The Therapeutic Effects and Pathophysiology of Botulinum Toxin A on Voiding Dysfunction Due to Urethral Sphincter Dysfunction

Abstract

Neurogenic and non-neurogenic urethral sphincter dysfunction are common causes of voiding dysfunction. Injections of botulinum toxin A (BoNT-A) into the urethral sphincter have been used to treat urethral sphincter dysfunction (USD) refractory to conventional treatment. Since its first use for patients with detrusor sphincter dyssynergia in 1988, BoNT-A has been applied to various causes of USD, including dysfunctional voiding, Fowler's syndrome, and poor relaxation of the external urethral sphincter. BoNT-A is believed to decrease urethral resistance via paralysis of the striated sphincter muscle through inhibition of acetylcholine release in the neuromuscular junction. Recovery of detrusor function in patients with detrusor underactivity combined with a hyperactive sphincter also suggested the potential neuromodulation effect of sphincteric BoNT-A injection. A large proportion of patients with different causes of USD report significant improvement in voiding after sphincteric BoNT-A injections. However, patient satisfaction might not increase with an improvement in the symptoms because of concomitant side effects including exacerbated incontinence, urinary urgency, and over-expectation. Nonetheless, in terms of efficacy and safety, BoNT-A is still a reasonable option for refractory voiding function. To date, studies focusing on urethral sphincter BoNT-A injections have been limited to the heterogeneous etiologies of USD. Further well-designed studies are thus needed. Key Contribution:This article summarized the effects of sphincteric BoNT-A injections among various USDs in view of pathophysiology, urodynamic outcome, and subjective patient reports.

Therapeutic Effects of Urethral Sphincter Botulinum Toxin A Injection on Dysfunctional Voiding with Different Videourodynamic Characteristics in Non-Neurogenic Women

“…In VUDS of female DV, different characteristics are observed in the urethral obstruction, such as a typical downward spiral shape mid-urethra, a narrow distal urethra, and a narrow mid-urethra after incision of previous bladder neck (BN) obstruction. These different VUDS characteristics suggest a different underlying pathophysiology of female DV [ 15 , 16 ]. This study retrospectively evaluated the therapeutic efficacy of urethral BoNT-A on non-neurogenic female DV and searched for predictive factors for a successful treatment outcome.…”

Therapeutic Efficacy of Urethral Sphincteric Botulinum Toxin Injections for Female Sphincter Dysfunctions and a Search for Predictive Factors

“…Many of these studies focused on patients with DSD, but only a handful of them discussed DV and PRES patients. The rates of subjective improvement were around 70%-87%, 61%-88%, and 79%-96% for DV, DSD, and PRES after the sphincteric BoNT-A injection [16] among gender-mixed patients, respectively. These reported outcomes were similar to the results in the present study, where the subjective and objective improvement rates were 65%/74%, 75%/50% for DV, DSD, and 65%/68% for PRES, respectively, in female patients.…”

“…For DV and DSD patients, the bladder outlet obstruction, induced by the dyssynergic EUS activity during detrusor contraction, is responsible for a high-pressure, low-flow pattern with proximal urethral dilatation [13]. In contrast, poorly relaxed EUS activity caused by an incompletely reversed guarding reflex may have a reflex effect inhibiting the contraction of the detrusor muscle [14][15][16], which may explain the low-pressure low-flow pattern without STU in patients diagnosed with PRES. The hypothesis of a EUS-induced inhibitory effect on the micturition reflex [17] in PRES is supported by the finding of an increased recovery rate of detrusor contractility in patients with DU with concomitant PRES after sphincteric BoNT-A injections [18].…”

Fowler’s Syndrome—The Cause of Urinary Retention in Young Women, Often Forgotten, but Significant and Challenging to Treat

“…In the following years, transurethral or periurethral injections of 50–100 U BoNT-A were attempted several times, resulting in an improvement of 37%–43% of female patients. The limitations of the trials were the small size of the study groups, the lack of control groups, various injection techniques, and different doses of BoNT-A [ 28 ].…”