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Bladder Management

Other Miscellaneous Treatments to Enhance Bladder Emptying

In addition to those noted in the previous sections, there are a variety of other approaches that have been investigated to address the consequences of neurogenic bladder associated with SCI. These include the use of desmopressin acetate (DDAVP) as an adjuvant therapy to manage the effects of an overactive bladder otherwise refractory to conventional treatment such as nocturnal enuresis (i.e., night-time emission of urine) or the requirement for too frequent catheterizations. It is important to note that overactive bladder may be caused by other urologic abnormalities (e.g., benign prostatic hyperplasia, or UTI that can coexist with other consequences of neurogenic bladder secondary to SCI. Therefore, urodynamic evaluation is critical to assessing overactive bladder before adjuvant therapy is administered. If needed, DDAVP is a synthetic analogue of antidiuretic hormone most commonly administered by intravenous infusion for treatment of bleeding disorders. It can also be taken in the form of a pill or intranasal spray for reducing urine production as in the present application (Chancellor et al. 1994Zahariou et al. 2007). DDAVP is thought to bind to V2 receptors in renal collecting ducts to increase water reabsorption.

Others have employed alternative approaches such as electroacupuncture (Cheng et al. 1998) or nerve crossover surgery / spinal root anastomoses (Livshits et al. 2004Lin et al. 2008Lin et al. 2009) to enhance recovery of bladder function. The utility of spinal root anastomosis in SCI came from groups rediverting the ipsilaterial C7 root to repair brachial plexus injuries with significant long-term effects of motor and sensory function of the upper extremities as a result of compensatory action of the other nerve roots (Gu et al. 2005). Since the brachial and sacral plexuses are organized similarly, the rediversion of local lower extremity nerve roots has been considered a possible, albeit highly invasive, treatment option.

Author Year; Country
Research Design
Score
Total Sample Size
Methods Outcome
Desmopressin Acetate

Zahariou et al. 2007; Greece
Pre-Post
N=11

Population: SCI in inindividual rehabilitation: Gender: males=7, females=4; Level of injury: above T6=6, below T6=5.
Intervention: Desmopressin acetate (DDAVP) was given intranasally (20µg before bedtime) in association with other standard therapy including anticholignergic drugs (Oxybutynin 5mg, 1×3 daily), evening antibiotic prophylaxis and clean intermittent catheterization (IC).
Outcome Measures: Urine production/ output, clean IC rate. Urine samples collected at 6am and 6pm.
  1. DDAVP produced a statistically significant increase in urine production rate during the day (p<0.001) and a decrease in nocturnal urine production (p<0.001).
  2. DDAVP treatment showed a significant increase on urine asmolarity during the night (p<0.001).
  3. Treatment produced a significant decrease in individuals performing clean intermittent catheterizations in the night while still maintaining continence.
  4. No serious adverse effects were seen.
Chancellor et al. 1994; USA
Case Series
N=7
Population: SCI with detrusor hyperreflexia unresponsive to conventional therapy: Age range 22-52 yr; Gender: males=3, females=4.
Intervention: 10ug/d intranasal desmopressin acetate (DDAVP) over 1 mo.
Outcome Measures: Episodes of nocturia, time between catheterizations.
  1. No statistical results reported.
  2. Decreased nocturia for 4 individuals treated at night (Nocturnal enuresis eliminated in 2 individuals).
  3. Increased duration between catheterizations for 3 individuals treated during the day.
Locomotor Training

