**7. Urethral Sphincter BoNT-A Injections in Patients with Poor Relaxation of The External Urethral Sphincter**

PRES as a diagnosis was first described by Kuo in 2000 and was determined based on non-relaxed surface EMG activity combined with a narrow membranous urethra during the voiding phase in the vUDS [82]. It was believed to have a different pathophysiology beyond prostatic obstruction or bladder neck dysfunction in non-neurogenic male voiding dysfunction refractory to alpha-blocker or transurethral resection of prostate [83,84]. The concept was further applied to non-neurogenic females with the same EMG findings and narrowing of the distal urethra in vUDS [85]. The cause of PRES was posited to be multifactorial, including learned habituation, pelvic floor hypertonicity, increased bladder sensitivity, or occult neuropathy [86]. However, the exact etiology responsible for the poor relaxation of the EUS or pelvic floor remains to be elucidated [82].

The cardinal symptoms of PRES are hesitancy, small urine caliber, and terminal dribbling with an IPSS voiding-to-storage subscore ratio >1 [82,87]. PRES is characterized by relatively small but stable bladder [88] and low-pressure low-flow during voiding phase [89], which is different from the typical high-pressure low-flow presentation in DV or extremely large, compliant bladder in FS. The prevalence rates were 12–20% [87,89,90] and 17.6% [4] in male and female non-neurogenic VD refractory to medication patients, respectively. The incidence increased in young males [89] in patients with bladder pain syndrome [88] and in idiopathic DU patients [91]. Sphincteric BoNT-A injections might provide chemo-denervation of the EUS by inhibition of acetylcholine release in the neuromuscular junction to relieve the USD in PRES [23].

The improvement rate in clinical or urodynamic parameters after injection of 100 units of BoNT-A in patients with PRES was reported to be 79 to 96% [48,55]. However, with a stricter definition of excellent outcome, only 42% of such patients had restored spontaneous voiding or had a >25% improvement in urodynamic parameters [48]. Great patient satisfaction was also reported to be approximately 47–52% [81]. It was concluded that the major predictive factors for a successful outcome were opening of the bladder neck and a higher baseline Qmax, but not the type of USD [81]. An increased recovery rate of detrusor contractility was further reported in idiopathic DU combined with PRES [25]. This result supported the hypothesis suggesting that the low-pressure low-flow dysfunction presented in PRES might be the result of detrusor suppression induced by non-relaxed EUS activity. With the aid of EUS relaxation after BoNT-A injections, the suppressed detrusor function was resumed. Clinical studies on sphincteric BoNT-A efficacy and adverse events of PRES are summarized in Table 3. Notably, most of the therapeutic effects of EUS BoNT-A injections in PRES came from studies conducted by Kuo's research group. Further work from other clinical facilities and laboratories might lead to more prudent inferences.
