Vol 19 No 1 January-February 2022 138 FEMALE UROLOGY Evaluation of the Clinical Effects of Abobotolinum Toxin A (Dysport) Injection in the Treatment of Neurogenic Lower Urinary Tract Dysfunction Farzaneh Sharifiaghdas1, Maryam Taheri2, Nasrin Boroumandnia2, Zhila Sheikhi3* Purpose: Neurogenic lower urinary tract dysfunction (NLUTD) is one of the most challenging problems in urol- ogy. In recent years, Onabotulinum toxin A (Botox) is considered a second-line treatment in these patients. This study aimed to evaluate the clinical effects of Abobotolinum toxin A (Dysport) into the bladder and urethra. Materials and Methods: We classified our patients with NLUTD into three groups: neurogenic detrusor overac- tivity (group 1), detrusor sphincter dyssynergia (group 2), and patients with both symptoms (group 3). The severity of the patient’s symptoms was assessed using the Urinary Distress Inventory- Short form (UDI-6), urodynamic study, and post-void residual urine (PVR) at baseline. After injection of Dysport, the patients were evaluated by the change in UDI-6 score, PVR, and the patient’s general satisfaction. In group 1, 500-900 U diluted Dysport injected intra-vesical. If associated with detrusor sphincter dyssynergia (group 3), 100 U diluted Dysport injected peri-urethral. In group 2, only 100 U diluted Dysport injected peri-urethral. Results: Data from 52 women with NLUTD were analyzed. The mean age was 51.3 ± 21.6 years. The prevalence of detrusor overactivity and the value of Q max was more in group 1. However, the amount of PVR was more in groups 2 and 3. The overall success rate was acceptable in all three groups. In addition, there were significant improvements in UDI-6 parameters. Conclusion: Peri-urethral injection of Abobotolinum toxin A is effective and safe. However, the selection of the patients and the dose of toxin needs more studies. Keywords: Abobotolinum toxin A; neurogenic; urethra; voiding dysfunction INTRODUCTION Appropriate diagnosis and management of patients with neurogenic lower urinary tract dysfunction (NLUTD) are among the most challenging problems in urology through significant medical and social aspects. Various disorders or injuries of the central or periph- eral nervous system (i.e., stroke, spinal cord injury, Parkinson’s disease, multiple sclerosis, etc.) may cause NLUTD. These events' consequences depend on the location and extent of the neurologic lesion leading to neurogenic dysfunction of the urinary bladder with or without adverse effects on the urethra(1). Neurogenic de- trusor overactivity (NDO), detrusor sphincter dyssyner- gia (DSD), incomplete voiding and high pressure often lead to structural bladder damage, upper urinary tract dilation, vesicoureteral reflux, and renal insufficiency. Therefore, the main goals of NLUTD treatment consist of preserving renal function, achieving urinary conti- nence, prevention and control of urinary tract infection, with improved quality of life(1). The current methods to manage NLUTD include med- ications, botulinum toxin A (BTX-A) injection, neuro- 1Urology and Nephrology Research Center, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3Department of Urology, Mashhad University of Medical Sciences, Mashhad, Iran. *Correspondence: Assistant professor of Urology, Fellowship of Female Urology, Department of Urology, Mashhad University of Medical Sciences, Mashhad, Iran Email: Sheikhizh@mums.ac.ir, dr.sheikhi@yahoo.com. Received February 2021 & Accepted October 2021 modulation, and surgical procedures. Each of these has advantages and disadvantages(2). Nowadays, the combi- nation of anticholinergic drugs with clean contamina- tion catheterization (CIC) is the gold standard treatment for NDO(2). Onabotulinumtoxin A (Botox) has been ap- proved to treat NDO in certain parts of the world, such as the USA(3), on the theoretical basis that injection into the detrusor muscle would temporarily block the pre- synaptic release of acetylcholine from parasympathetic innervation. Therefore, Botox injection can result in the paralysis of the detrusor smooth muscle that may last for an estimated nine months(2). One of the common