Clinical guidelines of patient-centered bladder management of neurogenic lower urinary tract dysfunction due to chronic spinal cord injury - Part 2: Conservative and minimally invasive treatment

Yao-Lin Kao; Jian-Ting Chen; Sung-Lang Chen; I-Hung Shao; Chung-Cheng Wang; I-Ni Chiang; Yu-Chao Hsu; Kau-Han Lee; Wei-Chia Lee; Ting-Chun Yeh; Yuh-Chen Kuo; Bing-Juin Chiang; Chun-Hou Liao; Po-Cheng Chen; En Meng; Yung-Chin Lee; Hann-Chorng Kuo

doi:10.4103/UROS.UROS_116_22

REVIEW ARTICLE

Year : 2023 | Volume : 34 | Issue : 1 | Page : 10-17

Clinical guidelines of patient-centered bladder management of neurogenic lower urinary tract dysfunction due to chronic spinal cord injury - Part 2: Conservative and minimally invasive treatment

Yao-Lin Kao¹, Jian-Ting Chen², Sung-Lang Chen³, I-Hung Shao⁴, Chung-Cheng Wang⁵, I-Ni Chiang⁶, Yu-Chao Hsu⁷, Kau-Han Lee⁸, Wei-Chia Lee⁹, Ting-Chun Yeh¹⁰, Yuh-Chen Kuo¹¹, Bing-Juin Chiang¹², Chun-Hou Liao¹², Po-Cheng Chen¹³, En Meng¹⁴, Yung-Chin Lee¹⁵, Hann-Chorng Kuo¹⁶
¹ Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
² Division of Urology, Department of Surgery, Yuanlin Christian Hospital, Changhua, Taiwan
³ Department of Urology, Chung Shan Medical University Hospital and School of Medicine, Chung Shan Medical University, Taichung, Taiwan
⁴ Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
⁵ Department of Urology, En Chu Kong Hospital, New Taipei City; Department of Biomedical Engineering, Chung Yuan Christian University, Chungli, Taiwan
⁶ Department of Urology, National Taiwan University Hospital, and College of Medicine, National Taiwan University, Taipei, Taiwan
⁷ Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou Branch; School of Medicine, Chang Gung University, Taoyuan, Taiwan
⁸ Division of Urology, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan
⁹ Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan
¹⁰ Division of Urology, Department of Surgery, Taiwan Adventist Hospital, Taipei, Taiwan
¹¹ Department of Urology, Taipei City Hospital, Yangming Branch, Taipei, Taiwan
¹² Department of Urology, Cardinal Tien Hospital, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
¹³ Department of Urology, En Chu Kong Hospital, New Taipei City, Taiwan
¹⁴ Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
¹⁵ Department of Urology, Kaohsiung Municipal Siao Gang Hospital, Kaohsiung, Taiwan
¹⁶ Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and Tzu Chi University, Hualien, Taiwan

Date of Submission	25-Oct-2022
Date of Decision	01-Jan-2023
Date of Acceptance	13-Jan-2023
Date of Web Publication	16-Mar-2023

Correspondence Address:
Hann-Chorng Kuo
Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 707, Section 3, Chung-Yang Road, Hualien 97002
Taiwan

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/UROS.UROS_116_22

Abstract

Bladder management of chronic spinal cord injured (SCI) patients usually starts with conservative treatment or minimally invasive procedures. This article reports the current evidence and expert opinions on the patient-centered bladder management of neurogenic lower urinary tract dysfunction (NLUTD) among patients with chronic SCI in Taiwan. We evaluated the role of clean intermittent catheterization (CIC), cystostomy, medical treatment, and minimally invasive therapy for treating urinary incontinence and voiding dysfunction in patients with chronic SCI. The bladder management for chronic SCI patients should be individualized. A balance between upper urinary tract protection and life quality improvement should be considered. Hand dexterity, abdominal muscle power, bladder sensation, and degree of urethral sphincter dyssynergia might affect the improvement of voiding efficiency and NLUTD. Intradetrusor Botulinum Toxin Type A (BoNT-A) injection has been proven to effectively treat neurogenic detrusor overactivity in SCI patients. However, CIC is still required in some patients after treatment. The urethral sphincter BoNT-ABoNT-A injection can effectively relax the dyssynergic sphincter; however, exacerbation of urinary incontinence usually limits its application in SCI patients. Repeat BoNT-ABoNT-A injection is necessary to maintain the therapeutic efficacy; therefore, some SCI patients might discontinue the treatment and convert to a permanent bladder management by surgical intervention. Identification of high-risk SCI patients is important to prevent renal functional deterioration in those with chronic SCI-NLUTD. Avoiding renal function deterioration and improving the quality of life of SCI patients with NLUTD are the most important aspects of treatment. Annual active surveillance of bladder and renal function is necessary.

Keywords: Guidelines, lower urinary tract dysfunction, neurogenic bladder, spinal cord injury

How to cite this article:
Kao YL, Chen JT, Chen SL, Shao IH, Wang CC, Chiang IN, Hsu YC, Lee KH, Lee WC, Yeh TC, Kuo YC, Chiang BJ, Liao CH, Chen PC, Meng E, Lee YC, Kuo HC. Clinical guidelines of patient-centered bladder management of neurogenic lower urinary tract dysfunction due to chronic spinal cord injury - Part 2: Conservative and minimally invasive treatment. Urol Sci 2023;34:10-7

How to cite this URL:
Kao YL, Chen JT, Chen SL, Shao IH, Wang CC, Chiang IN, Hsu YC, Lee KH, Lee WC, Yeh TC, Kuo YC, Chiang BJ, Liao CH, Chen PC, Meng E, Lee YC, Kuo HC. Clinical guidelines of patient-centered bladder management of neurogenic lower urinary tract dysfunction due to chronic spinal cord injury - Part 2: Conservative and minimally invasive treatment. Urol Sci [serial online] 2023 [cited 2023 May 28];34:10-7. Available from: https://www.e-urol-sci.com/text.asp?2023/34/1/10/371880

