Combined Cystometrography and Electromyography of the External Urethral Sphincter Following Complete Primary Repair of Bladder Exstrophy Joseph G. Borer,* Ruth Strakosha, Stuart B. Bauer, David A. Diamond, Melanie Pennison, Ilina Rosoklija and Shahram Khoshbin From the Departments of Urology, Boston Children’s Hospital and Brigham and Women’s Hospital (SK), Boston, Massachusetts
Purpose: Concern in patients with bladder exstrophy after reconstruction regarding potential injury to pelvic neurourological anatomy and a resultant functional deficit prompted combined (simultaneous) cystometrography and electromyography after complete primary repair of bladder exstrophy. We determined whether complete primary repair of bladder exstrophy would adversely affect the innervation controlling bladder and external urethral sphincter function. Materials and Methods: Complete primary repair of bladder exstrophy was performed via a modified Mitchell technique in newborns without osteotomy. Postoperative evaluation included combined cystometrography and needle electrode electromyography via the perineum, approximating the external urethral sphincter muscle complex. Electromyography was done to evaluate the external urethral sphincter response to sacral reflex stimulation and during voiding. Results: Nine boys and 4 girls underwent combined cystometrography/electromyography after complete primary repair of bladder exstrophy. Age at study and time after complete primary repair of bladder exstrophy was 3 months to 10 years (median 11.5 months). Cystometrography revealed absent detrusor overactivity and the presence of a sustained detrusor voiding contraction in all cases. Electromyography showed universally normal individual motor unit action potentials of biphasic pattern, amplitude and duration. The external urethral sphincter sacral reflex response was intact with a normal caliber with respect to Valsalva, Cred e, bulbocavernosus and anocutaneous (bilateral) stimulation. Synergy was documented by abrupt silencing of external urethral sphincter electromyography activity during voiding. Conclusions: After complete primary repair of bladder exstrophy combined cystometrography/electromyography in patients with bladder exstrophy showed normal neurourological findings, including sacral reflex responses, sustained detrusor voiding contraction and synergic voiding, in all patients postoperatively. These findings confirm the safety of complete primary repair of bladder exstrophy. Based on our results we have discontinued routine electromyography in these patients.
Abbreviations and Acronyms BE ¼ bladder exstrophy CMG ¼ cystometrography CPRE ¼ BE complete primary repair EMG ¼ electromyography EUS ¼ external urethral sphincter UDS ¼ urodynamic study Accepted for publication October 23, 2013. Study received institutional review board approval. * Correspondence: Department of Urology, Boston Children’s Boston, 300 Longwood Ave., Boston, Massachusetts 02115 (telephone: 617355-7796; FAX: 617-730-0474; e-mail: joseph. [email protected]).
Key Words: bladder exstrophy, reconstructive surgical procedures, complications, urodynamics, electromyography
0022-5347/14/1915-1547/0 THE JOURNAL OF UROLOGY® © 2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2013.10.104 Vol. 191, 1547-1552, May 2014 Printed in U.S.A.
www.jurology.com
j
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CYSTOMETROGRAPHY AND ELECTROMYOGRAPHY FOLLOWING REPAIR OF EXSTROPHY
BLADDER exstrophy is a rare, complex congenital anomaly involving the urological, skeletal and reproductive systems, and at times the gastrointestinal system. Contemporary studies show that classic BE has an incidence of 2.15/100,000 live births with an approximately equal male-to female ratio and a higher incidence in white newborns than in other racial groups.1 Initial surgical reconstruction with modern staged repair of exstrophy2 or CPRE3 is complex and challenging. At our institution the preferred method of initial repair is the CPRE (Mitchell) technique, as described by Grady and Mitchell.3 Epispadias repair, a component of CPRE, is performed via a complete penile disassembly technique.4 Modern staged exstrophy repair and CPRE involve extensive dissection in the pelvis, along the lateral aspects of the bladder and bladder neck, and on the penis (CPRE). Given the delicate nature and small size of these structures in the newborn period, there is potential for significant peripheral nerve injury. After CPRE in the newborn a 26% rate of minor and major complications were reported.5 Shnorhavorian et al similarly reported an 18% complication rate in a cohort of 39 children treated with CPRE who were prospectively followed since 1989.6 Given the extent of dissection, concerns have been raised regarding the potential for neurourological deficits resulting from CPRE, specifically impaired or absent detrusor contractility and/or erectile function. Our routine evaluation of patients with BE included UDS. Upon adopting the CPRE technique at our institution we decided to perform UDS in our patients after CPRE in the same manner as we study neurologically impaired individuals, such as those with spina bifida or spinal cord injury. We did this to determine whether extensive pelvic dissection during CPRE adversely affected innervation of the bladder and/or external urethral sphincter muscle complex. Our initial experience with this evaluation method was reported previously.7 Our current purpose was to detail our UDS findings when combining CMG and EMG after CPRE and discuss implications regarding lower urinary tract function.
MATERIALS AND METHODS We retrospectively reviewed records from our prospectively maintained BE database of patients cared for at our institution. Institutional review board approval was obtained.
