Application of Botulinum Neurotoxin in Lower Urinary Tract Dysfunctions: Where Are We Now?

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 31108

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Special Issue Editor

Special Issue Information

Dear Colleagues,

In recent decades, botulinum toxin A has been widely used in the treatment of several lower urinary tract dysfunctions (LUTDs), such as overactive bladder syndrome (OAB), neurogenic detrusor overactivity (NDO), interstitial cystitis (IC), and voiding dysfunction. Although botulinum toxin A intravesical injection has been approved for OAB and NDO, the other application of this neurotoxin in LUTDs is yet to be approved. Because some clinical experiences of adverse events have limited its wide application, this treatment has gradually been considered as an unpopular procedure for LUTDs. However, evidence has shown that botulinum toxin A has advantages in LUTDs compared with oral pharmacological medications, especially in elderly OAB patients with cognitive dysfunction, patients with bladder neck dysfunction or dysfunctional voiding, idiopathic voiding dysfunction due to poor relaxation of the external sphincter, or intractable bladder pain syndrome due to IC or ketamine-induced cystitis, male patients with lower urinary tract symptoms and a small prostate, and pediatric patients with OAB or dysfunctional voiding. In addition, botulinum toxin A can also be carried across the urothelial barrier by the aid of bladder treatment such as liposomes or low-energy shock waves. There are several LUTDs other than OAB and NDO that can benefit from botulinum toxin A injection or intravesical instillation. This Special Issue welcomes original or review articles that fucus on the novel applications of botulinum toxin A in LUTDs, either in human or animal studies. The collection of this Special Issue of Toxins will provide updated knowledge and information on the current position of botulinum toxin A in functional urology and LUTDs.

Prof. Dr. Hann-Chorng Kuo
Guest Editor

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Keywords

  • overactive bladder
  • interstitial cystitis
  • neurogenic detrusor overactivity
  • voiding dysfunction
  • lower urinary tract symptoms

Published Papers (14 papers)

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Editorial

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3 pages, 201 KiB  
Editorial
Botulinum Toxin Brings a Light to the Shadow of Functional Urology
by Hann-Chorng Kuo
Toxins 2023, 15(5), 321; https://doi.org/10.3390/toxins15050321 - 6 May 2023
Viewed by 1321
Abstract
Functional urology involves a large scale of lower urinary tract dysfunctions (LUTDs), including bladder dysfunctions and bladder outlet dysfunctions [...] Full article