Introduction

Neurogenic lower urinary tract dysfunction (NLUTD) includes dysfunction of the urinary bladder and urethra due to central nervous system or peripheral nerve lesions. NLUTD in spinal cord injury (SCI) patients remains a difficult disorder to manage. Patients with SCI might have NLUTD, such as failure to store urine due to detrusor overactivity (DO) or urethral sphincter incompetence, failure to empty the bladder due to detrusor areflexia (DA), detrusor underactivity (DU), bladder neck dysfunction (BND), or detrusor sphincter dyssynergia (DSD), or combined failure to store and empty urine due to DSD or detrusor hyperreflexia and inadequate contractility.^[1],[2] The NLUTD in SCI leads to autonomic dysreflexia (AD), reduction in bladder compliance, upper urinary tract damage, significant morbidity, and occasionally mortality. NLUTD in SCI patients not only brings a considerable disease burden on patients, but also adversely affects their quality of life (QoL), self-esteem, and family relationships.^[3]

The major goals of therapy and treatment for NLUTD have been well discussed, including kidney protection from progressive damage, preservation of renal function, and reduction of the severity of urinary incontinence to improve patients' QoL.^[4],[5] Treatment implementation should be based on the urodynamic study findings and individualized according to the severity of disability, patients' mental and physical conditions, and status of urinary tract function.^[6],[7] The purposes of the clinical guidelines reported in this article are to provide information on the indication, effectiveness, and complications related to conservative and minimally invasive treatments for NLUTD in patients with chronic SCI. These guidelines may be useful for physicians to manage patients with chronic SCI and NLUTD in a patient-centered manner.

Clean Intermittent Catheterization in Patients with Chronic Spinal Cord Injury

Bladder emptying using clean intermittent catheterization (CIC), clean intermittent self-catheterization (CISC), and an indwelling catheter is suitable for SCI patients with difficulty in spontaneous urination.^[8] Among them, CIC is considered the safest method of bladder management for renal protection.^[9] However, an indwelling catheter for bladder emptying is still needed in some SCI patients who are unsuitable for CIC use.^[10] CIC is a superior method for preserving bladder compliance and preventing upper tract complications associated with low bladder compliance.^[11] Aseptic intermittent catheterization is the method of choice; however, CIC is also feasible if the patients can perform the procedure using the correct technique. Using a nonsterile but clean catheter for CIC does not increase the risk of urinary tract infection (UTI).^[12] Less frequent CIC might result in a higher catheterization volume and a higher risk of UTI.^[13],[14] The safety bladder volume for CIC should be measured through a urodynamic study, and the average frequency for CIC is 4–6 times/day.^{[13],[15],[16]} SCI patients might shift from CIC during hospitalization to indwelling catheter after primary rehabilitation, especially elderly patients with tetraplegia.^[17] In SCI patients who desire spontaneous voiding, surgical intervention to decrease bladder outlet resistance is feasible. However, the grade of urinary incontinence may be exacerbated, and SCI patients may need condom catheter drainage or diapers, which may be inconvenient for those with poor hand function. Patient-centered guidelines are necessary to provide educational information regarding the advantages and disadvantages of each bladder management and surgical procedure for NLUTD.^[18]

Recommendations

Treatment strategy and priority of SCI patients should be flexible and aimed at relieving NLUTD, resolving complications, and improving patients' QoL.
CIC should be used as a standard treatment for SCI patients who are unable to empty their bladder.
Instruct patients on the technique, associated behavior modifications, and risks of CIC, using a multidisciplinary approach if possible.

Cystostomy and Indwelling Foley Catheter in Patients with Chronic Spinal Cord Injured

Long-term indwelling catheters should be avoided, except for patients with tetraplegia and those who are bed-bound, for whom an indwelling urethral catheter or suprapubic cystostomy may be an alternative choice.^[19],[20] When the patients return to the community with a longer disease duration, more convenient methods for daily living and the prevention of urological complications are necessary.^[16] The occurrence of UTI and formation of bladder stones do not increase in patients using an indwelling catheter or who have undergone a cystostomy in comparison with other bladder management strategies.^[21] Indwelling transurethral and suprapubic catheterization should be used only exceptionally and under close control, and the catheter should be changed frequently. Silicone catheters are preferred and should be changed every 2–4 weeks.^[19],[20] Patients using an indwelling catheter should be monitored for the development of UTI and progressive urinary incontinence. Patients being managed with a urethral catheter should have regular physical examinations to identify urethral erosion. CIC or CISC for bladder emptying is frequently used by patients with SCI duration of ≤5 years, whereas an indwelling catheter or a cystostomy is frequently used by those with SCI duration of >5 years.^[22] A recent survey revealed that there is a shift toward bladder evacuation by CISC during hospitalization, but this is converted to suprapubic cystostomy after primary rehabilitation.^[17]

Recommendations

CIC is recommended for SCI patients with chronic urinary retention.
If an indwelling catheter is needed for long-term management, a suprapubic catheter is preferred over a urethral catheter.
The development of urinary tract complications, UTI, and urethral erosion should be carefully monitored and treated in SCI patients with long-term indwelling urethral catheterization.

