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Striated urethral sphincter activity does not alter urethral pressure during filling cystometry
American Journal of Obstetrics and Gynecology (2005) 192, 55e9
www.ajog.org
Striated urethral sphincter activity does not alter urethral pressure during filling cystometry Kimberly Kenton, MD, Mary P. Fitzgerald, MD, Linda Brubaker, MD Loyola University Medical Center, Maywood, Ill Received for publication February 9, 2004; revised July 14, 2004
KEY WORDS Striated urethral sphincter activity Urethral pressure
Objective: The purpose of this study was to determine the relationship between urethral pressure and the neuromuscular activity of the urethral sphincter with the use of quantitative electromyography during bladder filling. Study design: Women who underwent multichannel urodynamic testing with concentric needle electromyography of the striated urethral sphincter between December 2000 and February 2002 were studied. Raw electromyography signals were processed by a electromyography instrument that was equipped with automated motor unit analysis software programs. Quantitative electromyography software was used to analyze the electrical activity of the urethral sphincter during filling cystometry. Results: One hundred women (mean age, 60 years [range, 22-82 years]; median parity, 3 children [range, 0-8 children]) were studied. Most women (79%) were postmenopausal, and 68% of those women were receiving hormone replacement therapy. Quantitative electromyography values increased significantly at 300 mL and maximum cystometric capacity; however, there was no significant increase in urethral pressure. The median change in urethral pressure at 300 mL and maximum cystometric capacity were 4 cm water (interquartile range, 0-8 cm) and 0 cm water (interquartile range, ÿ4-8 cm), respectively (P =.229). The median change in quantitative electromyography at 300 mL and maximum cystometric capacity were 9 mV (range, 5-14 mV) and 10 mV (range, 7-19 mV), respectively (P ! .0005). There was no correlation between change in urethral pressure and motor unit activation on quantitative electromyography at 300 mL or maximum cystometric capacity. Fifty-six women had no change or a decreased urethral pressure at maximum cystometric capacity, yet all but 1 of these women had increased motor unit activation on quantitative electromyography. Conclusion: Urethral pressure does not increase during filling cystometry, despite increased activity of the striated urethral sphincter, which suggests that urethral pressure change does not reflect the integrity of the striated urethral sphincter. Ó 2005 Elsevier Inc. All rights reserved.
The urethral sphincter is important in maintaining urinary continence, but its neuromuscular function
Reprints not available from the authors. 0002-9378/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.07.016
remains poorly understood. The urethra is composed of striated and smooth muscles, which are innervated by somatic and autonomic nerves, respectively.1 The striated urethral sphincter is composed of 3 separate muscles that function together as a single continence
56
Kenton, Fitzgerald, and Brubaker Table I
Urodynamic and electromyographic parameters
Parameter Baseline Urethral pressure (cm water) Quantitative electromyography (mV) Maximum Cystometric capacity (mL) Urethral closure pressure (cm water) Quantitative electromyography (mV)
Figure 1 Percentage of subjects with different urodynamic diagnoses are displayed.
unit.2 These muscles are comprised mostly of slow twitch fibers (type I), with an approximate concentration of 35% fast twitch fibers (type II).3 This design allows the urethra to respond to pressure increases during bladder filling and to contract quickly in times of increased intra-abdominal pressure.4 During urinary storage, bladder distention produces low-level afferent input from sensory neurons, which activate urethral motor nuclei in Onuf’s nucleus and increase striated urethral sphincter firing. Norepinephrine and serotonin are the primary ganglionic neurotransmitters.5,6 Contraction of the striated urethral sphincter activates afferent fibers that inhibit bladder activity. Abnormalities in striated urethral sphincter activity have been implicated in stress urinary incontinence.7 Urethral pressure measurements reflect various anatomic components of the urethra, which include the striated sphincter, smooth muscle, fibroelastic tissue, and vascular plexus.8 Urethral pressure measurements have been used to predict urethral function and surgical outcomes.8,9 A linear relationship exists between maximal urethral closure pressure and both the striated muscle and the smooth muscle in the urethra.10 The correlation between urethral closure pressures and the thickness of the striated and smooth muscle components of the urethral sphincter support the fact that urethral pressure measurements alone may reflect incompletely the striated urethral sphincter integrity.11 Electromyography is the gold standard for the determination of neuromuscular function because it most accurately reflects the integrity of the nerve and muscle under study. Quantitative electromyography allows the amount of neural activity to be recorded directly and quantified and is being used increasingly to study neuromuscular activity of the pelvic floor.7,12 Previous studies demonstrated that urethral sphincter quantitative electromyography better predicted the outcome of
Median (25th-75th quartile range) 54 (27-94) 8 (6-14) 500 (400-600) 51 (28-92) 19 (14-31)
incontinence surgery than maximum urethral closure measurements.13 The aim of this study was to determine the relationship between urethral pressure measurements on multichannel urodynamics and the activity of the striated urethral sphincter with quantitative electromyography during filling cystometry.