Research

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11 pages, 540 KiB  
Article
Comparison of the Clinical Efficacy and Adverse Events between Intravesical Injections of Platelet-Rich Plasma and Botulinum Toxin A for the Treatment of Interstitial Cystitis Refractory to Conventional Treatment
by Jia-Fong Jhang, Wan-Ru Yu and Hann-Chorng Kuo
Toxins 2023, 15(2), 121; https://doi.org/10.3390/toxins15020121 - 2 Feb 2023
Cited by 2 | Viewed by 2271
Abstract
Background: Intravesical injection of Botulinum toxin A (BoNT-A) and platelet-rich plasma (PRP) have been reported to alleviate bladder pain and decrease nocturia in patients with refractory interstitial cystitis/bladder pain syndrome (IC/BPS). Both treatments are novel and there has no comparison between them. This [...] Read more.
Background: Intravesical injection of Botulinum toxin A (BoNT-A) and platelet-rich plasma (PRP) have been reported to alleviate bladder pain and decrease nocturia in patients with refractory interstitial cystitis/bladder pain syndrome (IC/BPS). Both treatments are novel and there has no comparison between them. This study compared the therapeutic effects and adverse events between IC/BPS patients receiving PRP or BoNT-A injections. Materials and Methods: This study retrospectively analyzed female patients with IC/BPS who were refractory to conventional treatment and received BoNT-A (n = 26) or PRP (n = 30) injections within the previous two years. Patients were arbitrarily treated with four monthly injections of PRP or a single injection of 100 U of BoNT-A. All injections were followed by cystoscopic hydrodistention. The primary endpoint was the global response assessment (GRA), and secondary endpoints were changes in the O’Leary-Sant IC symptom score, visual analog score (VAS) of bladder pain, voiding diary, and uroflow measures from baseline to six months after the first injection day. Results: The baseline demographics revealed no significant difference between groups. The GRA at one, three, and six months was similar between groups. A significant improvement in IC symptom scores was noted in both groups. Although VAS was significantly improved in overall patients, no significant difference was noted between the PRP and BoNT-A groups at 6 months. Only half of the study cohort had a GRA ≥2 at six months. An increase in the post-void residual was noted one month after the BoNT-A injection, but there was no difference between groups at three and six months. More patients reported dysuria (19.2% vs. 3.3%, p = 0.086) and urinary tract infection (UTI, 15.4% vs. 0%, p = 0.041) after BoNT-A injection than after the PRP injections. The time from the first injection to receiving alternative treatment was similar between groups. Conclusion: Both intravesical PRP and BoNT-A injections have similar efficacy in IC symptom improvement. However, only half of the study cohort had a GRA of ≥2 at the six-month follow-up BoNT-A injection carries a potential risk of UTI after treatment. Full article
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10 pages, 265 KiB  
Article
Botulinum Toxin A Injection for Autonomic Dysreflexia—Detrusor Injection or Urethral Sphincter Injection?
by Po-Ming Chow and Hann-Chorng Kuo
Toxins 2023, 15(2), 108; https://doi.org/10.3390/toxins15020108 - 26 Jan 2023
Cited by 4 | Viewed by 1878
Abstract
Spinal cord injuries (SCI) have a profound impact on autonomic systems, sometimes resulting in multi-organ dysfunction, including of the neurogenic bladder. Autonomic dysreflexia (AD) is commonly seen in patients with SCI above T6 when the injured cord develops a deregulated sympathetic reflex, which [...] Read more.
Spinal cord injuries (SCI) have a profound impact on autonomic systems, sometimes resulting in multi-organ dysfunction, including of the neurogenic bladder. Autonomic dysreflexia (AD) is commonly seen in patients with SCI above T6 when the injured cord develops a deregulated sympathetic reflex, which can be induced by bladder sensation and can cause hypertensive crisis. While intravesical injection of botulinum toxin A (Botox) is a standard therapy for neurogenic detrusor overactivity, the role of Botox for AD has rarely been described. This study reviewed the medical records of SCI patients who reported AD and received either detrusor or urethral sphincter injection with Botox. The primary endpoint is the subjective improvement of AD. The secondary endpoint is a change in videourodynamic parameters before and after Botox injection. A total of 200 patients were enrolled for analysis. There were 125 (62.5%) patients in the detrusor injection group, and 75 (37.5%) in the urethral sphincter injection group. There were 79 (63.2%) patients in the detrusor injection group and 43 (57.3%) in the urethral sphincter injection group reporting moderate or marked improvement. Detrusor injection leads to a greater improvement in AD, probably because of decreased detrusor pressure and increased compliance after Botox injection. Urethral sphincter injection appears to have a modest effect on AD, despite general improvements in the voiding parameters of videourodynamic study. Full article
