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Role of Limited Evaluation and Aggressive Medical Management in Multiple Sclerosis: A Review of 113 Patients
0022-534 7/94/1514-0946$03.00/0 THE JOURNAL OF UROLOGY Copyright© 1994 by AMERICAN UROLOGICAL ASSOCIATION, INC.
Vol. 151, 946-950, April 1994
Printed in U.S.A.
ROLE OF LIMITED EVALUATION AND AGGRESSIVE MEDICAL MANAGEMENT IN MULTIPLE SCLEROSIS: A REVIEW OF 113 PATIENTS LARRY T. SIRLS, PHILIPPE E. ZIMMERN
AND
GARY E. LEACH*
From the Kaiser Permanente Medical Center, Los Angeles, California
ABSTRACT
Multiple sclerosis has frequent urological manifestations. Medical management, based on clinical symptoms and urodynamic findings, incorporates clean intermittent catheterization, oral pharmacological agents (that is oral oxybutynin) or their combination (the desired end point of treatment being complete retention with clean intermittent catheterization). Our objectives were to evaluate the efficacy of medical management in multiple sclerosis patients, determine the incidence of hydronephrosis at presentation and during treatment, and evaluate the impact of electromyography on patient management. We reviewed retrospectively 113 patients with documented multiple sclerosis (mean age 45 years, range 20 to 75 years and mean followup 41 months, range 6 to 136 months). Presenting symptoms were irritative alone or combined with obstructive symptoms in 94 patients (83%). On cystometrography 79 patients (70%) had detrusor hyperreflexia and 17 (15%) had an areflexic bladder. Coaxial needle electromyography was performed on 54 patients and 15 (28%) had detrusor-sphincter dyssynergia. Patients with detrusor-sphincter dyssynergia had more advanced neurological disease. A total of 105 patients had radiological imaging of the upper tracts. Only 7 patients (6.6%) had hydronephrosis at presentation and all were stable or improved with medical management. No patient had hydronephrosis with aggressive medical management. No patient with detrusor-sphincter dyssynergia had hydronephrosis or elevated creatinine levels at presentation or during treatment. Medical management failed in 8 patients (7%) who required surgical intervention. Limited evaluation (voiding symptoms, post-void residual and cystometrography) of multiple sclerosis patients is sufficient to formulate an effective treatment program. Electromyography is not necessary in the routine evaluation of patients with documented multiple sclerosis. After baseline upper tract imaging, routine yearly evaluations are unnecessary (unless initially abnormal or indicated by a change in clinical status). Medical management of patients with multiple sclerosis is safe and effective. In this series, no patient had hydronephrosis on therapy, and only 7% of the patients failed aggressive medical management and required surgical intervention. KEY WORDS:
multiple sclerosis, urinary catheterization, oxybutynin, electromyography
Up to 90% of the patients with multiple sclerosis will have lower urinary tract symptoms during the course of the disease. 1 The diverse neurological lesions of multiple sclerosis may cause various urological presentations, ranging from detrusor hyperreflexia with urge incontinence to areflexia and urinary retention. The majority of patients with voiding dysfunction from multiple sclerosis present with irritative symptoms (frequency and urgency, with or without urge incontinence) and demonstrate detrusor hyperreflexia on cystometrography. 1• 2 More than half of the patients with multiple sclerosis have detrusor hyperreflexia with hypocontractility (a poorly sustained detrusor contraction), leading to symptoms of urinary frequency and urgency associated with incomplete bladder emptying.3• 4 Previous studies have suggested electromyography as an important part of the evaluation of patients with multiple sclerosis, with the electromyographic findings used to classify the type of voiding dysfunction present. 1• 2 •6 Blaivas and Barbalis identified men with detrusor-sphincter dyssynergia as a subgroup of patients with multiple sclerosis at increased risk for urological complications, even with appropriate therapy, such as clean intermittent catheterization and oral anticholinergic agents. 6 Others find electromyography difficult to perform Accepted for publication October 1, 1993. * Requests for reprints: 4900 Sunset Blvd., Los Angeles, California 90027.
and interpret, and do not use it in the routine evaluation of patients with multiple sclerosis. 4 • 7 After evaluation, the initial treatment for patients with voiding dysfunction from multiple sclerosis is medical, usually with oral pharmacological agents, with or without clean intermittent catheterization.8 When severe irritative symptoms predominate or incomplete bladder emptying is present, the goal of therapy is complete urinary retention and clean intermittent catheterization when possible. We emphasize an approach using clinical symptoms (obstructive and/or irritative, and incontinence), post-void residual urine volumes, basic urodynamic information (cystometrography) and baseline upper tract evaluation (serum creatinine and radiographic imaging) as the criteria from which a treatment plan is formulated. The objectives of treatment are to lower detrusor pressures if elevated, control incontinence if present, reverse or stabilize upper tract changes and accomplish complete bladder emptying. We evaluate the efficacy of medical management for multiple sclerosis patients based upon the interpretation of clinical and basic urodynamic information. The specific objectives of this review were to assess the safety and efficacy of medical management, and the incidence of management failure requiring surgical intervention, determine the incidence of hydronephrosis at presentation and during treatment, and evaluate the impact of electromyography on patient management.