Material and methods After institutional review board approval was obtained, the women who underwent multichannel urodynamic testing with concentric needle electromyography of the striated urethral sphincter between December 2000 and February 2002 were studied. Consecutive women were included who had interpretable urodynamic and electromyographic data. Standardized urodynamic assessment was performed with the use of a multichannel urodynamic instrument (model 1106; Life-Tech, Inc, Houston, Tex) and included retrograde water cystometry at a fill rate of 80 mL/min and static urethral pressure profilometry. Cystometry was performed with the subject in a birthing chair that was reclined at 45 degrees. An 8F catheter was placed in the subject’s vagina or rectum to record abdominal pressure. An 8F dual micro-tipped catheter with infusion port (Millar Instruments, Houston, Tex) was placed with the distal transducer in the bladder and the proximal transducer was placed in the mid urethra facing the 9-o’clock position to record vesical pressure and urethral pressure, respectively. True detrusor pressure and urethral closure pressure were subtracted electronically and recorded throughout the study. Stage II or greater prolapse was reduced during filling cystometry and urethral profilometry with the examiner’s hand. Maximum urethral closure pressures were obtained at maximum cystometric capacity (MCC) with a profilometer that was set at a withdrawal rate of 1 mm per second. Urodynamic and pelvic organ prolapse quantification methods, definitions, and units conformed to the standards that are recommended by the International Continence Society,14 which include the use of the Pelvic Organ Prolapse Quantification (POP-Q) System.15
Kenton, Fitzgerald, and Brubaker
57
Table II
Urethral pressure and electromyography differences in women before and after menopause
Variable
Before menopause (n = 21)*
After menopause (n = 79)*
P value (Mann-Whitney test)
96 (55-113) 10 (7-17)
47 (23-75) 8 (5-11)
! .0005 .040
98 (65-113) 26 (18-37)
46 (25-80) 18 (14-29)
! .0005 .032
Baseline Urethral pressure (cm water) Quantitative electromyography (mV) Maximum Urethral pressure (cm water) Quantitative electromyography (mV)
* Data are given as median (25th-75th interquartile range).
Urethral sphincter electromyography was performed routinely on all subjects during filling cystometry in our unit. A disposable 30-gauge, 1-inch concentric needle electrode (Medelec, Surrey, UK) was inserted into the striated urethral sphincter at the 12-o’clock position, 5 mm from the external urethral meatus. The raw electromyographic signal was processed by an electromyographic instrument (Viking IVp; Nicolet Instrument Corporation, Madison, Wis) that was equipped with automated motor unit analysis software programs. Data were recorded during the filling phase after audio and oscilloscopic findings established the correct needle placement. Quantitative maximum voluntary activity software was used to quantify the electrical activity of the striated urethral sphincter with the mean rectified voltage. Mean rectified voltage is the mean amplitude calculated over a 5-second period of tracing after the waveform has been made positive. Urethral closure pressures and quantitative electromyography values were measured at baseline and at 100-mL increments during filling cystometry. Urethral closure pressure changes from baseline to 300 mL and baseline to MCC were compared with changes in urethral sphincter quantitative electromyography values. Differences in urethral pressure and quantitative electromyography values in women before and after menopause were also investigated. Data was analyzed retrospectively with SPSS software (SPSS Inc, Chicago, Ill). Urethral pressure and quantitative electromyography changes during filling cystometry were analyzed using the Sign test. Spearman correlations were used to investigate the relationship between urethral pressure and quantitative electromyography values at 300 mL and MCC. The Mann Whitney test was used to compare urethral pressure and electromyography data in women before and after menopause.