CPRE Technique From 1996 to 2004 all newborns with BE who were deemed anatomically appropriate, specifically those with an adequate bladder plate to allow for primary closure based on experienced clinician examination, underwent
closure with CPRE within 72 hours of birth. CPRE without osteotomy was performed via a previously described variation of the Mitchell technique.5,8 One patient was treated with planned delayed CPRE, which was further delayed by respiratory illness, and repeat CPRE at reoperation for dehiscence. In this case bilateral iliac osteotomy was done via the posterior approach. Briefly, the bladder and urethral plate perimeter were incised with needle electrocautery. Deep pelvic dissection was continued with incision of the intersymphyseal bands on either side of the midline and of the corpora to the pubic insertion laterally and to the bladder neck level medially. In 1 patient urethral lengthening with full-thickness skin graft and bilateral ureteral reimplantation were also performed. The pubis was approximated using heavy interrupted absorbable sutures. Postoperative immobilization was achieved by modified Bryant traction.
Urodynamic Study The CMG component of UDS was performed using a 7.4Fr triple lumen catheter passed via the urethra. No sedation was used. Distraction, relaxation techniques and bottle or breastfeeding aided in obtaining these studies. The bladder was filled by a slow filling technique (10% or less of predicted bladder capacity in ml per minute) using body temperature normal saline. A rectal catheter was used to record abdominal pressure during CMG. A concentric needle electrode was placed via the perineum in boys and at a periurethral location in girls, approximating the EUS muscle complex, to assess the effect of deep pelvic dissection on lower urinary tract and EUS innervation and function. All patients underwent complete neurological examination immediately after UDS according to routine. Individual motor unit action potentials were analyzed on an oscilloscopic screen. The EUS response to sacral reflex stimulation, including Valsalva, Cred e, bulbocavernosus and anocutaneous (bilateral) stimulation, was recorded. EUS EMG activity was monitored during CMG filling and voiding phases. UDS were interpreted by a urologist (JGB or SBB) and a neurologist (SK). For UDS we used Menuet (Dantec, Skovlunde, Denmark) and Dorado (Laborie Medical Technologies, Williston, Vermont) instruments to record and analyze multichannel UDS data. A Cantata unit (Dantec) and the TECA Synergy T2X System (Oxford Instruments Medical, Hawthorne, New York) were used for EMG. Cystometric bladder capacity was recorded as the volume of body temperature saline instilled just before the onset of voiding or leaking, or at the sensation of fullness reported by the patient. Bladder compliance was calculated as the change in volume from the outset of the CMG filling phase to capacity (dV) divided by the change in detrusor pressure (dP) from the outset of filling to pressure at capacity, such that bladder compliance in ml/cm H2O ¼ dV/dP. Detrusor overactivity was defined as any detrusor contraction or immediate increase in detrusor pressure greater than 15 cm H2O above baseline that occurred during the CMG filling phase. Patients were prospectively followed after CPRE according to a published protocol.9
CYSTOMETROGRAPHY AND ELECTROMYOGRAPHY FOLLOWING REPAIR OF EXSTROPHY
All combined CMG/EMG UDS were performed with a staff urologist and neurologist present, who oversaw study quality and tenor. In patients with the lowest volumes several cycles of the micturition cycle filling and voiding phases were performed to attain a reproducible, accurate impression of bladder capacity, and detrusor muscle stability and contractility. Sequential EUS relaxation (silenced EUS EMG activity), followed immediately by detrusor muscle contraction and expulsion via the urethra, was considered a normal voiding phase. In the setting of normal lower urinary tract function a resting or baseline minimal level of EUS activity exists with the bladder empty. During the filling/storage phase an appropriate gradual increase in EUS activity on EMG was consistent with an intact guarding reflex. An appropriate increase in this context was considered to exist in patients with a gradual increase in EUS EMG activity above the resting baseline, including normal motor unit potential amplitude, duration and frequency. During assessment of the EUS response to sacral reflex stimulation an immediate acute increase in EUS activity in amplitude, duration and frequency was considered evidence that the individual and aggregate motor unit potential response was appropriate by EMG standards.
RESULTS From 1996 to 2004 at our institution 23 children with BE were cared for after CPRE. One patient underwent closure with CPRE elsewhere in 1994 with later relocation and transfer of care. The first 13 consecutive patients in our care after CPRE, including 9 boys and 4 girls, were studied by combined CMG/EMG. In all 13 patients normal findings prompted the elimination of EMG from routine postCPRE UDS. Average age at combined CMG/EMG was 24 months (median 11.5, range 3 months to 10 years). Median age at CPRE was 43 hours of life
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with a range of 24 to 72 hours in patients treated with early CPRE. Patient 14 underwent delayed CPRE with bilateral iliac osteotomy at 169 days of life, in part due to medical comorbidities that precluded early surgical intervention (see table). In our recent experience this boy underwent combined CMG and EMG to assess any potential change in neurourological outcome as a result of delayed CPRE and/or evolution of surgical technique. Patient 12 experienced dehiscence and underwent reoperation with bilateral iliac osteotomy at age 13 months (see table). Patient 1 underwent CPRE elsewhere but was evaluated at our institution with combined CMG and EMG in the same manner as our operative cohort (see table). Average bladder capacity in our series was 40 ml (range 7 to 175). Average end filling pressure was 2.3 cm H2O (range 1 to 10) when measured at cystometric capacity immediately before voiding initiation. Post-void residual urine volume measured by CMG was 0 to 35 ml (see table). CMG revealed detrusor stability during filling as well as a sustained detrusor voiding contraction at cystometric capacity in all patients (fig. 1). CMG was performed with abdominal pressure monitoring with a rectal balloon catheter. No patient showed an abdominal or Valsalva component of voiding. EMG revealed individual motor unit action potentials with a normal biphasic pattern, amplitude and duration. On sacral reflex stimulation, including Valsalva, Crede, bulbocavernosus and anocutaneous (bilateral) stimulation, appropriate increases in activity from baseline were noted in the EUS (fig. 2). Synergic voiding with coordinated silence of EUS EMG activity and simultaneous detrusor contraction during voiding were noted in
Patient and CMG data Age
PtdSex No.