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ROLE OF LIMITED EVALUATION AND MEDl:CAL MANAGEMENT IN MULTIPLE SCLEROSIS MATERIALS AND METHODS
We reviewed retrospectively 72 women and 41 men with the confirmed diagnosis of multiple sclerosis (mean age 45 years, range 20 to 75 years and mean followup 41 months, range 6 to 136 months). In patients with an established diagnosis of multiple sclerosis the duration of disease was 9.9 years before urological evaluation (range 1 month to 30 years). Patient evaluation included a detailed history and physical examination, including a focused neurological examination consisting of assessment of anal sphincter tone, bulbocavernosus reflex, knee and ankle reflexes, Babinski sign, and sensation to pinprick and light touch in the lumbar and sacral dermatomes. If hyperreflexia was noted the presence or absence of clonus was assessed. Urinalysis, urine culture and voided urine cytology studies were performed when indicated. Serum creatinine, and renal ultrasound or excretory urogram (IVP) were used to assess renal function and the upper tracts. Urodynamic evaluation began with noninvasive uroflowmetry and residual urine volume measurement. Medium fill water cystometry (50 cc per minute) was performed through a urethral catheter (7F double lumen or 8F feeding tube). The presence of uninhibited detrusor contractions was noted. Cystoscopy was routinely performed. The definitions, terminology and units used conform to the standards established by the International Continence Society. 9 However, uninhibited detrusor contractions less than 15 cm. yvater associated wit~ urgency were considered clinically significant. Bladder compliance was calculated as the ratio of bladder volume increment to the change in intravesical pressure (cc/ cm. water). Decreased compliance was defined as compliance less than 12.5 cc/cm. water). 10 Electromyography was performed on all patients in the early years of the study. More recently, electromyography was used onl?' in patients with an uncertain diagnosis of multiple scler0S1s (to document a neurological abnormality). Electromyography of the external anal sphincter was performed using coaxial needle electrodes under oscilloscopic and auditory controls. The bulbocavernosus reflex was tested and voluntary contraction of the pelvic floor musculature was noted (full interference pattern). Abnormal wave forms (such as polyphas1c potentials, positive sharp waves and giant waves) indicating various degrees of sacral arc denervation were identified. In':'oluntary sphincter activity during voiding was indicative of detrusor-sphincter dyssynergia. After the evaluation, the treatment guidelines were observation for those with a normal study and no upper tract deterioration, oral pharmacological agents with or without clean intermittent catheterization, depending on the post-void residual volume at evaluation, and on therapy for patients with detrusor hyperreflexia (with symptomatic urgency and/or urge incontinence) and clean intermittent catheterization for patients with elevated post-void residual urine volumes alone (normal bladder pressure). Patients not responding to therapy or with changes in clinical symptoms were reevaluated as indicated. Routi.ne f?llowup consiste? of yearly evaluations with physical exammat10n, upper tract imaging, serum creatinine noninvasive uroflowmetry and post-void residual urine meas~rement. RESULTS
In 11 patients the diagnosis of multiple sclerosis was first suspected by the urologist and subsequently confirmed. The majority of the 113 patients had irritative symptoms (urgency, frequency or urge incontinence) with or without obstructive sympt?ms (decreased force of stream, sensation of incomplete emptym~ and so forth): 56 (49.5%) had irritative, 16 (14%) had obstructive and 38 (34%) had combined irritative and obstructive symptoms. Two patients (1.7%) had urinary tract infection and 1 (0.8%) was asymptomatic. Associated symptoms discov-
ered with the detailed history included impotence in 9 men, recurrent or J?ersist~nt 1:1rinary tract infections in 22 patients and absent eJaculat10n m 2 men. A total of 19 patients was wheelchair bound at presentation. Abnormalities were noted on the focused neurological examination in 82 patients, while 21 had a normal examination and in 10 the results were equivocal. Results of the urodynamic evaluation are presented in table 1. Detrusor hyperreflexia was the most common finding. Electromyography was performed in 51 patients (48%) and demons~rated ~etrusor-sphincter dyssynergia in 15 (28%). The patients with detrusor-sphincter dyssynergia had more advanced neurological disease than the study group as a whole. Of the 15 patients with detrusor-sphincter dyssynergia 7 (4 7%) were wheelchair bound at presentation. Obstructive and irri~at_ive .voiding symptoms occurred in 12 of the 15 patients and irnta~ive s)'.mptoms alone ~n 2, while 1 was referred for urinary tr~ct mfect10ns. Seven patients had elevated post-void residual urme volumes (mean 185 cc) and 8 patients emptied the bladder completely. All patients had detrusor hyperreflexia and 1 also had poor compliance. In 11 patients the diagnosis of multiple sclerosis was first suspected during the urological evaluation (and subsequently confirr_n~d by 1:1agnetic resonance imaging). Seven patients had a susp1c10us history, 8 had an abnormal neurological examination and 10 h~d an ab.normal c)'.stometrogram. Electromyography.wa~ done m 8 patients and identified a neurological abnormaht:y m .6. When combined with a suspicious history, physical ~xammat10n or cystometrography, electromyography assisted m docu!11enting. a spe?ific neurological abnormality, further supportmg the diagnosis of multiple sclerosis. '.J'he results in 105 patients who underwent radiological imaging of the upper tracts :,vith either IVP or renal ultrasonography also are presented m table 1. Although 17 patients had an abnormal finding, only 7 (6.6%) had upper tract dilatation. Five patients (4.7%) had urinary stones. With medical management, hydronephrosis resolved in all patients and did not occur subsequently in any. The medical management of the study group is presented in table 2 .. ThE; majority of patients (64 of 113) were managed with a combmat10n of oral pharmacological agents and clean intermittent. ~atheterization. A total of 25 patients (32%) required the addit10n of a second oral medication to control the irritative voiding symptoms. Eighteen patients (23%) required a change 1. Urodynamic, electromyographic and upper tract imaging ([VP or ultrasound) findings in patients with multiple sclerosis
TABLE
No. Pts. (%) Urodynamic findings (113 pts.): Detrusor hyperreflexia Acontractile detrusor Decreased compliance (less than 12.5 cc/cm. water) Outlet obstruction secondary to benign prostatic hyperplasia Genuine stress urinary incontinence Normal Electromyographic study (54 pts.): Sacral arc denervation Detrusor-sphincter dyssynergia Normal Upper tract imaging at initial urological evaluation (105 pts.): Hyc:lronephrosis: Unilat., 3 Bilat., 2 Ureterectasis Urinary stones: Renal, 1 Bladder, 4 Vesicoureteral reflux Other
79 (70) 17 (15)
3 (2.6) 2 (1.7)
2 (1.7)
10 (9) 23 (42) 15 (28) 16 (30)
5 (4.7) 2 (1.9)
5 (4.7) 2 (1.9) 3 (2.8)
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ROLE OF LIMITED EVALUATION AND MEDICAL MANAGEMENT IN MULTIPLE SCLEROSIS
Medical management in 113 patients based upon clinical and urodynamic information, and subsequent changes in therapy
TABLE 2.
Medical Management Oral pharmacological agent with clean intermittent catheterization (oxybutynin, propantheline or imipramine) Oral pharmacological agent alone Clean intermittent catheterization alone Behavioral therapy
TABLE 3.