Current Medical Treatment for Neurogenic Lower Urinary Tract Dysfunction in Chronic Spinal Cord Injured Patients

The goal of the medical treatment for NLUTD in SCI patients is to achieve urinary continence and facilitate bladder emptying. Anticholinergics have been recommended for this purpose by the European Association of Urology^[23] and the UK consensus group.^[24] DO can be treated effectively with anticholinergics (e.g., oxybutynin, tolterodine, trospium, or propiverine), and the long-term efficacy and safety of antimuscarinic therapy for neurogenic DO (NDO) have been well documented.^[25],[26] Solifenacin has also been proven to be effective and well-tolerated in SCI patients with NDO.^[27] Anticholinergic treatment in patients with NDO is associated with better patient-reported cure or improvement and a significant reduction in maximum detrusor pressure (Pdet) compared to placebo.^[28] In SCI patients with indwelling catheters, antimuscarinic treatment can improve bladder function and may protect the upper urinary tract.^[29] Beta 3-agonists can improve the storage symptoms of NLUTD; however, it has not been proven to be effective in urodynamic studies.^[30]

Alpha-blockers (e.g., terazosin or alfuzosin) and skeletal muscle relaxants (e.g., baclofen or diazepam) have been reported to be partly successful in decreasing bladder outlet resistance.^[31],[32] However, there is a lack of prospective, randomized, controlled studies in the medical management of NLUTD. Alpha-blockers have been used in the treatment of poor bladder compliance, emptying difficulty, and AD.^[5],[33] Increasing bladder outlet resistance may be achieved using adrenoceptor agonists.

NDO is commonly treated with antimuscarinics,^[4] BND with alpha-blockers, and striated sphincter spasticity with skeletal muscle relaxants or nitric oxide donors.^[34] The combination of alpha-adrenergic blockers and antimuscarinic agents is thought to be more beneficial than the use of either drug alone for treating voiding dysfunction.^[35] The addition of desmopressin may improve the treatment efficacy.^[36] In one study, only 18% of patients received pharmacotherapy without urinary catheterization;^[10] this may imply the limited role of pharmacotherapy as a single and main therapy. Combination therapy can be used to improve bladder storage and facilitate bladder emptying. However, careful monitoring of the postvoid residual (PVR) volume and development of any UTI is necessary; urinary incontinence might be exacerbated and the risk of upper tract deterioration might be increased if the detrusor leak point pressure is high.^[10]

Recommendations

For storage symptoms of NLUTD, antimuscarinics, both oral and intravesical, could be the first-line therapy.
For voiding symptoms of NLUTD, alpha-blockers could decrease the bladder outlet resistance; parasympathomimetics are not suggested for DU.

Intravesical Botulinum Toxin a Injection in Chronic Spinal Cord Injured Patients with Neurogenic Detrusor Overactivity and Urinary Incontinence

Botulinum toxin Type A (BoNT-A) can selectively modulate neurotransmission from motor nerve endings, causing muscular paralysis, act on sensory receptors and sensory disorders, and has anti-inflammatory effects to improve chronic inflammation and related functional disorders. Detrusor BoNT-A injection reduces DO and intravesical pressure and improves urinary incontinence.^[37],[38] Further clinical trials all confirmed the superior therapeutic efficacy of BoNT-A detrusor injection over placebo treatment in patients with SCI or multiple sclerosis.^[39],[40] A decrease in daily incontinence, decrease in CIC episodes, increase in cystometric bladder capacity, increase in reflex bladder volume, and decrease in maximal Pdet were noted in the pool data analysis of detrusor BoNT-A injection for NDO in SCI patients.^[41] A further analysis of the treatment outcomes also revealed a significant improvement in health-related QoL indexes^[42] and a significant decrease in the incidence of symptomatic UTI after detrusor BoNT-A injections in SCI patients.^[43],[44] In patients with failure after augmentation enterocystoplasty performed for NDO, BoNT-A injection in the augmented bladder was effective in over half of the cases with low morbidity.^[45] However, UTI remains the most bothersome adverse event, which hinders its widespread use in real-life settings.

Recommendations

Detrusor BoNT-A injection is effective in treating SCI patients with NDO refractory to anticholinergic therapy
Urodynamic study is recommended to evaluate the treatment efficacy of BoNT-A injection at 6–12 weeks' postinjection.

Efficacy and Adverse Events of Intravesical Bont-a Injection in Chronic Spinal Cord Injured Patients

Intravesical BoNT-A injection has been demonstrated to be effective for the restoration of urinary continence, and it remains durable for up to 9 months.^{[46],[47],[48]} BoNT-A treatment of DO due to a spinal cord lesion has been reported to provide satisfactory results.^[49],[50] A previous study reported that 73% of patients with NLUTD achieved continence after BoNT-A treatment.^[38] BoNT-A at doses of 200 and 300 U had the same therapeutic effects on NDO, and the 200-U dose has been approved by the US Food and Drug Administration.^[51],[52] There were no statistically significant differences in the outcomes between BoNT-A injections into the detrusor versus the submucosa.^[53] Subsequent BoNT-A detrusor injections seem to be as effective as the first injection.^[40] For NDO, BoNT-A injections that included the trigone were found to be superior in treating both incontinence episodes and urodynamic parameters compared with injections that did not include the trigone.^[54] Shifting to a higher dose, switching to another botulinum toxin, or prolonging the injection intervals may rescue the BoNT-A treatment failure.^[55] However, a large PVR volume or urinary retention may develop after detrusor BoNT-A injection in patients with NDO. Approximately 70% of patients require periodic CIC, and subsequent UTI could become a de novo problem.^[38]

Recommendations

Detrusor BoNT-A injection at a dose of 200 U is effective in treating SCI patients with NDO and urinary incontinence refractory to anticholinergic therapy.
The therapeutic duration may last for 9 months. Urinary retention and UTI are potential adverse events that need to be monitored.
Patients with SCI and voiding dysfunction should learn to perform CIC before the BoNT-A injection. Trigonal including BoNT-A injection is feasible.

