deSeze et al. 2002
France
PEDro=7
RCT
N=13

Population: Mean age = 45.5 yrs; Gender: males = 12, females = 1; Level of injury: paraplegic = 9, tetraplegic = 4.
Treatment: Patients were randomly placed into two groups: (1) botulinum A toxin group (BG) received one injection of 100 IU BTx Botox in 4 ml of 9% saline and (2) lidocaine group (LG) received an injection of 4 ml of 0.5% lidocaine.
Outcome Measures: Maximal urethral pressure, maximum detrusor pressure and detrusor sphincter dyssynergia. One month after the injections, the efficacy and tolerance was assessed.

• The botulinum A toxin group showed significant decrease in post-voiding residual volume (PRUV; p<0.01) and maximal urethral pressure (p<0.04). However, no significant change was seen in the lidocaine group.
• After one month, autonomic dysreflexia disappeared in patients from BG but remained unchanged in the lidocaine group.
• Patients in BG gave a significantly higher mean efficacy score to their treatment than LG patients.
• No significant difference was seen in tolerance between the two groups.

Sidi 1990
USA
PEDro=5
RCT 
N=5

Population: Mean age = 32 yrs; Gender: males = 5; Level of injury: cervical; Severity of injury: complete = 4, incomplete = 1; Mean time since injury = 14 yrs.
Treatment: Injection of 140 (50ng) units of botulinum A toxin (or saline) into 3-4 sites on the external urethral sphincter via cytoscope followed by 2 more injections of 240 units. Injections interspersed by 1 week for a total treatment time of 3 weeks. (Note: subjects receiving saline were provided the 3 week experimental treatment of Botox A but those receiving Botox A were not treated with saline.)
Outcome Measures: Cystometry to obtain post-void residual volume, urethral pressure profiles, bladder pressure on voiding obtained pre-post 3 week treatment periods.

• Botox A reduced bladder flow obstruction as indicated by decreases in all measures.
• A mean decrease from baseline to 3 weeks post injection was seen in:
• Urethral pressure profiles: 22 cm H2O,
• Post void residual volume: 118 cc
• Bladder pressure: 25 cm H2O
• No changes were seen with saline injections (n=2) for these parameters.
• The effects lasted for ~ 60 days.
• 3 of 5 patients noted mild, generalized upper extremity weakness that caused difficulty with transfers and some ADLs, gradually subsiding over 2-3 weeks. No other adverse events reported.

Dykstra et al. 1988
USA
PEDro=3
RCT
N=11

Population: Mean age = 29 yrs; Gender: males = 11; Level of injury: cervical = 10, thoracic = 1; Severity of injury: complete = 11.
Treatment: Three protocols were created: 1) subjects were injected (into the urethra) 20 units of toxin initially and 40 units in the second week.  All subsequent weeks the patients were given 80 unit doses.  2) The initial dose was 80 units and the second week dose was 160 units, followed by weekly doses of 240 units. 3) Patients were injected with 140 units of toxin the first week and all subsequent weekly doses were of 240 units. 
Outcome Measures: Detrusor responses, urethral pressure, post-void residual urine volume, autonomic dysreflexia.

• In all patients detrusor responses were unchanged after the injections. 
• All patients evaluated with electromyography after injection showed signs of sphincter denervation, however these results returned to normal as the effects of the toxin decreased.
• The urethral pressure decreased an average of 27cm after treatment.
• Post-void residual urine volume decreased by an average of 146cc after the toxin injections.
• However an increase in post-void residual volume and urethral pressure was observed as the effects of the toxin diminished.
• No UTIs occured as a result of the cytoscopic injections.
• More than half the patients who suffered from autonomic dysreflexia noticed improvement in the dysreflexia after toxin injections.

Schurch et al. 1996
USA
Downs & Black =19
Prospective Controlled trial
N=24

Population: Mean age = 32.2 yrs; Gender: males = 24; Level of injury: paraplegic = 11, tetraplegic = 13; Mean time since injury = 40.6 months.
Treatment: Patients were divided into one of three treatment protocols: 1) 4 transurethral injections of 25 IU botulinum A toxin repeated 1 to 3 months; 2) 4 injections of 25 IU botulinum A toxin given monthly for 3 months and repeated after 6 or 12 months; 3) 1 transperineal injection of 250 IU botulinum A toxin per month for 3 months and then repeated after 6 or 12 months.
Outcome Measures: Post-void residual volume, cultures of urine samples, and complete urodynamic examination was performed.  For the first protocol measures were taken after 1 and 3 months.  The 2 other protocols measures were taken at intervals of 6 and 12 months.