problems in patients with NLUTD is detrusor sphincter dyssynergia, which increases the post-void residual urine (PVR)(4) and results in urinary tract infection or upper urinary tract deterioration. Ure- thral injections of Botox were proposed by Dykstra et al. in 1988(5). Steinhardt et al. were the first to report Botox’s injections into the urethral sphincter of children with neurogenic voiding dysfunction in 1997(6). After that, Botox injection in the urethral sphincter has be- come popular in various neurogenic or non-neurogenic Urology Journal/Vol 19 No. 1/ January-February 2022/ pp. 63-68. [DOI: 10.22037/uj.v18i.6720] conditions, including voiding dysfunction, detrusor un- deractivity, or chronic urinary retention(7). According to the literature, this treatment's effectiveness is reported in 60–100% of patients with spinal cord injury, which can last up to six months without significant side effects (8). However, dosage, injection schedule, and period of efficacy vary from article to article(9). Most of the existing studies have focused on inject- ing Onabotulinum toxin A (Botox) in patients with NLUTD. In this study, we evaluate the clinical efficacy of Abobotolinum toxin A (Dysport) injection into the bladder, peri-urethra, or both. Abobotolinum toxin A (Dysport) is the only commercially available BTX-A in our country, which there is very little evidence in this regard in the literature till now. MATERIALS AND METHODS Study population In this prospective study, patients with symptoms of NLUTD who were referred to a tertiary urology clinic were recruited during 2018- 2019, based on conveni- ence sampling. The patient’s symptoms including ur- gency, frequency, urinary incontinence (urge or stress), incomplete voiding, and pain or discomfort during void- ing. All patients were female, ≥18 years old with re- fractory to medical treatment (for at least three months), and no BTX-A injection history. In those with active or recurrent urinary tract infection (UTI), prompt medical therapy was prescribed, and in persistent UTIs, effec- tive suppressive antibiotic treatment was registered. The exclusion criteria were the inability to complete the questionnaire, significant stress incontinence, intersti- tial cystitis, bladder carcinoma, urinary tract stones, in- tolerance or inability to perform clean self-intermittent catheterization, and pregnancy or lactation. In addition, we excluded any patients with moderate to high hydro- ureteronephrosis or serum creatinine ≥1.5 mg/dl. The patient’s symptoms were assessed by validated Urinary Distress Inventory- Short form (UDI-6)(10), uro- dynamic study (UDS), and the amount of PVR at base- line. The patient’s outcome was assessed by change in the UDI score, the amount of PVR, and patients’ gener- al satisfaction.(11) UDI-6 questionnaire is defined by six items with a total score ranging from 0 to 18, with high- er scores indicating increasing symptom severity(10). The UDS parameters including; detrusor overactivity (DO), defined by involuntary detrusor contractions dur- ing the filling phase and, DSD, defined as a detrusor contraction concurrent with an involuntary contraction of the urethral or periurethral striated muscles(12). The patients’ general satisfaction was evaluated by the sum- mation of improvement in urinary incontinence, diffi- cult urination, and the need for CIC. After treatment, the patient’s satisfaction scored 0–3, representing not, mild, moderate, and very satisfied. The final therapeutic result was categorized as a successful outcome, includ- ing moderate, and very satisfied and failed outcomes representing those without or low satisfaction. Written informed consent was obtained from all patients before enrollment in the study. The ethics committee of the Urology Nephrology Research Center of Shahid Beheshti University of Medical Sciences approved this study (ethic code: IR. SBMU.UNRC.1397.16). Also, this is under the Helsinki declaration of 1964 and its lat- er amendments. Patients were informed about the study objectives in their language. Procedure All patients were assessed at baseline by routine histo- ry, physical examination, urine