Current (yrs)
At CPRE
At UDS (mos)
Bladder Capacity (ml)
End Filling Pressure (cm H2O)
CMG-PVR (ml)
1dM* 2dM 3dM 4dM 5dF 6dM 7dF 8dM 9dF 10dM 11dM 12dF† 13dM 14dM‡
20 16 15 12 12 12 11 11 11 11 11 10 10 1
24 Hrs 36 Hrs 48 Hrs 48 Hrs 48 Hrs 24 Hrs 48 Hrs 48 Hrs 72 Hrs 48 Hrs 48 Hrs 48 Hrs 24 Hrs 169 Days
122 73 3 46 17 11 11 3 6 12 5 19 4 12
175 62 20 35 50 30 35 14 22 25 20 25 7 20
10 2 8 1 1 1 1 1 0 2 1 1 1 10
0 35 5 6 10 0 20 3 15 0 4 13 0 0
* Initial closure done elsewhere. † Dehiscence, later reoperation with bilateral iliac osteotomy at age 13 months and full UDS 6 months after reoperation. ‡ Delayed CPRE with concomitant bilateral iliac osteotomy.
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Figure 1. CMG after CPRE shows detrusor stability during filling and sustained detrusor contraction during voiding phase. Pves, intravesical pressure. Pabd, abdominal pressure. Pdet, detrusor pressure.
each patient, including patient 12, who underwent reoperation (see table). Figure 3 shows the combined study in this case.
DISCUSSION Since 1996, CPRE has been performed at our institution in all appropriate newborns who present with BE. We evaluated initial post-CPRE cases with the same meticulous scrutiny with which we evaluate
Figure 2. Normal EMG of EUS. A, rectangle indicates normal individual motor unit action potentials. B, blue arrow and green oval indicate baseline EUS activity. Green arrow and oval indicate normal increased EUS activity in response to reflex stimulation. C, oval indicates EUS Valsalva and Crede response during bulbocavernosus reflex stimulation. D, oval indicates EUS response with intact anocutaneous reflex.
our spina bifida cases or any other cases of potential neurological impairment. There may be an increased risk of pelvic neurourological compromise in patients with BE who require reoperation in the pelvis. However, our patient with the most complex condition (patient 12), who required reoperation at age 13 months after dehiscence of initial repair, had normal findings on combined CMG and EMG (see table). This is potentially significant in light of the multiple additional surgical procedures that are often necessary after CPRE.8 In no patient in our series did delayed CPRE or evolution of our CPRE technique in a 10-year period lead to a neurourological deficit, as documented by normal combined CMG and EMG UDS evaluation in patient 14 (see table).
Figure 3. CMG and EMG 6 months after reoperative CPRE in patient 12. Blue arrow and orange rectangle indicate absent detrusor contraction during filling with concurrent EUS complex activity on EMG. Green arrow and orange rectangle indicate detrusor contraction with synergic relaxation of EUS complex during voiding with no EMG activity.
CYSTOMETROGRAPHY AND ELECTROMYOGRAPHY FOLLOWING REPAIR OF EXSTROPHY
In a previous review of our patient series we reported several advantages after CPRE.7 Primarily, the bladder compliance rate was 124.4% greater in our CPRE group than in patients treated with modern staged repair regardless of gender (p ¼ 0.01). Moreover, detrusor overactivity was not detected in the CPRE group but it was seen in 46% of patients after staged repair (p ¼ 0.002). All of these factors are important when aiming to achieve adequate continence intervals and dryness in our BE population and they demonstrate detrusor stability in patients after CPRE. Shnorhavorian et al also reported the continence characteristics of their cohort.6 Of children older than 4 years 74% achieved daytime continence and volitional voiding. Our current results of documented detrusor muscle stability and contractility at capacity confirm the maintained integrity of pelvic sympathetic and parasympathetic innervation, respectively (see Appendix). Detrusor muscle stability and compliance in particular confirm an intact afferent and efferent sympathetic signal along the hypogastric nerve arising from the tenth thoracic to the second lumbar nerve roots. Detrusor muscle contractility demonstrates intact afferent and efferent parasympathetic activity of the pelvic nerve arising from the second through fourth sacral roots. Normal detrusor function after pelvic reconstructive surgery, including detrusor stability and an appropriate detrusor contraction at capacity, is well documented. Kaefer et al performed UDS in children without exstrophy after modified CantwellRansley epispadias repair and found that 46% generated a voiding contraction at capacity.9 Of the 9 patients evaluated postoperatively 44% showed detrusor stability and the absence of detrusor overactivity and poor compliance. The investigators noted that the prevalence of abnormal compliance might decrease further at longer followup, allowing for healing to progress. Detrusor acontractility was not observed in any of our patients. Therefore, when observed in older patients with BE, acontractility may be an acquired phenomenon. It may be due to excessive bladder outlet resistance and detrusor muscle impairment with time. Our findings of normal EMG activity, that is intact reflexes on Valsalva, Cred e, bulbocavernosus and anocutaneous (bilateral) stimulation, and synergy between the detrusor contraction and EUS during voiding confirm the integrity of the complex innervation of the external urethral sphincter muscle. These findings also demonstrate that the afferent and efferent function of the pelvic plexus and pudendal nerves remained intact. Documentation of neurourological integrity provides evidence of the preservation of sympathetic