Hubscher et al. 2018; USA
Prospective Controlled Trial
N=12

Population: Activity-based training (ABT): Mean age=27.37±5.63yr; Gender: males=5, females=3; Etiology: SCI=8. Time since injury=4.25±3.55yr.Non-trained (NT): Mean age=30.25±4.49yr; Gender: males=4, females=0; Etiology: SCI=4; Time since injury; 6.70±2.23yr. Inclusion criteria (both groups): clear indications that the spinal shock period has concluded as determined by the presence of muscle tone, deep tendon reflexes or muscle spasms, and discharged from standard inindividual rehabilitation.
Intervention: Participants in the ABT received locomotor training (LT) alone or LT+ stand training. LT was completed on a treadmill using body weight support consisting of a harness and lift. 1hr/d, for 80 d. Participants who received LT + stand training received the same locomotor training with the addition of stand training through the use of a custom designed standing frame with horizontal bars anterior and lateral to the participant for upper extremity support and balance assistance. Stand training was 1 hr/d separated at least 3 hr from LT. Participants in NT received standard care (no training). Outcome measures were assessed at baseline and post-intervention.
Outcome Measures: Bladder capacity (BC); voiding efficiency (VE); leak point pressure (LPP); size of bladder contraction; detrusor contraction time (Tdet).
  1. BC, VE, Tdet, and size of bladder contraction increased significantly post-intervention for the ABT group (p<0.05). LPP decreased significantly post-intervention for the ABT group (p<0.05).
  2. There was no significant change in BC, VE, Tdet, and size of bladder contraction for the NT group (p>0.05).
Electroacupunture
Gu et al. 2015; China
RCT
PEDro=7
N=107
Population: Urinary retention; Mean age: 35.7 yr; Gender: males=80, females=27; ASIA classification: B=37, C=53, D=17.
Intervention: Individuals were randomized to Clean intermittent catheterization (CIC) (group 1) (n=35), Electroacupuncture combined with CIC (group 2) (n=38), or Sham acupuncture combined with CIC (group 3).
Outcome Measures: Residual urine volume, voided volume, bladder balance, frequency of CIC.
  1. At 1 mo follow-up, group 2 had a significantly higher number of bladder participants compared to group 1 (p=0.019) or group 3 (p=0.019).
  2. At 1 mo follow-up, group 2 participants had significantly lower frequency of CIC compared to group 1 (p<0.001) or group 3 (p<0.001), and group 3 was also significantly lower than group 1 (p<0.01).
  3. In terms of residual urine volume at 1 mo follow-up, group 2 was significantly lower than group 3 (p<0.001) and group 3 was significantly lower than group 1 (p=0.018).
  4. At 1 mo follow-up, group 2 had a significantly higher voided volume compared to 1 (p<0.001) and group 3 (p<0.001), with no significant differences between groups 1 and 3.
  5. At 3 mo follow-up, significant differences were found between groups in terms of residual urine volume (p<0.001), with groups ordered as 1, 3, and 2 in terms of decreasing volume.
  6. At 3 mo follow-up, significant differences were found between groups in terms of voided volume (p<0.001), with groups ordered as 1, 3, and 2 in terms of increasing volume.

Xia et al. 2014; China
RCT
PEDro=6
N=42

Population: Neurogenic bladder; Treatment group: Mean age: 37.2 yr, Gender: males=13, females=8; Time post-injury: 2.4 mo; Control group: Mean age: 37.5 yr; Gender: males=14, females=7; Mean time post-injury: 2.6 mo.
Intervention: Individuals were randomized to 1) Treatment group (n=21): Acupuncture treatment, consisting of 10 stimulations over 2 weeks or 2) Control group (n=21): Bladder training, including interval water drinking, timed voiding, and intermittent catheterization.
Outcome Measures: Bladder capacity, residual urine volume, bladder pressure, rectal pressure, detrusor pressure, bladder compliance, International Prostate Symptom Score (IPSS), and efficacy rate.
  1. Compared with control group, the treatment group had significantly increased bladder capacity and compliance, and significantly reduced residual urine volume, bladder pressure, rectal pressure, and detrusor pressure (p<0.05).
  2. IPSS values for both groups were significantly lower post-treatment (p<0.05), with treatment group scores significantly lower than control group score (p<0.05).
  3. The total efficacy rate in the treatment group was significantly higher than the control group (p=0.043).

Cheng et al. 1998; Taiwan
RCT
PEDro=4
N=60

Population: SCI: Acupuncture versus Control Group; Mean age: 39.4 yr versus 34.3 yr; Gender (M/F): 24/8 versus 23/5; Level of injury: above T11=34, below T11=26; Severity of injury: Frankel A=25, B=35; Time post-injury=23.7 d versus 26.1 d.
Intervention: Electroacupuncture to 4 points (CV3,CV4,UB32 bilateral)+conventional bladder training=32 versus control group of conventional bladder training=28.
Outcome Measures: Time from SCI-bladder balanced, urodynamic assessment in n=20 of acupuncture group.
  1. ↓ time to achieve bladder balancing for those with upper motor lesions – acupuncture versus control, 57.1±22.5 d versus 85.2±27.4 d (p<0.005).
  2. Similar for lower motor neuron lesions, 55.4± 22.6 d versus 83.4 ±26.1 d (p<0.01).
  3. If it was started within 3 wk of SCI, bladder balancing was achieved sooner, 46.6±13.2 d versus 65.8±15.4 d (p<0.005).
  4. No significant changes seen in urodynamic assessment associated with 1st acupuncture session but ↑ in bladder capacity and ↓ voiding pressure seen by time bladder was balanced.
Rectus Abdominus Detrusor Myoplasty (RADM)