Results One hundred women with a mean age of 60 years (range, 22-82 years) and a median vaginal parity of 3 children (range, 0-8 children) were studied. Ninety-one percent of
the women were white; 6% of the women were Hispanic, and 3% of the women were black. Most of the women (79%) were postmenopausal, and 68% of those women were receiving hormone replacement therapy. Figure 1 shows the urodynamic diagnoses of the women. Thirtynine percent of the women had advanced stage III or IV prolapse; 36% of the women had stage II prolapse, and 25% of the women had stage 0 or I prolapse. Urodynamic and electromyography parameters at baseline and MCC are displayed in Table I. Quantitative electromyography values increased significantly during bladder filling (P !.005). The change in quantitative electromyography from baseline to 300 mL and baseline to MCC were 9 mV (interquartile range, 5-14 mV) and 10 mV (interquartile range, 7-19 mV), respectively. However, there was no significant increase in urethral pressure during filling (P =.229). The change in urethral pressure from baseline to 300 mL and baseline for MCC were 4 cm water (range, 0-8 cm water) and 0 cm water (range, ÿ4 to 8), respectively. There was no significant correlation between the change in urethral pressure on urodynamics and motor unit activation on quantitative electromyography at 300 mL or MCC (Spearman’s r = ÿ0.027 and P =.794 and Spearman’s r = ÿ0.170 and P =.094, respectively). Fifty-six women had no change or a decrease in urethral pressure at MCC, yet all but 1 of these women had increased motor unit activation on quantitative electromyography. Premenopausal women had significantly higher urethral pressures and quantitative electromyography values at baseline and MCC than postmenopausal women (Table II). Hormone replacement therapy did not affect this difference.
Comment Our findings suggest that the activation of the striated urethral sphincter during bladder filling is not reflected in urethral pressure measurements in incontinent women. Urethral pressure measurements likely reflect multiple components of urethral function and may not be sensitive enough to detect neuromuscular changes in the striated urethral sphincter. Pressure measurements
58 have been used for decades in an attempt to quantify urethral function in women with stress incontinence to predict disease severity and surgical outcome. Our data suggest that urethral pressure measurements alone may not provide sufficient evidence of neural injury to the striated urethral sphincter, although electromyography is more sensitive to neuropathic changes. More than one half of the women in this study demonstrated no change or a decrease in urethral closure pressure during filling cystometry. This could be due to a physiologic decrease in urethral activity at MCC in women with poor urethral function; however, all but 1 of the women had a significant increase in quantitative electromyography activity in the striated urethral sphincter, which further suggests that urethral pressure measurements do not reflect neuromuscular activity adequately. The failure of standardized urethral pressure measurements to detect changes in sphincter activity may be due to poor sensitivity of the test or to catheter artifact/movement. Regardless, electromyography seems to be superior to urethral pressure measurements for the determination of striated urethral sphincter activity. Consistent with what previous authors have found, urethral pressure measurements in this study were significantly lower in postmenopausal women.16-18 Quantitative electromyography values were also significantly lower in postmenopausal study subjects, although the difference was less pronounced. Pandit et al19 and Perucchini et al20,21 have shown that the number and density of striated urethral sphincter nerve and muscle fibers decreases with age. This absolute decline in nerve and muscle with age likely contributes to the differences between the women who were pre- and post-menopausal in this study. Postmenopausal women receiving hormone replacement therapy still had significantly lower urethral pressures and quantitative electromyography values, which suggests that age rather than the presence of estrogen may be responsible for these changes. Estrogen has been shown to exert a neuroprotective effect in the central nervous system in multiple studies, although the mechanism of the effect is unknown.22 The potential neuroprotective effect of estrogen on pudendal motor neurons warrants further investigation. Although no obvious effect of estrogen was found in this study, our observations are limited by the unknown time and duration of estrogen exposure in our study population. It may be that increased estrogen exposure must be present at the time of immediate nerve injury (eg, childbirth), that it needs to be on-going, or that effects of aging on nerve function cannot be halted with endogenous estrogen exposure. The importance of the striated urethral sphincter in maintaining urinary continence has been well established. Authors have demonstrated that the striated urethral sphincter plays a crucial role in urethral closure
Kenton, Fitzgerald, and Brubaker function and that urethral smooth muscle minimally contributes to the generation of resting urethral pressure.23 Additional studies have demonstrated electromyography changes in the striated urethral sphincter consistent with advanced neuropathy in women who undergo unsuccessful surgery for stress incontinence.7,24 More recently, pharmacotherapy has been introduced to increase striated urethral sphincter activity in women with stress incontinence. A selective norepinephrine and serotonin re-uptake inhibitor, duloxetine hydrochloride, has been used in animal studies to increase striated sphincter activity through centrally mediated modulation of afferent and efferent output to the striated urethral sphincter.5 Follow-up studies in humans (phase II and III trials) demonstrated the efficacy of duloxetine in the treatment of stress incontinence in women,25 hypothesizing that the treatment is due to increased striated sphincter activity that is mediated by pudendal motor neurons in Onuf’s nucleus. This plausible mechanism of action requires confirmation in human subjects. Future studies should focus on the sensitive electrodiagnostic evaluation of urethral sphincter neuromuscular function to better understand the role of this muscle in stress incontinence. This understanding will aid in the prevention and treatment of this common disorder, which has a dramatic impact on the quality of life of millions of women.
