**1. Introduction**

Voiding dysfunction may result from detrusor underactivity (DU), bladder outlet obstruction (BOO), urethral sphincter hyperactivity, or poor relaxation of the external urethral sphincter (PRES) during micturition. A previous urodynamic study reported DU in 12.4% of men [1] and in 23.1% of women [2] with voiding lower urinary tract symptoms (LUTS). Urethral sphincter hyperactivity was noted in 17.0% of women [3], and PRES in 39.5% of men [1] and 17.6% of women [3] with voiding dysfunction. Voiding dysfunction may be neurogenic or non-neurogenic in origin, with symptoms of dysuria and large post-void residual (PVR) volume, and might result in upper urinary tract deterioration. Recently, botulinum toxin A (BoNT-A) has been applied as an injection into the urethral sphincter to treat voiding dysfunction refractory to medical treatment.

In the beginning, BoNT-A was used to treat patients with severe dysuria due to spinal cord injury (SCI) and detrusor sphincter dyssynergia (DSD) [4]. Reduction of the urethral sphincter hypertonicity through chemical denervation was noted after treatment. Patients usually can urinate more efficiently. BoNT-A has been safely used for treatment of neurogenic urethral sphincter spasticity in patients with DSD due to SCI, Parkinson's disease, cerebrovascular accidents (CVA), and multiple sclerosis (MS). The treatment outcome was initially reported satisfactorily, with adverse events of the increase of urinary incontinence and incomplete bladder emptying [5].

Because BoNT-A can improve voiding efficiency and detrusor contractility, this treatment has been further applied to treat patients with non-neurogenic voiding dysfunction (NNVD) due to urethral sphincter hyperactivity, PRES, and a non-relaxing urethral sphincter in patients with dysfunctional voiding (DV) or DU [6,7]. After BoNT-A injection, two thirds of patients voided smoothly and had significant decreases in PVR; the voiding derusor pressure was also decreased [7]. Even a dose of 50 U onabotulinumtoxinA could result in excellent and improved results overall in 39% of patients [8]. However, because the therapeutic outcome is not consistent and the therapeutic duration was short, urethral BoNT-A injection for voiding dysfunction remains an off-label treatment. In contrast, BoNT-A detrusor injection has already been licensed for use in patients with neurogenic detrusor overactivity (NDO) or non-neurogenic overactive bladder (OAB) to treat urinary incontinence [9]. Nevertheless, for patients with voiding dysfunction not due to BOO, urethral BoNT-A injections remain an attractive treatment modality for various types of adults with pediatric voiding dysfunctions [10,11].

Although BoNT-A has been used in treatment of voiding dysfunction for a long time, the success rate varies widely and patients might not be satisfied with the treatment outcome. Urethral BoNT-A injection had been shown to decrease voiding pressure in NNVD, but the success rate was not superior to normal saline injection [12]. For patients with Fowler's syndrome and urinary retention due to urethral sphincter hyperactivity, onabotulinumtoxinA injection could improve subjective and objective parameters [13]. In patients with DU and voiding dysfunction, a 60% success rate can be achieved after urethral BoNT-A injection [14]. Because voiding is a combination of detrusor contraction and relaxation of the bladder outlet structures, including the bladder neck, prostatic urethra (in men), urethral sphincter, pelvic floor muscles, and the urethra, voiding dysfunction might be caused by a different combination of bladder and bladder outlet dysfunctions during voiding. In patients with DU, a powerful abdominal pressure by straining is necessary, while in patients with DV or DSD, adequate relaxation of the urethral resistance is needed to achieve efficient voiding. BoNT-A urethral sphincter injection can reduce urethral sphincter resistance, but this therapeutic effect might not be adequate to restore voiding efficiency in all patients. This study retrospectively analyzed the results of our previously treated patients with voiding dysfunction and compared the therapeutic efficacy between patients with voiding dysfunction due to neurogenic versus non-neurogenic origin, and between different detrusor functions (DU versus non-DU) or urethral dysfunction (DV versus PRES).