Agarwal et al. 2018; India
Pre-Post
N=5

Population: Median age=38.31yr; Gender: males=5, females=0; Etiology: SCI=5. Time since injury=1-3yr; Inclusion criteria: acontractile/hypocontractile bladder.
Intervention: All participants underwent rectus abdominus detrusor myoplasty (RADM). Outcome measures assessed preoperatively and post-operatively.
Outcome Measures: Post-void residual volume (PVRV); detrusor pressure (Pdet); urine flow rate (Vmax); bladder contractility index (BCI)
  1. There was no significant difference in PVRV post-intervention (p>0.05).
  2. There was a significant increase in BCI (p<0.007), Pdet (p<0.006), and Vmax (p<0.013).
  3. All individuals no longer had recurrent UTIs or vesicoureteral reflux post-intervention or at follow up (15 mo post-intervention).
Sphincterectomy
Takahashi et al. 2018; Japan
Pre-Post
N=37
Population: Mean age=35.4±2.4yr; Gender: males=13; female=4; Etiology: incomplete SCI=12; complete SCI=25; Time since injury=17.9±3.7yr.
Intervention: Medical records of individuals who underwent external sphincterectomy (ES) for treatment of detrusor overactivity (DO) or detrusor-sphincter dyssenergia (DSD) and were followed for at least 5 years were reviewed. External sphincterectomy was performed using electrocautery. Adequate division of the striated muscles of the external sphincter were achieved by an incision from the midprostatic urethra through the bulbomembraneous junction. Individuals were divided Individuals were divided into two groups; success and failure. Success was defined as individuals who maintained reflex voiding using a condom catheter and did not need to change their lower urinary tract management. Failure was defined as individuals who required a change in lower urinary tract management due to deterioration of voiding efficiency or autonomic dysreflexia. Individuals underwent urodynamic assessment pre- and post-operatively (2-3 months, and 1,3,5,10,15,20 years after ES).
Outcome Measures: Mean bladder pressure (MBP); bladder volume at first DO (VDO); maximum bladder capacity (MBC).
  1. MBP of all individuals decreased over time. The decrease in MBP was observed for more than 10 years after ES. Both the success and failure groups showed similar trends as all individuals for MBP over time.
  2. VDO increased gradually over time.
  3. The presence of DO increased after ES up until 10 years, after which there was a marked decrease.
Nerve Crossover Surgery – Spinal Root Anastomoses

Sievert et al. 2016; Germany
Pre-Post
N=8

Population: Mean age: 30 yr; Gender: males=6, females=2; Level of injury: cervical=4, thoracic=4; ASIA classification: A; Mean time post-injury: 83 mo.
Intervention: Four individuals with detrusor sphincter dyssynergia and four individuals with detrusor overactivity underwent the Xiao procedure, consisting of the creation of an artificial somato-autonomic reflex arch through intradural anastomosis.
Outcome Measures: Occurrence of voiding upon stimulation of skin, bladder capacity, maximum detrusor pressure, bladder compliance.
  1. At a mean follow-up of 71 mo post-treatment, no participants could void upon stimulation of the skin, as assessed by videourodynamics or individual diary.
  2. No significant improvements in terms of bladder capacity, maximum detrusor pressure, and bladder compliance were observed post-treatment.

Rasmussen et al. 2015; Denmark
Pre-Post
N=10

Population: Neurogenic bladder dysfunction; Mean age: 43.3 yr; Gender: males=9, females=1; Level of injury: cervical=4, thoracic=6; ASIA classification: A=7, B=3; Mean time post-injury: 6.5 yr.
Intervention: The Xiao procedure, which involved creation of an artificial somato-autonomic reflex arch through intradural anastomosis.
Outcome Measures: Maximum cystometric bladder capacity, bladder compliance, detrusor overactivity, urinary leakage, detrusor contractions/relaxations during stimulation, International Spinal Cord Injury Data Set, Lower Urinary Tract Function Basic Data Set.
  1. No participant could void voluntarily at baseline or follow-up; bladder emptying and changes in detrusor pressure could not be induced by stimulating the reflex arch.
  2. Compared to baseline, no significant differences were observed after treatment in terms of maximum cystometric bladder capacity, or bladder compliance.
  3. Significantly less leakage (p=0.03) was observed at follow-up compared to baseline.
  4. In terms of the International Spinal Cord Injury Data Set and Lower Urinary Tract Function Basic Data Set, neurogenic bladder dysfunction symptoms did not change from baseline to follow-up, with no consistent changes observed in terms of bladder emptying, incontinence episodes, means of bladder emptying, or use of medication.
  5. Three participants subjectively reported less urinary incontinence, 1 reported decreased incidence or urinary tract infections, 1 reported fewer kidney stone symptoms, 2 reported improved bowel empting, 4 reported no change, and 1 reported increased intervals between catheterizations.