Urethral or Detrusor Bont-a Injections in Spinal Cord Injured Patients with Incontinence and Incomplete Bladder Emptying

Bladder management in SCI patients is a challenge to urologists. Only one-third of patients have normal bladder function restoration and complete bladder emptying at 1 year following SCI.^[56] Some patients with DSD prefer spontaneous voiding without CIC and some might prefer being dry after treatment, even if CIC is necessary. Approximately 95% of patients with suprasacral lesions demonstrate DO with or without DSD.^[57] Hand dexterity, abdominal muscle power, bladder sensation, and degree of urethral sphincter dyssynergia can affect voiding efficiency and NLUTD. Urethral BoNT-A injections can reduce urethral resistance.^[46],[56] Combined detrusor and urethral BoNT-A injections may achieve the desired goals of both continence and complete emptying.^[49] To improve incontinence, decrease urgency episodes, and retain spontaneous voiding function, a lower dose of BoNT-A for detrusor injections could provide a satisfactory result for the majority of patients with spinal cord lesions and DSD^[58],[59] [Table 1].

Table 1: The reported dose, number, and sites of botulinum toxin Type A injections and therapeutic efficacy and adverse events in patients with spinal cord injured and neurogenic lower urinary tract dysfunction

Click here to view

Urethral sphincter BoNT-A injection was first used to treat DSD in SCI patients to facilitate spontaneous urination without self-catheterization.^[60] After the BoNT-A injection, the PVR volume and maximal urethral closure pressure decrease, and the maximum flow rate increases.^[61],[62] The emerging adverse event of the increase in urinary incontinence and persistent incomplete bladder emptying remain problems after injection.^{[56],[63],[64],[65]} The exacerbation of urinary incontinence in SCI patients usually results in patients switching from urethral BoNT-A injection to detrusor BoNT-A injection to gain urinary continence, although CIC or CISC is required.^{[63],[66],[67]}

Recommendations

Detrusor BoNT-A injection can effectively treat urinary incontinence in SCI patients by increasing the bladder capacity and can achieve urinary continence.
Urethral sphincter BoNT-A injection effectively relaxes the dyssynergic sphincter by reducing bladder outlet resistance and protects the upper urinary tract.
The choice between detrusor and urethral sphincter BoNT-A injections or a combination of the two injections should be considered according to the personal and extrinsic factors.
For patients who cannot use CIC or cannot undergo injection therapies or surgeries, close follow-up is suggested, ensuring a Pdet of < 40 cmH₂O and preventing renal function deterioration.

Long-Term Adherence to Botulinum Toxin Injection and Patients' Satisfaction

The treatment of NDO and DSD may be different between the sexes. Women with SCI and DSD may prefer to be dry and stop using diapers. Male SCI patients can use an external device to collect urine and prevent urine soiling. The desire to be dry is not as great in men as it is in women. Contrarily, male SCI patients might not appreciate being completely dry and may need CIC after the detrusor BoNT-A injection.^[68] SCI patients who received a 200U BoNT-A detrusor injection for NDO had significantly greater satisfaction regarding the improvement of urinary incontinence and QoL than those receiving a 100U BoNT-A urethral sphincter injection to improve bladder emptying.^[66] Among SCI patients who received BoNT-A injections for NDO, 48.4%–67% continued to receive repeat BoNT-A injections at follow-up for 5–10 years and 90% of the patients had a high satisfaction and considered undergoing BoNT-A treatments as long-term management in the following 5 years.^{[69],[70],[71],[72]} Recurrent UTI, AD during a BoNT-A injection, CIC-related issues, and persistent urinary incontinence are the primary causes for detrusor BoNT-A injection discontinuation.

The most common reason for discontinuation of BoNT-A injections is treatment failure,^[70],[71] and the most frequent adverse events were UTI and urinary retention requiring CIC.^[72],[73] An increase in incontinence was the leading cause of dissatisfaction with urethral BoNT-A injection, and an increase in PVR volume requiring CIC was the primary cause of dissatisfaction with detrusor injection.^[63] The satisfaction rate reported by patients improved from 25.4% at baseline to 74% at 3 months after the fourth injection and then decreased slightly.^[74] Repeat BoNT-A injections provided sustained improvements in the voided volume and QoL in SCI patients with NDO who could continue to receive detrusor BoNT-A injections.^[75] Repeat BoNT-A injections in the treatment of NDO is recommended at a 6–9-month interval.^[39] In some patients, the treatments were converted to augmentation enterocystoplasty after repeat detrusor BoNT-A injections because they wished to have a permanent correction without the need for periodical injections.^[72] SCI patients with minor complications after BoNT-A injections can usually tolerate the complications and continue to undergo detrusor BoNT-A injections if the therapeutic efficacy meets their expectations.

Recommendations

The most common reason for discontinuation of BoNT-A injection is treatment failure; therefore, patient selection and pretreatment education are important.
A urodynamic study at baseline and after the first BoNT-A injection can predict long-term adherence to BoNT-A injection.
Repeat BoNT-A injections can achieve a persistent therapeutic effect.