• All groups showed significant improvement in:
  • Maximum urethral pressure (p<0.0001).
  • Duration of detrusor sphincter dyssynergia (p=0.02).
  • Basic urethral sphincter pressure (p=0.01).
• Decreased post-void residual volumes from 450 to 50 ml were seen in 9 out of 24 patients.
• Injection of botulinum A toxin improved vesicourethral function for only 2 to 3 months, while repeated injections lasted 9 to 13 months.
• Transperineal injections were not as effective as transurethral injections on maximum urethral pressure.
• None of the treatments resulted in side effects.

Petit et al. 1998
France
Downs & Black =19
Prospective Controlled trial
N=17

Population: Mean age = 35 yrs; Gender: males = 17; Level of injury: paraplegic = 3, tetraplegic = 8.
Treatment: All patients received endoscopic injection of 150 IU BTx diluted to 4 ml with 0.9% saline solution into the external urethral sphincter at 3 or 4 points. 
Outcome Measures: Post voiding residual urine volume (PRUV), bladder pressure on voiding, urethral pressure, tolerance. Assessment was made after 15 days, 1 month, 2 months, 3 months, 6 months, and 1 year.

• One month after BTx injection a significant decrease was seen in PRUV (p<0.001), urethral (p<0.001) and bladder pressure on voiding (p<0.01).
• Modality of voiding was improved in 10 patients.
• The effect of BTx lasted from 2 to 3 months in 3 patients and 3 to 5 months in 2 patients. 

Tsai et al. 2009
Taiwan
Downs & Black=16
Pre-Post
N=18

Population: Mean age=33.8yrs; Level of injury: C=8, T=10; Severity of injury: AIS A=14, B=1, C=3
Treatment: SCI patients with detrusor sphincter dyssynergia, voiding difficulty, and inadequate response to oral medications  were injected with 100 units of BTX-A transperineally into the external urethral sphincter with EMG and fluoroscopic guidance.
Outcome Measures: Postvoid residual volume, leak point pressure, maximal intravescical pressure, urethral pressure, QoL

•  Post BTX-A injections, significant improvement and clinically successful results were seen in postvoid residual volume (100%), leak point pressure (down to < 40 cm H20 in 72%), maximal intravesical pressure (down to < 40 cm H20 in 72%) and urethral pressure (94%) (p<0.05).
• BTX-A injection also resulted in improvement in the quality of life index, p<0.01.
• Injection of BTX-A did not result in any side effects.
• Improvement in autonomic dysreflexia (6/7 subjects - 86%), vescicoureteral reflux (1/1 - 100%), hydronephrosis (7/9 - 78%) and UTIs (11/13 - 85%) was seen post injection.
• Mode of voiding changed dramatically post injection, with only 1 person still using intermittent catheterization >/= 5x/day, vs 15 preinjection. 11/14 used IC 2x/day and 3/14 resumed spontaneous voiding post injection.  3 other subjects removed ind. Catheters and used spontaneous voiding post injection

Kuo 2008
Taiwan
Downs & Black=16
Prospective Case series
N=33

Population: Mean age=41yrs; Gender: males=22, females=11; Level of Injury: C=9, T=12, L=5, MS=5, Transverse myelitis=2
Treatment: Prospective investigation of satisfaction and QoL after urethral injection of 100u BoNT-A in patients with chronic suprasacral SCI & DESD
Outcome Measures: UDS, PVR, incontinence grade (0 – 3), difficulty urinating (0 – 3), QoL. Successful outcome = moderate or very satisfied whereas not or mildly satisfied = failure of treatment.

• Significant decrease in voiding detrusor pressure was seen 45.7+/- 22.7 vs. 30.7 +/-15.5 cm H20 (p=0.016)
• Significant increase in max flow rate (p=0.047) and decrease in PVR (p=0.025) was seen.
• 60.6% of patients had successful results at 3 month follow-up.
• A decrease was seen in difficulty urinating (78.8%), PVR (69.7%), UTI frequency (67%), AD (50%).
• Significant improvement in QoL index of IIQ-7 (incontinence impact Questionnaire) was seen at 3 months compared to baseline (p=0.001) but no such improvement was seen in UDI-6 (urogenital Distress inventory).
• Adverse effects include increase incontinence grade (48.5%), increase number of urgency incontinence episodes (15.2%).

Phelan et al. 2001
USA
Downs & Black score=9
Case Series
N=21

Population: Age = 34-74 yrs; Gender: males = 8, females = 13.
Treatment: Botulinum A toxin (80-100 units) injected via cytoscopic collagen needle/cytoscope into the external sphincter at 3, 6, 9 and 12 o'clock. Outcome Measures: Able to void without catheterization.

• No statistics provided.
• 19/21 subjects voiding without catheterization after injection. 
• 14 (67%) reported significant subjective improvement in voiding patterns.
• Postoperative post void residual decreased by 71%.