References 1. de Groat WC, Booth AM, Yoshimura N. Neurophysiology of micturition and its modification in animal models of human disease. In: Maggi CA, editor. The autonomic nervous system. London: Harwood Academic; 1993. p. 227-89. 2. Oelrich TM. The striated urogenital sphincter muscle in the female. Anat Rec 1983;205:223-32. 3. Hale DS, Benson JT, Brubaker L, Heidkamp MC, Russell B. Histologic analysis of needle biopsy of urethral sphincter from women with normal and stress incontinence with comparison of electromyographic findings. Am J Obstet Gynecol 1999;180: 342-8. 4. Gosling J. The structure of the bladder and urethra in relation to function. Urol Clin North Am 1979;6:31-8. 5. Thor KB, Katofiasc MA. Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neural control of lower urinary tract function in the chloralose-anesthetized female cat. J Pharmacol Exp Ther 1995;274:1014-24. 6. Thor KB. Serotonin and norepinephrine involvement in efferent pathways to the urethral rhabdosphincter: implications for treating stress urinary incontinence. Urology 2003;62(suppl):3-9. 7. Kenton K, Fitzgerald MP, Shott S, Brubaker L. Role of urethral electromyography in predicting outcome of Burch retropubic urethropexy. Am J Obstet Gynecol 2001;185:51-5. 8. Constantinou CE. Resting and stress urethral pressures as a clinical guide to the mechanism of continence in the female patient. Urol Clin North Am 1985;12:247-58. 9. Bowen LW, Sand PK, Ostergard DR, Franti CE. Unsuccessful Burch retropubic urethropexy: a case-controlled urodynamic study. Am J Obestet Gynecol 1989;160:452-8.
Kenton, Fitzgerald, and Brubaker 10. Heit M. Intraurethral ultrasonography: correlation of urethral anatomy with functional urodynamic parameters in stress incontinent women. Int Urogynecol J 2000;11:204-11. 11. Lose G, Tanko A, Colstrup H, Andersen JT. Urethral sphincter electromyography with vaginal surface electrodes: a comparison with sphincter electromyography recorded via periurethral coaxial, anal sphincter needle and perianal surface electrodes. J Urol 1985;133:815-8. 12. Weidner AC, Sanders DB, Nandedkar SD, Bump RC. Quantitative electromyographic analysis of levator ani and external anal sphincter muscles of nulliparous women. Am J Obstet Gynecol 2000;183:1249-56. 13. Kenton K, Oldham L, Brubaker L. Open Burch urethropexy has a low rate of peri-operative complications. Obstet Gynecol [in press]. 14. Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-Committee of the International Continence Society. Neurourol Urodyn 2002;21:16778. 15. Bump RC, Mattiasson A, Bo K, Brubaker LP, DeLancey JO, Klarskov P, et al. The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 1996;175:10-7. 16. Henriksson L, Andersson KE, Ulmsten U. The urethral pressure profiles in continent and stress-incontinent women. Scand J Urol Nephrol 1979;13:5-10. 17. Obrink A, Bunne G, Ulmsten U. Intra-urethral and intra-vesical pressure in continent women. Acta Obstet Gynecol Scand 1977;56:525-9.
59 18. Rud T. Urethral pressure profile in continent women from childhood to old age. Acta Obstet Gynecol Scand 1980;59:331-5. 19. Pandit M, DeLancey JO, Ashton-Miller JA, Iyengar J, Blaivas M, Perucchini D. Quantification of intramuscular nerves within the female striated urogenital sphincter muscle. Obstet Gynecol 2000;95:797-800. 20. Perucchini D, DeLancey JO, Ashton-Miller JA, Galecki A, Schaer GN. Age effects on urethral striated muscle: II, anatomic location of muscle loss. Am J Obstet Gynecol 2002; 186:35660. 21. Perucchini D, DeLancey JO, Ashton-Miller JA, Peschers D, Kataria T. Age effects on urethral striated muscle: I, changes in number and diameter of striated muscle fibers in the ventral urethra. Am J Obstet Gynecol 2002;186:351-5. 22. Islamov RR, Hendricks WA, Katwa LC, McMurray RJ, Pak ES, Spanier NS, et al. Effect of 17 beta-estradiol on gene expression in lumbar spinal cord following sciatic nerve crush injury in ovariectomized mice. Brain Res 2003;966:65-75. 23. Thind P. The significance of smooth and striated muscles in the sphincter function of the urethra in healthy women. Neurourol Urodyn 1995;14:585-618. 24. Fisher JR, Benson JT. The use of urethral electrodiagnosis to select the method of surgery in women with intrinsic sphincter deficiency [abstract]. Int Urogynecol 2001;12(suppl):51. 25. Norton PA, Zinner NR, Yalcin I, Bump RC. Duloxetine versus placebo in the treatment of stress urinary incontinence. Am J Obstet Gynecol 2002;187:40-8.