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innervation in our patients. Several groups analyzed the long-term sexual outcome in patients treated with various reconstructive surgeries to correct BE in the preCPRE era. Ben-Chaim et al retrospectively reviewed the outcomes of 20 patients, including 16 men, who were treated at their institution.10 Mean age of the study population was 24 years (range 18 to 42). Six patients underwent primary repair at their institution, 14 were referred elsewhere for care after initial treatment and 15 of 16 males reported normal erection. Avolio et al described the long-term outcome after various repairs for BE and epispadias from 1970 to 1995 at their institution.11 Of the 29 patients between ages 18 and 53 years 25 underwent BE repair and 100% reported erection. Diseth et al reviewed the somatic functioning of children born with BE and epispadias.12 Of their 22 patients 19 had a history of BE, of whom 94% (16 of 17 boys) reported erection. Lastly, in a review of sexual function in boys with BE Woodhouse mentioned that erection was reported, although the incidence of erectile malformation was high with dorsal curvature in as many as 77% of males.13 Patients treated with CPRE have significant differences in postoperative anatomy compared to healthy controls. It is unclear what role, if any, postCPRE pelvic anatomy may have on future continence since no significant difference was reported between incontinent post-CPRE groups and matched controls.14 However, postoperative preservation of pelvic innervation is crucial to future continence and volitional voiding. Consequently, the finding of synergic voiding in our patients suggest that there is maintained, appropriate communication between multiple levels of the nervous system and end organs. While this does not guarantee future continence, it allows for the potential of future natural voiding. A limitation of our study is that the time between combined CMG and EMG testing in our patients with CPRE (range 3 months to 10 years) may have missed transient peripheral nerve injury in the immediate postoperative period. However, since our patients showed no sign of persistent neurourological deficit after CPRE, the clinical implications of missing a transient injury are minimal, although not insignificant. It is also possible that activity assessed by EMG was that of the pelvic floor muscle rather than the EUS. A potential limitation of UDS in some patients, such as those with bladder capacity markedly decreased from predicted normal, is the difficulty in differentiating between an overactive detrusor contraction causing leakage vs a normal voiding contraction. Lastly, we had a relatively small sample size of 14 patients with CPRE who were evaluated with combined CMG and
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CYSTOMETROGRAPHY AND ELECTROMYOGRAPHY FOLLOWING REPAIR OF EXSTROPHY
EMG. We had neither normative UDS data on a corresponding age group nor a control group.
CONCLUSIONS Our small series of post-CPRE cases evaluated by combined CMG and EMG showed normal detrusor and EUS muscle function. Synergic voiding was present and there were no overactive contractions. Due to these findings we discontinued routine EMG in this patient population.
APPENDIX Sacral reflexes, correlation with pelvic nerves and implications Pos EUS Response to Sacral Reflex
Intact Afferent Pathway
Valsalva
Pelvic nerves
Crede
Pelvic nerves
Bulbocavernosus Anocutaneous
Pudendal nerves Pudendal nerves
Intact Efferent Pathway Pudendal nerves, EUS Pudendal nerves, EUS S2-S4 (S5) S2-S4
Clinical Implication Phallic erection intact Synergic voiding Detrusor stability þ contractility
REFERENCES 1. Nelson CP, Dunn RL and Wei JT: Contemporary epidemiology of bladder exstrophy in the United States. J Urol 2005; 173: 1728.
6. Shnorhavorian M, Grady RW, Andersen A et al: Long-term followup of complete primary repair of exstrophy: the Seattle experience. J Urol 2008; 180: 1615.
2. Gearhart JP and Jeffs RD: State-of-the-art reconstructive surgery for bladder exstrophy at the Johns Hopkins Hospital. Am J Dis Child 1989; 143: 1475.
7. Borer JG, Gargollo PC, Kinnamon DD et al: Bladder growth and development after complete primary repair of bladder exstrophy in the newborn with comparison to staged approach. J Urol 2005; 174: 1553.
3. Grady RW and Mitchell ME: Newborn exstrophy closure and epispadias repair. World J Urol 1998; 16: 200. 4. Mitchell ME and Bagli DJ: Complete penile disassembly for epispadias repair: the Mitchell technique. J Urol 1996; 155: 300. 5. Borer JG, Gargollo PC, Hendren WH et al: Early outcome following complete primary repair of bladder exstrophy in the newborn. J Urol 2005; 174: 1674.
8. Gargollo PC, Borer JG, Diamond DA et al: Prospective followup in patients after complete primary repair of bladder exstrophy. J Urol 2008; 180: 1665. 9. Kaefer M, Andler R, Bauer SB et al: Urodynamic findings in children with isolated epispadias. J Urol 1999; 162: 1172. 10. Ben-Chaim J, Jeffs RD, Reiner WG et al: The outcome of patients with classic bladder exstrophy in adult life. J Urol 1996; 155: 1251.
11. Avolio L, Koo HP, Bescript AC et al: The long-term outcome in men with exstrophy/epispadias: sexual function and social integration. J Urol 1996; 156: 822. 12. Diseth TH, Bjordal R, Schultz A et al: Somatic function, mental health and psychosocial functioning in 22 adolescents with bladder exstrophy and epispadias. J Urol 1998; 159: 1684. 13. Woodhouse CR: Sexual function in boys born with exstrophy, myelomeningocele, and micropenis. Urology 1998; 52: 3. 14. Gargollo PC, Borer JG, Retik AB et al: Magnetic resonance imaging of pelvic musculoskeletal and genitourinary anatomy in patients before and after complete primary repair of bladder exstrophy. J Urol 2005; 174: 1559.