No. Pts. (%) 64 (57) 15 (13) 17 (15) 17 (15)
Surgical procedures required in 16 of 113 patients with multiple sclerosis (mean followup 41 months) Surgical Procedure
Suprapubic catheter with bladder neck closure Cystolitholapaxy Augmentation cystoplasty Ilea! loop diversion Other (orchiectomy, penile prosthesis, urethral diverticulectomy or radical nephrectomy)
No. Pts. (%) 4 (3.5) 4 (3.5) 3 (2.6) 1 (0.8) 4 (3.5)
in the oral anticholinergic agent because of side effects and 18 (23%) required nontraditional pharmacological therapy, including an oral calcium channel blocker (verapamil) or intravesical oxybutynin instillations. Of the patients 17 were managed with behavioral modification, including timed voiding, fluid restriction and avoidance of dietary stimulants, such as caffeine. This group includes patients who did not follow recommended therapy (9 refused clean intermittent catheterization and 4 refused pharmacotherapy) and 4 with low amplitude detrusor hyperreflexia with minimal or no voiding symptoms. Of the 13 patients who refused recommended therapy 4 had complications (2 required suprapubic catheter placement and urosepsis developed in 2), 4 had persistent incontinence and 5 remained clinically stable. The 4 patients with minimal voiding symptoms responded to behavioral modification techniques and remained clinically stable. No patient in this subgroup suffered upper tract deterioration. A total of 24 patients (21 %) had symptomatic urinary tract infections before initiation of medical management, while 13 (11 %) had recurrent urinary tact infections after medical management was instituted, requiring low dose antibiotic suppression. Of these 13 patients, 10 were on clean intermittent catheterization. Nine patients with voiding symptoms refractory to oral pharmacological agents or experiencing intolerable systemic side effects were placed on an intravesical oxybutynin protocol (5 mg. oxybutynin tablet dissolved in 30 cc saline, instilled for 30 minutes by catheter twice daily). Eight patients reported significant improvement in the voiding symptoms and 6 continued the protocol after a mean of 24 months. The results of radiographic imaging of the upper tracts are presented in table 1. Five patients had hydronephrosis at presentation, 3 had acontractile bladders on cystometrography and 2 had detrusor hyperreflexia (1 with poor compliance). All 3 patients with an acontractile bladder had resolution of the hydronephrosis with clean intermittent catheterization alone. Although both patients with detrusor hyperreflexia had evidence of sacral arc denervation on electromyography, there was no evidence of detrusor-sphincter dyssynergia. In both patients the hydronephrosis resolved with medical management, although 1 ultimately required augmentation cystoplasty (for refractory irritative symptoms). The 2 patients with bilateral ureterectasis and detrusor hyperreflexia responded to medical management with resolution of the radiographic findings. A total of 16 surgical procedures was performed in the group (table 3). Four patients with progressive neurological disease (unable to perform clean intermittent catheterization) required suprapubic catheter placement (with bladder neck closure) and 1 underwent an ileal loop diversion. Three patients underwent
augmentation cystoplasty (failed medical management) and 8 underwent miscellaneous operations for pathological conditions not indicative of treatment failure. Therefore, 8 of 113 patients (7%) required surgical intervention secondary to failure of aggressive medical management. DISCUSSION
The hallmark of multiple sclerosis is a changing neurological picture with varying clinical symptoms, usually in a stepwise progression. 1 The clinical course may be indolent or rapidly progressive. The goal of therapy in the patient with multiple sclerosis is to protect and preserve renal function, and eradicate symptomatic voiding dysfunction and incontinence to provide a normal life-style. Lower urinary tract symptoms do not correlate with the underlying pathophysiology of bladder dysfunction and urodynamic evaluation is necessary. Although it has been suggested that the evaluation of multiple sclerosis patients should be limited to physical examination and post-void residual urine measurement,7 most agree that urodynamic assessment of bladder function is critical to direct therapy. 1- 4• 12 In our study the evaluation process involved clinical symptomatology and basic urodynamic information to establish a treatment program with the aforementioned goals. As demonstrated in our study, medical management of patients with voiding dysfunction from multiple sclerosis, using pharmacotherapy to suppress detrusor hyperreflexia when present and clean intermittent catheterization when residual urine volumes are elevated, is safe and effective. Few patients (7 of 105) had upper tract dilatation on presentation and none had upper tract deterioration with medical management. Furthermore, few patients failed aggressive medical management (9 of 113 in this series) and required subsequently surgical intervention. The majority of patients after initial evaluation are treated with oral anticholinergic agents with or without clean intermittent catheterization. Patients with an acontractile bladder can be managed with clean intermittent catheterization alone. The pharmacotherapy program may require adjustment to find an agent that is effective and tolerated by the patient. Of 59 patients started on single agent pharmacotherapy 25 required the addition of a second agent to control persistent irritative voiding symptoms. Intolerable systemic side effects required 18 patients to change to alternative oral pharmacological agents. Finally, 18 patients refractory to standard oral agents (failure to control voiding symptoms or intolerable systemic side effects) required alternative pharmacological therapy, including intravesical oxybutynin instillations. An interesting observation of this study was the efficacy of intravesical oxybutynin in multiple sclerosis patients with voiding symptoms refractory to oral pharmacological agents or unable to tolerate systemic side effects. Of 9 patients placed on an intravesical oxybutynin protocol 8 responded with significant improvement of the voiding complaints. With a 2-year followup 6 patients continue the intravesical instillations. Other patient groups with refractory irritative voiding symptoms (that is detrusor instability, spinal cord injury and others) have used the same intravesical protocol. Despite similar symptomatic improvement, patients in other groups had a much higher dropout rate from the intravesical oxybutynin protocol than did multiple sclerosis patients.13 Few studies report the long-term results of medical management of patients with multiple sclerosis. McGuire and Savastano reported their experience with the management of multiple sclerosis patients based upon urodynamic findings. 1 Of 25 patients with detrusor areflexia or detrusor hyperreflexia (with a coordinated external sphincter) 21 were asymptomatic on therapy. However, of 21 patients with detrusor-sphincter dyssynergia 9 failed therapy, usually from progression of the neurological disease. Many investigators have shown that the
ROLE OF LI1vHTED EVALUATION AND M:EDICAL MANAGEMENT IN MULTIPLE SCLEROSIS
