysfunction is a common finding in patients afflicted with multiple sclerosis, the reported incidence being as high as 80 per cent. Despite this fact, few comprehensive studies of urodynamic findings have been published. This is owing partly to the tacit clinical assumption that careful history and physical examination usually will belie the underlying abnormalities and that urodynamic evaluation is unnecessary in managing these patients. Since our experience has been contrary to this premise we examined prospectively 41 consecutive multiple sclerosis patients to define the underlying pathophysiology and to learn if urodynamic findings correlate with bladder symptoms.
located 1 cm. from the tip, is used to transduce vesical pressure electronically. Rectal pressures are measured with a fluid-filled balloon mounted on a rectal catheter. The 2 concentric surface electrodes for determining anal sphincter electromyography are mounted just distal to a second channel, which is connected to a retention balloon. Electromyography of the external urethral sphincter is done by an experienced electromyographer, using needle electrodes placed directly into the external urethral sphincter. Urinary flow rates are measured with a uroflowmeter. Since the bladder infusant is a radiographic contrast material the entire filling and voiding process is monitored fluoroscopically.
MATERIALS AND METHODS
Forty-one patients afflicted with multiple sclerosis underwent urodynamic investigation because of persistent bladder symptoms. The urodynamic technique used is an adaptation of methods that we have described previously. 1• 2 The basic examination consists of simultaneous measurement of intravesical, intraurethral and intra-abdominal pressure, electromyography of the external urethral and external anal sphincters, urinary flow rate and voiding cystourethrography with fluoroscopy. A triple lumen 8 to lOF catheter is inserted transurethrally into the bladder. Approximately 8 cm. from the tip of the catheter are 2 side holes, approximately 1 mm. in diameter, connected to the urethral pressure channel. Normal saline is infused at a rate of almost 2 ml. per minute according to the method described by Gleason and associates. 3 Urethral pressure is transduced electronically with a pressure transducer and uromanometer. The second channel is located at the tip of the catheter and is used to infuse radiographic contrast material (meglumine diatrizoate) for bladder filling. The third channel, Accepted for publication November 17, 1978. Read at annual meeting of American Urological Association, Washington, D. C., May 21-25, 1978. Supported in part by Grant GR 1108-A-1 from the National Multiple Sclerosis Foundation. * Requests for reprints: Department of Urology, Tufts-New England Medical Center Hospital, 171 Harrison Ave., Boston, Massachusetts 02111.
342
RESULTS
The 41 patients ranged in age from 22 to 74 years, with an average of 43 years. There were 25 women and 16 men. The duration of multiple sclerosis ranged from 2 to 39 years, with an average of 12 years. The duration of bladder symptoms ranged from 1 to 19 years, with an average of 7 years. Of the 41 patients evaluated 4 had repeat studies because of a change in symptomatology or poor response to treatment after initial success and 2 others had repeat cystometrograms only. Accordingly, 45 complete studies were available for review. The bladder symptoms and cystometric data are provided in figure 1. Over-all, only 4 per cent of the patients had normal cystometrograms; 56 per cent had detrusor hyperreflexia and 40 per cent had detrusor areflexia. Of the 18 patients with detrusor areflexia 14 had a flat tonus limb, while 4 had a slope of approximately 45 degrees that was suggestive of detrusor fibrosis as described by Bradley and associates. 4 The relationship between the bladder symptoms and cystometric findings was studied (figs. 2 and 3). Of the patients with irritative bladder symptoms 53 per cent of the women and 88 per cent of the men were found to have uninhibited bladder contractions. All 4 women with pure obstructive symptoms had detrusor areflexia, whereas only 57 per cent of the men with these symptoms had an areflexic bladder. Because of procedural artifacts early in this series only 37
343
VESICOURETHRAL DYSFUNCTION IN MULTIPLE SCLEROSIS
A
BLADDER SYMPTOMS IN MULTIPLE SCLEROSIS
20
19 MEN~ WOMEN
IRRITATIVE
1111
BOTH
OBSTRUCT/VE
B CMG FINDINGS IN MULTIPLE SCLEROSIS MEN~
~
15
14 WOMENm
~
~ 10
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~ .....~
5
:ti:: NORMAL
OETRUSOR HYPERREFLEXIA
OETRUSOR AREFLEX/A
Fm. 1
sphincter electromyograms were acceptable for evaluation technically (fig. 4). The external sphincter was normal in only 16 per cent. Uninhibited sphincter relaxation is defined as a sudden, complete, involuntary relaxation (electromyogram silence) of the external sphincter, which precedes and continues throughout an uninhibited bladder contraction. A non-relaxing sphincter is one in which there is increased electromyographic activity during attempts to void (Crede's and Valsalva's maneuvers) in the absence of a bladder contraction. In at least 6 patients there was a disparity between the electromyographic response of the external anal and external urethral sphincters (fig. 5). Unfortunately, these data were not recorded routinely so that the actual incidence could not be calculated. Complete data on sphincteric function were available in 36 instances (fig. 6) and normal sphincteric function was demonstrated in 11 per cent. In this classification the internal and external sphincters are not distinguished from one another. A competent sphincter (22 per cent) can interrupt the voided stream and withstand stress from increased intra-abdominal pressure, whereas an incompetent sphincter (78 per cent) cannot prevent urinary leakage. An obstructive sphincter (44 per cent) offers increased resistance to urine flow as evidenced by increased urethral pressure, increased electromyographic activity and a poor urinary flow rate during a bladder contraction. The sphincter may be obstructive and incompetent, as in bladder-external sphincter dyssynergia. Vesicoureteral reflux was encountered in 6 patients (15 per cent). In 1 of these cases reflux was into the ureter only (grade I) but in the other 5 cases there was total reflux (grade IIA or