www.ajog.org
Striated urethral sphincter activity does not alter urethral pressure during filling cystometry Kimberly Kenton, MD, Mary P. Fitzgerald, MD, Linda Brubaker, MD Loyola University Medical Center, Maywood, Ill Received for publication February 9, 2004; revised July 14, 2004
KEY WORDS Striated urethral sphincter activity Urethral pressure
Objective: The purpose of this study was to determine the relationship between urethral pressure and the neuromuscular activity of the urethral sphincter with the use of quantitative electromyography during bladder filling. Study design: Women who underwent multichannel urodynamic testing with concentric needle electromyography of the striated urethral sphincter between December 2000 and February 2002 were studied. Raw electromyography signals were processed by a electromyography instrument that was equipped with automated motor unit analysis software programs. Quantitative electromyography software was used to analyze the electrical activity of the urethral sphincter during filling cystometry. Results: One hundred women (mean age, 60 years [range, 22-82 years]; median parity, 3 children [range, 0-8 children]) were studied. Most women (79%) were postmenopausal, and 68% of those women were receiving hormone replacement therapy. Quantitative electromyography values increased significantly at 300 mL and maximum cystometric capacity; however, there was no significant increase in urethral pressure. The median change in urethral pressure at 300 mL and maximum cystometric capacity were 4 cm water (interquartile range, 0-8 cm) and 0 cm water (interquartile range, ÿ4-8 cm), respectively (P =.229). The median change in quantitative electromyography at 300 mL and maximum cystometric capacity were 9 mV (range, 5-14 mV) and 10 mV (range, 7-19 mV), respectively (P ! .0005). There was no correlation between change in urethral pressure and motor unit activation on quantitative electromyography at 300 mL or maximum cystometric capacity. Fifty-six women had no change or a decreased urethral pressure at maximum cystometric capacity, yet all but 1 of these women had increased motor unit activation on quantitative electromyography. Conclusion: Urethral pressure does not increase during filling cystometry, despite increased activity of the striated urethral sphincter, which suggests that urethral pressure change does not reflect the integrity of the striated urethral sphincter. Ó 2005 Elsevier Inc. All rights reserved.
The urethral sphincter is important in maintaining urinary continence, but its neuromuscular function
Reprints not available from the authors. 0002-9378/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.07.016
remains poorly understood. The urethra is composed of striated and smooth muscles, which are innervated by somatic and autonomic nerves, respectively.1 The striated urethral sphincter is composed of 3 separate muscles that function together as a single continence
56
Kenton, Fitzgerald, and Brubaker Table I
Urodynamic and electromyographic parameters
Parameter Baseline Urethral pressure (cm water) Quantitative electromyography (mV) Maximum Cystometric capacity (mL) Urethral closure pressure (cm water) Quantitative electromyography (mV)
Figure 1 Percentage of subjects with different urodynamic diagnoses are displayed.
unit.2 These muscles are comprised mostly of slow twitch fibers (type I), with an approximate concentration of 35% fast twitch fibers (type II).3 This design allows the urethra to respond to pressure increases during bladder filling and to contract quickly in times of increased intra-abdominal pressure.4 During urinary storage, bladder distention produces low-level afferent input from sensory neurons, which activate urethral motor nuclei in Onuf’s nucleus and increase striated urethral sphincter firing. Norepinephrine and serotonin are the primary ganglionic neurotransmitters.5,6 Contraction of the striated urethral sphincter activates afferent fibers that inhibit bladder activity. Abnormalities in striated urethral sphincter activity have been implicated in stress urinary incontinence.7 Urethral pressure measurements reflect various anatomic components of the urethra, which include the striated sphincter, smooth muscle, fibroelastic tissue, and vascular plexus.8 Urethral pressure measurements have been used to predict urethral function and surgical outcomes.8,9 A linear relationship exists between maximal urethral closure pressure and both the striated muscle and the smooth muscle in the urethra.10 The correlation between urethral closure pressures and the thickness of the striated and smooth muscle components of the urethral sphincter support the fact that urethral pressure measurements alone may reflect incompletely the striated urethral sphincter integrity.11 Electromyography is the gold standard for the determination of neuromuscular function because it most accurately reflects the integrity of the nerve and muscle under study. Quantitative electromyography allows the amount of neural activity to be recorded directly and quantified and is being used increasingly to study neuromuscular activity of the pelvic floor.7,12 Previous studies demonstrated that urethral sphincter quantitative electromyography better predicted the outcome of
Median (25th-75th quartile range) 54 (27-94) 8 (6-14) 500 (400-600) 51 (28-92) 19 (14-31)
incontinence surgery than maximum urethral closure measurements.13 The aim of this study was to determine the relationship between urethral pressure measurements on multichannel urodynamics and the activity of the striated urethral sphincter with quantitative electromyography during filling cystometry.