analysis, urine culture, and urinary tract ultrasound (to measure PVR). The pa- tients were also assessed by the UDI-6 questionnaire and urodynamic examination. Before cysto-urethroscopy, 500-900 U Abobotolinum toxin A (Dysport, 500 U/vial, ISPEN, UK) was diluted in 6 ml of saline 0.9%. The amount of required Dysport was calculated according to the patient’s weight, ten units per kilogram. In patients with NDO, diluted Dysport was injected intra-vesical by a 27-G dispos- able needle into 30 sites in the bladder wall to distribute drugs better. If associated DSD, 100 U Dysport (equal to 35 U of Botox) was injected peri-urethral, at 3, 9, and 12 O’clock in presumed external urethral sphincter place. In patients who only had DSD symptoms, such as an intermittent urinary stream or low maximal flow rate, 100 U of Dysport diluted in 1 cc normal saline injected peri-urethral using 31-gauge insulin syringe (Figure 1). After the procedure, a 14 Fr. Foley catheter was placed and removed the next day, routinely. Broad-spectrum antibiotics were given for 3 to 5 days after injection. At discharge note, patients were advised to come to the emergency department for any acute problems. Patients visited one month then followed four months after the procedure in the outpatient clinic. During this time, anticholinergic drugs were discontinued after Dysport injection. Statistical analysis For data analysis, the first normal distribution of data was evaluated by the Shapiro-Wilks test. Mean, stand- ard deviation (SD), median, interquartile range (IQR), frequency, and percent were reported to describe vari- ables. A Fischer exact test was used to explore the as- sociation between categorical variables. ANOVA (or Kruskal-Wallis test) and paired t-test (or Wilcoxon test) Dysport injection in bladder and urethra- Sharifiaghdas et al. Female Urology 64 Table 1. Determination and comparison of demographic variables in the two groups. NDO (n=36) DSD (n=8) NDO with DSD (n=8) p-value Age: mean± SD 48 ± 20 57 ± 27 49 ± 18 0.583a BMI: mean± SD 26.52 ± 5.16 29.35 ± 8.11 30.10 ± 5.31 0.181a UDS DO: n (%) 22 (61.1) 1 (12.5) 6 (75.0) 0.028b Capacity: mean± SD 288 ± 115 408 ± 230 330 ± 91 0.153a Q max: median (IQR) 13 (10.4-15) 8.3 (6.5-15) 8 (5-8) 0.004c PVR: median (IQR) 15 (9.5-37.5) 100 (20-200) 80 (24-237) 0.053c *Significant at level of 0.05, a. ANOVA, b, Fischer exact test, c. Kruskal-Wallis test Abbreviations: NDO. Neurogenic detrusor overactivity, DSD. Detrusor sphincter dyssynergia, BMI. Body mass index, UDS. Urodynamic study, DO. Detrusor overactivity, PVR. Post void residual urine, SD. Standard deviation, IQR. Interquartile range. Vol 19 No 1 January-February 2022 138 were used for between and within-group comparisons in terms of numeric variables. P < 0.05 is considered significant. Statistical analysis was done using SPSS (statistical product and service solution) 21. RESULTS Fifty-two consecutive adult women with symptoms of NLUTD were included. The mean age was 51.3 ± 21.6 years. Table 1 shows the characteristics of three groups of patients with NLUTD; group 1: neurogenic detru- sor overactivity (NDO), group 2: patients with detrusor sphincter dyssynergia (DSD), and group 3: patients with NDO accompanied with DSD. Regarding comorbid dis- eases, four patients had a history of diabetes, 13 patients had high blood pressure and, the cause of NLUTD in 17 patients was spinal canal diseases (Intervertebral disc prolapse, trauma, or after disc surgery). The prevalence of detrusor overactivity and higher Q max was more in group 1 of patients, as the PVR amount was lower than the other two groups (Table 1). Peri-operatively, there were no acute complications during the injection. Post-injection adverse events, in- cluding hematuria, were found in 11 patients (21.15%), urinary tract infection in 8 patients (15.38%), and fever in 3 patients (5.76%) who responded to outpatient med- ical treatment. Four months after Dysport injection, the overall suc- cess rate in valid cases was 61.3% in group 1, 71.4% in group 2, and all of the patients in group 3 (according to the general patient’s satisfaction). There is no sig- nificant