Purpose: Concern in patients with bladder exstrophy after reconstruction regarding potential injury to pelvic neurourological anatomy and a resultant functional deficit prompted combined (simultaneous) cystometrography and electromyography after complete primary repair of bladder exstrophy. We determined whether complete primary repair of bladder exstrophy would adversely affect the innervation controlling bladder and external urethral sphincter function. Materials and Methods: Complete primary repair of bladder exstrophy was performed via a modified Mitchell technique in newborns without osteotomy. Postoperative evaluation included combined cystometrography and needle electrode electromyography via the perineum, approximating the external urethral sphincter muscle complex. Electromyography was done to evaluate the external urethral sphincter response to sacral reflex stimulation and during voiding. Results: Nine boys and 4 girls underwent combined cystometrography/electromyography after complete primary repair of bladder exstrophy. Age at study and time after complete primary repair of bladder exstrophy was 3 months to 10 years (median 11.5 months). Cystometrography revealed absent detrusor overactivity and the presence of a sustained detrusor voiding contraction in all cases. Electromyography showed universally normal individual motor unit action potentials of biphasic pattern, amplitude and duration. The external urethral sphincter sacral reflex response was intact with a normal caliber with respect to Valsalva, Cred e, bulbocavernosus and anocutaneous (bilateral) stimulation. Synergy was documented by abrupt silencing of external urethral sphincter electromyography activity during voiding. Conclusions: After complete primary repair of bladder exstrophy combined cystometrography/electromyography in patients with bladder exstrophy showed normal neurourological findings, including sacral reflex responses, sustained detrusor voiding contraction and synergic voiding, in all patients postoperatively. These findings confirm the safety of complete primary repair of bladder exstrophy. Based on our results we have discontinued routine electromyography in these patients.
Abbreviations and Acronyms BE ¼ bladder exstrophy CMG ¼ cystometrography CPRE ¼ BE complete primary repair EMG ¼ electromyography EUS ¼ external urethral sphincter UDS ¼ urodynamic study Accepted for publication October 23, 2013. Study received institutional review board approval. * Correspondence: Department of Urology, Boston Children’s Boston, 300 Longwood Ave., Boston, Massachusetts 02115 (telephone: 617355-7796; FAX: 617-730-0474; e-mail: joseph. [email protected]).
Key Words: bladder exstrophy, reconstructive surgical procedures, complications, urodynamics, electromyography
0022-5347/14/1915-1547/0 THE JOURNAL OF UROLOGY® © 2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2013.10.104 Vol. 191, 1547-1552, May 2014 Printed in U.S.A.
www.jurology.com
j
1547
1548
CYSTOMETROGRAPHY AND ELECTROMYOGRAPHY FOLLOWING REPAIR OF EXSTROPHY
BLADDER exstrophy is a rare, complex congenital anomaly involving the urological, skeletal and reproductive systems, and at times the gastrointestinal system. Contemporary studies show that classic BE has an incidence of 2.15/100,000 live births with an approximately equal male-to female ratio and a higher incidence in white newborns than in other racial groups.1 Initial surgical reconstruction with modern staged repair of exstrophy2 or CPRE3 is complex and challenging. At our institution the preferred method of initial repair is the CPRE (Mitchell) technique, as described by Grady and Mitchell.3 Epispadias repair, a component of CPRE, is performed via a complete penile disassembly technique.4 Modern staged exstrophy repair and CPRE involve extensive dissection in the pelvis, along the lateral aspects of the bladder and bladder neck, and on the penis (CPRE). Given the delicate nature and small size of these structures in the newborn period, there is potential for significant peripheral nerve injury. After CPRE in the newborn a 26% rate of minor and major complications were reported.5 Shnorhavorian et al similarly reported an 18% complication rate in a cohort of 39 children treated with CPRE who were prospectively followed since 1989.6 Given the extent of dissection, concerns have been raised regarding the potential for neurourological deficits resulting from CPRE, specifically impaired or absent detrusor contractility and/or erectile function. Our routine evaluation of patients with BE included UDS. Upon adopting the CPRE technique at our institution we decided to perform UDS in our patients after CPRE in the same manner as we study neurologically impaired individuals, such as those with spina bifida or spinal cord injury. We did this to determine whether extensive pelvic dissection during CPRE adversely affected innervation of the bladder and/or external urethral sphincter muscle complex. Our initial experience with this evaluation method was reported previously.7 Our current purpose was to detail our UDS findings when combining CMG and EMG after CPRE and discuss implications regarding lower urinary tract function.
MATERIALS AND METHODS We retrospectively reviewed records from our prospectively maintained BE database of patients cared for at our institution. Institutional review board approval was obtained.
CPRE Technique From 1996 to 2004 all newborns with BE who were deemed anatomically appropriate, specifically those with an adequate bladder plate to allow for primary closure based on experienced clinician examination, underwent
closure with CPRE within 72 hours of birth. CPRE without osteotomy was performed via a previously described variation of the Mitchell technique.5,8 One patient was treated with planned delayed CPRE, which was further delayed by respiratory illness, and repeat CPRE at reoperation for dehiscence. In this case bilateral iliac osteotomy was done via the posterior approach. Briefly, the bladder and urethral plate perimeter were incised with needle electrocautery. Deep pelvic dissection was continued with incision of the intersymphyseal bands on either side of the midline and of the corpora to the pubic insertion laterally and to the bladder neck level medially. In 1 patient urethral lengthening with full-thickness skin graft and bilateral ureteral reimplantation were also performed. The pubis was approximated using heavy interrupted absorbable sutures. Postoperative immobilization was achieved by modified Bryant traction.