Lin & Hou, 2013; China
Pre-Post
N=9

Population: Mean age: 36 yr (range 29-51); Gender: males=7, females=2; Level of injury: L1 vertebral body fracture =6, L2 vertebral body fracture=3; Mean time post-injury: 8 mo (range=6-12 mo); all individuals urinated via bladder stoma with no residual urine in the bladder=4 or after applying abdominal pressure when the residual urine volume was>100 mL=5.
Intervention: All individuals underwent a standard laminectomy from L5-S3, and S1 ventral nerve root (VR) surgery was performed strength tests of the muscles innervated by the S1 nerve (i.e. gastrocnemius, soleus, abductor hallucis, and extensor digitorum brevis resp.) were completed on the second day post-surgery and at 1,3,6 and 12 mo postoperatively
Outcome Measures: Muscle strength (Medical Research Council (MRC) Grade), Bladder capacity, Urine volume, Residual urine volume, Max detrusor pressure, Maximum flow. Urodynamic tests were completed at 1, 3, 6, 12, 18, 24 and 36 mo postoperatively.
  1. Mean follow-up time: 30 mo (range=18-36 mo).
  2. On the second day post-surgery, the power of the S1-innervated muscles decreased by 1 (MRC) grade, while at 3 mo the muscles of all individuals had recovered to their preoperative strength levels.
  3. By 8-12 mo postoperatively, 7/9 individuals (78%) had recovery of bladder storage, voiding functions (able to void voluntarily), no nocturnal urinary incontinence, and had also regained bladder sensory function (i.e. able to sense a full bladder and perceive the desire to void).
  4. Pre- and postoperative urodynamic tests showed significant improvements in bladder function by 12 mo.
  5. Of the 7 individuals responding to treatment, average bladder capacity pre- versus post-op decreased from 496±75 ml to 377±64 ml resp. which was statistically significant (p=0.0042).
  6. Of the 7 individuals, urine volume pre- versus post-op increased from 44±16.2 ml to 320.6±44.2 ml resp. which was statistically significant (p=0.0000).
  7. Of the 7 individuals, residual urine volume pre- versus post-op decreased from 186±35 ml to 43±10 ml resp. which was statistically significant (p=0.0000).
  8. Of the 7 individuals, maximum detrusor pressure pre- versus post-op increased from 3.6±1.8 cm H2O to 85±30 cm H2O resp. which was statistically significant (p=0.0005).
  9. Of the 7 individuals, maximum flow rate pre- versus post-op increased from 3.0±0.8 ml/s to 31.4±7.2 ml/s resp. which was statistically significant (p=0.0001).
  10. The frequency of urinary tract infections gradually decreased after 6 mo and disappeared completely as voiding recovered.

Lin et al. 2009; China
Pre-Post
N=12

Population: SCI individuals with detrusor-external sphincter dyssyergia; Mean age: 30 yr; Gender: males=8, females=4; Level of injury: C=2, T=10.
Intervention: Spinal root anastomosis of S1 to S2 ventral root.
Outcome Measures: Incontinence, bladder capacity, flow rate, urinary tract infection (UTI), adverse events and were followed for up to 6 yr (mean=3 yr).
  1. 9 individuals had recovery of bladder storage without nocturnal urinary incontinence.
  2. An increase was seen in average bladder capacity (p=0.0011) and maximum flow rate (p=0.0002) postsurgery.
  3. Residual urine (p=0.0004) and maximum detrusor pressure (p=0.0435) decreased post surgery.
  4. At 6 mo post surgery, incidence of urinary tract infections stopped.
  5. Adverse effects included cerebrospinal fluid leakage and headache.

Lin et al. 2008; China
Pre-Post
N=10

Population: Complete conus medullaris injury with atonic bladder; Mean age:38 yr; Gender: males=6, females=4; Level of injury: T12=3, L1=5, L2=4; Severity of injury: complete.
Intervention: Spinal root anastomosis of T11 to S2 ventral root.
Outcome Measures: Bladder capacity, urine volume, residual urine volume, max detrusor pressure, max flow collected at regular intervals up to 2 yr.
  1. 7 individuals found improvements in bladder storage and voiding functions.
  2. Signficant improvement in urodynamic outcomes were seen 2 yr post reconstruction:
    1. Bladder capacity, p=0.0031.
    2. Urine volume, p=0.0026.
    3. Residial urine volume, p=0.0005.
    4. Max detrusor pressure, p=0.00001.
    5. Max flow, p=0.0001.
    6. Mild postoperative spinal fluid leakage was seen in 1 individual.