difference in success rate between the three groups of patients (Table 2). Table 3 shows the chang- es in UDI-6 scores (each question) at baseline and four months after Dysport injection in patient groups. Sig- nificant improvements in frequency (Question 1) and difficult voiding (Question 5) were observed in all pa- tients. However, PVR significantly decreased in group 2 (DSD), and group 3 (NDO associated with DSD). DISCUSSION Onabotulinumtoxin A (Botox) has been approved to treat neurogenic detrusor overactivity in certain parts of the world, such as the US and the UK(3). Herein; we present our experience of Abobotolinum toxin A (Dysport) injection in patients with NLUTD. There was a significant improvement in urinary symptoms and general patient satisfaction in three groups of our pa- tients with NDO, DSD, and NDO with DSD. Post void residual urine was significantly decreased in patients with DSD as NDO associated with DSD. BTX-A is a potent neurotoxin, which can inhibit the release of neurotransmitters from efferent nerve termi- nals at neuromuscular junctions, thereby paralyzing the muscle(13). Therefore, the use of Botox in the bladder detrusor muscle and urethral muscles has been consid- ered for many years. However, since central and pe- ripheral nerve pathways are related to the bladder and urethra's function, injection of BTX-A in one of them will affect another. According to the literature, when the bladder is filled, stimulation of some afferent nerves in the bladder in- fluences external urethral sphincter activity by central neural mechanisms such as guarding reflex(14,15). In ad- dition, Shafik et al.(16) described that during bladder fill- ing, when the vesical pressure increases, the pressure in the internal urethral meatus (urethral smooth muscle) rises. Based on the literature referenced above, detrusor relaxation by BTX-A injections in the bladder muscle induces fewer triggering of the mechanoreceptors in the Female Urology 672 Failed Success NDO: n (%) 12 (38.7%) 19 (61.3%) DSD: n (%) 2 (28.6% 5 (71.4%) NDO with DSD: n (%) 0 (28.6%) 6 (100.0%) Total: n (%) 14 (28.6%) 30 (68.2%) Table 2. The overall success rate of the three groups of patients according to the general patient’s satisfaction after four months of Abobotolinum toxin A (Dysport) injection. Abbreviations: NDO. Neurogenic detrusor overactivity, DSD. Detrusor sphincter dyssynergia. UDI-6 NDO Median (IQR) DSD Median (IQR) NDO with DSD Median (IQR) Question 1: BL 3 (3-3) 3 (3-3) 3 (3-3) Question 1: 4M 1 (1-3) 1 (1-3) 1 (1-1) p-valueb <.001 .034 * .008 * Question 2: BL 3 (3-3) 1 (0-3) 2 (1-3) Question 2: 4M 0 (0-1) 1 (1-2) 1 (1-2) p-valueb <.001 .157 .038 * Question 3: BL 1 (0-3) 1 (0-2) 1 (0-2) Question 3: 4M 0 (0-2) 1 (0-2) 0 (0-1) p-valueb .010 * 0.998 .180 Question 4: BL 3 (2-3) 2 (1-3) 2 (1-3) Question 4: 4M 1 (0-3) 0 (0-2) 2 (1-3) p-valueb <.001 .028 * 0.998 Question 5: BL 0 (0-1) 3 (3-3) 3 (2-3) Question 5: 4M 0 (0-1) 1 (1-2) 1 (1-2) p-valueb .046 * .024 * .034 * Question 6: BL 1 (0-3) 3 (3-3) 2 (1-3) Question 6: 4M 0 (0-2) 0 (0-2) 2 (1-3) p-value b .038 * .018 * 0.998 PVR-BL 22.50 (10.00-50.00) 120.00 (50.00-350) 140.00 (39.00-225.50) PVR-4M 25.00 (15.00-45.00) 55.00 (32.50-150.00) 65.00 (15.00-125.00) p-value b .104 .027 .017 a.Kruskal-Wallis, b. Wilcoxon Abbreviations: UDI-6. Urinary Distress Inventory- Short form, NDO. Neurogenic detrusor overactivity, DSD. Detrusor sphincter dyssynergia, PVR. Post void residual urine, BL. Baseline, 4M. Four months after injection. Table 3. Comparing the UDI-6 score and post-void residual urine in three groups of patients with neurogenic lower urinary tract dysfunction at baseline and four months after Abobotolinum toxin A (Dysport) injection. Dysport injection in bladder and urethra- Sharifiaghdas et al. Vol 19 No 1 January-February 2022 65 bladder wall and consequently a decrease in urethral pressure(9). Therefore, the use of intravesical BTX-A in NDO could improve bladder outlet obstruction; since the patient experienced easier CIC. On the other hand, urinary bladder emptying requires the relaxation of the bladder neck and urethral sphincter followed by the contraction