Urodynamic Study The CMG component of UDS was performed using a 7.4Fr triple lumen catheter passed via the urethra. No sedation was used. Distraction, relaxation techniques and bottle or breastfeeding aided in obtaining these studies. The bladder was filled by a slow filling technique (10% or less of predicted bladder capacity in ml per minute) using body temperature normal saline. A rectal catheter was used to record abdominal pressure during CMG. A concentric needle electrode was placed via the perineum in boys and at a periurethral location in girls, approximating the EUS muscle complex, to assess the effect of deep pelvic dissection on lower urinary tract and EUS innervation and function. All patients underwent complete neurological examination immediately after UDS according to routine. Individual motor unit action potentials were analyzed on an oscilloscopic screen. The EUS response to sacral reflex stimulation, including Valsalva, Cred e, bulbocavernosus and anocutaneous (bilateral) stimulation, was recorded. EUS EMG activity was monitored during CMG filling and voiding phases. UDS were interpreted by a urologist (JGB or SBB) and a neurologist (SK). For UDS we used Menuet (Dantec, Skovlunde, Denmark) and Dorado (Laborie Medical Technologies, Williston, Vermont) instruments to record and analyze multichannel UDS data. A Cantata unit (Dantec) and the TECA Synergy T2X System (Oxford Instruments Medical, Hawthorne, New York) were used for EMG. Cystometric bladder capacity was recorded as the volume of body temperature saline instilled just before the onset of voiding or leaking, or at the sensation of fullness reported by the patient. Bladder compliance was calculated as the change in volume from the outset of the CMG filling phase to capacity (dV) divided by the change in detrusor pressure (dP) from the outset of filling to pressure at capacity, such that bladder compliance in ml/cm H2O ¼ dV/dP. Detrusor overactivity was defined as any detrusor contraction or immediate increase in detrusor pressure greater than 15 cm H2O above baseline that occurred during the CMG filling phase. Patients were prospectively followed after CPRE according to a published protocol.9
CYSTOMETROGRAPHY AND ELECTROMYOGRAPHY FOLLOWING REPAIR OF EXSTROPHY
All combined CMG/EMG UDS were performed with a staff urologist and neurologist present, who oversaw study quality and tenor. In patients with the lowest volumes several cycles of the micturition cycle filling and voiding phases were performed to attain a reproducible, accurate impression of bladder capacity, and detrusor muscle stability and contractility. Sequential EUS relaxation (silenced EUS EMG activity), followed immediately by detrusor muscle contraction and expulsion via the urethra, was considered a normal voiding phase. In the setting of normal lower urinary tract function a resting or baseline minimal level of EUS activity exists with the bladder empty. During the filling/storage phase an appropriate gradual increase in EUS activity on EMG was consistent with an intact guarding reflex. An appropriate increase in this context was considered to exist in patients with a gradual increase in EUS EMG activity above the resting baseline, including normal motor unit potential amplitude, duration and frequency. During assessment of the EUS response to sacral reflex stimulation an immediate acute increase in EUS activity in amplitude, duration and frequency was considered evidence that the individual and aggregate motor unit potential response was appropriate by EMG standards.
RESULTS From 1996 to 2004 at our institution 23 children with BE were cared for after CPRE. One patient underwent closure with CPRE elsewhere in 1994 with later relocation and transfer of care. The first 13 consecutive patients in our care after CPRE, including 9 boys and 4 girls, were studied by combined CMG/EMG. In all 13 patients normal findings prompted the elimination of EMG from routine postCPRE UDS. Average age at combined CMG/EMG was 24 months (median 11.5, range 3 months to 10 years). Median age at CPRE was 43 hours of life
1549
with a range of 24 to 72 hours in patients treated with early CPRE. Patient 14 underwent delayed CPRE with bilateral iliac osteotomy at 169 days of life, in part due to medical comorbidities that precluded early surgical intervention (see table). In our recent experience this boy underwent combined CMG and EMG to assess any potential change in neurourological outcome as a result of delayed CPRE and/or evolution of surgical technique. Patient 12 experienced dehiscence and underwent reoperation with bilateral iliac osteotomy at age 13 months (see table). Patient 1 underwent CPRE elsewhere but was evaluated at our institution with combined CMG and EMG in the same manner as our operative cohort (see table). Average bladder capacity in our series was 40 ml (range 7 to 175). Average end filling pressure was 2.3 cm H2O (range 1 to 10) when measured at cystometric capacity immediately before voiding initiation. Post-void residual urine volume measured by CMG was 0 to 35 ml (see table). CMG revealed detrusor stability during filling as well as a sustained detrusor voiding contraction at cystometric capacity in all patients (fig. 1). CMG was performed with abdominal pressure monitoring with a rectal balloon catheter. No patient showed an abdominal or Valsalva component of voiding. EMG revealed individual motor unit action potentials with a normal biphasic pattern, amplitude and duration. On sacral reflex stimulation, including Valsalva, Crede, bulbocavernosus and anocutaneous (bilateral) stimulation, appropriate increases in activity from baseline were noted in the EUS (fig. 2). Synergic voiding with coordinated silence of EUS EMG activity and simultaneous detrusor contraction during voiding were noted in
Patient and CMG data Age
PtdSex No.