Xiao et al. 2003; China/USA
Pre-Post
N=15

Population: SCI individuals with detrusor-external sphincter dyssyergia; Mean age:39 yr; Severity of injury: AIS A.
Intervention: L5-S3 ventral root anastomosis to establish a new reflex pathway.
Outcome Measures: Residual urine volume, urinary tract infections, detrusor pressure, adverse events.
  1. 10 individuals had recovery of bladder storage and emptying functions.
  2. A decrease was seen in average residual urine (332 to 31mL) and incidence of urinary tract infections 8 mo post surgery.
  3. Two individuals were still dependent on a stimulator for voiding.
  4. Post surgery, 4 individuals showed almost normal bladder activity on a cystometrogram (CMG) and electromyography.
  5. Significant improvement was seen in mean detrusor pressure (p<0.05).
  6. 3 individuals had mild postoperative spinal fluid leakage for 2 to 5 d.
  7. Bowel control was also regained in individuals who regained bladder control.
Bladder Cancer

Lee et al. 2014a; Taiwan
Cohort
N=272005

Population: Spinal cord injury (SCI cohort): Mean age: 52.2 yr; Gender: males=34173, females=20228; Level of injury: cervical=29565, thoracic=16451, lumbar=16451, unclassified=77. No spinal cord injury (Non-SCI cohort): Mean age: 52.2 yr; Gender: males=136692, females=80912.
Intervention: Data from the National Health Insurance Research Database were accessed for the SCI group with each member randomly frequency matched with four non-SCI people.
Outcome Measures: Bladder cancer diagnosis, prostate cancer diagnosis, death.
  1. The overall incidence of bladder cancer was 12% lower in the SCI cohort than the non-SCI cohort with a non-significant adjusted hazard ratio of 0.91.
  2. The overall incidence of prostate cancer was 33% lower in the SCI cohort than the non-SCI cohort with a significant adjusted hazard ratio of 0.73 (p<0.01).

No significant differences in bladder cancer risk were found between different levels of SCI and non-SCI.

Bladder Stones

Eyre et al. 2015; United Kingdom
Cohort
N=112

Population: Median age: 44 yr; Gender: males=83, females=39; Level of injury: cervical=15, thoracic=87, lumbar=9, unknown=1; Frankel classification: A=68, B=34, C=6, D=1, unknown=3.
Intervention: Spinal cord injury individuals with bladder stones received either simple washout (n=11), Mauermeyer stone punch (n=49), electrohydraulic lithotripsy (EHL) (n=15), combination of stone punch and EHL (combined) (n=36), or open cystolithotomy (n=1).
Outcome Measures: Post-operative complications, length of stay.
  1. Of the 112 participants, 19 had a post-operative complication (0 associated with simple washout, 5 associated with stone punch, 3 associated with EHL, 10 associated with combined, and 1 associated with open cystolithotomy).
  2. In the multivariable model for complication predictors, cervical injury (p=0.033) and the combined procedure (p=0.046) were associated with increased odds for complications. Age, sex, Frankel classification, and bladder management method had no significant differences in terms of complications.

Of the 106 participants with length of stay data, the multivariable predictors of increased length of stay were complication (p<0.001) and combined procedure (p=0.028). Age, sex, Frankel classification, and bladder management method had no significant differences in terms of complications.

Bartel et al. 2014; Switzerland
Case Series
N=2825
Population: Bladder stone group (n=93): Mean age: 50 yr; Gender: males=69, females=24; Level of injury: cervical=34, thoracic=49, lumbar=9, sacral=1; Severity of injury: complete=75, incomplete=18; ASIA classification: A=53, B=22, C=13, D=5; Injury etiology: trauma=74, multiple sclerosis=10, other=9; Time post-injury: 9.5 yr.
Intervention: Charts were reviewed for spinal cord injury individuals who had a bladder stone.
Outcome Measures: Bladder management method, period to stone development, bladder stone recurrence rate.
  1. Of the 2825 SCI individuals, 93 had bladder stones (2.8%).
  2. In terms of bladder management methods, bladder stones were observed in 11% of suprapubic catheter, 6.6% of transurethral catheter, 2% of intermittent catheterization, and 1.1% of reflex micturition.
  3. In terms of period to stone development, the mean for suprapubic catheter was 59 mo, transurethral catheter was 31 mo, intermittent catheterization was 116 mo, and reflex micturition was 211 mo.

The bladder stone recurrence rate was 28% for suprapubic catheter, 40% for transurethral catheter, 22% for intermittent catheterization, and 0% for reflex micturition.

Other

Virseda et al. 2014; Spain
Case Control
N=76

Population: Vesicoureteral reflux (VUR); Mean age: 48.9 yr; Gender: males=60, females=16; Level of injury: cervical=21, thoracic=49, lumbar=6; Mean time post-injury: 179 mo.
Intervention: Records were reviewed for VUR individuals who had undergone endoscopic treatment by a bulking treatment, comparing treatment successes to failures.
Outcome Measures: Recurrence rate, time post-intervention, gender, age, bulking agent, reflux grade, neurogenic detrusor overactivity (NDO), stress urinary incontinence, bladder capacity, filling pressure, maximum flow rate.
  1. Overall, resolution of VUR was achieved in 61% of participants, with the recurrence rate being 37% for participants undergoing a first intervention and 50% for those undergoing a second intervention.
  2. Cured participants were significantly younger than non-cured participants (p=0.033).
  3. No significant differences between groups were observed in terms of gender or bulking agent.
  4. The percentage of cure was significantly higher with lower reflux grade (p=0.020).
  5. The odds of reflux persistence in NDO participants was 4.57 times greater than those without NDO (p=0.008).
  6. The odds of reflux persistence in participants without SUI was significantly greater that those with SUI (p=0.032).
  7. No significant associations with treatment success were found for bladder capacity, filling pressure, or maximum flow rate.