B). In 3 instances reflux was bilateral and in 3 instances it was unilateral. Of the 6 patients 5 had detrusor hyperreflexia and 1 had detrusor areflexia. Three patients had detrusor-external sphincter dyssynergia, 1 had a non-relaxing sphincter and 1 had uninhibited sphincter relaxation. In 6 patients there was a change in cystometric findings discovered at repeat examination, performed because of poor response to treatment or change in symptomatology. The 5 p~tients with detrusor hyperreflexia on initial examination were found to have detrusor areflexia and 1 patient had recurring episodes of hyperreflexia and areflexia associated with exacerbations and remissions of other neurologic symptoms of multiple sclerosis. Before urodynamic study only 11 patients (27 per cent) were being treated effectively (absence of incontinence, infection and retention), while 30 patients (73 per cent) were receiving ineffective therapy. Of these 30 patients 20 actually were receiving treatment antagonistic to the underlying pathophysiology, for example urinary incontinence owing to uninhibited bladder contractions being treated with bethanechol. When therapy was dictated by the results of urodynamic study 83 per cent of the patients had effective treatment and in 12 per cent treatment failed to alleviate the symptoms. Two patients (5 per cent) refused treatment. DISCUSSION
Bladder symptoms are a significant cause of morbidity in patients afflicted with multiple sclerosis. Several large series
344
BLAIV AS, BHIMANI AND LABIB
IRRITATIVE BLADDER SYMPTOMS
A
vs CYSTOMETRIC FINDINGS MEN~ WOMEN
lffll
10
DETRUSOR HYPERREFLEXIA
NORMAL
DETRUSOR AREFLEXIA
OBSTRUCTIVE BLADDER SYMPTOMS
B
~
vs CYSTOMETRIC FINDINGS
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~
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WOMEN
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~
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DETRUSOR HYPERREFLEXIA
DETRUSOR AREFLEXIA
FIG. 2
OBSTRUCTIVE AND IRRITATIVE BLADDER SYMPTOMS
vs CYSTOMETRIC FINDINGS MEN~
WOMEN
OETRUSOR HYPERREFLEXIA
1111
OETRUSOR AREFLEXIA FIG. 3
have documented an incidence varying from 40 to 80 per cent. 5• 6 Bladder symptoms are part of the initial symptom complex in 1 to 12 per cent of the patients and comprise the sole initial complaint in another 2 per cent. Miller and associates reviewed 297 patients with probable multiple sclerosis and found a 78 per cent incidence of bladder symptoms. 5 The severity of bladder symptoms was unrelated to the age of the patient, the duration
of the symptoms or the duration of the neurologic disease. In general, the severity of the bladder symptoms paralleled the severity of the other neurologic symptoms, particularly those involving the corticospinal tracts. Irritative bladder symptoms (urinary urgency, urge incontinence and frequency) were seen in approximately 60 per cent of the patients. Obstructive symptoms (hesitancy, weak stream post-void dribbling and retention) were seen in 33 per cent of patients. These data are similar to ours (60 per cent irritative, 25 per cent obstructive and 15 per cent both) and support the findings of Bradley and associates,6 and Andersen and Bradley. 7 Our cystometric data are comparable to other reported series. 5-7 Fifty-six per cent of the patients had detrusor hyperreflexia and 40 per cent had detrusor areflexia. Only 4 per cent demonstrated normal cystometrograms. Four of the patients with detrusor areflexia had an increased slope of the tonus limb of the cystometric curve, suggestive of detrusor fibrosis as described by Bradley and associates. 4 All of these patients were women who had had prior treatment with long-term indwelling bladder catheters because of unmanageable urinary incontinence. This suggests that chronic bladder inflammation and infection from the catheter may be etiologic factors in the development of detrusor fibrosis. Electromyography of the external urethral sphincter was abnormal in 84 per cent of the patients. 1 Four basic abnormalities were observed: 1) bladder-external sphincter dyssynergia,
345
VESICOURETHRAL DYSFUNCTION IN MULTIPLE SCLEROSIS
EXTERNAL URETHRAL SPHINCTER EMG IN MULTIPLE SCLEROSIS 10 ~
~
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8
~=;
~
7
i:::
~
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0
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NONRELAXIN(:/
t/REFLEXlC
FIG. 4
FIG. 5. Note disparity between electromyographic activity of external urethral and external anal sphincters. During uninhibited bladder contraction there was electrical silence of urethral sphincter whereas anal sphincter had increase in activity. EUS-extemal urethral sphincter. EMG, PIPrtrorn
earlier :reports. 6· 7 We believe that rn1""''rnPncn,i exists when 2 muscles are contracting against one another. Accordingly, when the detrusor fails to contract during attempts to void (Valsalva's or Crede's maneuver) or bladder filling failure of the external sphincter to relax is considered to be a non-relaxing sphincter rather than dyssynergia. Since many normal patients are unable to relax the sphincter during urodynamic study we do not consider this an """'"""'"" sign of 7 We agree neurologic impairment, as do Andersen and that in some instances this is a reflection of interruption of the corticospinal tracts but in others it may represent merely the patients' psychic inhibitions because of the embarrassing and unfamiliar setting in which the examination is performed. True bladder-external sphincter dyssynergia is characterized by an involuntary contraction of the external sphincter (increased urethral pressure and trusor contraction and, in our experience, is almost associated with a suprasacral spinal cord lesion. Uninhibited relaxation of the external urethral "'f'"""'--""" is an involuntary phenomenon in which there is a sudden decrease in urethral pressure associated with a cessation of electromyographic activity. The patients usually have a severe sense of urgency coincident with relaxation of the sphincter and an uninhibited bladder contraction occurs 2 to 30 seconds later. Some patients are able to inhibit voiding temporarily by voluntarily contracting the external sphincter but as soon as this voluntary effort ceases sphincter relaxation occurs again and involuntary voiding ensues eventually. All of the patients with uninhibited sphincter relaxation had objective evidence of supraspinal neurologic lesion involvement. In fact, we have never observed this pattern in patients whose only neurologic lesion was in the spinal cord. In many patients there was a disparity between the electromyographic response of the external anal and external urethral sphincters. It has been claimed a number of authors that the pubococcygeus, transverse perineum, and external anal and external urethral spn1J1c1;ers can all contract independently of one another 1• 8 • 9 but this fact has been others. 10 It is clear that -"'-"'""'"~''"·'