of detrusor smooth mus- cles, and voluntary coordinated urethral sphincter re- laxation completes the voiding process(17). Coordination between the urethral sphincter and the urinary bladder is mediated by complex neural control and reflex path- ways. So, during the voiding phase, when the urethral sphincter is poorly relaxed, a forceful detrusor contrac- tion may be inhibited by inhibiting the detrusor con- traction micturition center at the sacral spinal cord(18). Whenever the urethral sphincter contraction during the voiding phase can also inhibit detrusor muscle con- traction by activating the inhibiting afferent reflex(14). Therefore, both a poorly relaxed urethral sphincter and a urethral sphincter with contraction during voiding not only interfere with urinary flow, causing a functional bladder outlet obstruction but also affect the detru- sor contractions contributing to bladder dysfunctions, such as detrusor underactivity. Conceptually, urethral sphincter injection with BTX-A might facilitate void- ing by reducing urethral resistance due to its paralyzing effect and enhancing detrusor contraction due to its po- tential neuromodulation effects(7). Another mechanism that can explain BTX-A injection on the neighboring structure might be the spread of tox- ins in contiguous structures. It means that besides the effect on bladder function, BTX-A may affect the blad- der neck. Caremel et al. have discussed this idea of dis- persion of detrusor-injected toxin towards the internal sphincter(19). In this retrospective study of 11 patients with spinal cord injury and repeated Botox treatment, Caremel et al. found a decreased ejaculated volume in 10 patients following Botox treatment compared to pretreatment patients, concerning the increased inci- dence of retrograde ejaculation. With the same idea of passive distribution, some others described that fewer injection sites of toxin in detrusor were as useful as the established technique with more injection areas(20). De- spite the limited injection sites, it implies migration of BTX-A throughout the whole detrusor, meaning a local and systemic diffusion(9). Although BTX-A injections into the bladder and ure- thra have been widely used in recent years, various studies have different success rates. The possible rea- sons for this discrepancy or failure of some studies are not fully understood. The difference in success rate is the dose and site of injection (bladder or urethra or both). In a study involving patients with low detrusor contractility, 48% (13 of 27) of patients who received an injection of 50–100 U Botox into the urethral sphinc- ter showed improvement in detrusor contractility, indi- cating the neuromodulation effects between the urethral sphincter and bladder(21). Another study by Kuo et al. revealed that in patients with DSD, urethral sphincter injection of 100 U Botox reported to achieve an overall satisfactory result of 60.6% with significant improve- ment in the reduction of voiding detrusor pressure and post-void residual urine volume and an increase in max- imal urinary flow rate(22). They showed that in spinal cord injured patients with DSD, de novo urge urinary incontinency (48.5%) was the main reason for patient dissatisfaction with urethral sphincter Botox injection therapy(22). In adult patients, Liao et al. reported that urethral sphincter injection with a usual dose of 50–100 U Botox resulted in an overall success rate of 86.7% in patients with dysfunctional voiding and a success rate of 95.7% in patients with poor relaxation of the urethral sphincter(23). Franco et al. reported that increasing the Botox dose to 200–300 U resulted in increased efficacy without increasing the morbidity rate(24). Botox's repeat- ed injection in urethral sphincter with better therapeu- tic effects in both dysfunctional voiding and detrusor underactivity patients, indicating that a higher dose or repeated injection of Botox is necessary for optimal pharmacologic effects in these patients. Other reasons for the differences in the success rate of BTX-A injection in patients with NLUTD are the type and brand of toxin(25) and associated