In the multivariable analysis, presence of NDO (p=0.012) and reflux grade (p=0.017) independently influenced the cure of VUR.

Summarized Level 5 Evidence Studies

Nahm et al. (2015) reported that despite lower rates of bladder and prostate cancer in people with SCI vs people without SCI, bladder cancer related mortality is higher with more severe injuries. Sammer et al. (2015) suggested that screening strategies to prevent bladder cancers may be considered for people with SCI where those with more severe injuries are more at risk.

Discussion

Desmopressin Acetate

Zahariou et al. (2007) and Chancellor et al. (1994) conducted a pre-post (n=11) and a case series (n=7) investigation, respectively, to investigate the use of intranasal DDAVP as an alternative therapy to reduce urine production in the hopes of reducing nocturnal emissions or reducing the need for overly frequent catheterization during the day. In each case, DDAVP was employed as an adjuvant therapy in addition to standard therapies of anticholinergics and intermittent catheterization which had resulted in less than satisfactory results. With use of DDAVP just before bedtime, Zahariou et al. (2007) reported a statistically significant increase in urine production rate during the day (p<0.001) and a decrease in nocturnal urine production (p<0.001). After DDAVP treatment, participants had reduced or complete elimination of nocturnal enuresis (Chancellor et al. 1994; Zahariou et al. 2007). In addition, the proportion of persons requiring clean IC in the night while still maintaining continence was greatly reduced (Zahariou et al. 2007) and three individuals used DDAVP during the day at work and were able to achieve an additional 3.5 hours between catheterizations (Chancellor et al. 1994). These improvements persisted for a mean of 12 months. These small-scale studies provide only preliminary evidence and encourages further study, although DDAVP is in fairly widespread use for SCI-related neurogenic bladder.

Locomotor Training

A prospective controlled trial by Hubscher et al. (2018) studied the effects of locomotor training (LT) for improving motor outcomes post-SCI, specifically whether it can improve bladder, bowel and sexual function. Eight subjects used LT on a treadmill using body-weight support therapy, or LT and standing training. Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. Authors concluded that these results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions.

Electroacupuncture

Another adjunctive therapy that has been investigated is the use of electroacupuncture (EA). For example, Cheng et al. (1998) conducted a RCT (n=60) investigating the effectiveness of electroacupuncture administered in combination with conventional bladder management method (i.e., clean intermittent catheterization (CIC), tapping and trigger point stimulation) as compared to those not receiving electroacupuncture. Their primary outcome measure was the time to achieve bladder balancing which was defined as the time when: 1) the individual could easily pass adequate urine at low pressure, 2) residual urine of approximately 100 ml or less and 3) absent UTIs. Although employing a randomized, controlled design, some limitations (i.e., lack of blinding, concealed allocation or intent to treat) constrained the level of evidence assigned to this trial (i.e., Level 2). Regardless, those receiving electroacupuncture had a reduced time to achieve bladder balancing for both those with upper motor lesions (p<0.005) and lower motor neuron lesions (p<0.01). In addition, if electroacupuncture was started within three weeks of SCI, bladder balancing was achieved sooner than those who started after three weeks (p<0.005). Gu et al. (2015) also reported the superiority of EA+CIC effectiveness (vs CIC alone) in reducing residual urine volume (p<0.001) and frequency of CIC (p<0.001), increased voided volume (p<0.001), and promoting the balance of vesical function (p<0.05). Similarly, EA with bladder function training vs bladder function training alone is significantly more effective in increasing bladder volume and compliance, decreased residual urine volume, bladder pressure, rectal pressure, and detrusor pressure (p<0.05) (Xia et al. 2014). Modest improvements were also reported with bladder function training alone. The treatment group also had lower IPSS (International Prostate Symptom Score that describes various characteristics of urination) and better therapeutic efficacy (p<0.05) compared to controls.