13 pages, 318 KiB  
Article
Intravesical Injection of Botulinum Toxin Type A in Patients with Refractory Overactive Bladder—Results between Young and Elderly Populations, and Factors Associated with Unfavorable Outcomes
by Yin-Chien Ou, Yao-Lin Kao, Yi-Hui Ho, Kuan-Yu Wu and Hann-Chorng Kuo
Toxins 2023, 15(2), 95; https://doi.org/10.3390/toxins15020095 - 19 Jan 2023
Cited by 3 | Viewed by 2301
Abstract
Intravesical botulinum toxin type A (BoNT-A) injection has been recognized as the standard treatment for refractory overactive bladder (OAB). However, its therapeutic efficacy and safety have not been thoroughly reviewed in elderly patients. This study aims to provide treatment outcomes for patients aged [...] Read more.
Intravesical botulinum toxin type A (BoNT-A) injection has been recognized as the standard treatment for refractory overactive bladder (OAB). However, its therapeutic efficacy and safety have not been thoroughly reviewed in elderly patients. This study aims to provide treatment outcomes for patients aged ≥75 years, and to identify factors associated with unfavorable outcomes. Patients receiving intradetrusor injections of 100 U onabotulinumtoxinA for refractory OAB between 2011 and 2021 were retrospectively reviewed. Urodynamic parameters, underlying comorbidities, subjective success, and unfavorable outcomes were assessed. A total of 192 patients were included, and 65 of them were classified into the elderly group. For the elderly group, 60.0% experienced subjective dryness, and 84.6% remained subjective success at 6 months after the injections. The prevalence rates of common unfavorable outcomes, including urinary tract infections, large post-void residual urine volume, and urinary retention, were 9.2%, 27.7%, and 12.3%, respectively. Multivariate analysis revealed that female, baseline urodynamic parameters, and diabetes mellitus were associated with unfavorable outcomes in the elderly group. Intravesical BoNT-A injections provide comparable therapeutic efficacy and safety concerns in elderly patients with refractory OAB. A thorough consultation for treatment benefits and possible adverse events is mandatory before the procedure. Full article
9 pages, 500 KiB  
Article
Urethral Sphincter Botulinum Toxin A Injection for Non-Spinal Cord Injured Patients with Voiding Dysfunction without Anatomical Obstructions: Which Patients Benefit Most?
by Sheng-Fu Chen and Hann-Chorng Kuo
Toxins 2023, 15(2), 87; https://doi.org/10.3390/toxins15020087 - 17 Jan 2023
Viewed by 2034
Abstract
Objective: Treating voiding dysfunction without anatomical obstructions is challenging. Urethral onabotulinum toxin A (BoNT-A) is used in treating voiding dysfunction; however, the success rate varies widely, and patients may not be satisfied with the treatment outcome. This study compared the efficacy of the [...] Read more.
Objective: Treating voiding dysfunction without anatomical obstructions is challenging. Urethral onabotulinum toxin A (BoNT-A) is used in treating voiding dysfunction; however, the success rate varies widely, and patients may not be satisfied with the treatment outcome. This study compared the efficacy of the urethral BoNT-A injection between patients with different non-spinal cord injury (SCI) voiding dysfunctions. Materials and Methods: This study retrospectively analyzed patients with refractory voiding dysfunction, including detrusor underactivity (DU), dysfunctional voiding (DV), and poor relaxation of the external sphincter (PRES) who received the urethral sphincter 100 U BoNT-A injection. The treatment outcomes were assessed via a global response assessment (GRA) one month after treatment. Baseline and follow-up videourodynamic study (VUDS) parameters were also compared. Results: Totally, 161 patients (60 with DU, 77 with DV, and 24 with PRES) with a mean age of 58.8 ± 20.2 were enrolled, of which 62.1% had a good response (GRA ≥ 2) after urethral BoNT-A injection. DV patients had a higher success rate (76.6%) than DU (50%) and PRES (45.8%) patients (p = 0.002). A diagnosis of DV, higher voided volume and recurrent urinary tract infection were predictors of a good treatment response, while the cervical cancer status post-radical surgery predicted a poor response. Receiver operating characteristic (ROC) curve analyses identified PVR > 250 mL as a negative predictor (p = 0.008) in DU patients. Conclusions: The urethral BoNT-A injection provides a satisfactory success rate for non-SCI voiding dysfunction. Patients with DV benefit most from both subjective and objective parameters. Approximately 50% of patients with DU and PRES also had a fair response. PVR > 250 mL was a negative predictor in DU patients. Full article