presence of detrusor-sphincter dyssynergia correlates with the severity of neurological disease. In our study 7 of 15 patients with documented detrusor-sphincter dyssynergia were wheelchair bound at presentation. An explanation for the management failure in patients with detrusor-sphincter dyssynergia may be the advanced stage of the multiple sclerosis itself (with upper extremity involvement limiting the ability to perform clean intermittent catheterization) and not specifically the detrusor-sphincter dyssynergia. In this series the information gained from the electromyography did not change the treatment plan or adversely impact the outcome of medical management. All of our 15 patients with documented detrusor-sphincter dyssynergia had significant voiding symptoms and detrusor hyperreflexia, and 7 of 15 had significantly elevated post-void residual urine volumes. Sufficient information was obtained from a limited evaluation (post-void residual urine and cystometrography) and the severity of clinical symptoms to formulate a treatment program. Although the subgroup with detrusor-sphincter dyssynergia did require proportionately more surgical procedures than the study group as a whole, this probably reflects the severity of neurological disease (that is inability to use the hands for clean intermittent catheterization) and not specifically the detrusorsphincter dyssynergia. Based on these results electromyography is not used routinely in the evaluation of patients with documented multiple sclerosis. However, electromyography was useful to identify a specific neurological abnormality in patients in whom the diagnosis of multiple sclerosis was first suspected during the urological evaluation. 12 Thus, electromyography is used only as a diagnostic tool to document a neurological abnormality in patients with the suspected diagnosis of multiple sclerosis. The incidence of hydronephrosis observed in our study compares with the incidence of upper tract changes reported by others. 3• 4 Gonor et al reported only 1 of 64 patients with hydronephrosis, 4 and Mayo and Chetner in a series of 89 patients found vesicoureteral reflux in 2 (grade II) but no patient had hydronephrosis. 3 This incidence of hydronephrosis in multiple sclerosis patients is less than that noted in the spinal cord injury patient population. 14 This observation may relate to a protective effect from a poorly sustained detrusor contraction (hypocontractility) that may be seen in as many as 50% of multiple sclerosis patients with detrusor hyperreflexia. 4· 13 Another explanation may be that the nature of the uninhibited detrusor contraction and detrusor-sphincter dyssynergia is different in multiple sclerosis and spinal cord injury patients. The uninhibited detrusor contraction and detrusorsphincter dyssynergia in spinal cord injury may be more severe than in multiple sclerosis, exposing the upper tracts to high detrusor pressures for longer periods. Staskin demonstrated that the risk of upper tract deterioration in spinal cord injury patients was related to the interval that the upper tracts were exposed to high pressures. 15 Interestingly, 3 of the 5 patients with hydronephrosis in this study had an acontractile bladder on urodynamic evaluation, with resolution of the upper tract changes on clean intermittent catheterization alone. This hydronephrosis may have reflected overflow incontinence and explains its prompt resolution with treatment. However, patients with detrusor hyperreflexia with or without detrusor-sphincter dyssynergia were not at increased risk for hydronephrosis. In fact, no patient in our series had hydronephrosis on conservative medical management. These results support the finding that patients with multiple sclerosis who are clinically stable after an initial complete evaluation do not need annual evaluation of the upper tracts (unless indicated for other reasons). Only 8 of 113 patients (7%) required surgical intervention secondary to failure of medical management. Five patients required supravesical diversion for progression of neurological
949
disease limiting the to rno·,t·.~,·~ clean intermittent catheterization and/or symptoms refractory to medical management. Three patients with severe detrusor hyperreflexia refractory to medical management yet able to perform clean intermittent catheterization underwent augmentation cystoplasty. The subgroup of 13 patients who refused the recommended medical management may be compared to the remaining group. Although the numbers are too small for a valid conclusion, of the "untreated" group 31 % had urological complications, 15% required an operation, 31 % had persistent incontinence and 38% remained clinically stable. Of the 96 patients following the treatment protocol 11 % had recurrent or persistent urinary tract infections requiring therapy and 7% "failed" requiring surgical intervention. These finding further support the efficacy of a clinical and urodynamic based medical treatment regimen. The 21 % incidence of urinary tract infections before the institution of medical management is similar to the 19% rate reported by others. 3 • 4 The 11 % incidence of patients with recurrent symptomatic urinary tract infections on medical management requiring suppressive prophylaxis cannot be attributed to intermittent catheterization alone, since 3 patients were not on clean intermittent catheterization. Although little data exist for comparison, the recurrent infections are probably multifactorial and also relate to the neurological decrease in the population. CONCLUSION
The goal of management of the patient with multiple sclerosis is to preserve and protect renal function, and to control bothersome voiding symptoms. In our experience, electromyography results have not routinely changed the therapeutic plan and the presence of detrusor-sphincter dyssynergia itself has not had an adverse impact on patient outcome. This finding suggests that electromyography is not necessary in the routine evaluation of patients with the documented diagnosis of multiple sclerosis. Instead, electromyography is most useful for diagnostic purposes when evaluating the patient with suspected multiple sclerosis. We believe that clinical symptoms, post-void residual urine volume and basic urodynamic evaluation (uroflowmetry and cystometrography) are sufficient to formulate an effective treatment program. A baseline upper tract imaging study should be obtained but in the absence of an abnormality or a change in clinical status routine yearly evaluations are unnecessary. In the clinically stable patient we recommend annual serum creatinine levels. Finally, medical management of patients with multiple sclerosis is safe and effective, In our 8% series no patient had hydronephrosis on therapy and failed conservative medical management to require surgical intervention. REFERENCES 1. McGuire, E. and Savastano, J. A.: Urodynamic findings and long-
term outcome management of patients with multiple sclerosisinduced lower urinary tract dysfunction. J. Urol., 132: 713, 1984.
2. Piazza, D. H. and Diokno, A. C.: Review of neurogenic bladder in multiple sclerosis. Urology, 14: 33, 1979. 3. Mayo, M. E. and Chetner, M. P.: Lower urinary tract dysfunction in multiple sclerosis. Urology, 39: 67, 1992. 4. Gonor, S. E., Carroll, D. J. and Metcalf, J.B.: Vesical dysfunction in multiple sclerosis. Urology, 25: 429, 1985. 5. Blaivas, J. G., Bhimani, G. and Labib, K.: Vesicoureteral dysfunction in multiple sclerosis. J. Urol., 122: 342, 1979, 6. Blaivas, J. G. and Barbalis, G. A.: Detrusor-external sphincter dyssynergia in men with multiple sclerosis: an ominous urologic condition. J. Urol., 131: 91, 1984. 7. Kornhuber, H. H. and Schulz, A.: Efficient treatment of neurogenic bladder disorders in multiple sclerosis with initial intermittent catheterization and ultrasound-controlled training. Eur. Neurol., 30: 260, 1990.
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ROLE OF LIMITED EVALUATION AND MEDICAL MANAGEMENT IN MULTIPLE SCLEROSIS
8. Lapides, J., Diokno, A. C., Silber, S. J. and Lowe, B. S.: Clean, intermittent self-catheterization in the treatment of urinary tract disease. J. Urol., 107: 458, 1972. 9. Abrams, P., Blaivas, J. G., Stanton, S. L. and Anderson, J. T.: The standardisation of terminology of lower urinary tract function. The International Continence Society Committee on Standardization of Terminology. Scand. J. Urol. Nephrol., suppl., 114: 5, 1988. 10. Toppercer, A. and Tetreault, J. P.: Compliance of the bladder: an attempt to establish normal values. Urology, 14: 204, 1979. 11. Wheeler, J. S., Jr., Siroky, M. B., Pavlakis, A. J., Goldstein, I. and Krane, R. J.: The changing neurourologic pattern of multiple sclerosis. J. Urol., 130: 1123, 1983.
12. Dula, E. and Leach, G. E.: Role of urologist in the diagnosis of multiple sclerosis. Urology, 37: 311, 1991. 13. Sirls, L., Weese, D., Zimmern, P., Roskamp, D., Ganabathi, K. and Leach, G.: Intravesical oxybutynin for refractory detrusor over activity (abstract). Presented at annual meeting of Urodynamics Society, San Antonio, Texas, 1993. 14. Anderson, R. U.: Urodynamic patterns after acute spinal cord injury: association with bladder trabeculation in male patients. J. Urol., 129: 777, 1983. 15. Staskin, D. R.: Hydroureteronephrosis after spinal cord injury. Effects of lower urinary tract dysfunction on upper tract anatomy. Urol. Clin. N. Amer., 18: 309, 1991.