Active Management of Chronic Spinal Cord Injured Patients with Autonomic Dysreflexia

AD is characterized by severe paroxysmal hypertension (episodic high blood pressure) associated with throbbing headaches, profuse sweating, flushing of the skin above the level of the lesion, and bradycardia, which is sometimes accompanied by cognitive impairment.^[76] The most common causes of AD are bladder distention and stool impaction. UTI can also trigger AD, regardless of the presence of an indwelling catheter.^[77] The incidence of AD in patients with SCI above T6 ranges from 19% to 70%. Patients with DSD have a higher incidence of AD. Alpha-blockers (e.g., tamsulosin, naftopidil, and silodosin), external sphincterotomy, and detrusor BoNT-A injections have been proven to be able to alleviate AD.^[23] AD is a urological consequence in SCI patients with high-level spinal cord lesions, which may result in hypertension, headache, and even stroke if not appropriately treated.^[78] In some SCI patients, AD was reported to disappear or decrease in severity after a detrusor or urethral sphincter BoNT-A injection.^{[46],[79],[80],[81]} A previous study demonstrated that AD may resolve, persist, or be exacerbated after detrusor BoNT-A injections in SCI patients with NDO. However, some patients may develop acute AD during detrusor BoNT-A injection.^[66] Improved AD after transurethral incision of the bladder neck (TUI-BN) was noted in one case series that included patients with SCI and BND.^[82] Urethral sphincter BoNT-A injection,^[78] external sphincterotomy,^[83] and urethral stenting also demonstrated treatment benefits in patients with DSD.^[84] However, caution should be taken because a large percentage of patients that received urethral stenting required stent removal at a mean of 20 months due to stent migration, stone formation, AD, or recurrent obstruction.^[85] In high-level SCI patients with AD refractory to conventional medical treatment, detrusor BoNT-A injection, which is relatively safe and reversible, may be considered to alleviate the severity of AD and improve the patients' QoL.^[74]

Recommendations

AD is a urological emergency in patients with SCI above the T6–T8 level.
Selective α1-blockers or nifedipine may be considered for the initial management of repeated AD attacks.
Intravesical BoNT-A injection, urethral sphincter BoNT-A injection, or external sphincterotomy may be options in the active management of chronic AD.
There is limited evidence for TUI-BN, bladder augmentation, or sacral denervation in the management of AD.

Conclusion

The ideal treatment scheme for NLUTD in patients with SCI should include the preservation of renal function and optimization of their QoL. Pharmacotherapy, such as with antimuscarinics or alpha-blockers, could alleviate the storage and voiding dysfunction to a certain degree but combination with other treatment modalities is often required. Under urodynamic study guidance to assess their safety bladder volume, CIC might serve as the safest method for patients with voiding dysfunction. An indwelling catheter should be considered if the patient is unsuitable for CIC. However, the occurrence of UTI, bladder stones, and urethral erosion should be carefully monitored in such patients. Intravesical BoNT-A injection could treat NDO and urinary incontinence that is refractory to anticholinergic therapy, while urethral sphincter BoNT-A injection may improve bladder emptying in cases of DSD, DU, and DA. Before initiation of the treatment, the risk of UTI and potential need for CIC due to increased PVR should be determined in the former and the exacerbation of urinary incontinence should be determined in the latter. BoNT-A injections in both locations could be done repeatedly if clinically required. BoNT-A injections also serve as reversible options for chronic AD in high-level SCI that is refractory to conventional medical treatment. The choice among these bladder management treatments should be individualized and balanced between the efficacy and complications of each treatment and should fulfill the major concern of the patients' urinary condition, which might be different according to their gender, capability, and the disease severity.

Financial support and sponsorship

This study was funded by TCMF-MP 110-03-01 (111), Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.

Conflicts of interest

Dr. Chung-Cheng Wang, Chun-Hou Liao, En Meng and Hann-Chorng Kuo, an editorial board member at Urological Science, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.