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9 pages, 273 KiB  
Article
Predictive Factors for a Successful Treatment Outcome in Patients with Different Voiding Dysfunction Subtypes Who Received Urethral Sphincter Botulinum Injection
by Yao-Lin Kao, Yin-Chien Ou, Kuen-Jer Tsai and Hann-Chorng Kuo
Toxins 2022, 14(12), 877; https://doi.org/10.3390/toxins14120877 - 15 Dec 2022
Viewed by 1502
Abstract
Voiding dysfunction is a common but bothersome problem in both men and women. Urethral sphincter botulinum toxin A (BoNT-A) injections could serve as an option in refractory cases. This study analyzed the efficacy and outcome predictors of the injections in patients with functional, [...] Read more.
Voiding dysfunction is a common but bothersome problem in both men and women. Urethral sphincter botulinum toxin A (BoNT-A) injections could serve as an option in refractory cases. This study analyzed the efficacy and outcome predictors of the injections in patients with functional, non-neurogenic voiding dysfunction. Patients who received urethral sphincter BoNT-A injection for refractory voiding dysfunction due to detrusor underactivity (DU) or urethral sphincter dysfunction were retrospectively reviewed. A successful outcome was defined as a marked improvement as reported in the global response assessment. The study evaluated the therapeutic efficacy of urethral sphincter BoNT-A injections and measured the changes in urodynamic parameters after the procedure in the patients. A total of 181 patients including 138 women and 43 men were included. The overall success rate was 64%. A lower success rate was noted in patients with DU compared to those with urethral sphincter dysfunction in both genders. In the multivariable analysis, recurrent urinary tract infection (UTI) and bladder voiding efficiency (BVE) were positive predictors for a successful outcome, while DU was a negative predictor. Urethral sphincter BoNT-A injection is an effective treatment for refractory non-neurogenic voiding dysfunction. Baseline BVE and history of recurrent UTI positively predict a successful outcome. DU is a negative outcome predictor. Full article
11 pages, 519 KiB  
Article
Treatment Outcomes of Intravesical Botulinum Toxin A Injections on Patients with Interstitial Cystitis/Bladder Pain Syndrome
by Wan-Ru Yu, Yuan-Hong Jiang, Jia-Fong Jhang, Wei-Chuan Chang and Hann-Chorng Kuo
Toxins 2022, 14(12), 871; https://doi.org/10.3390/toxins14120871 - 11 Dec 2022
Cited by 5 | Viewed by 1697
Abstract
Botulinum toxin A (BoNT-A) is effective in reducing bladder hypersensitivity and increasing capacity through the effects of anti-inflammation in the bladder urothelium; however, studies on the treatment outcome of interstitial cystitis/bladder pain syndrome (IC/BPS) are lacking. We investigated the treatment outcome in IC/BPS [...] Read more.
Botulinum toxin A (BoNT-A) is effective in reducing bladder hypersensitivity and increasing capacity through the effects of anti-inflammation in the bladder urothelium; however, studies on the treatment outcome of interstitial cystitis/bladder pain syndrome (IC/BPS) are lacking. We investigated the treatment outcome in IC/BPS patients receiving intravesical BoNT-A injections. This retrospective study included IC/BPS patients who had 100U BoNT-A intravesical injections in the past 20 years. The treatment outcomes at 6 months following the BoNT-A treatment were evaluated using the global response assessment (GRA) scale. The treatment outcomes according to the GRA scale include clinical symptoms, urodynamic parameters, cystoscopic characteristics, and urinary biomarkers, and it was these predictive factors for achieving satisfactory outcomes which were investigated. Among the 220 enrolled patients (180 women, 40 men) receiving BoNT-A injections, only 87 (40%) had significantly satisfactory treatment outcomes. The satisfactory group showed significantly larger voided volumes, and lower levels of both the urinary inflammatory protein MCP-1 and the oxidative stress biomarker 8-isoprostane in comparison to the unsatisfactory group. The IC severity and detrusor pressure are predictive factors of BoNT-A treatment outcomes. IC/BPS patients with less bladder inflammation showed satisfactory outcomes with intravesical BoNT-A injections. Patients with severe bladder inflammation might require more intravesical BoNT-A injections to achieve a satisfactory outcome. Full article