Vol. 151, 946-950, April 1994
Printed in U.S.A.
ROLE OF LIMITED EVALUATION AND AGGRESSIVE MEDICAL MANAGEMENT IN MULTIPLE SCLEROSIS: A REVIEW OF 113 PATIENTS LARRY T. SIRLS, PHILIPPE E. ZIMMERN
AND
GARY E. LEACH*
From the Kaiser Permanente Medical Center, Los Angeles, California
ABSTRACT
Multiple sclerosis has frequent urological manifestations. Medical management, based on clinical symptoms and urodynamic findings, incorporates clean intermittent catheterization, oral pharmacological agents (that is oral oxybutynin) or their combination (the desired end point of treatment being complete retention with clean intermittent catheterization). Our objectives were to evaluate the efficacy of medical management in multiple sclerosis patients, determine the incidence of hydronephrosis at presentation and during treatment, and evaluate the impact of electromyography on patient management. We reviewed retrospectively 113 patients with documented multiple sclerosis (mean age 45 years, range 20 to 75 years and mean followup 41 months, range 6 to 136 months). Presenting symptoms were irritative alone or combined with obstructive symptoms in 94 patients (83%). On cystometrography 79 patients (70%) had detrusor hyperreflexia and 17 (15%) had an areflexic bladder. Coaxial needle electromyography was performed on 54 patients and 15 (28%) had detrusor-sphincter dyssynergia. Patients with detrusor-sphincter dyssynergia had more advanced neurological disease. A total of 105 patients had radiological imaging of the upper tracts. Only 7 patients (6.6%) had hydronephrosis at presentation and all were stable or improved with medical management. No patient had hydronephrosis with aggressive medical management. No patient with detrusor-sphincter dyssynergia had hydronephrosis or elevated creatinine levels at presentation or during treatment. Medical management failed in 8 patients (7%) who required surgical intervention. Limited evaluation (voiding symptoms, post-void residual and cystometrography) of multiple sclerosis patients is sufficient to formulate an effective treatment program. Electromyography is not necessary in the routine evaluation of patients with documented multiple sclerosis. After baseline upper tract imaging, routine yearly evaluations are unnecessary (unless initially abnormal or indicated by a change in clinical status). Medical management of patients with multiple sclerosis is safe and effective. In this series, no patient had hydronephrosis on therapy, and only 7% of the patients failed aggressive medical management and required surgical intervention. KEY WORDS:
multiple sclerosis, urinary catheterization, oxybutynin, electromyography
Up to 90% of the patients with multiple sclerosis will have lower urinary tract symptoms during the course of the disease. 1 The diverse neurological lesions of multiple sclerosis may cause various urological presentations, ranging from detrusor hyperreflexia with urge incontinence to areflexia and urinary retention. The majority of patients with voiding dysfunction from multiple sclerosis present with irritative symptoms (frequency and urgency, with or without urge incontinence) and demonstrate detrusor hyperreflexia on cystometrography. 1• 2 More than half of the patients with multiple sclerosis have detrusor hyperreflexia with hypocontractility (a poorly sustained detrusor contraction), leading to symptoms of urinary frequency and urgency associated with incomplete bladder emptying.3• 4 Previous studies have suggested electromyography as an important part of the evaluation of patients with multiple sclerosis, with the electromyographic findings used to classify the type of voiding dysfunction present. 1• 2 •6 Blaivas and Barbalis identified men with detrusor-sphincter dyssynergia as a subgroup of patients with multiple sclerosis at increased risk for urological complications, even with appropriate therapy, such as clean intermittent catheterization and oral anticholinergic agents. 6 Others find electromyography difficult to perform Accepted for publication October 1, 1993. * Requests for reprints: 4900 Sunset Blvd., Los Angeles, California 90027.
and interpret, and do not use it in the routine evaluation of patients with multiple sclerosis. 4 • 7 After evaluation, the initial treatment for patients with voiding dysfunction from multiple sclerosis is medical, usually with oral pharmacological agents, with or without clean intermittent catheterization.8 When severe irritative symptoms predominate or incomplete bladder emptying is present, the goal of therapy is complete urinary retention and clean intermittent catheterization when possible. We emphasize an approach using clinical symptoms (obstructive and/or irritative, and incontinence), post-void residual urine volumes, basic urodynamic information (cystometrography) and baseline upper tract evaluation (serum creatinine and radiographic imaging) as the criteria from which a treatment plan is formulated. The objectives of treatment are to lower detrusor pressures if elevated, control incontinence if present, reverse or stabilize upper tract changes and accomplish complete bladder emptying. We evaluate the efficacy of medical management for multiple sclerosis patients based upon the interpretation of clinical and basic urodynamic information. The specific objectives of this review were to assess the safety and efficacy of medical management, and the incidence of management failure requiring surgical intervention, determine the incidence of hydronephrosis at presentation and during treatment, and evaluate the impact of electromyography on patient management.