2) uninhibited sphincter and4) 01
differs frorn that of
'The most
in this
poor
346
BLAIVAS, BHIMANI AND LABIB
SPHINCTERIC FUNCTION IN MULTIPLE SCLEROSIS 11 10
~MEN fflmlwoMEN
\. Obstructive
Non-Obstructive) \. Obstructive
'
Non-Obstructive1
'--------,-------'
COMPETENT
INCOMPETENT FIG. 6
correlation between the urinary symptoms before the urodynamic study and the underlying pathophysiology. For example, only 53 per cent of the women with urinary frequency, urgency and urge incontinence actually were found to have uninhibited bladder contractions during cystometry, while 42 per cent had detrusor areflexia. The latter patients were in varying degrees of urinary retention. With a full bladder they had an urge to void (urgency) and often small amounts of urine leaked, which was interpreted as urge incontinence. The urgency disappeared after voiding but the urge and incontinence returned quickly (frequency) since bladder volume changed little. Of the women with irritative symptoms and uninhibited bladder contractions 44 per cent also had external sphincter dyssynergia. Although the major complaint was incontinence because of the uninhibited contractions they also were partially obstructed by the external sphincter dyssynergia. Treatment directed at relieving the bladder contractions may render them more susceptible to urinary retention and treatment of the external sphincter dyssynergia may make them more incontinent. In a similar fashion, patients who complain of obstructive symptoms actually may be unobstructed but because of a corticospinal tract lesion they may be unable to initiate a bladder contraction voluntarily. When such a patient tries to void he does so by straining but he cannot initiate a bladder contraction voluntarily. Instead, he may force urine past a closed sphincter, resulting in a hesitant, dribbling stream. Although this type of patient often has uninhibited bladder contractions he may be unaware of them and they may be of inadequate amplitude or duration to cause incontinence. Before urodynamic evaluation only 27 per cent of the entire group had been on treatment regimens that had any physiologic rationale, whereas afterwards treatment response was excellent in 83 per cent. We believe that these findings support the notion that an accurate pathophysiologic diagnosis is essential before initiating treatment, which should be directed at the underlying disorder rather than the symptom alone. For example, when a patient complains of urge incontinence empiric treatment suggests an anticholinergic drug. However, when cystometry demonstrates detrusor areflexia the most reasonable treatment might be either intermittent self-catheterization or a cholinergic agent. The distressingly high incidence of vesicoureteral reflex demonstrated in this series (15 per cent) has not been reported previously, to our knowledge. In fact, several authors have suggested that the multiple sclerosis patient is much less likely to have the well known urologic complications that plague the
spinal cord injury patient whose pathophysiology is similar. None of our patients with reflux has had clinical episodes of pyelonephritis and all had normal excretory urograms but followup in this group has averaged 2 years only. Leibowitz and associates reviewed the records of 260 patients with multiple sclerosis followed for 10 years. 12 Of 73 deaths only 2 were caused by uremia and another 2 were caused by urinary tract infection. On the other hand, Samellas and Rubin found that 55 per cent of 20 deaths were attributable to hydronephrosis, pyelonephritis or septicemia arising from the urinary tract. 13 Further investigation of the natural history of lower urinary tract dysfunction obviously is necessary to clarify the reported discrepancies and to permit meaningful therapy. REFERENCES
1. Blaivas, J. G., Labib, K. L., Bauer, S. B. and Retik, A. B.: A new approach to electromyography of the external urethral sphincter. J. Urol., 117: 773, 1977. 2. Blaivas, J. G., Labib, K. L., Bauer, S. B. and Retik, A. B.: Changing concepts in the urodynamic evaluation of children. J. Urol., 117: 778, 1977. 3. Gleason, D. M., Reilly, R. J., Bottaccini, M. R. and Pierce, M. J.: The urethral continence zone and its relation to stress incontinence. J. Urol., 112: 81, 1974. 4. Bradley, W., Chou, S., Markland, C. and Swaiman, K.: Biochemical assay technique for estimation of bladder fibrosis. Invest. Urol., 3: 59, 1965. 5. Miller, H., Simpson, C. A. and Yeates, W. K.: Bladder dysfunction in multiple sclerosis. Brit. Med. J., 1: 1265, 1965. 6. Bradley, W. E., Logothetis, J. L. and Timm, G. W.: Cystometric and sphincter abnormalities in multiple sclerosis. Neurology, 23: 1131, 1973. 7. Andersen, J. T. and Bradley, W. E.: Abnormalities of detrusor and sphincter function in multiple sclerosis. Brit. J. Urol., 48: 193, 1976. 8. Vereeken, R. L. and Verduyn, H.: The electrical activity of the · paraurethral and perinea! muscles in normal and pathological conditions. Brit. J. Urol., 42: 457, 1970. 9. Donker, D. J., lvanovici, F. and Noach, E. L.: Analyses of the urethral pressure profile by means of electromyography and the administration of drugs. Brit. J. Urol., 44: 180, 1972. 10. Bradley, W. E., Scott, F. B. and Tinlm, G. W.: Sphincter electromyography. Urol. Clin. N. Amer., 1: 69, 1974. 11. Blaivas, J. G. and Labib, K. B.: Acute urinary retention in women. Complete urodynamic evaluation. Urology, 10: 383, 1977. 12. Leibowitz, U., Kahana, E., Jacobson, S. G. and Alter, M.: The cause of death in multiple sclerosis. In: Progress in Multiple Sclerosis: Research and Treatment. Edited by U. Leibowitz. New York: Academic Press, p. 196, 1972.