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10 pages, 636 KiB  
Article
Preliminary Exploration of a New Therapy for Interstitial Cystitis/Bladder Pain Syndrome: Botulinum Toxin A Combined with Sapylin
by Wenshuang Li, Zhenming Zheng, Kaiqun Ma, Caixia Zhang, Kuiqing Li, Paierhati Tayier and Yousheng Yao
Toxins 2022, 14(12), 832; https://doi.org/10.3390/toxins14120832 - 30 Nov 2022
Cited by 2 | Viewed by 1650
Abstract
Interstitial cystitis/bladder pain syndrome (IC/BPS) is an intractable disease without long-term effective therapy. This study aims to evaluate the efficacy and safety of botulinum toxin A (BoNT/A) plus Sapylin, which might modulate the immune response of the bladder in the treatment of IC/BPS [...] Read more.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is an intractable disease without long-term effective therapy. This study aims to evaluate the efficacy and safety of botulinum toxin A (BoNT/A) plus Sapylin, which might modulate the immune response of the bladder in the treatment of IC/BPS patients. We retrospectively investigated the clinical outcomes among 34 patients who accepted repeated Sapylin instillations after 200 U of BoNT/A submucosally injected into bladder walls (Mix group) and 28 patients who received BoNT/A alone (Control group). Each of the bladder walls (left, right, anterior and posterior) was injected six times with 8 U of BoNT/A per injection. The primary outcome measure was the global response assessment. The results showed that at 6 months post-injection, the response rate in the Mix group was remarkably higher than that in the Control group (58.8% vs. 28.6%, p < 0.05). The mean effective duration of the responders in the Mix group was apparently better than that in the Control group (27.5 (range 0–89) vs. 4.9 (range 0–11) months, p < 0.05). None of the patients experienced serious adverse events. In conclusion, repeated intravesical instillations of Sapylin after BoNT/A injection can produce significantly better clinical outcomes than BoNT/A alone in IC/PBS patients. Full article
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11 pages, 1542 KiB  
Article
Effect of Intratrigonal Botulinum Toxin in Patients with Bladder Pain Syndrome/Interstitial Cystitis: A Long-Term, Single-Center Study in Real-Life Conditions
by Pedro Abreu-Mendes, António Ferrão-Mendes, Francisco Botelho, Francisco Cruz and Rui Pinto
Toxins 2022, 14(11), 775; https://doi.org/10.3390/toxins14110775 - 10 Nov 2022
Cited by 1 | Viewed by 2061
Abstract
The high percentage of treatment failures seen in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) managed conservatively frequently demands invasive treatment options. We aimed to evaluate the long-term efficacy and adverse events of intratrigonal botulinum toxin injection in such circumstances, as well as [...] Read more.
The high percentage of treatment failures seen in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) managed conservatively frequently demands invasive treatment options. We aimed to evaluate the long-term efficacy and adverse events of intratrigonal botulinum toxin injection in such circumstances, as well as to determine possible predictors of response to toxin treatment. A retrospective cohort study included 47 female BPS/IC patients treated with onabotulinum toxin A (OnabotA) in a tertiary hospital between the years 2009 and 2022. All patients received 100 U of OnabotA in ten injections limited to the trigonal area. Patients were divided into three groups based on their treatment response as responders, non-responders and lost to follow-up due to non-medical reasons. The clinical and surgical records of the individuals were retrieved, including the 10-point visual analogue scale (VAS), the number of treatments, the time between injections, and the age at the first injection. A total of 25 patients (>50% of the cohort) were long-term responders, but none of the evaluated parameters was a predictor for this circumstance: age, pain intensity, or duration of improvement following the injection. The time between injections was stable (around 1 year). No severe adverse events were registered. The intratrigonal injection of botulinum toxin in patients with BPS/IC was an effective and safe long-term treatment for patients’ refractory to conservative forms of treatment. Age, basal pain intensity, and time to injection request did not predict long-term response to OnaBotA. Full article
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Review