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ROLE OF LIMITED EVALUATION AND MEDl:CAL MANAGEMENT IN MULTIPLE SCLEROSIS MATERIALS AND METHODS
We reviewed retrospectively 72 women and 41 men with the confirmed diagnosis of multiple sclerosis (mean age 45 years, range 20 to 75 years and mean followup 41 months, range 6 to 136 months). In patients with an established diagnosis of multiple sclerosis the duration of disease was 9.9 years before urological evaluation (range 1 month to 30 years). Patient evaluation included a detailed history and physical examination, including a focused neurological examination consisting of assessment of anal sphincter tone, bulbocavernosus reflex, knee and ankle reflexes, Babinski sign, and sensation to pinprick and light touch in the lumbar and sacral dermatomes. If hyperreflexia was noted the presence or absence of clonus was assessed. Urinalysis, urine culture and voided urine cytology studies were performed when indicated. Serum creatinine, and renal ultrasound or excretory urogram (IVP) were used to assess renal function and the upper tracts. Urodynamic evaluation began with noninvasive uroflowmetry and residual urine volume measurement. Medium fill water cystometry (50 cc per minute) was performed through a urethral catheter (7F double lumen or 8F feeding tube). The presence of uninhibited detrusor contractions was noted. Cystoscopy was routinely performed. The definitions, terminology and units used conform to the standards established by the International Continence Society. 9 However, uninhibited detrusor contractions less than 15 cm. yvater associated wit~ urgency were considered clinically significant. Bladder compliance was calculated as the ratio of bladder volume increment to the change in intravesical pressure (cc/ cm. water). Decreased compliance was defined as compliance less than 12.5 cc/cm. water). 10 Electromyography was performed on all patients in the early years of the study. More recently, electromyography was used onl?' in patients with an uncertain diagnosis of multiple scler0S1s (to document a neurological abnormality). Electromyography of the external anal sphincter was performed using coaxial needle electrodes under oscilloscopic and auditory controls. The bulbocavernosus reflex was tested and voluntary contraction of the pelvic floor musculature was noted (full interference pattern). Abnormal wave forms (such as polyphas1c potentials, positive sharp waves and giant waves) indicating various degrees of sacral arc denervation were identified. In':'oluntary sphincter activity during voiding was indicative of detrusor-sphincter dyssynergia. After the evaluation, the treatment guidelines were observation for those with a normal study and no upper tract deterioration, oral pharmacological agents with or without clean intermittent catheterization, depending on the post-void residual volume at evaluation, and on therapy for patients with detrusor hyperreflexia (with symptomatic urgency and/or urge incontinence) and clean intermittent catheterization for patients with elevated post-void residual urine volumes alone (normal bladder pressure). Patients not responding to therapy or with changes in clinical symptoms were reevaluated as indicated. Routi.ne f?llowup consiste? of yearly evaluations with physical exammat10n, upper tract imaging, serum creatinine noninvasive uroflowmetry and post-void residual urine meas~rement. RESULTS
In 11 patients the diagnosis of multiple sclerosis was first suspected by the urologist and subsequently confirmed. The majority of the 113 patients had irritative symptoms (urgency, frequency or urge incontinence) with or without obstructive sympt?ms (decreased force of stream, sensation of incomplete emptym~ and so forth): 56 (49.5%) had irritative, 16 (14%) had obstructive and 38 (34%) had combined irritative and obstructive symptoms. Two patients (1.7%) had urinary tract infection and 1 (0.8%) was asymptomatic. Associated symptoms discov-
ered with the detailed history included impotence in 9 men, recurrent or J?ersist~nt 1:1rinary tract infections in 22 patients and absent eJaculat10n m 2 men. A total of 19 patients was wheelchair bound at presentation. Abnormalities were noted on the focused neurological examination in 82 patients, while 21 had a normal examination and in 10 the results were equivocal. Results of the urodynamic evaluation are presented in table 1. Detrusor hyperreflexia was the most common finding. Electromyography was performed in 51 patients (48%) and demons~rated ~etrusor-sphincter dyssynergia in 15 (28%). The patients with detrusor-sphincter dyssynergia had more advanced neurological disease than the study group as a whole. Of the 15 patients with detrusor-sphincter dyssynergia 7 (4 7%) were wheelchair bound at presentation. Obstructive and irri~at_ive .voiding symptoms occurred in 12 of the 15 patients and irnta~ive s)'.mptoms alone ~n 2, while 1 was referred for urinary tr~ct mfect10ns. Seven patients had elevated post-void residual urme volumes (mean 185 cc) and 8 patients emptied the bladder completely. All patients had detrusor hyperreflexia and 1 also had poor compliance. In 11 patients the diagnosis of multiple sclerosis was first suspected during the urological evaluation (and subsequently confirr_n~d by 1:1agnetic resonance imaging). Seven patients had a susp1c10us history, 8 had an abnormal neurological examination and 10 h~d an ab.normal c)'.stometrogram. Electromyography.wa~ done m 8 patients and identified a neurological abnormaht:y m .6. When combined with a suspicious history, physical ~xammat10n or cystometrography, electromyography assisted m docu!11enting. a spe?ific neurological abnormality, further supportmg the diagnosis of multiple sclerosis. '.J'he results in 105 patients who underwent radiological imaging of the upper tracts :,vith either IVP or renal ultrasonography also are presented m table 1. Although 17 patients had an abnormal finding, only 7 (6.6%) had upper tract dilatation. Five patients (4.7%) had urinary stones. With medical management, hydronephrosis resolved in all patients and did not occur subsequently in any. The medical management of the study group is presented in table 2 .. ThE; majority of patients (64 of 113) were managed with a combmat10n of oral pharmacological agents and clean intermittent. ~atheterization. A total of 25 patients (32%) required the addit10n of a second oral medication to control the irritative voiding symptoms. Eighteen patients (23%) required a change 1. Urodynamic, electromyographic and upper tract imaging ([VP or ultrasound) findings in patients with multiple sclerosis
TABLE
No. Pts. (%) Urodynamic findings (113 pts.): Detrusor hyperreflexia Acontractile detrusor Decreased compliance (less than 12.5 cc/cm. water) Outlet obstruction secondary to benign prostatic hyperplasia Genuine stress urinary incontinence Normal Electromyographic study (54 pts.): Sacral arc denervation Detrusor-sphincter dyssynergia Normal Upper tract imaging at initial urological evaluation (105 pts.): Hyc:lronephrosis: Unilat., 3 Bilat., 2 Ureterectasis Urinary stones: Renal, 1 Bladder, 4 Vesicoureteral reflux Other
79 (70) 17 (15)
3 (2.6) 2 (1.7)
2 (1.7)
10 (9) 23 (42) 15 (28) 16 (30)
5 (4.7) 2 (1.9)
5 (4.7) 2 (1.9) 3 (2.8)
948
ROLE OF LIMITED EVALUATION AND MEDICAL MANAGEMENT IN MULTIPLE SCLEROSIS
Medical management in 113 patients based upon clinical and urodynamic information, and subsequent changes in therapy
TABLE 2.
Medical Management Oral pharmacological agent with clean intermittent catheterization (oxybutynin, propantheline or imipramine) Oral pharmacological agent alone Clean intermittent catheterization alone Behavioral therapy
TABLE 3.