Rectus Abdominus Detrusor Myoplasty (RADM)

Urinary bladder dysfunction in the form of acontractile/ hypocontractile bladder is very common after spinal cord injury and it may lead to recurrent urinary tract infection (UTI), stones formation, and deteriorating renal function. This is conventionally treated through the use of life-long clean intermittent catheterization (CIC) or an indwelling catheter (IC). For these individuals, another option is to use innervated skeletal muscle wrap around the bladder to augment detrusor function and voluntary evacuation of bladder. Agarwal et al. (2018) studied five individuals that underwent Rectus Abdominis Detrusor Myoplasty (RADM) to treat acontractile/hypocontractile bladder. These individuals were assessed by urodynamic study for post void residual volume (PVRV), detrusor pressure (Pdet), urine flow rate (Vmax), and bladder contractility index (BCI). Complete spontaneous voiding was achieved in all individuals. RADM elicits a statistically significant reduction in PVRV and statistically significant increase in urine flow rate, bladder contractility and detrusor pressure after six months. Another effect of treatment was all recurrent UTIs ceased in subjects.

Spincterectomy

External sphincterotomy (ES) in the treatment of SCI individuals with detrusor sphincter dyssynergia (DSD) is used to achieve low pressure urine storage and low pressure emptying of the bladder. By decreasing bladder outlet obstruction, reflex voiding can be performed with a lower bladder pressure, leading to more effective voiding, lesser incidence of UTI, preservation of upper urinary tract function, and reduction of autonomic dysreflexia (AD). Takahashi et al. (2018) conducted a long- term follow-up study after ES to determine if urodynamic parameters improved after the therapeutic procedure in male SCI individuals with DSD. Of the 37 SCI individuals studied, 27 are still managed with reflex voiding to a condom catheter (success group), while 10 needed to change their bladder management. Mean maximum bladder pressure (MBP) was maintained at a low level over 20 years after ES. However, neurogenic detrusor overactivity (NDO) gradually decreases over time, which might be one of the reasons for failure after ES.

Nerve Crossover Surgery – Spinal Root Anastomoses

Reports regarding microanastamosis to reinnervate the paralyzed bladder reveal recovery of neurogenic bladder dysfunction. These include surgical anastomosis of the intercostal nerve (Livshits et al. 2004, n=11), T11 nerve root (Lin et al. 2008, n=10), L5 nerve root (Xiao et al. 2003, n=15) or the S1 nerve root (Lin et al. 2009, n=12; Lin & Hou. 2013, n=9) to the S2 or S3 spinal nerve roots. Mean follow-up of individuals was between 2 to 3 years and restitution of bladder function was observed in the majority of individuals. Significant results were reported for pre and post-surgical findings including reduced bladder capacity with increased urine volume under increased force of detrusor contractions and increased voiding pressure. There was also reduced residual urine volume and both detrusor tone and sphincter resistance were increased. Results from individual subjects in Livshits et al. (2004) were presented for each of these showing consistency across these measures although statistical analysis techniques were inappropriate consisting of individual Wilcoxon signed rank tests for each variable. Individual self-report measures showed increases within a few months following surgery. Similar findings were evident in 100%, 67%, 71%, and 78% of individuals undergoing T11, L5, and S1 microanastamosis, respectively (Lin et al. 2009; Xiao et al. 2003; Lin et al. 2008; Lin & Hou 2013). Full recovery of renal function and an absence of UTI was observed at follow-up (i.e., 6-18 months). Of the 7 of 9 individuals in the Lin and Hou (2013) study that recovered full bladder storage and voiding function, the return of bladder sensation (able to sense full bladder and desire to void) also accompanied the lack of nocturnal urinary incontinence by 8-12 months postoperatively. Important considerations of this surgical approach are that it is far more invasive than other approaches (i.e., indwelling catherization); and some individuals do not show any improvement postoperatively. In particular, accidental voiding may be triggered by unintentional dermatomal stimulation or Achilles tendon stretch. Furthermore, considering the potential for up to 30% failure rates and serious side effects (i.e. neuromas) this invasive procedure must be weighed cautiously against other approaches to treatment of bladder dysfunction. However, more recently, 2 small, independent pre-post studies confirmed that the Xiao procedure for intradural anastomosis to improve bladder function, was ineffective (Sievert et al. 2016, Rasmussen et al. 2015).

Bladder Cancer

Contrary to morbidity rates for many secondary conditions in spinal cord injured individuals, the overall incidence of bladder and prostate cancer is reported to be lower by 12 and 33%, respectively for a cohort of people with SCI vs non-SCI (Lee et al 2014; n=27,2005). Although Nahm et al. (2015, n=45,486) did not confirm lower rates of bladder cancer in people with SCI, they did report that people with SCI are not at increased risk compared to people with SCI. However, this large US database did reveal increased bladder cancer mortality in people with more severe injuries (e.g. AIS A, B, C) with AIS D individuals, who typically do not have problems with neurogenic bladder or UTIs, having the risk of mortality as the general population. This group did not observe an increased mortality rate in ventilator dependent or high cervical injury individuals and postulated that their overall shortened life expectancy might have bypassed the development of bladder cancer. These results advocate for screening strategies to identify at-risk groups with contributing factors for bladder cancer related deaths. Urethro-cystoscopy and/or bladder washing cytology and histology are relevant screening strategies that report 10% and 5%, respectively, identification rates in individuals with at least 5 years’ history of neurogenic lower urinary tract dysfunction (Sammer et al. 2015).