Jump to: Editorial, Research

12 pages, 308 KiB  
Review
Treating Neurogenic Lower Urinary Tract Dysfunction in Chronic Spinal Cord Injury Patients—When Intravesical Botox Injection or Urethral Botox Injection Are Indicated
by Po-Cheng Chen, Kau-Han Lee, Wei-Chia Lee, Ting-Chun Yeh, Yuh-Chen Kuo, Bing-Juin Chiang, Chun-Hou Liao, En Meng, Yao-Lin Kao, Yung-Chin Lee and Hann-Chorng Kuo
Toxins 2023, 15(4), 288; https://doi.org/10.3390/toxins15040288 - 17 Apr 2023
Cited by 3 | Viewed by 1794
Abstract
Lower urinary tract symptoms (LUTS), such as urgency, urinary incontinence, and/or difficulty voiding, hamper the quality of life (QoL) of patients with spinal cord injury (SCI). If not managed adequately, urological complications, such as urinary tract infection or renal function deterioration, may further [...] Read more.
Lower urinary tract symptoms (LUTS), such as urgency, urinary incontinence, and/or difficulty voiding, hamper the quality of life (QoL) of patients with spinal cord injury (SCI). If not managed adequately, urological complications, such as urinary tract infection or renal function deterioration, may further deteriorate the patient’s QoL. Botulinum toxin A (BoNT-A) injection within the detrusor muscle or urethral sphincter yields satisfactory therapeutic effects for treating urinary incontinence or facilitating efficient voiding; however, adverse effects inevitably follow its therapeutic efficacy. It is important to weigh the merits and demerits of BoNT-A injection for LUTS and provide an optimal management strategy for SCI patients. This paper summarizes different aspects of the application of BoNT-A injection for lower urinary tract dysfunctions in SCI patients and provides an overview of the benefits and drawbacks of this treatment. Full article
10 pages, 638 KiB  
Review
Intravesical Injection of Botulinum Toxin Type A in Men without Bladder Outlet Obstruction and Post-Deobstructive Prostate Surgery
by Hsiang-Ying Lee and Hann-Chorng Kuo
Toxins 2023, 15(3), 221; https://doi.org/10.3390/toxins15030221 - 15 Mar 2023
Cited by 3 | Viewed by 1930
Abstract
Purpose: A significant proportion of men without bladder outlet obstruction (BOO) have been reported to have overactive bladders (OAB). This article aimed to review the specific group of reports on the use of botulinum toxin type A (BTX-A) injections into the bladder wall. [...] Read more.
Purpose: A significant proportion of men without bladder outlet obstruction (BOO) have been reported to have overactive bladders (OAB). This article aimed to review the specific group of reports on the use of botulinum toxin type A (BTX-A) injections into the bladder wall. Materials and methods: Original articles reporting men with small prostates without BOO were identified through a literature search using the PubMed and EMBASE databases. Finally, we included 18 articles that reviewed the efficacy and adverse effects of BTX-A injections in men. Results: Of the 18 articles screened, 13 demonstrated the therapeutic efficacy and adverse effects of BTX-A injections in men. Three studies compared BTX-A injection response between patients without prior prostate surgery and those undergoing prior prostate surgery, including transurethral resection of the prostate and radical prostatectomy (RP). Patients with prior RP experienced better efficacy and had a low risk of side effects. Two studies focused on patients who had undergone prior surgery for stress urinary incontinence, including male sling and artificial urethral sphincter surgery. The BTX-A injection was a safe and effective procedure for this specific group. OAB in men was found to have a different pathophysiology mechanism from that in female patients, which may decrease the efficacy of BTX-A injection in men. However, patients with small prostates and low prostate-specific antigen levels demonstrated better efficacy and tolerability after BTX-A injection. Conclusions: Although intravesical injection of BTX-A was a good option for controlling refractory OAB in men, the evidence-based guidelines are still limited. Further research is necessary to better understand the role of BTX-A injections on various aspects and histories. Therefore, treating patients using strategies tailored to their individual conditions is important. Full article
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14 pages, 2588 KiB  
Review
Role of Urological Botulinum Toxin-A Injection for Overactive Bladder and Voiding Dysfunction in Patients with Parkinson’s Disease or Post-Stroke
by Ju-Chuan Hu, Lin-Nei Hsu, Wei-Chia Lee, Yao-Chi Chuang and Hung-Jen Wang
Toxins 2023, 15(2), 166; https://doi.org/10.3390/toxins15020166 - 17 Feb 2023
Cited by 9 | Viewed by 3772
Abstract
Botulinum toxin A (BoNT-A) paralyzes muscle by blocking acetylcholine release at the synaptic junction. BoNT-A has shown its therapeutic effects in neurological disorders such as Parkinson’s disease (PD) and post-stroke spasticity. A high proportion of patients with PD and post-stroke develop neurogenic detrusor [...] Read more.