Current (yrs)
At CPRE
At UDS (mos)
Bladder Capacity (ml)
End Filling Pressure (cm H2O)
CMG-PVR (ml)
1dM* 2dM 3dM 4dM 5dF 6dM 7dF 8dM 9dF 10dM 11dM 12dF† 13dM 14dM‡
20 16 15 12 12 12 11 11 11 11 11 10 10 1
24 Hrs 36 Hrs 48 Hrs 48 Hrs 48 Hrs 24 Hrs 48 Hrs 48 Hrs 72 Hrs 48 Hrs 48 Hrs 48 Hrs 24 Hrs 169 Days
122 73 3 46 17 11 11 3 6 12 5 19 4 12
175 62 20 35 50 30 35 14 22 25 20 25 7 20
10 2 8 1 1 1 1 1 0 2 1 1 1 10
0 35 5 6 10 0 20 3 15 0 4 13 0 0
* Initial closure done elsewhere. † Dehiscence, later reoperation with bilateral iliac osteotomy at age 13 months and full UDS 6 months after reoperation. ‡ Delayed CPRE with concomitant bilateral iliac osteotomy.
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Figure 1. CMG after CPRE shows detrusor stability during filling and sustained detrusor contraction during voiding phase. Pves, intravesical pressure. Pabd, abdominal pressure. Pdet, detrusor pressure.
each patient, including patient 12, who underwent reoperation (see table). Figure 3 shows the combined study in this case.
DISCUSSION Since 1996, CPRE has been performed at our institution in all appropriate newborns who present with BE. We evaluated initial post-CPRE cases with the same meticulous scrutiny with which we evaluate
Figure 2. Normal EMG of EUS. A, rectangle indicates normal individual motor unit action potentials. B, blue arrow and green oval indicate baseline EUS activity. Green arrow and oval indicate normal increased EUS activity in response to reflex stimulation. C, oval indicates EUS Valsalva and Crede response during bulbocavernosus reflex stimulation. D, oval indicates EUS response with intact anocutaneous reflex.
our spina bifida cases or any other cases of potential neurological impairment. There may be an increased risk of pelvic neurourological compromise in patients with BE who require reoperation in the pelvis. However, our patient with the most complex condition (patient 12), who required reoperation at age 13 months after dehiscence of initial repair, had normal findings on combined CMG and EMG (see table). This is potentially significant in light of the multiple additional surgical procedures that are often necessary after CPRE.8 In no patient in our series did delayed CPRE or evolution of our CPRE technique in a 10-year period lead to a neurourological deficit, as documented by normal combined CMG and EMG UDS evaluation in patient 14 (see table).
Figure 3. CMG and EMG 6 months after reoperative CPRE in patient 12. Blue arrow and orange rectangle indicate absent detrusor contraction during filling with concurrent EUS complex activity on EMG. Green arrow and orange rectangle indicate detrusor contraction with synergic relaxation of EUS complex during voiding with no EMG activity.
CYSTOMETROGRAPHY AND ELECTROMYOGRAPHY FOLLOWING REPAIR OF EXSTROPHY
In a previous review of our patient series we reported several advantages after CPRE.7 Primarily, the bladder compliance rate was 124.4% greater in our CPRE group than in patients treated with modern staged repair regardless of gender (p ¼ 0.01). Moreover, detrusor overactivity was not detected in the CPRE group but it was seen in 46% of patients after staged repair (p ¼ 0.002). All of these factors are important when aiming to achieve adequate continence intervals and dryness in our BE population and they demonstrate detrusor stability in patients after CPRE. Shnorhavorian et al also reported the continence characteristics of their cohort.6 Of children older than 4 years 74% achieved daytime continence and volitional voiding. Our current results of documented detrusor muscle stability and contractility at capacity confirm the maintained integrity of pelvic sympathetic and parasympathetic innervation, respectively (see Appendix). Detrusor muscle stability and compliance in particular confirm an intact afferent and efferent sympathetic signal along the hypogastric nerve arising from the tenth thoracic to the second lumbar nerve roots. Detrusor muscle contractility demonstrates intact afferent and efferent parasympathetic activity of the pelvic nerve arising from the second through fourth sacral roots. Normal detrusor function after pelvic reconstructive surgery, including detrusor stability and an appropriate detrusor contraction at capacity, is well documented. Kaefer et al performed UDS in children without exstrophy after modified CantwellRansley epispadias repair and found that 46% generated a voiding contraction at capacity.9 Of the 9 patients evaluated postoperatively 44% showed detrusor stability and the absence of detrusor overactivity and poor compliance. The investigators noted that the prevalence of abnormal compliance might decrease further at longer followup, allowing for healing to progress. Detrusor acontractility was not observed in any of our patients. Therefore, when observed in older patients with BE, acontractility may be an acquired phenomenon. It may be due to excessive bladder outlet resistance and detrusor muscle impairment with time. Our findings of normal EMG activity, that is intact reflexes on Valsalva, Cred e, bulbocavernosus and anocutaneous (bilateral) stimulation, and synergy between the detrusor contraction and EUS during voiding confirm the integrity of the complex innervation of the external urethral sphincter muscle. These findings also demonstrate that the afferent and efferent function of the pelvic plexus and pudendal nerves remained intact. Documentation of neurourological integrity provides evidence of the preservation of sympathetic