No. Pts. (%) 64 (57) 15 (13) 17 (15) 17 (15)
Surgical procedures required in 16 of 113 patients with multiple sclerosis (mean followup 41 months) Surgical Procedure
Suprapubic catheter with bladder neck closure Cystolitholapaxy Augmentation cystoplasty Ilea! loop diversion Other (orchiectomy, penile prosthesis, urethral diverticulectomy or radical nephrectomy)
No. Pts. (%) 4 (3.5) 4 (3.5) 3 (2.6) 1 (0.8) 4 (3.5)
in the oral anticholinergic agent because of side effects and 18 (23%) required nontraditional pharmacological therapy, including an oral calcium channel blocker (verapamil) or intravesical oxybutynin instillations. Of the patients 17 were managed with behavioral modification, including timed voiding, fluid restriction and avoidance of dietary stimulants, such as caffeine. This group includes patients who did not follow recommended therapy (9 refused clean intermittent catheterization and 4 refused pharmacotherapy) and 4 with low amplitude detrusor hyperreflexia with minimal or no voiding symptoms. Of the 13 patients who refused recommended therapy 4 had complications (2 required suprapubic catheter placement and urosepsis developed in 2), 4 had persistent incontinence and 5 remained clinically stable. The 4 patients with minimal voiding symptoms responded to behavioral modification techniques and remained clinically stable. No patient in this subgroup suffered upper tract deterioration. A total of 24 patients (21 %) had symptomatic urinary tract infections before initiation of medical management, while 13 (11 %) had recurrent urinary tact infections after medical management was instituted, requiring low dose antibiotic suppression. Of these 13 patients, 10 were on clean intermittent catheterization. Nine patients with voiding symptoms refractory to oral pharmacological agents or experiencing intolerable systemic side effects were placed on an intravesical oxybutynin protocol (5 mg. oxybutynin tablet dissolved in 30 cc saline, instilled for 30 minutes by catheter twice daily). Eight patients reported significant improvement in the voiding symptoms and 6 continued the protocol after a mean of 24 months. The results of radiographic imaging of the upper tracts are presented in table 1. Five patients had hydronephrosis at presentation, 3 had acontractile bladders on cystometrography and 2 had detrusor hyperreflexia (1 with poor compliance). All 3 patients with an acontractile bladder had resolution of the hydronephrosis with clean intermittent catheterization alone. Although both patients with detrusor hyperreflexia had evidence of sacral arc denervation on electromyography, there was no evidence of detrusor-sphincter dyssynergia. In both patients the hydronephrosis resolved with medical management, although 1 ultimately required augmentation cystoplasty (for refractory irritative symptoms). The 2 patients with bilateral ureterectasis and detrusor hyperreflexia responded to medical management with resolution of the radiographic findings. A total of 16 surgical procedures was performed in the group (table 3). Four patients with progressive neurological disease (unable to perform clean intermittent catheterization) required suprapubic catheter placement (with bladder neck closure) and 1 underwent an ileal loop diversion. Three patients underwent
augmentation cystoplasty (failed medical management) and 8 underwent miscellaneous operations for pathological conditions not indicative of treatment failure. Therefore, 8 of 113 patients (7%) required surgical intervention secondary to failure of aggressive medical management. DISCUSSION
The hallmark of multiple sclerosis is a changing neurological picture with varying clinical symptoms, usually in a stepwise progression. 1 The clinical course may be indolent or rapidly progressive. The goal of therapy in the patient with multiple sclerosis is to protect and preserve renal function, and eradicate symptomatic voiding dysfunction and incontinence to provide a normal life-style. Lower urinary tract symptoms do not correlate with the underlying pathophysiology of bladder dysfunction and urodynamic evaluation is necessary. Although it has been suggested that the evaluation of multiple sclerosis patients should be limited to physical examination and post-void residual urine measurement,7 most agree that urodynamic assessment of bladder function is critical to direct therapy. 1- 4• 12 In our study the evaluation process involved clinical symptomatology and basic urodynamic information to establish a treatment program with the aforementioned goals. As demonstrated in our study, medical management of patients with voiding dysfunction from multiple sclerosis, using pharmacotherapy to suppress detrusor hyperreflexia when present and clean intermittent catheterization when residual urine volumes are elevated, is safe and effective. Few patients (7 of 105) had upper tract dilatation on presentation and none had upper tract deterioration with medical management. Furthermore, few patients failed aggressive medical management (9 of 113 in this series) and required subsequently surgical intervention. The majority of patients after initial evaluation are treated with oral anticholinergic agents with or without clean intermittent catheterization. Patients with an acontractile bladder can be managed with clean intermittent catheterization alone. The pharmacotherapy program may require adjustment to find an agent that is effective and tolerated by the patient. Of 59 patients started on single agent pharmacotherapy 25 required the addition of a second agent to control persistent irritative voiding symptoms. Intolerable systemic side effects required 18 patients to change to alternative oral pharmacological agents. Finally, 18 patients refractory to standard oral agents (failure to control voiding symptoms or intolerable systemic side effects) required alternative pharmacological therapy, including intravesical oxybutynin instillations. An interesting observation of this study was the efficacy of intravesical oxybutynin in multiple sclerosis patients with voiding symptoms refractory to oral pharmacological agents or unable to tolerate systemic side effects. Of 9 patients placed on an intravesical oxybutynin protocol 8 responded with significant improvement of the voiding complaints. With a 2-year followup 6 patients continue the intravesical instillations. Other patient groups with refractory irritative voiding symptoms (that is detrusor instability, spinal cord injury and others) have used the same intravesical protocol. Despite similar symptomatic improvement, patients in other groups had a much higher dropout rate from the intravesical oxybutynin protocol than did multiple sclerosis patients.13 Few studies report the long-term results of medical management of patients with multiple sclerosis. McGuire and Savastano reported their experience with the management of multiple sclerosis patients based upon urodynamic findings. 1 Of 25 patients with detrusor areflexia or detrusor hyperreflexia (with a coordinated external sphincter) 21 were asymptomatic on therapy. However, of 21 patients with detrusor-sphincter dyssynergia 9 failed therapy, usually from progression of the neurological disease. Many investigators have shown that the
ROLE OF LI1vHTED EVALUATION AND M:EDICAL MANAGEMENT IN MULTIPLE SCLEROSIS