Botulinum toxin A (BoNT-A) paralyzes muscle by blocking acetylcholine release at the synaptic junction. BoNT-A has shown its therapeutic effects in neurological disorders such as Parkinson’s disease (PD) and post-stroke spasticity. A high proportion of patients with PD and post-stroke develop neurogenic detrusor overactivity (nDO) and then develop urinary incontinence and overactive bladder (OAB) symptoms. This study aimed to disclose the safety and efficacy of BoNT-A injection in treating bladder and voiding dysfunction in PD and post-stroke patients by reviewing the current evidence. At present, intradetrusor injection of BoNT-A is a Food and Drug Administration (FDA)-approved third-line therapy for nDO and idiopathic OAB. Although intradetrusor injection of onaBoNT-A 200 U is already approved for nDO treatment, most researchers would like to manage PD and post-stroke patients by using onaBoNT-A 100 U intradetrusor injection to achieve long-term efficacy and reduce adverse effects. However, in contrast to its inclusion in the International Continence Society guidelines for PD treatment, the clinical use of BoNT-A for post-stroke patients is limited to experimental use due to the development of urinary retention in about one-fifth of patients. For treating urethral pseudodyssynergia, half of patients may respond to onaBoNT-A 100 U urethral injection. However, refinement is needed to reduce unwanted urinary incontinence. Full article
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11 pages, 1487 KiB  
Review
Liposome-Encapsulated Botulinum Toxin A in Treatment of Functional Bladder Disorders
by Fan-Ching Hung and Hann-Chorng Kuo
Toxins 2022, 14(12), 838; https://doi.org/10.3390/toxins14120838 - 1 Dec 2022
Cited by 6 | Viewed by 2172
Abstract
Botulinum toxin A (BoNT-A) intravesical injections have been used to treat patients with refractory functional bladder disorders such as overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS), but the risk of adverse events and the need for repeated injections continue to prevent [...] Read more.
Botulinum toxin A (BoNT-A) intravesical injections have been used to treat patients with refractory functional bladder disorders such as overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS), but the risk of adverse events and the need for repeated injections continue to prevent widespread application of this treatment. Liposomes are vesicles that comprise concentric phospholipid layers and an aqueous core; their flexible compositions enable them to adsorb and fuse with cell membranes and to deliver drugs or proteins into cells. Therefore, liposomes have been considered as promising vehicles for the less invasive delivery of BoNT-A. In previous placebo-controlled trials including patients with OAB refractory to medical treatment, it was shown that liposomal BoNT-A could significantly decrease the frequency and urgency of urination. In patients with IC/BPS, it was shown that liposomal BoNT-A could also improve bladder pain, but the therapeutic efficacy was not superior to that of the placebo. As the therapeutic mechanisms of BoNT-A include the decreased expression of nerve growth factors, P2X3 receptors, and vanilloid receptors on C-fibers, liposomal BoNT-A might play a more promising role in the treatment of bladder oversensitivity. This article features the contemporary literature regarding BoNT-A, liposomes, and liposomal BoNT-A treatment for functional bladder disorders and potential clinical applications in the future. Full article
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19 pages, 408 KiB  
Review
Clinical Application of Botulinum Neurotoxin in Lower-Urinary-Tract Diseases and Dysfunctions: Where Are We Now and What More Can We Do?
by Hann-Chorng Kuo
Toxins 2022, 14(7), 498; https://doi.org/10.3390/toxins14070498 - 18 Jul 2022
Cited by 9 | Viewed by 3713
Abstract
Botulinum toxin A (Botox) had been considered a promising drug that has an effect on functional disorders of the lower urinary tract. Because Botox exhibits anti-inflammatory and antispasmodic effects, Botox injection into the bladder can decrease detrusor contractility, reduce bladder hypersensitivity, and eliminate [...] Read more.
Botulinum toxin A (Botox) had been considered a promising drug that has an effect on functional disorders of the lower urinary tract. Because Botox exhibits anti-inflammatory and antispasmodic effects, Botox injection into the bladder can decrease detrusor contractility, reduce bladder hypersensitivity, and eliminate painful sensations. Injecting Botox into the bladder outlet can relax the hyperactivity of the bladder neck, and of the urethral smooth and striated muscles. Based on these therapeutic effects, Botox has been widely applied to treat lower-urinary-tract dysfunctions (LUTDs) such as overactive bladder and neurogenic detrusor overactivity. However, this treatment has not been licensed for use in other LUTDs such as interstitial cystitis, voiding dysfunction due to benign prostatic hyperplasia in men, and dysfunctional voiding in women. Botox has also not been approved for the treatment of children with overactive bladder and dysfunctional voiding; in patients with spinal cord injuries with detrusor sphincter dyssynergia and autonomic dysreflexia; or for poorly relaxed external sphincter in non-neurogenic patients. This article reviews the current knowledge regarding Botox treatment for LUTDs and discusses the potential clinical applications of Botox, as well as work that can be conducted in the future. Full article
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