347
VESICOURETHRAL DYSFUNCTION IN MULTIPLE SCLEROSIS
13. Samellas, W. and Rubin, B.: Management of upper urinary tract complications in multiple sclerosis by means of urinary diversion to an ileal conduit. J. Urol., 93: 548, 1965. EDITORIAL COMMENT These authors describe an extensive urodynamic study in 41 multiple sclerosis patients. They found that the symptoms often did not correlate with the results of the urodynamic evaluation. For example, 27 patients with symptoms of detrusor hyperreflexia actually had either detrusor areflexia (8) or normal cystometrograms (2) when evaluated urodynamically. This observation surprises me, since I cannot recall having encountered a multiple sclerosis patient with clear-cut symptoms of urgency incontinence in whom I could not demonstrate detrusor hyperreflexia on cystometry. In any case, treatment based on physiological data derived from urodynamic testing was successful in 34 of 41 patients (83 per cent), whereas before testing the majority (73 per cent) had failed to respond to similar treatment modalities designed to control the urinary symptoms. The authors are to be commended on their therapeutic skill. Certainly my success rate in similar patients has been much lower irrespective of the tests performed or the treatment initiated. I am sure a more comprehensive description of the treatment modalities used by these authors would be of value to those of us who struggle, more often unsuccessfully than not, with these unfortunate voiding abnormalities. The authors found that there was a disparity between the electromyogram response of the external urethral and the anal sphincters, and attributed this disparity to differences in the innervation of the 2 muscles. Our unpublished data also suggest that the exte~al urethral and anal sphincter electromyograms often differ in multiple sclerosis patients. However, it should be pointed out that in the present study needle electrodes were used to monitor external urethral sphincter activity, whereas surface electrodes were used to monitor the anal sphincter activity. Thus, the disparities observed could, at least in part, reflect differences in technique rather than differences in innervation. This is so because surface electrodes often provide tracings that are difficult to interpret. The difficulty in interpretation results from the fact that surface electrodes are relatively insensitive and, thus, the gain must be turned high to record sphincter activity. Unfortunately, increasing the gain also increases noise to the point that it often may be difficult to differentiate electrical activity from artifact. The anal electromyogram tracing in this article is a good example of a surface electromyogram in which it is difficult or impossible to differentiate between electromyogram muscle activity and artifact. Finally, the authors found that 4 patients who had been subjected to
long-term catheterization had a 45-degree increase in the slope of the cystometrogram, suggesting detrusor fibrosis. They conclude that chronic bladder inflammation and infection from the catheter may have contributed to the development of detrusor fibrosis in these patients. It seems reasonable to assume that chronic cystitis can cause detrusor fibrosis. However, the data from these patients cannot be used to support this contention because normal patients have an identical shift to the left in bladder tonus if the bladders are drained continuously for 3 or more weeks. Thus, the finding of hypertonus in a chronically catheterized patient is meaningless unless appropriate followup (removal of catheter and repeat cystometry) studies are made. The hypertonus recorded on the cystometrograms of normal patients subjected to continuous catheter drainage (detrusor disuse) will revert to normal after the catheter has been removed and they have been allowed to void for a few days. If the patients cannot void such studies cannot be made and cystometry is of little value in evaluating bladder wall viscoelastic properties.
Daniel C. Merrill Urology Section Veterans Administration Hospital Martinez, California REPLY BY AUTHORS After reviewing our data we were no less surprised than Merrill at the poor correlation between symptoms and urodynamic findings. There are 4 possible explanations for this disparity, 3 of which we have observed during urodynamic study. Patients with detrusor areflexia may have a totally incompetent sphincter mechanism. Minor increases in intra-abdominal pressure cause stress or overflow incontinence, 1 which the patient perceives as urge incontinence. One patient experienced urge incontinence because of sudden uncontrollable relaxation of the external sphincter, which resulted in total voiding in the absence of bladder contraction. The patient may experience uninhibited bladder contractions, which for one reason or another are simply not demonstrated during urodynamic study. The history itself may be inaccurate, although we made every effort to prevent this from being a factor. We agree wholeheartedly with the comment about the comparison between surface anal plug electrodes and needle urethral sphincter electrodes. However, since most commercially available cystometrogram-electromyogram units are using surface anal electrodes it is important that the clinician be aware of this discrepancy even if it is an artifact. The specifics of treatment will be the subject of a future publication.
THE JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
Printed in U.S.A.
