**1. Introduction**

Neurogenic or non-neurogenic voiding dysfunction, with symptoms of difficulty voiding and large post-void residual (PVR) volumes, which may result in upper urinary tract deterioration if not well managed. Voiding dysfunction without neurogenic insult may be due to detrusor underactivity (DU) and bladder outlet obstruction (BOO, such as benign prostate hyperplasia, bladder neck dysfunction, or urethral sphincter hyperactivity, like dysfunctional voiding (DV) [1] or poor relaxation of the external urethral sphincter (PRES) during micturition [2].

DU is a common urological condition whose treatment has remained challenging. In a recent study, detrusor contractility may be reversed by the medical or surgical treatment [3]. Surgical techniques such as transurethral incision of the bladder neck (TUI-BN) or transurethral resection of the prostate (TUR-P) and urethral onabulinumtoxinA (BoNT-A)

**Citation:** Chen, S.-F.; Kuo, H.-C. Urethral Sphincter Botulinum Toxin A Injection for Non-Spinal Cord Injured Patients with Voiding Dysfunction without Anatomical Obstructions: Which Patients Benefit Most? *Toxins* **2023**, *15*, 87. https:// doi.org/10.3390/toxins15020087

Received: 28 November 2022 Revised: 25 December 2022 Accepted: 11 January 2023 Published: 17 January 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

injection aim to decrease bladder outlet resistance [3]. Urethral injections of BoNT-A were first used for patients with detrusor sphincter dyssynergia or patients with spinal cord injury (SCI), and it effectively decreased the urethral pressure profile and PVR volume [4]. Phelan et al. confirmed the therapeutic efficacy of sphincteric BoNT-A injections in SCI patients with various etiologies of DSD in both men and women. BoNT-A decreases urethral resistance in pharmacology by paralyzing the striated sphincter muscle through the inhibition of acetylcholine release from the neuromuscular junction [5]. In recent years, some studies reported different causes of urethral sphincter dysfunction, be it neurogenic or non-neurogenic, and significant improvements in voiding after sphincteric BoNT-A injections [6].

Although urethral BoNT-A injections have been used in treating non-SCI patients with voiding dysfunction in recent years, the success rate varies widely, and patients could be unsatisfied with the outcome. A previous randomized, double-blind, placebo-controlled trial showed the success rate was not superior to that of normal saline injections [7]. We believe inducing powerful abdominal pressure by straining is necessary for voiding in DU patients; conversely, in patients with DV or PRES, adequate relaxation of the urethral resistance is needed to achieve efficient voiding. Therefore, some patients have benefits in terms of subjective or objective responses. Our previous study reported a 60% success rate in DU and voiding dysfunction after BoNT-A injections [8]. Nowadays, it still is an alternative treatment and not a standard one, and which of them benefits patients with voiding dysfunction most is unclear. We aimed to analyze the efficacy of urethral BoNT-A injections in treating voiding dysfunction in non-SCI patients and compare the therapeutic efficacy between the different etiologies of voiding dysfunction (DU, DV, and PRES).