Material and methods After institutional review board approval was obtained, the women who underwent multichannel urodynamic testing with concentric needle electromyography of the striated urethral sphincter between December 2000 and February 2002 were studied. Consecutive women were included who had interpretable urodynamic and electromyographic data. Standardized urodynamic assessment was performed with the use of a multichannel urodynamic instrument (model 1106; Life-Tech, Inc, Houston, Tex) and included retrograde water cystometry at a fill rate of 80 mL/min and static urethral pressure profilometry. Cystometry was performed with the subject in a birthing chair that was reclined at 45 degrees. An 8F catheter was placed in the subject’s vagina or rectum to record abdominal pressure. An 8F dual micro-tipped catheter with infusion port (Millar Instruments, Houston, Tex) was placed with the distal transducer in the bladder and the proximal transducer was placed in the mid urethra facing the 9-o’clock position to record vesical pressure and urethral pressure, respectively. True detrusor pressure and urethral closure pressure were subtracted electronically and recorded throughout the study. Stage II or greater prolapse was reduced during filling cystometry and urethral profilometry with the examiner’s hand. Maximum urethral closure pressures were obtained at maximum cystometric capacity (MCC) with a profilometer that was set at a withdrawal rate of 1 mm per second. Urodynamic and pelvic organ prolapse quantification methods, definitions, and units conformed to the standards that are recommended by the International Continence Society,14 which include the use of the Pelvic Organ Prolapse Quantification (POP-Q) System.15
Kenton, Fitzgerald, and Brubaker
57
Table II
Urethral pressure and electromyography differences in women before and after menopause
Variable
Before menopause (n = 21)*
After menopause (n = 79)*
P value (Mann-Whitney test)
96 (55-113) 10 (7-17)
47 (23-75) 8 (5-11)
! .0005 .040
98 (65-113) 26 (18-37)
46 (25-80) 18 (14-29)
! .0005 .032
Baseline Urethral pressure (cm water) Quantitative electromyography (mV) Maximum Urethral pressure (cm water) Quantitative electromyography (mV)
* Data are given as median (25th-75th interquartile range).
Urethral sphincter electromyography was performed routinely on all subjects during filling cystometry in our unit. A disposable 30-gauge, 1-inch concentric needle electrode (Medelec, Surrey, UK) was inserted into the striated urethral sphincter at the 12-o’clock position, 5 mm from the external urethral meatus. The raw electromyographic signal was processed by an electromyographic instrument (Viking IVp; Nicolet Instrument Corporation, Madison, Wis) that was equipped with automated motor unit analysis software programs. Data were recorded during the filling phase after audio and oscilloscopic findings established the correct needle placement. Quantitative maximum voluntary activity software was used to quantify the electrical activity of the striated urethral sphincter with the mean rectified voltage. Mean rectified voltage is the mean amplitude calculated over a 5-second period of tracing after the waveform has been made positive. Urethral closure pressures and quantitative electromyography values were measured at baseline and at 100-mL increments during filling cystometry. Urethral closure pressure changes from baseline to 300 mL and baseline to MCC were compared with changes in urethral sphincter quantitative electromyography values. Differences in urethral pressure and quantitative electromyography values in women before and after menopause were also investigated. Data was analyzed retrospectively with SPSS software (SPSS Inc, Chicago, Ill). Urethral pressure and quantitative electromyography changes during filling cystometry were analyzed using the Sign test. Spearman correlations were used to investigate the relationship between urethral pressure and quantitative electromyography values at 300 mL and MCC. The Mann Whitney test was used to compare urethral pressure and electromyography data in women before and after menopause.
Results One hundred women with a mean age of 60 years (range, 22-82 years) and a median vaginal parity of 3 children (range, 0-8 children) were studied. Ninety-one percent of
the women were white; 6% of the women were Hispanic, and 3% of the women were black. Most of the women (79%) were postmenopausal, and 68% of those women were receiving hormone replacement therapy. Figure 1 shows the urodynamic diagnoses of the women. Thirtynine percent of the women had advanced stage III or IV prolapse; 36% of the women had stage II prolapse, and 25% of the women had stage 0 or I prolapse. Urodynamic and electromyography parameters at baseline and MCC are displayed in Table I. Quantitative electromyography values increased significantly during bladder filling (P !.005). The change in quantitative electromyography from baseline to 300 mL and baseline to MCC were 9 mV (interquartile range, 5-14 mV) and 10 mV (interquartile range, 7-19 mV), respectively. However, there was no significant increase in urethral pressure during filling (P =.229). The change in urethral pressure from baseline to 300 mL and baseline for MCC were 4 cm water (range, 0-8 cm water) and 0 cm water (range, ÿ4 to 8), respectively. There was no significant correlation between the change in urethral pressure on urodynamics and motor unit activation on quantitative electromyography at 300 mL or MCC (Spearman’s r = ÿ0.027 and P =.794 and Spearman’s r = ÿ0.170 and P =.094, respectively). Fifty-six women had no change or a decrease in urethral pressure at MCC, yet all but 1 of these women had increased motor unit activation on quantitative electromyography. Premenopausal women had significantly higher urethral pressures and quantitative electromyography values at baseline and MCC than postmenopausal women (Table II). Hormone replacement therapy did not affect this difference.
