Botulinium toxin type A injections as an effective treatment in rehabilitation of neurogenic bladder in spinal cord lesions

ABSTRACT

Bladder management after a spinal cord injury [SCI] is a critical consideration from the onset of the condition. Inadequate management resulted in a high incidence of morbidity and mortality in the past. As better awareness has been generated, a dramatic decline in associated pathologies has occurred. The medication commonly called Botox is a purified toxin made from the botulinum bacillus. It has become standard therapy in the management of a variety of muscle spasm disorders and has found new uses in certain Urological conditions, as well. To evaluate the effectiveness of focal injections of botulinum toxin type A [BTX-A] for treating neurogenic detrusor overactivity [NDO] in patients with SCI for relieving symptoms of urinary incontinence [UI] and reducing raised detrusor pressure associated with the risk of renal complications. This randomized, placebo-controlled study investigated the effect of 2 doses of BTX-A versus placebo in patients with post-traumatic SCI, who were suffering from NDO that was inadequately managed on oral anticholinergics and required clean intermittent self catheterization [CISC]. We included 54 patients who were randomized into three treatment groups [A, B, C]. Group A received a total of 200 IU of BTX-A; included 19 patients [14 males and 5 females], their mean age was 33.4 years [yr] +/- 9.8 SD, ranged from 16 to 53 yrs with disease duration of NDO was 16.2 +/- 7.3 months [ranged from 8 to 36 months]. Group B received a total of 300 IU of BTX-A, consisted of 20 patients,16 males and 4 females, their mean age was 34.5 yrs +/- 8.7 SD, ranged from 16 to 47 yrs, with disease duration of NDO was 14.5 +/- 9.1 months [ranged from 5 to 33 months]. Group C [placebo], included 15 patients, 12 males and 3 females, their mean age was 32 yrs +/- 8.0 SD, ranged from 16 to 44 yrs with disease duration of NDO was 16.8 +/- 8.6 months [ranged from 7- 36 months]. Patients were randomized to receive a single intravesical dose of BTX- A 200 U [group A] or 300 U BTX-A [group B] or placebo [group C] administered evenly over the detrusor muscle via 30 intradetrusor injections, each of 1 ml, into the detrusor via cystoscopy, avoiding the trigone and base. For outcome analysis, we used a bladder diary, an urodynamic examination, and a questionnaire of life. Changes in UI frequency, Urodynamic parameters were maximum cystometric capacity [MCC], maximum detrusor pressure [MDP] during bladder contraction, reflex detrusor volume [RDV], and quality of life [using the Incontinence Quality of Life [I-QOL] questionnaire] at baseline and over 24 weeks following injection. Both BTX-A treatment groups showed significant changes at all time points following injection, whereas no such changes were seen with placebo. Changes in bladder diary at week 2,6,12,18 and 24 weeks after BTX-A injection as follows frequency of UI episode was reduced by 31%, 47%, 47%, 53% and 63%, respectively in group A and by 50%, 60%, 65%, 65% and 73%, respectively, in group B. Favorable significant changes in urodynamic parameters from baseline were also seen for both BTX-A groups, including increased MCC, decreased MDP and increased in RDV. Scores for [I-QOL] were significantly improved for both BTX-A groups from baseline and differed significantly from placebo at all time points; The MCC were significantly increased [p<0.05] from 276.3 +/- 17.4 mL to 465.0 +/- 39.4 mL and from 281.8 +/- 16.8 mL to 463.5 +/- 38.9 mL in both groups A and B at week 2, respectively. MCC had increased by 68%, 61%, and 57%, respectively, at the same intervals at week 2, 8 and 24, respectively in group A patient group and by 64%, 61% and 59% in group B. The MDP had decreased by 41%, 38% and 33% at week 2, 8 and 24, respectively in group A and by 42%, 39% and 33% in group B. The RDV had increased by 22%, 10% and 23% at week 2, 8 and 24, respectively in group A and by 11%, 4% and 10% in group B. BTX-A was well tolerated with virtually no side effects. The overall improvement in QOL was maintained up to 24 weeks. BTX-A was effective in reducing UI episodes and improving urodynamic parameters in patients with UI due to NDO. BOTOX may be an important therapeutic option for improving neurogenic bladder management and reducing the risk of vesicoureteric reflux, potentially preventing upper urinary tract deterioration and kidney damage. BTX-A has excellent safety profiles indicates that this treatment may also be beneficial for patients with UI of non-neurogenic origin