References

1.	Hamid R, Averbeck MA, Chiang H, Garcia A, Al Mousa RT, Oh SJ, et al. Epidemiology and pathophysiology of neurogenic bladder after spinal cord injury. World J Urol 2018;36:1517-27.
2.	Wada N, Karnup S, Kadekawa K, Shimizu N, Kwon J, Shimizu T, et al. Current knowledge and novel frontiers in lower urinary tract dysfunction after spinal cord injury: Basic research perspectives. Urol Sci 2022;33:101-13. [Full text]
3.	Ku JH. The management of neurogenic bladder and quality of life in spinal cord injury. BJU Int 2006;98:739-45.
4.	Chancellor MB, Anderson RU, Boone TB. Pharmacotherapy for neurogenic detrusor overactivity. Am J Phys Med Rehabil 2006;85:536-45.
5.	Cameron AP. Pharmacologic therapy for the neurogenic bladder. Urol Clin North Am 2010;37:495-506.
6.	Wing PC. Early acute management in adults with spinal cord injury: A clinical practice guideline for health-care providers. Who should read it? J Spinal Cord Med 2008;31:360.
7.	Watanabe T, Rivas DA, Chancellor MB. Urodynamics of spinal cord injury. Urol Clin North Am 1996;23:459-73.
8.	Ginsberg DA, Boone TB, Cameron AP, Gousse A, Kaufman MR, Keays E, et al. The AUA/SUFU guideline on adult neurogenic lower urinary tract dysfunction: Treatment and follow-up. J Urol 2021;206:1106-13.
9.	Jamil F. Towards a catheter free status in neurogenic bladder dysfunction: A review of bladder management options in spinal cord injury (SCI). Spinal Cord 2001;39:355-61.
10.	Lai EC, Kao Yang YH, Kuo HC. Complication rate of neurogenic lower urinary tract dysfunction after spinal cord injury in Taiwan. Int Urol Nephrol 2014;46:1063-71.
11.	Weld KJ, Graney MJ, Dmochowski RR. Differences in bladder compliance with time and associations of bladder management with compliance in spinal cord injured patients. J Urol 2000;163:1228-33.
12.	Lapides J, Diokno AC, Silber SJ, Lowe BS. Clean, intermittent self-catheterization in the treatment of urinary tract disease. J Urol 1972;107:458-61.
13.	Madersbacher H, Wyndaele JJ, Igawa Y, Chancellor M, Chartier-Kastler E, Kovindha A. Conservative management in neuropatic urinary incontinence. In: Abrams P, Khoury S, Wein A, editors. Incontinence. 2^nd ed. Plymouth Health Publication Ltd; 2002. p. 697-754.
14.	Wyndaele JJ. Intermittent catheterization: Which is the optimal technique? Spinal Cord 2002;40:432-7.
15.	Sauerwein D. Urinary tract infection in patients with neurogenic bladder dysfunction. Int J Antimicrob Agents 2002;19:592-7.
16.	Bakke A, Digranes A, Høisaeter PA. Physical predictors of infection in patients treated with clean intermittent catheterization: A prospective 7-year study. Br J Urol 1997;79:85-90.
17.	Krebs J, Wöllner J, Rademacher F, Pannek J. Bladder management in individuals withspinal cord injury or disease during and after primary rehabilitation: A retros pective cohort study. World J Urol 2022;40:1737-42.
18.	Kuo HC, Chen SL, Chou CL, Chuang YC, Huang YH, Juan YS, et al. Taiwanese continence society clinical guidelines for diagnosis and management of neurogenic lower urinary tract dysfunction. Urol Sci 2014;25:35-41.
19.	Mitsui T, Minami K, Furuno T, Morita H, Koyanagi T. Is suprapubic cystostomy an optimal urinary management in high quadriplegics? A comparative study of suprapubic cystostomy and clean intermittent catheterization. Eur Urol 2000;38:434-8.
20.	Weld KJ, Wall BM, Mangold TA, Steere EL, Dmochowski RR. Influences on renal function in chronic spinal cord injured patients. J Urol 2000;164:1490-3.
21.	Katsumi HK, Kalisvaart JF, Ronningen LD, Hovey RM. Urethral versus suprapubic catheter: Choosing the best bladder management for male spinal cord injury patients with indwelling catheters. Spinal Cord 2010;48:325-9.
22.	Chen SF, Jiang YH, Jhang JF, Lee CL, Kuo HC. Bladder management and urological complications in patients with chronic spinal cord injuries in Taiwan. Tzu Chi Med J 2014;26:25-8.
23.	Stöhrer M, Blok B, Castro-Diaz D, Chartier-Kastler E, Del Popolo G, Kramer G, et al. EAU guidelines on neurogenic lower urinary tract dysfunction. Eur Urol 2009;56:81-8.
24.	Fowler CJ, Panicker JN, Drake M, Harris C, Harrison SC, Kirby M, et al. A UK consensus on the management of the bladder in multiple sclerosis. Postgrad Med J 2009;85:552-9.
25.	Goessl C, Sauter T, Michael T, Bergé B, Staehler M, Miller K. Efficacy and tolerability of tolterodine in children with detrusor hyperreflexia. Urology 2000;55:414-8.
26.	Stöhrer M, Madersbacher H, Richter R, Wehnert J, Dreikorn K. Efficacy and safety of propiverine in SCI-patients suffering from detrusor hyperreflexia – A double-blind, placebo-controlled clinical trial. Spinal Cord 1999;37:196-200.
27.	Amarenco G, Sutory M, Zachoval R, Agarwal M, Del Popolo G, Tretter R, et al. Solifenacin is effective and well tolerated in patients with neurogenic detrusor overactivity: Results from the double-blind, randomized, active- and placebo-controlled SONIC urodynamic study. Neurourol Urodyn 2017;36:414-21.
28.	Madhuvrata P, Singh M, Hasafa Z, Abdel-Fattah M. Anticholinergic drugs for adult neurogenic detrusor overactivity: A systematic review and meta-analysis. Eur Urol 2012;62:816-30.
29.	Sugiyama H, Uemura O, Mori T, Okisio N, Unai K, Liu M. Effect of imidafenacin on the urodynamic parameters of patients with indwelling bladder catheters due to spinal cord injury. Spinal Cord 2017;55:187-91.
30.	Akkoc Y. Efficacy and safety of mirabegron for treatment of neurogenic detrusor overactivity in adults with spinal cord injury or multiple sclerosis: A systematic review. Spinal Cord 2022;60:854-61.
31.	Sullivan J, Abrams P. Alpha-adrenoceptor antagonists in neurogenic lower urinary tract dysfunction. Urology 1999;53:21-7.