Comment Our findings suggest that the activation of the striated urethral sphincter during bladder filling is not reflected in urethral pressure measurements in incontinent women. Urethral pressure measurements likely reflect multiple components of urethral function and may not be sensitive enough to detect neuromuscular changes in the striated urethral sphincter. Pressure measurements
58 have been used for decades in an attempt to quantify urethral function in women with stress incontinence to predict disease severity and surgical outcome. Our data suggest that urethral pressure measurements alone may not provide sufficient evidence of neural injury to the striated urethral sphincter, although electromyography is more sensitive to neuropathic changes. More than one half of the women in this study demonstrated no change or a decrease in urethral closure pressure during filling cystometry. This could be due to a physiologic decrease in urethral activity at MCC in women with poor urethral function; however, all but 1 of the women had a significant increase in quantitative electromyography activity in the striated urethral sphincter, which further suggests that urethral pressure measurements do not reflect neuromuscular activity adequately. The failure of standardized urethral pressure measurements to detect changes in sphincter activity may be due to poor sensitivity of the test or to catheter artifact/movement. Regardless, electromyography seems to be superior to urethral pressure measurements for the determination of striated urethral sphincter activity. Consistent with what previous authors have found, urethral pressure measurements in this study were significantly lower in postmenopausal women.16-18 Quantitative electromyography values were also significantly lower in postmenopausal study subjects, although the difference was less pronounced. Pandit et al19 and Perucchini et al20,21 have shown that the number and density of striated urethral sphincter nerve and muscle fibers decreases with age. This absolute decline in nerve and muscle with age likely contributes to the differences between the women who were pre- and post-menopausal in this study. Postmenopausal women receiving hormone replacement therapy still had significantly lower urethral pressures and quantitative electromyography values, which suggests that age rather than the presence of estrogen may be responsible for these changes. Estrogen has been shown to exert a neuroprotective effect in the central nervous system in multiple studies, although the mechanism of the effect is unknown.22 The potential neuroprotective effect of estrogen on pudendal motor neurons warrants further investigation. Although no obvious effect of estrogen was found in this study, our observations are limited by the unknown time and duration of estrogen exposure in our study population. It may be that increased estrogen exposure must be present at the time of immediate nerve injury (eg, childbirth), that it needs to be on-going, or that effects of aging on nerve function cannot be halted with endogenous estrogen exposure. The importance of the striated urethral sphincter in maintaining urinary continence has been well established. Authors have demonstrated that the striated urethral sphincter plays a crucial role in urethral closure
Kenton, Fitzgerald, and Brubaker function and that urethral smooth muscle minimally contributes to the generation of resting urethral pressure.23 Additional studies have demonstrated electromyography changes in the striated urethral sphincter consistent with advanced neuropathy in women who undergo unsuccessful surgery for stress incontinence.7,24 More recently, pharmacotherapy has been introduced to increase striated urethral sphincter activity in women with stress incontinence. A selective norepinephrine and serotonin re-uptake inhibitor, duloxetine hydrochloride, has been used in animal studies to increase striated sphincter activity through centrally mediated modulation of afferent and efferent output to the striated urethral sphincter.5 Follow-up studies in humans (phase II and III trials) demonstrated the efficacy of duloxetine in the treatment of stress incontinence in women,25 hypothesizing that the treatment is due to increased striated sphincter activity that is mediated by pudendal motor neurons in Onuf’s nucleus. This plausible mechanism of action requires confirmation in human subjects. Future studies should focus on the sensitive electrodiagnostic evaluation of urethral sphincter neuromuscular function to better understand the role of this muscle in stress incontinence. This understanding will aid in the prevention and treatment of this common disorder, which has a dramatic impact on the quality of life of millions of women.