pathology such as detrusor underactivity or bladder neck dyssynergia(26). For example, in patients with detrusor underactivity, urethral sphincter Botox injection might result in a re- duction in urethral resistance, which allowed patients to void more easily with the aid of abdominal pressure. However, if the patient is weak and cannot generate ad- equate abdominal pressure to void, voiding difficulty and large post-void residual volume might persist. Also, an open bladder neck is essential because abdominal pressure can passively overcome the urethral resistance. If patients with detrusor underactivity cannot open the bladder neck by abdominal straining, urethral sphincter Botox injection might not be successful(7). A stricter definition of successful results in some stud- ies is also mentioned. Psychogenic factors can also affect sphincter relaxation. In a randomized, dou- ble-blind, placebo-controlled trial study by Jiang et al., Female Urology 546 Figure 1. Injection of diluted Dysport in peri-urethra at 12 o’clock using 31-gauge insulin syringe. Dysport injection in bladder and urethra- Sharifiaghdas et al. Female Urology 66 Vol 19 No 1 January-February 2022 138 comparing the efficacy of Botox with placebo (normal saline) injections into the urethral sphincter in patients with dysfunctional voiding and detrusor underactivity had been shown. Interestingly, the therapeutic effects of the placebo were similar to those of Botox subgroups. It seems that the local injection of either substance into the urethral sphincter might result in reduced spasticity of the urethral sphincter in patients with dysfunctional voiding. Stimulation of the urethral sphincter via solu- tion injection might provide partial urethrolytic effects on a spastic, poorly relaxed, and non-relaxed urethral sphincter, ameliorating voiding symptoms and facilitat- ing bladder emptying that increased relaxation of the urethral sphincter in patients with detrusor underactiv- ity, regardless of the pharmacologic effects of BTX-A. However, only toxin injection in the urethra resulted in increased maximum flow rate and voided volume, and reduced detrusor pressure, which demonstrates the par- alytic effect of BTX-A(7). Our study's primary limitations are the small number of patients with a lack of control groups. Also, the heter- ogeneous underlying pathogenesis of our patients with NLUTD. The third limitation was the relatively short follow-up period. A longer follow-up might reveal bet- ter pharmacologic effects of BTX-A on the urethral sphincter and eliminate the placebo effects. CONCLUSIONS According to our findings and previous studies, the periurethral injection of BTX-A (Botox or Dysport) is effective and safe in decreasing urethral resistance in DSD besides the routine use of Botox in patients with NDO. Therefore, the urethra is a potential therapeutic target in patients with NLUTD. However, dosage, in- jection schedule, and patient selection should be stand- ardized to facilitate bladder emptying, improve subjec- tive symptoms, and life quality. Our findings can help clinicians choose an alternative treatment in some pa- tients, especially those unwilling or unable to perform clean intermittent catheterization. CONFLICT ON INTEREST The authors have no conflicts of interest to declare. REFERENCES 1. Przydacz M, Denys P, Corcos J. What do we know about neurogenic bladder prevalence and management in developing countries and emerging regions of the world? Ann Phys Rehabil Med 2017; 60: 341-6. 2. Liao L. Evaluation and Management of Neurogenic Bladder: What Is New in China? Int J Mol Sci 2015; 16: 18580-600. 3. Seth JH, Dowson C, Khan MS, et al. Botulinum toxin-A for the treatment of overactive bladder: UK contributions. J Clin Urol 2013; 6: 77-83. 4. Schurch B, Hauri D, Rodic B, Curt A, Meyer M, Rossier AB. Botulinum-A toxin as a treatment of detrusor-sphincter dyssynergia: a prospective study in 24 spinal cord injury patients. J Urol 1996; 155: 1023-9. 5. Dykstra DD, Sidi AA, Scott AB, Pagel JM, Goldish GD. Effects of botulinum A toxin on detrusor-sphincter dyssynergia in spinal cord injury patients. J Urol 1988; 139: 919-22. 