32.	Schulte-Baukloh H, Michael T, Miller K, Knispel HH. Alfuzosin in the treatment of high leak-point pressure in children with neurogenic bladder. BJU Int 2002;90:716-20.
33.	Ouslander JG. Management of overactive bladder. N Engl J Med 2004;350:786-99.
34.	Reitz A, Knapp PA, Müntener M, Schurch B. Oral nitric oxide donors: A new pharmacological approach to detrusor-sphincter dyssynergia in spinal cord injured patients? Eur Urol 2004;45:516-20.
35.	Ruggieri MR Sr., Braverman AS, Pontari MA. Combined use of alpha-adrenergic and muscarinic antagonists for the treatment of voiding dysfunction. J Urol 2005;174:1743-8.
36.	Chancellor MB, Rivas DA, Staas WE Jr. DDAVP in the urological management of the difficult neurogenic bladder in spinal cord injury: Preliminary report. J Am Paraplegia Soc 1994;17:165-7.
37.	Schürch B. Neurogenic voiding disorders. Current status of diagnosis and therapy. Schweiz Med Wochenschr 2000;130:1618-26.
38.	Reitz A, Stöhrer M, Kramer G, Del Popolo G, Chartier-Kastler E, Pannek J, et al. European experience of 200 cases treated with botulinum-A toxin injections into the detrusor muscle for urinary incontinence due to neurogenic detrusor overactivity. Eur Urol 2004;45:510-5.
39.	Schurch B, de Sèze M, Denys P, Chartier-Kastler E, Haab F, Everaert K, et al. Botulinum toxin type a is a safe and effective treatment for neurogenic urinary incontinence: Results of a single treatment, randomized, placebo controlled 6-month study. J Urol 2005;174:196-200.
40.	Akbar M, Abel R, Seyler TM, Bedke J, Haferkamp A, Gerner HJ, et al. Repeated botulinum-A toxin injections in the treatment of myelodysplastic children and patients with spinal cord injuries with neurogenic bladder dysfunction. BJU Int 2007;100:639-45.
41.	Mangera A, Apostolidis A, Andersson KE, Dasgupta P, Giannantoni A, Roehrborn C, et al. An updated systematic review and statistical comparison of standardised mean outcomes for the use of botulinum toxin in the management of lower urinary tract disorders. Eur Urol 2014;65:981-90.
42.	Schurch B, Denys P, Kozma CM, Reese PR, Slaton T, Barron RL. Botulinum toxin A improves the quality of life of patients with neurogenic urinary incontinence. Eur Urol 2007;52:850-8.
43.	Gamé X, Castel-Lacanal E, Bentaleb Y, Thiry-Escudié I, De Boissezon X, Malavaud B, et al. Botulinum toxin A detrusor injections in patients with neurogenic detrusor overactivity significantly decrease the incidence of symptomatic urinary tract infections. Eur Urol 2008;53:613-8.
44.	Ni J, Wang X, Cao N, Si J, Gu B. Is repeat botulinum toxin A injection valuable for neurogenic detrusor overactivity-A systematic review and meta-analysis. Neurourol Urodyn 2018;37:542-53.
45.	Michel F, Ciceron C, Bernuz B, Boissier R, Gaillet S, Even A, et al. Botulinum toxin type a injection after failure of augmentation enterocystoplasty performed for neurogenic detrusor overactivity: Preliminary results of a salvage strategy. The enterotox study. Urology 2019;129:43-7.
46.	Schurch B, Stöhrer M, Kramer G, Schmid DM, Gaul G, Hauri D. Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: A new alternative to anticholinergic drugs? Preliminary results. J Urol 2000;164:692-7.
47.	Ehren I, Volz D, Farrelly E, Berglund L, Brundin L, Hultling C, et al. Efficacy and impact of botulinum toxin A on quality of life in patients with neurogenic detrusor overactivity: A randomised, placebo-controlled, double-blind study. Scand J Urol Nephrol 2007;41:335-40.
48.	Patki PS, Hamid R, Arumugam K, Shah PJ, Craggs M. Botulinum toxin-type A in the treatment of drug-resistant neurogenic detrusor overactivity secondary to traumatic spinal cord injury. BJU Int 2006;98:77-82.
49.	Schulte-Baukloh H, Weiss C, Stolze T, Herholz J, Stürzebecher B, Miller K, et al. Botulinum-A toxin detrusor and sphincter injection in treatment of overactive bladder syndrome: Objective outcome and patient satisfaction. Eur Urol 2005;48:984-90.
50.	Grosse J, Kramer G, Stöhrer M. Success of repeat detrusor injections of botulinum a toxin in patients with severe neurogenic detrusor overactivity and incontinence. Eur Urol 2005;47:653-9.
51.	Cruz F, Herschorn S, Aliotta P, Brin M, Thompson C, Lam W, et al. Efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: A randomised, double-blind, placebo-controlled trial. Eur Urol 2011;60:742-50.
52.	Ginsberg D, Gousse A, Keppenne V, Sievert KD, Thompson C, Lam W, et al. Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. J Urol 2012;187:2131-9.
53.	Li GP, Wang XY, Zhang Y. Efficacy and safety of OnabotulinumtoxinA in patients with neurogenic detrusor overactivity caused by spinal cord injury: A systematic review and meta-analysis. Int Neurourol J 2018;22:275-86.
54.	Abdel-Meguid TA. Botulinum toxin-A injections into neurogenic overactive bladder – To include or exclude the trigone? A prospective, randomized, controlled trial. J Urol 2010;184:2423-8.
55.	Apostolidis A, Cameron AP. Neurourological management after failed intradetrusor onabotulinumtoxina injections. Eur Urol Focus 2020;6:814-6.
56.	Weld KJ, Dmochowski RR. Association of level of injury and bladder behavior in patients with post-traumatic spinal cord injury. Urology 2000;55:490-4.
57.	Kuo HC. Therapeutic effects of suburothelial injection of botulinum a toxin for neurogenic detrusor overactivity due to chronic cerebrovascular accident and spinal cord lesions. Urology 2006;67:232-6.
58.	Chiang BJ, Kuo HC, Liao CH. Can botulinum toxin A still have a role in treatment of lower urinary tract symptoms/benign prostatic hyperplasia through inhibition of chronic prostatic inflammation? Toxins (Basel) 2019;11:547.