Urological Neurology and Urodynamics VESICOURETHRAL DYSFUNCTION IN MULTIPLE SCLEROSIS JERRY G. BLAIVAS,* GULAM BHIMANI
AND
KAMAL B. LABIB
From the Departments of Urology, and Physical Medicine and Rehabilitation, Tufts-New England Medical Center Hospital and the Tufts University School of Medicine, Boston, Massachusetts
ABSTRACT
Urodynamic evaluation was done 45 times on 41 consecutive patients with multiple sclerosis. Bladder symptoms correlated poorly with any single urodynamic finding and, accordingly, a comprehensive evaluation was necessary to define the underlying pathophysiology. Only 63 per cent of the patients with symptoms of urgency, frequency and urge incontinence actually were found to have uninhibited bladder contractions, while 73 per cent of the patients with obstructive symptoms had detrusor areflexia. Six patients (15 per cent) had a marked change in urodynamic findings upon repeat examination either because of a change in symptomatology or poor response to treatment. An additional 6 patients had vesicoureteral reflux. Bladder symptoms in multiple sclerosis patients should serve more to alert the clinician to the need for urodynamic testing than to mandate specific treatment. Vesicourethral dysfunction is a common finding in patients afflicted with multiple sclerosis, the reported incidence being as high as 80 per cent. Despite this fact, few comprehensive studies of urodynamic findings have been published. This is owing partly to the tacit clinical assumption that careful history and physical examination usually will belie the underlying abnormalities and that urodynamic evaluation is unnecessary in managing these patients. Since our experience has been contrary to this premise we examined prospectively 41 consecutive multiple sclerosis patients to define the underlying pathophysiology and to learn if urodynamic findings correlate with bladder symptoms.
located 1 cm. from the tip, is used to transduce vesical pressure electronically. Rectal pressures are measured with a fluid-filled balloon mounted on a rectal catheter. The 2 concentric surface electrodes for determining anal sphincter electromyography are mounted just distal to a second channel, which is connected to a retention balloon. Electromyography of the external urethral sphincter is done by an experienced electromyographer, using needle electrodes placed directly into the external urethral sphincter. Urinary flow rates are measured with a uroflowmeter. Since the bladder infusant is a radiographic contrast material the entire filling and voiding process is monitored fluoroscopically.
MATERIALS AND METHODS
Forty-one patients afflicted with multiple sclerosis underwent urodynamic investigation because of persistent bladder symptoms. The urodynamic technique used is an adaptation of methods that we have described previously. 1• 2 The basic examination consists of simultaneous measurement of intravesical, intraurethral and intra-abdominal pressure, electromyography of the external urethral and external anal sphincters, urinary flow rate and voiding cystourethrography with fluoroscopy. A triple lumen 8 to lOF catheter is inserted transurethrally into the bladder. Approximately 8 cm. from the tip of the catheter are 2 side holes, approximately 1 mm. in diameter, connected to the urethral pressure channel. Normal saline is infused at a rate of almost 2 ml. per minute according to the method described by Gleason and associates. 3 Urethral pressure is transduced electronically with a pressure transducer and uromanometer. The second channel is located at the tip of the catheter and is used to infuse radiographic contrast material (meglumine diatrizoate) for bladder filling. The third channel, Accepted for publication November 17, 1978. Read at annual meeting of American Urological Association, Washington, D. C., May 21-25, 1978. Supported in part by Grant GR 1108-A-1 from the National Multiple Sclerosis Foundation. * Requests for reprints: Department of Urology, Tufts-New England Medical Center Hospital, 171 Harrison Ave., Boston, Massachusetts 02111.
342
RESULTS
The 41 patients ranged in age from 22 to 74 years, with an average of 43 years. There were 25 women and 16 men. The duration of multiple sclerosis ranged from 2 to 39 years, with an average of 12 years. The duration of bladder symptoms ranged from 1 to 19 years, with an average of 7 years. Of the 41 patients evaluated 4 had repeat studies because of a change in symptomatology or poor response to treatment after initial success and 2 others had repeat cystometrograms only. Accordingly, 45 complete studies were available for review. The bladder symptoms and cystometric data are provided in figure 1. Over-all, only 4 per cent of the patients had normal cystometrograms; 56 per cent had detrusor hyperreflexia and 40 per cent had detrusor areflexia. Of the 18 patients with detrusor areflexia 14 had a flat tonus limb, while 4 had a slope of approximately 45 degrees that was suggestive of detrusor fibrosis as described by Bradley and associates. 4 The relationship between the bladder symptoms and cystometric findings was studied (figs. 2 and 3). Of the patients with irritative bladder symptoms 53 per cent of the women and 88 per cent of the men were found to have uninhibited bladder contractions. All 4 women with pure obstructive symptoms had detrusor areflexia, whereas only 57 per cent of the men with these symptoms had an areflexic bladder. Because of procedural artifacts early in this series only 37
343
VESICOURETHRAL DYSFUNCTION IN MULTIPLE SCLEROSIS
A
BLADDER SYMPTOMS IN MULTIPLE SCLEROSIS
20
19 MEN~ WOMEN
IRRITATIVE
1111
BOTH
OBSTRUCT/VE
B CMG FINDINGS IN MULTIPLE SCLEROSIS MEN~
~
15
14 WOMENm
~
~ 10
i....::
~ .....~
5
:ti:: NORMAL
OETRUSOR HYPERREFLEXIA
OETRUSOR AREFLEX/A
Fm. 1
sphincter electromyograms were acceptable for evaluation technically (fig. 4). The external sphincter was normal in only 16 per cent. Uninhibited sphincter relaxation is defined as a sudden, complete, involuntary relaxation (electromyogram silence) of the external sphincter, which precedes and continues throughout an uninhibited bladder contraction. A non-relaxing sphincter is one in which there is increased electromyographic activity during attempts to void (Crede's and Valsalva's maneuvers) in the absence of a bladder contraction. In at least 6 patients there was a disparity between the electromyographic response of the external anal and external urethral sphincters (fig. 5). Unfortunately, these data were not recorded routinely so that the actual incidence could not be calculated. Complete data on sphincteric function were available in 36 instances (fig. 6) and normal sphincteric function was demonstrated in 11 per cent. In this classification the internal and external sphincters are not distinguished from one another. A competent sphincter (22 per cent) can interrupt the voided stream and withstand stress from increased intra-abdominal pressure, whereas an incompetent sphincter (78 per cent) cannot prevent urinary leakage. An obstructive sphincter (44 per cent) offers increased resistance to urine flow as evidenced by increased urethral pressure, increased electromyographic activity and a poor urinary flow rate during a bladder contraction. The sphincter may be obstructive and incompetent, as in bladder-external sphincter dyssynergia. Vesicoureteral reflux was encountered in 6 patients (15 per cent). In 1 of these cases reflux was into the ureter only (grade I) but in the other 5 cases there was total reflux (grade IIA or