Bladder Stones

Compared to the general population, individuals with SCI have a higher risk of bladder stone formation (Chen et al. 2002; Bartel et al. 2014). Secondary complications arising from urinary stasis, hypercalciuria due to immobilization, and long-term catheter use are all contributing factors to the higher prevalence of bladder stone formation in people with SCI. Bartel et al. (2014) associated bladder stones in individuals using suprapubic catheters (SPC, 11%), transurethral catheters (TC, 6.6%), intermittent catheterization (IC, 2%) and reflex micturition (RM, 1.1%). The time interval to bladder stone development for TC, SPC, IC, and RM was 31, 59, 116 months and 211 months, respectively. Similarly, recurrence rates were 40, 28, 22 and 0%, respectively. Conversely, time to recurrence for the TC group was the longest at 31 months and 26 and 14 months for IC and SPC groups, respectively. Once a stone required treatment, Eyre et al. (2015) reported overall complication rates ranging from 0% to 11% to 25% following washout, stone punch and electrohydraulic lithotripsy (EHL) techniques, respectively. Combining stone punch and EHL yielded significantly higher overall rate of complications (38%, p=0.046), which was further exacerbated when these combined procedures were carried out on individuals with cervical-level injuries (p=0.032). Having a complication, a combined procedure, and age contributed to significantly longer lengths of stay (p<0.001) than when stone punch alone is chosen.

Other

Endoscopic application of bulking agents is a treatment option for vesicoureteral reflux (VUR) in individuals with chronic SCI. Virseda et al. (2014) found that the greatest success was achieved after neurogenic detrusor overactivity (NDO) was first eradicated. Otherwise, individuals with NDO experienced a high failure rate even though reflux was independent of involuntary detrusor contraction. Although individual age, presence of stress urinary incontinence (SUI), bilaterality were also thought to be predictive factors of success, multivariate analysis revealed that only degree of reflux and NDO were independent factors affecting success rate for anti- reflux procedures.

Conclusion

There is level 1a evidence (from three RCTs: Cheng et al. 1998; Xia et al. 2014; Gu et al 2015) that supports using electroacupuncture to significantly improve bladder function, when combined with conventional methods of bladder management.

There is level 2 evidence (from one prospective controlled trial: Hubshcer et al. 2018) that the use of locomotor training may increase bladder capacity, voiding efficiency and detrusor contraction time, as well as significant decreases in voiding pressure post-training.

There is level 4 evidence (from one pre-post study and one case series study: Zahariou et al. 2007; Chancellor et al. 1994) that intranasal DDVAP may reduce nocturnal urine production with fewer night-time emissions and also may reduce the need for more frequent catheterizations in persons with SCI with neurogenic bladder that is otherwise unresponsive to conventional therapy.

There is level 4 evidence (from one pre-post study: Agarwal et al. 2018) that Rectus abdominis detrusor myoplasty (RADM) appears to be a promising option in a individual with acontractile/ hypocontractile bladder to restore the bladder function.

There is level 4 evidence (from one pre-post study: Takahashi et al. 2018) that Mean maximum bladder pressure (MBP) is preserved at a low level following external sphincterotomy (ES), however neurogenic detrusor overactivity (NDO) gradually decreases over time over the years after ES, which would be one of the causes of failure of ES.

There is level 4 evidence (from three pre-post studies: Lin et al. 2009; Lin et al. 2008; Lin & Hou 2013) that nerve crossover surgery (anastomosis of T11 or S1 to S2-S3 spinal nerve roots) may result in improved bladder function in chronic SCI.

The balance of level 4 evidence (from three pre-post studies: Xiao et al. 2003 (positive results); Rasmussen et al. 2015 (negative results); Sievert et al. 2016 (negative results)) suggests that the Xiao procedure (L5-S3 ventral root anastomosis to establish a new reflex pathway) is ineffective for improving bladder function).

There is level 2 evidence (from one cohort study: Lee et al. 2014a, n=27,2005) that reported a lower rate of bladder and prostate cancer in people with SCI vs people without SCI.

There is level 2 evidence (from one cohort study: Eyre et al. 2015) that reports higher complication rates for combined bladder stone procedures vs stone punch alone.

There is level 4 evidence (from one case series study: Bartel et al. 2014) suggesting that bladder stone development occurs with suprapubic, transurethral, intermittent catheter use in descending frequency with reflex micturition have the lowest occurrence.

There is level 3 evidence (from one case control study: Virseda et al. 2014) suggesting the eradication of NDO before proceeding with endoscopic application of bulking agents to treat VUR with a higher success rate.

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