presence of detrusor-sphincter dyssynergia correlates with the severity of neurological disease. In our study 7 of 15 patients with documented detrusor-sphincter dyssynergia were wheelchair bound at presentation. An explanation for the management failure in patients with detrusor-sphincter dyssynergia may be the advanced stage of the multiple sclerosis itself (with upper extremity involvement limiting the ability to perform clean intermittent catheterization) and not specifically the detrusor-sphincter dyssynergia. In this series the information gained from the electromyography did not change the treatment plan or adversely impact the outcome of medical management. All of our 15 patients with documented detrusor-sphincter dyssynergia had significant voiding symptoms and detrusor hyperreflexia, and 7 of 15 had significantly elevated post-void residual urine volumes. Sufficient information was obtained from a limited evaluation (post-void residual urine and cystometrography) and the severity of clinical symptoms to formulate a treatment program. Although the subgroup with detrusor-sphincter dyssynergia did require proportionately more surgical procedures than the study group as a whole, this probably reflects the severity of neurological disease (that is inability to use the hands for clean intermittent catheterization) and not specifically the detrusorsphincter dyssynergia. Based on these results electromyography is not used routinely in the evaluation of patients with documented multiple sclerosis. However, electromyography was useful to identify a specific neurological abnormality in patients in whom the diagnosis of multiple sclerosis was first suspected during the urological evaluation. 12 Thus, electromyography is used only as a diagnostic tool to document a neurological abnormality in patients with the suspected diagnosis of multiple sclerosis. The incidence of hydronephrosis observed in our study compares with the incidence of upper tract changes reported by others. 3• 4 Gonor et al reported only 1 of 64 patients with hydronephrosis, 4 and Mayo and Chetner in a series of 89 patients found vesicoureteral reflux in 2 (grade II) but no patient had hydronephrosis. 3 This incidence of hydronephrosis in multiple sclerosis patients is less than that noted in the spinal cord injury patient population. 14 This observation may relate to a protective effect from a poorly sustained detrusor contraction (hypocontractility) that may be seen in as many as 50% of multiple sclerosis patients with detrusor hyperreflexia. 4· 13 Another explanation may be that the nature of the uninhibited detrusor contraction and detrusor-sphincter dyssynergia is different in multiple sclerosis and spinal cord injury patients. The uninhibited detrusor contraction and detrusorsphincter dyssynergia in spinal cord injury may be more severe than in multiple sclerosis, exposing the upper tracts to high detrusor pressures for longer periods. Staskin demonstrated that the risk of upper tract deterioration in spinal cord injury patients was related to the interval that the upper tracts were exposed to high pressures. 15 Interestingly, 3 of the 5 patients with hydronephrosis in this study had an acontractile bladder on urodynamic evaluation, with resolution of the upper tract changes on clean intermittent catheterization alone. This hydronephrosis may have reflected overflow incontinence and explains its prompt resolution with treatment. However, patients with detrusor hyperreflexia with or without detrusor-sphincter dyssynergia were not at increased risk for hydronephrosis. In fact, no patient in our series had hydronephrosis on conservative medical management. These results support the finding that patients with multiple sclerosis who are clinically stable after an initial complete evaluation do not need annual evaluation of the upper tracts (unless indicated for other reasons). Only 8 of 113 patients (7%) required surgical intervention secondary to failure of medical management. Five patients required supravesical diversion for progression of neurological
949
disease limiting the to rno·,t·.~,·~ clean intermittent catheterization and/or symptoms refractory to medical management. Three patients with severe detrusor hyperreflexia refractory to medical management yet able to perform clean intermittent catheterization underwent augmentation cystoplasty. The subgroup of 13 patients who refused the recommended medical management may be compared to the remaining group. Although the numbers are too small for a valid conclusion, of the "untreated" group 31 % had urological complications, 15% required an operation, 31 % had persistent incontinence and 38% remained clinically stable. Of the 96 patients following the treatment protocol 11 % had recurrent or persistent urinary tract infections requiring therapy and 7% "failed" requiring surgical intervention. These finding further support the efficacy of a clinical and urodynamic based medical treatment regimen. The 21 % incidence of urinary tract infections before the institution of medical management is similar to the 19% rate reported by others. 3 • 4 The 11 % incidence of patients with recurrent symptomatic urinary tract infections on medical management requiring suppressive prophylaxis cannot be attributed to intermittent catheterization alone, since 3 patients were not on clean intermittent catheterization. Although little data exist for comparison, the recurrent infections are probably multifactorial and also relate to the neurological decrease in the population. CONCLUSION
The goal of management of the patient with multiple sclerosis is to preserve and protect renal function, and to control bothersome voiding symptoms. In our experience, electromyography results have not routinely changed the therapeutic plan and the presence of detrusor-sphincter dyssynergia itself has not had an adverse impact on patient outcome. This finding suggests that electromyography is not necessary in the routine evaluation of patients with the documented diagnosis of multiple sclerosis. Instead, electromyography is most useful for diagnostic purposes when evaluating the patient with suspected multiple sclerosis. We believe that clinical symptoms, post-void residual urine volume and basic urodynamic evaluation (uroflowmetry and cystometrography) are sufficient to formulate an effective treatment program. A baseline upper tract imaging study should be obtained but in the absence of an abnormality or a change in clinical status routine yearly evaluations are unnecessary. In the clinically stable patient we recommend annual serum creatinine levels. Finally, medical management of patients with multiple sclerosis is safe and effective, In our 8% series no patient had hydronephrosis on therapy and failed conservative medical management to require surgical intervention. REFERENCES 1. McGuire, E. and Savastano, J. A.: Urodynamic findings and long-
term outcome management of patients with multiple sclerosisinduced lower urinary tract dysfunction. J. Urol., 132: 713, 1984.
2. Piazza, D. H. and Diokno, A. C.: Review of neurogenic bladder in multiple sclerosis. Urology, 14: 33, 1979. 3. Mayo, M. E. and Chetner, M. P.: Lower urinary tract dysfunction in multiple sclerosis. Urology, 39: 67, 1992. 4. Gonor, S. E., Carroll, D. J. and Metcalf, J.B.: Vesical dysfunction in multiple sclerosis. Urology, 25: 429, 1985. 5. Blaivas, J. G., Bhimani, G. and Labib, K.: Vesicoureteral dysfunction in multiple sclerosis. J. Urol., 122: 342, 1979, 6. Blaivas, J. G. and Barbalis, G. A.: Detrusor-external sphincter dyssynergia in men with multiple sclerosis: an ominous urologic condition. J. Urol., 131: 91, 1984. 7. Kornhuber, H. H. and Schulz, A.: Efficient treatment of neurogenic bladder disorders in multiple sclerosis with initial intermittent catheterization and ultrasound-controlled training. Eur. Neurol., 30: 260, 1990.
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ROLE OF LIMITED EVALUATION AND MEDICAL MANAGEMENT IN MULTIPLE SCLEROSIS
8. Lapides, J., Diokno, A. C., Silber, S. J. and Lowe, B. S.: Clean, intermittent self-catheterization in the treatment of urinary tract disease. J. Urol., 107: 458, 1972. 9. Abrams, P., Blaivas, J. G., Stanton, S. L. and Anderson, J. T.: The standardisation of terminology of lower urinary tract function. The International Continence Society Committee on Standardization of Terminology. Scand. J. Urol. Nephrol., suppl., 114: 5, 1988. 10. Toppercer, A. and Tetreault, J. P.: Compliance of the bladder: an attempt to establish normal values. Urology, 14: 204, 1979. 11. Wheeler, J. S., Jr., Siroky, M. B., Pavlakis, A. J., Goldstein, I. and Krane, R. J.: The changing neurourologic pattern of multiple sclerosis. J. Urol., 130: 1123, 1983.
12. Dula, E. and Leach, G. E.: Role of urologist in the diagnosis of multiple sclerosis. Urology, 37: 311, 1991. 13. Sirls, L., Weese, D., Zimmern, P., Roskamp, D., Ganabathi, K. and Leach, G.: Intravesical oxybutynin for refractory detrusor over activity (abstract). Presented at annual meeting of Urodynamics Society, San Antonio, Texas, 1993. 14. Anderson, R. U.: Urodynamic patterns after acute spinal cord injury: association with bladder trabeculation in male patients. J. Urol., 129: 777, 1983. 15. Staskin, D. R.: Hydroureteronephrosis after spinal cord injury. Effects of lower urinary tract dysfunction on upper tract anatomy. Urol. Clin. N. Amer., 18: 309, 1991.