6. Steinhardt GF, Naseer S, Cruz OA. Botulinum toxin: novel treatment for dramatic urethral dilatation associated with dysfunctional voiding. J Urol 1997; 158: 190-1. 7. Jiang YH, Wang CC, Kuo HC. OnabotulinumtoxinA Urethral Sphincter Injection as Treatment for Non-neurogenic Voiding Dysfunction - A Randomized, Double-Blind, Placebo-Controlled Study. Sci Rep 2016; 6: 38905. 8. Soler JM, Previnaire JG, Hadiji N. Predictors of outcome for urethral injection of botulinum toxin to treat detrusor sphincter dyssynergia in men with spinal cord injury. Spinal Cord 2016; 54: 452-6. 9. Hervé F, Viaene A, Everaert K. Onabotulinumtoxin A injections in detrusor facilitate self-catheterisation in a patient with paraplegia and bladder outlet dyssynergia. BMJ case Rep 2017. 10. Uebersax JS, Wyman JF, Shumaker SA, McClish DK. Short forms to assess life quality and symptom distress for urinary incontinence in women: the Incontinence Impact Questionnaire and the Urogenital Distress Inventory. Neurourol Urodyn 1995; 14: 131-9. 11. Kuo HC. Therapeutic outcome and quality of life between urethral and detrusor botulinum toxin treatment for patients with spinal cord lesions and detrusor sphincter dyssynergia. Int J Clin Pract 2013; 67: 1044-9. 12. Schurch B, Yasuda K, Rossier AB. Detrusor bladder neck dyssynergia revisited. J Urol 1994; 152: 2066-70. 13. Chancellor MB, Fowler CJ, Apostolidis A, et al. Drug Insight: biological effects of botulinum toxin A in the lower urinary tract. Nat Clin Pract Urol 2008; 5: 319-28. 14. de Groat WC, Fraser MO, Yoshiyama M., et al. Neural control of the urethra. Scand J Urol Nephrol 2001; 35: 35-43. 15. Kakizaki H, Fraser M, De Groat W. Reflex pathways controlling urethral striated and smooth muscle function in the male rat. Am J Physiol Regul Integr Comp Physiol 1997; 272: R1647-R56. 16. Shafik A. Study of the effect of vesical filling and voiding on ureterovesical junctions and internal urethral meatus: the filling and meato‐ vesico‐ureteral reflexes. Int J Urol 1998; 5: 449-53. 17. Blaivas J. Pathophysiology of lower urinary tract dysfunction. Urol Clin North Am 1985; 12: 215-24. 18. Elbadawi A, Schenk EA. A new theory of the innervation of bladder musculature. Part 4. Innervation of the vesicourethral junction and external urethral sphincter. J Urol 1974; 111: 613-5. 19. Caremel R, Courtois F, Charvier K, Ruffion A, Journel NM. Side effects of intradetrusor botulinum toxin injections on ejaculation and fertility in men with spinal cord injury: preliminary findings. BJU Int 2012; 109: Female Urology 674 Dysport injection in bladder and urethra- Sharifiaghdas et al. Vol 19 No 1 January-February 2022 67 1698-702. 20. Siegel S, Noblett K, Mangel J, et al. Results of a prospective, randomized, multicenter study evaluating sacral neuromodulation with InterStim therapy compared to standard medical therapy at 6‐months in subjects with mild symptoms of overactive bladder. Neurourol Urodyn 2015; 34: 224-30. 21. Kuo H-C. Recovery of detrusor function after urethral botulinum A toxin injection in patients with idiopathic low detrusor contractility and voiding dysfunction. Urology 2007; 69: 57- 61. 22. Kuo HC. Satisfaction with urethral injection of botulinum toxin A for detrusor sphincter dyssynergia in patients with spinal cord lesion. Neurourol Urodyn 2008; 27: 793-96. 23. Liao Y-M, Kuo H-C. Causes of failed urethral botulinum toxin A treatment for emptying failure. Urology 2007; 70: 763-6. 24. Franco I, Landau-Dyer L, Isom-Batz G, Collett T, Reda EF. The use of botulinum toxin A injection for the management of external sphincter dyssynergia in neurologically normal children. J Urol 2007; 178: 1775-80. 25. Emami M, Shadpour P, Kashi AH, Choopani M, Zeighami M. Abobotulinum - a toxin injection in patients with refractory idiopathic detrusor overactivity: injections in detrusor, trigone and bladder neck or prostatic urethra, versus detrusor - only injections. Int Braz J Urol 2017; 43: 1122-8. 26. Liao YM, Kuo HC. Causes of failed urethral botulinum toxin A treatment for emptying failure. Urology 2007; 70: 763-6. Dysport injection in bladder and urethra- Sharifiaghdas et al. Female Urology 68