B). In 3 instances reflux was bilateral and in 3 instances it was unilateral. Of the 6 patients 5 had detrusor hyperreflexia and 1 had detrusor areflexia. Three patients had detrusor-external sphincter dyssynergia, 1 had a non-relaxing sphincter and 1 had uninhibited sphincter relaxation. In 6 patients there was a change in cystometric findings discovered at repeat examination, performed because of poor response to treatment or change in symptomatology. The 5 p~tients with detrusor hyperreflexia on initial examination were found to have detrusor areflexia and 1 patient had recurring episodes of hyperreflexia and areflexia associated with exacerbations and remissions of other neurologic symptoms of multiple sclerosis. Before urodynamic study only 11 patients (27 per cent) were being treated effectively (absence of incontinence, infection and retention), while 30 patients (73 per cent) were receiving ineffective therapy. Of these 30 patients 20 actually were receiving treatment antagonistic to the underlying pathophysiology, for example urinary incontinence owing to uninhibited bladder contractions being treated with bethanechol. When therapy was dictated by the results of urodynamic study 83 per cent of the patients had effective treatment and in 12 per cent treatment failed to alleviate the symptoms. Two patients (5 per cent) refused treatment. DISCUSSION
Bladder symptoms are a significant cause of morbidity in patients afflicted with multiple sclerosis. Several large series
344
BLAIV AS, BHIMANI AND LABIB
IRRITATIVE BLADDER SYMPTOMS
A
vs CYSTOMETRIC FINDINGS MEN~ WOMEN
lffll
10
DETRUSOR HYPERREFLEXIA
NORMAL
DETRUSOR AREFLEXIA
OBSTRUCTIVE BLADDER SYMPTOMS
B
~
vs CYSTOMETRIC FINDINGS
15 MEN~
~
~ 10
WOMEN
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~
....
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DETRUSOR AREFLEXIA
FIG. 2
OBSTRUCTIVE AND IRRITATIVE BLADDER SYMPTOMS
vs CYSTOMETRIC FINDINGS MEN~
WOMEN
OETRUSOR HYPERREFLEXIA
1111
OETRUSOR AREFLEXIA FIG. 3
have documented an incidence varying from 40 to 80 per cent. 5• 6 Bladder symptoms are part of the initial symptom complex in 1 to 12 per cent of the patients and comprise the sole initial complaint in another 2 per cent. Miller and associates reviewed 297 patients with probable multiple sclerosis and found a 78 per cent incidence of bladder symptoms. 5 The severity of bladder symptoms was unrelated to the age of the patient, the duration
of the symptoms or the duration of the neurologic disease. In general, the severity of the bladder symptoms paralleled the severity of the other neurologic symptoms, particularly those involving the corticospinal tracts. Irritative bladder symptoms (urinary urgency, urge incontinence and frequency) were seen in approximately 60 per cent of the patients. Obstructive symptoms (hesitancy, weak stream post-void dribbling and retention) were seen in 33 per cent of patients. These data are similar to ours (60 per cent irritative, 25 per cent obstructive and 15 per cent both) and support the findings of Bradley and associates,6 and Andersen and Bradley. 7 Our cystometric data are comparable to other reported series. 5-7 Fifty-six per cent of the patients had detrusor hyperreflexia and 40 per cent had detrusor areflexia. Only 4 per cent demonstrated normal cystometrograms. Four of the patients with detrusor areflexia had an increased slope of the tonus limb of the cystometric curve, suggestive of detrusor fibrosis as described by Bradley and associates. 4 All of these patients were women who had had prior treatment with long-term indwelling bladder catheters because of unmanageable urinary incontinence. This suggests that chronic bladder inflammation and infection from the catheter may be etiologic factors in the development of detrusor fibrosis. Electromyography of the external urethral sphincter was abnormal in 84 per cent of the patients. 1 Four basic abnormalities were observed: 1) bladder-external sphincter dyssynergia,
345
VESICOURETHRAL DYSFUNCTION IN MULTIPLE SCLEROSIS
EXTERNAL URETHRAL SPHINCTER EMG IN MULTIPLE SCLEROSIS 10 ~
~
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8
~=;
~
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~
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NORMAL
DYSSYNERGIA
U!VINN/8/TED REUiXtlTION
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FIG. 4
FIG. 5. Note disparity between electromyographic activity of external urethral and external anal sphincters. During uninhibited bladder contraction there was electrical silence of urethral sphincter whereas anal sphincter had increase in activity. EUS-extemal urethral sphincter. EMG, PIPrtrorn
earlier :reports. 6· 7 We believe that rn1""''rnPncn,i exists when 2 muscles are contracting against one another. Accordingly, when the detrusor fails to contract during attempts to void (Valsalva's or Crede's maneuver) or bladder filling failure of the external sphincter to relax is considered to be a non-relaxing sphincter rather than dyssynergia. Since many normal patients are unable to relax the sphincter during urodynamic study we do not consider this an """'"""'"" sign of 7 We agree neurologic impairment, as do Andersen and that in some instances this is a reflection of interruption of the corticospinal tracts but in others it may represent merely the patients' psychic inhibitions because of the embarrassing and unfamiliar setting in which the examination is performed. True bladder-external sphincter dyssynergia is characterized by an involuntary contraction of the external sphincter (increased urethral pressure and trusor contraction and, in our experience, is almost associated with a suprasacral spinal cord lesion. Uninhibited relaxation of the external urethral "'f'"""'--""" is an involuntary phenomenon in which there is a sudden decrease in urethral pressure associated with a cessation of electromyographic activity. The patients usually have a severe sense of urgency coincident with relaxation of the sphincter and an uninhibited bladder contraction occurs 2 to 30 seconds later. Some patients are able to inhibit voiding temporarily by voluntarily contracting the external sphincter but as soon as this voluntary effort ceases sphincter relaxation occurs again and involuntary voiding ensues eventually. All of the patients with uninhibited sphincter relaxation had objective evidence of supraspinal neurologic lesion involvement. In fact, we have never observed this pattern in patients whose only neurologic lesion was in the spinal cord. In many patients there was a disparity between the electromyographic response of the external anal and external urethral sphincters. It has been claimed a number of authors that the pubococcygeus, transverse perineum, and external anal and external urethral spn1J1c1;ers can all contract independently of one another 1• 8 • 9 but this fact has been others. 