References 1. de Groat WC, Booth AM, Yoshimura N. Neurophysiology of micturition and its modification in animal models of human disease. In: Maggi CA, editor. The autonomic nervous system. London: Harwood Academic; 1993. p. 227-89. 2. Oelrich TM. The striated urogenital sphincter muscle in the female. Anat Rec 1983;205:223-32. 3. Hale DS, Benson JT, Brubaker L, Heidkamp MC, Russell B. Histologic analysis of needle biopsy of urethral sphincter from women with normal and stress incontinence with comparison of electromyographic findings. Am J Obstet Gynecol 1999;180: 342-8. 4. Gosling J. The structure of the bladder and urethra in relation to function. Urol Clin North Am 1979;6:31-8. 5. Thor KB, Katofiasc MA. Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neural control of lower urinary tract function in the chloralose-anesthetized female cat. J Pharmacol Exp Ther 1995;274:1014-24. 6. Thor KB. Serotonin and norepinephrine involvement in efferent pathways to the urethral rhabdosphincter: implications for treating stress urinary incontinence. Urology 2003;62(suppl):3-9. 7. Kenton K, Fitzgerald MP, Shott S, Brubaker L. Role of urethral electromyography in predicting outcome of Burch retropubic urethropexy. Am J Obstet Gynecol 2001;185:51-5. 8. Constantinou CE. Resting and stress urethral pressures as a clinical guide to the mechanism of continence in the female patient. Urol Clin North Am 1985;12:247-58. 9. Bowen LW, Sand PK, Ostergard DR, Franti CE. Unsuccessful Burch retropubic urethropexy: a case-controlled urodynamic study. Am J Obestet Gynecol 1989;160:452-8.
Kenton, Fitzgerald, and Brubaker 10. Heit M. Intraurethral ultrasonography: correlation of urethral anatomy with functional urodynamic parameters in stress incontinent women. Int Urogynecol J 2000;11:204-11. 11. Lose G, Tanko A, Colstrup H, Andersen JT. Urethral sphincter electromyography with vaginal surface electrodes: a comparison with sphincter electromyography recorded via periurethral coaxial, anal sphincter needle and perianal surface electrodes. J Urol 1985;133:815-8. 12. Weidner AC, Sanders DB, Nandedkar SD, Bump RC. Quantitative electromyographic analysis of levator ani and external anal sphincter muscles of nulliparous women. Am J Obstet Gynecol 2000;183:1249-56. 13. Kenton K, Oldham L, Brubaker L. Open Burch urethropexy has a low rate of peri-operative complications. Obstet Gynecol [in press]. 14. Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-Committee of the International Continence Society. Neurourol Urodyn 2002;21:16778. 15. Bump RC, Mattiasson A, Bo K, Brubaker LP, DeLancey JO, Klarskov P, et al. The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 1996;175:10-7. 16. Henriksson L, Andersson KE, Ulmsten U. The urethral pressure profiles in continent and stress-incontinent women. Scand J Urol Nephrol 1979;13:5-10. 17. Obrink A, Bunne G, Ulmsten U. Intra-urethral and intra-vesical pressure in continent women. Acta Obstet Gynecol Scand 1977;56:525-9.
59 18. Rud T. Urethral pressure profile in continent women from childhood to old age. Acta Obstet Gynecol Scand 1980;59:331-5. 19. Pandit M, DeLancey JO, Ashton-Miller JA, Iyengar J, Blaivas M, Perucchini D. Quantification of intramuscular nerves within the female striated urogenital sphincter muscle. Obstet Gynecol 2000;95:797-800. 20. Perucchini D, DeLancey JO, Ashton-Miller JA, Galecki A, Schaer GN. Age effects on urethral striated muscle: II, anatomic location of muscle loss. Am J Obstet Gynecol 2002; 186:35660. 21. Perucchini D, DeLancey JO, Ashton-Miller JA, Peschers D, Kataria T. Age effects on urethral striated muscle: I, changes in number and diameter of striated muscle fibers in the ventral urethra. Am J Obstet Gynecol 2002;186:351-5. 22. Islamov RR, Hendricks WA, Katwa LC, McMurray RJ, Pak ES, Spanier NS, et al. Effect of 17 beta-estradiol on gene expression in lumbar spinal cord following sciatic nerve crush injury in ovariectomized mice. Brain Res 2003;966:65-75. 23. Thind P. The significance of smooth and striated muscles in the sphincter function of the urethra in healthy women. Neurourol Urodyn 1995;14:585-618. 24. Fisher JR, Benson JT. The use of urethral electrodiagnosis to select the method of surgery in women with intrinsic sphincter deficiency [abstract]. Int Urogynecol 2001;12(suppl):51. 25. Norton PA, Zinner NR, Yalcin I, Bump RC. Duloxetine versus placebo in the treatment of stress urinary incontinence. Am J Obstet Gynecol 2002;187:40-8.