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innervation in our patients. Several groups analyzed the long-term sexual outcome in patients treated with various reconstructive surgeries to correct BE in the preCPRE era. Ben-Chaim et al retrospectively reviewed the outcomes of 20 patients, including 16 men, who were treated at their institution.10 Mean age of the study population was 24 years (range 18 to 42). Six patients underwent primary repair at their institution, 14 were referred elsewhere for care after initial treatment and 15 of 16 males reported normal erection. Avolio et al described the long-term outcome after various repairs for BE and epispadias from 1970 to 1995 at their institution.11 Of the 29 patients between ages 18 and 53 years 25 underwent BE repair and 100% reported erection. Diseth et al reviewed the somatic functioning of children born with BE and epispadias.12 Of their 22 patients 19 had a history of BE, of whom 94% (16 of 17 boys) reported erection. Lastly, in a review of sexual function in boys with BE Woodhouse mentioned that erection was reported, although the incidence of erectile malformation was high with dorsal curvature in as many as 77% of males.13 Patients treated with CPRE have significant differences in postoperative anatomy compared to healthy controls. It is unclear what role, if any, postCPRE pelvic anatomy may have on future continence since no significant difference was reported between incontinent post-CPRE groups and matched controls.14 However, postoperative preservation of pelvic innervation is crucial to future continence and volitional voiding. Consequently, the finding of synergic voiding in our patients suggest that there is maintained, appropriate communication between multiple levels of the nervous system and end organs. While this does not guarantee future continence, it allows for the potential of future natural voiding. A limitation of our study is that the time between combined CMG and EMG testing in our patients with CPRE (range 3 months to 10 years) may have missed transient peripheral nerve injury in the immediate postoperative period. However, since our patients showed no sign of persistent neurourological deficit after CPRE, the clinical implications of missing a transient injury are minimal, although not insignificant. It is also possible that activity assessed by EMG was that of the pelvic floor muscle rather than the EUS. A potential limitation of UDS in some patients, such as those with bladder capacity markedly decreased from predicted normal, is the difficulty in differentiating between an overactive detrusor contraction causing leakage vs a normal voiding contraction. Lastly, we had a relatively small sample size of 14 patients with CPRE who were evaluated with combined CMG and
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EMG. We had neither normative UDS data on a corresponding age group nor a control group.
CONCLUSIONS Our small series of post-CPRE cases evaluated by combined CMG and EMG showed normal detrusor and EUS muscle function. Synergic voiding was present and there were no overactive contractions. Due to these findings we discontinued routine EMG in this patient population.
APPENDIX Sacral reflexes, correlation with pelvic nerves and implications Pos EUS Response to Sacral Reflex
Intact Afferent Pathway
Valsalva
Pelvic nerves
Crede
Pelvic nerves
Bulbocavernosus Anocutaneous
Pudendal nerves Pudendal nerves
Intact Efferent Pathway Pudendal nerves, EUS Pudendal nerves, EUS S2-S4 (S5) S2-S4
Clinical Implication Phallic erection intact Synergic voiding Detrusor stability þ contractility
REFERENCES 1. Nelson CP, Dunn RL and Wei JT: Contemporary epidemiology of bladder exstrophy in the United States. J Urol 2005; 173: 1728.
6. Shnorhavorian M, Grady RW, Andersen A et al: Long-term followup of complete primary repair of exstrophy: the Seattle experience. J Urol 2008; 180: 1615.
2. Gearhart JP and Jeffs RD: State-of-the-art reconstructive surgery for bladder exstrophy at the Johns Hopkins Hospital. Am J Dis Child 1989; 143: 1475.
7. Borer JG, Gargollo PC, Kinnamon DD et al: Bladder growth and development after complete primary repair of bladder exstrophy in the newborn with comparison to staged approach. J Urol 2005; 174: 1553.
3. Grady RW and Mitchell ME: Newborn exstrophy closure and epispadias repair. World J Urol 1998; 16: 200. 4. Mitchell ME and Bagli DJ: Complete penile disassembly for epispadias repair: the Mitchell technique. J Urol 1996; 155: 300. 5. Borer JG, Gargollo PC, Hendren WH et al: Early outcome following complete primary repair of bladder exstrophy in the newborn. J Urol 2005; 174: 1674.
8. Gargollo PC, Borer JG, Diamond DA et al: Prospective followup in patients after complete primary repair of bladder exstrophy. J Urol 2008; 180: 1665. 9. Kaefer M, Andler R, Bauer SB et al: Urodynamic findings in children with isolated epispadias. J Urol 1999; 162: 1172. 10. Ben-Chaim J, Jeffs RD, Reiner WG et al: The outcome of patients with classic bladder exstrophy in adult life. J Urol 1996; 155: 1251.
11. Avolio L, Koo HP, Bescript AC et al: The long-term outcome in men with exstrophy/epispadias: sexual function and social integration. J Urol 1996; 156: 822. 12. Diseth TH, Bjordal R, Schultz A et al: Somatic function, mental health and psychosocial functioning in 22 adolescents with bladder exstrophy and epispadias. J Urol 1998; 159: 1684. 13. Woodhouse CR: Sexual function in boys born with exstrophy, myelomeningocele, and micropenis. Urology 1998; 52: 3. 14. Gargollo PC, Borer JG, Retik AB et al: Magnetic resonance imaging of pelvic musculoskeletal and genitourinary anatomy in patients before and after complete primary repair of bladder exstrophy. J Urol 2005; 174: 1559.