10 It is clear that -"'-"'""'"~''"·'
2) uninhibited sphincter and4) 01
differs frorn that of
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346
BLAIVAS, BHIMANI AND LABIB
SPHINCTERIC FUNCTION IN MULTIPLE SCLEROSIS 11 10
~MEN fflmlwoMEN
\. Obstructive
Non-Obstructive) \. Obstructive
'
Non-Obstructive1
'--------,-------'
COMPETENT
INCOMPETENT FIG. 6
correlation between the urinary symptoms before the urodynamic study and the underlying pathophysiology. For example, only 53 per cent of the women with urinary frequency, urgency and urge incontinence actually were found to have uninhibited bladder contractions during cystometry, while 42 per cent had detrusor areflexia. The latter patients were in varying degrees of urinary retention. With a full bladder they had an urge to void (urgency) and often small amounts of urine leaked, which was interpreted as urge incontinence. The urgency disappeared after voiding but the urge and incontinence returned quickly (frequency) since bladder volume changed little. Of the women with irritative symptoms and uninhibited bladder contractions 44 per cent also had external sphincter dyssynergia. Although the major complaint was incontinence because of the uninhibited contractions they also were partially obstructed by the external sphincter dyssynergia. Treatment directed at relieving the bladder contractions may render them more susceptible to urinary retention and treatment of the external sphincter dyssynergia may make them more incontinent. In a similar fashion, patients who complain of obstructive symptoms actually may be unobstructed but because of a corticospinal tract lesion they may be unable to initiate a bladder contraction voluntarily. When such a patient tries to void he does so by straining but he cannot initiate a bladder contraction voluntarily. Instead, he may force urine past a closed sphincter, resulting in a hesitant, dribbling stream. Although this type of patient often has uninhibited bladder contractions he may be unaware of them and they may be of inadequate amplitude or duration to cause incontinence. Before urodynamic evaluation only 27 per cent of the entire group had been on treatment regimens that had any physiologic rationale, whereas afterwards treatment response was excellent in 83 per cent. We believe that these findings support the notion that an accurate pathophysiologic diagnosis is essential before initiating treatment, which should be directed at the underlying disorder rather than the symptom alone. For example, when a patient complains of urge incontinence empiric treatment suggests an anticholinergic drug. However, when cystometry demonstrates detrusor areflexia the most reasonable treatment might be either intermittent self-catheterization or a cholinergic agent. The distressingly high incidence of vesicoureteral reflex demonstrated in this series (15 per cent) has not been reported previously, to our knowledge. In fact, several authors have suggested that the multiple sclerosis patient is much less likely to have the well known urologic complications that plague the
spinal cord injury patient whose pathophysiology is similar. None of our patients with reflux has had clinical episodes of pyelonephritis and all had normal excretory urograms but followup in this group has averaged 2 years only. Leibowitz and associates reviewed the records of 260 patients with multiple sclerosis followed for 10 years. 12 Of 73 deaths only 2 were caused by uremia and another 2 were caused by urinary tract infection. On the other hand, Samellas and Rubin found that 55 per cent of 20 deaths were attributable to hydronephrosis, pyelonephritis or septicemia arising from the urinary tract. 13 Further investigation of the natural history of lower urinary tract dysfunction obviously is necessary to clarify the reported discrepancies and to permit meaningful therapy. REFERENCES
1. Blaivas, J. G., Labib, K. L., Bauer, S. B. and Retik, A. B.: A new approach to electromyography of the external urethral sphincter. J. Urol., 117: 773, 1977. 2. Blaivas, J. G., Labib, K. L., Bauer, S. B. and Retik, A. B.: Changing concepts in the urodynamic evaluation of children. J. Urol., 117: 778, 1977. 3. Gleason, D. M., Reilly, R. J., Bottaccini, M. R. and Pierce, M. J.: The urethral continence zone and its relation to stress incontinence. J. Urol., 112: 81, 1974. 4. Bradley, W., Chou, S., Markland, C. and Swaiman, K.: Biochemical assay technique for estimation of bladder fibrosis. Invest. Urol., 3: 59, 1965. 5. Miller, H., Simpson, C. A. and Yeates, W. K.: Bladder dysfunction in multiple sclerosis. Brit. Med. J., 1: 1265, 1965. 6. Bradley, W. E., Logothetis, J. L. and Timm, G. W.: Cystometric and sphincter abnormalities in multiple sclerosis. Neurology, 23: 1131, 1973. 7. Andersen, J. T. and Bradley, W. E.: Abnormalities of detrusor and sphincter function in multiple sclerosis. Brit. J. Urol., 48: 193, 1976. 8. Vereeken, R. L. and Verduyn, H.: The electrical activity of the · paraurethral and perinea! muscles in normal and pathological conditions. Brit. J. Urol., 42: 457, 1970. 9. Donker, D. J., lvanovici, F. and Noach, E. L.: Analyses of the urethral pressure profile by means of electromyography and the administration of drugs. Brit. J. Urol., 44: 180, 1972. 10. Bradley, W. E., Scott, F. B. and Tinlm, G. W.: Sphincter electromyography. Urol. Clin. N. Amer., 1: 69, 1974. 11. Blaivas, J. G. and Labib, K. B.: Acute urinary retention in women. Complete urodynamic evaluation. Urology, 10: 383, 1977. 12. Leibowitz, U., Kahana, E., Jacobson, S. G. and Alter, M.: The cause of death in multiple sclerosis. In: Progress in Multiple Sclerosis: Research and Treatment. Edited by U. Leibowitz. New York: Academic Press, p. 196, 1972.