59.	Dykstra DD, Sidi AA, Scott AB, Pagel JM, Goldish GD. Effects of botulinum A toxin on detrusor-sphincter dyssynergia in spinal cord injury patients. J Urol 1988;139:919-22.
60.	Schurch B, Hauri D, Rodic B, Curt A, Meyer M, Rossier AB. Botulinum-A toxin as a treatment of detrusor-sphincter dyssynergia: A prospective study in 24 spinal cord injury patients. J Urol 1996;155:1023-9.
61.	Lin YH, Chiang BJ, Liao CH. Mechanism of action of botulinum toxin A in treatment of functional urological disorders. Toxins (Basel) 2020;12:129.
62.	Kuo HC. Satisfaction with urethral injection of botulinum toxin A for detrusor sphincter dyssynergia in patients with spinal cord lesion. Neurourol Urodyn 2008;27:793-6.
63.	Smith CP, Nishiguchi J, O'Leary M, Yoshimura N, Chancellor MB. Single-institution experience in 110 patients with botulinum toxin A injection into bladder or urethra. Urology 2005;65:37-41.
64.	Gallien P, Reymann JM, Amarenco G, Nicolas B, de Sèze M, Bellissant E. Placebo controlled, randomised, double blind study of the effects of botulinum A toxin on detrusor sphincter dyssynergia in multiple sclerosis patients. J Neurol Neurosurg Psychiatry 2005;76:1670-6.
65.	Kuo HC. Therapeutic outcome and quality of life between urethral and detrusor botulinum toxin treatment for patients with spinal cord lesions and detrusor sphincter dyssynergia. Int J Clin Pract 2013;67:1044-9.
66.	Mahfouz W, Karsenty G, Corcos J. Injection of botulinum toxin type A in the urethral sphincter to treat lower urinary tract dysfunction: Review of indications, techniques and results: 2011 update. Can J Urol 2011;18:5787-95.
67.	Kuo HC. Therapeutic satisfaction and dissatisfaction in patients with spinal cord lesions and detrusor sphincter dyssynergia who received detrusor botulinum toxin a injection. Urology 2008;72:1056-60.
68.	Hori S, Patki P, Attar KH, Ismail S, Vasconcelos JC, Shah PJ. Patients' perspective of botulinum toxin-A as a long-term treatment option for neurogenic detrusor overactivity secondary to spinal cord injury. BJU Int 2009;104:216-20.
69.	Baron M, Peyronnet B, Aublé A, Hascoet J, Castel-Lacanal E, Miget G, et al. Long-term discontinuation of botulinum toxin a intradetrusor injections for neurogenic detrusor overactivity: A multicenter study. J Urol 2019;201:769-76.
70.	Hebert KP, Klarskov N, Bagi P, Biering-Sørensen F, Elmelund M. Long term continuation with repeated botulinum toxin A injections in people with neurogenic detrusor overactivity after spinal cord injury. Spinal Cord 2020;58:675-81.
71.	Chen SF, Jiang YH, Jhang JF, Kuo HC. Satisfaction with detrusor onabotulinumtoxinA injections and conversion to other bladder management in patients with chronic spinal cord injury. Toxins (Basel) 2022;14:35.
72.	Herschorn S, Gajewski J, Ethans K, Corcos J, Carlson K, Bailly G, et al. Efficacy of botulinum toxin A injection for neurogenic detrusor overactivity and urinary incontinence: A randomized, double-blind trial. J Urol 2011;185:2229-35.
73.	Chen SF, Kuo HC. Therapeutic outcome and patient adherence to repeated onabotulinumtoxinA detrusor injections in chronic spinal cord-injured patients and neurogenic detrusor overactivity. J Formos Med Assoc 2015;114:583-9.
74.	Kennelly M, Dmochowski R, Ethans K, Karsenty G, Schulte-Baukloh H, Jenkins B, et al. Long-term efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: An interim analysis. Urology 2013;81:491-7.
75.	Khastgir J, Drake MJ, Abrams P. Recognition and effective management of autonomic dysreflexia in spinal cord injuries. Expert Opin Pharmacother 2007;8:945-56.
76.	Karlsson AK. Autonomic dysreflexia. Spinal Cord 1999;37:383-91.
77.	Kasabian NG, Vlachiotis JD, Lais A, Klumpp B, Kelly MD, Siroky MB, et al. The use of intravesical oxybutynin chloride in patients with detrusor hypertonicity and detrusor hyperreflexia. J Urol 1994;151:944-5.
78.	Vallès M, Benito J, Portell E, Vidal J. Cerebral hemorrhage due to autonomic dysreflexia in a spinal cord injury patient. Spinal Cord 2005;43:738-40.
79.	Jiang YH, Jhang JF, Chen SF, Kuo HC. Videourodynamic factors predictive of successful onabotulinumtoxinA urethral sphincter injection for neurogenic or non-neurogenic detrusor underactivity. Low Urin Tract Symptoms 2019;11:66-71.
80.	Tsai SJ, Ying TH, Huang YH, Cheng JW, Bih LI, Lew HL. Transperineal injection of botulinum toxin A for treatment of detrusor sphincter dyssynergia: Localization with combined fluoroscopic and electromyographic guidance. Arch Phys Med Rehabil 2009;90:832-6.
81.	Fougere RJ, Currie KD, Nigro MK, Stothers L, Rapoport D, Krassioukov AV. Reduction in bladder-related autonomic dysreflexia after onabotulinumtoxinA treatment in spinal cord injury. J Neurotrauma 2016;33:1651-7.
82.	Ke QS, Kuo HC. Transurethral incision of the bladder neck to treat bladder neck dysfunction and voiding dysfunction in patients with high-level spinal cord injuries. Neurourol Urodyn 2010;29:748-52.
83.	Lepoittevin L, Leon G, Perrouin-Verbe B, Lefort M, Reiss B, Karam G, et al. External sphincterotomy in neurological patients with detrusor sphincter dyssynergia: Short and mid-term results. Prog Urol 2022;32:40-6.
84.	Gajewski JB, Chancellor MB, Ackman CF, Appell RA, Bennett J, Binard J, et al. Removal of UroLume endoprosthesis: Experience of the North American Study Group for detrusor-sphincter dyssynergia application. J Urol 2000;163:773-6.
85.	Hamid R, Arya M, Wood S, Patel HR, Shah PJ. The use of the Memokath stent in the treatment of detrusor sphincter dyssynergia in spinal cord injury patients: A single-Centre seven-year experience. Eur Urol 2003;43:539-43.