347
VESICOURETHRAL DYSFUNCTION IN MULTIPLE SCLEROSIS
13. Samellas, W. and Rubin, B.: Management of upper urinary tract complications in multiple sclerosis by means of urinary diversion to an ileal conduit. J. Urol., 93: 548, 1965. EDITORIAL COMMENT These authors describe an extensive urodynamic study in 41 multiple sclerosis patients. They found that the symptoms often did not correlate with the results of the urodynamic evaluation. For example, 27 patients with symptoms of detrusor hyperreflexia actually had either detrusor areflexia (8) or normal cystometrograms (2) when evaluated urodynamically. This observation surprises me, since I cannot recall having encountered a multiple sclerosis patient with clear-cut symptoms of urgency incontinence in whom I could not demonstrate detrusor hyperreflexia on cystometry. In any case, treatment based on physiological data derived from urodynamic testing was successful in 34 of 41 patients (83 per cent), whereas before testing the majority (73 per cent) had failed to respond to similar treatment modalities designed to control the urinary symptoms. The authors are to be commended on their therapeutic skill. Certainly my success rate in similar patients has been much lower irrespective of the tests performed or the treatment initiated. I am sure a more comprehensive description of the treatment modalities used by these authors would be of value to those of us who struggle, more often unsuccessfully than not, with these unfortunate voiding abnormalities. The authors found that there was a disparity between the electromyogram response of the external urethral and the anal sphincters, and attributed this disparity to differences in the innervation of the 2 muscles. Our unpublished data also suggest that the exte~al urethral and anal sphincter electromyograms often differ in multiple sclerosis patients. However, it should be pointed out that in the present study needle electrodes were used to monitor external urethral sphincter activity, whereas surface electrodes were used to monitor the anal sphincter activity. Thus, the disparities observed could, at least in part, reflect differences in technique rather than differences in innervation. This is so because surface electrodes often provide tracings that are difficult to interpret. The difficulty in interpretation results from the fact that surface electrodes are relatively insensitive and, thus, the gain must be turned high to record sphincter activity. Unfortunately, increasing the gain also increases noise to the point that it often may be difficult to differentiate electrical activity from artifact. The anal electromyogram tracing in this article is a good example of a surface electromyogram in which it is difficult or impossible to differentiate between electromyogram muscle activity and artifact. Finally, the authors found that 4 patients who had been subjected to
long-term catheterization had a 45-degree increase in the slope of the cystometrogram, suggesting detrusor fibrosis. They conclude that chronic bladder inflammation and infection from the catheter may have contributed to the development of detrusor fibrosis in these patients. It seems reasonable to assume that chronic cystitis can cause detrusor fibrosis. However, the data from these patients cannot be used to support this contention because normal patients have an identical shift to the left in bladder tonus if the bladders are drained continuously for 3 or more weeks. Thus, the finding of hypertonus in a chronically catheterized patient is meaningless unless appropriate followup (removal of catheter and repeat cystometry) studies are made. The hypertonus recorded on the cystometrograms of normal patients subjected to continuous catheter drainage (detrusor disuse) will revert to normal after the catheter has been removed and they have been allowed to void for a few days. If the patients cannot void such studies cannot be made and cystometry is of little value in evaluating bladder wall viscoelastic properties.
Daniel C. Merrill Urology Section Veterans Administration Hospital Martinez, California REPLY BY AUTHORS After reviewing our data we were no less surprised than Merrill at the poor correlation between symptoms and urodynamic findings. There are 4 possible explanations for this disparity, 3 of which we have observed during urodynamic study. Patients with detrusor areflexia may have a totally incompetent sphincter mechanism. Minor increases in intra-abdominal pressure cause stress or overflow incontinence, 1 which the patient perceives as urge incontinence. One patient experienced urge incontinence because of sudden uncontrollable relaxation of the external sphincter, which resulted in total voiding in the absence of bladder contraction. The patient may experience uninhibited bladder contractions, which for one reason or another are simply not demonstrated during urodynamic study. The history itself may be inaccurate, although we made every effort to prevent this from being a factor. We agree wholeheartedly with the comment about the comparison between surface anal plug electrodes and needle urethral sphincter electrodes. However, since most commercially available cystometrogram-electromyogram units are using surface anal electrodes it is important that the clinician be aware of this discrepancy even if it is an artifact. The specifics of treatment will be the subject of a future publication.
