Neuro-urologyNeurogenic Detrusor Overactivity Treated with English Botulinum Toxin A: 8-Year Experience of One Single Centre
Introduction
Botulinum neurotoxin type A (BoNTA) has proven to be a safe and effective therapy for a variety of somatic and autonomic motor disorders. Its use, in the urologic field, is especially advised when antimuscarinic medications are ineffective in decreasing incontinence episodes or cause intolerable side effects [1]. As recently shown, BoNTA treatment also seems to have a therapeutic role in idiopathic detrusor overactivity (IDO) and in painful bladder syndrome [2], [3], [4], [5]. Moreover, intradetrusor BoNTA injections result in significant improvements in the quality of life of patients with intractable detrusor overactivity (DO) of neurogenic or idiopathic origin [6].
The effect of fast paralysis, due to BoNTA injection, is evident in the detrusor, objectively and subjectively, and it lasts for a relatively long period, nearly 1 yr [7], [8]. Therefore, the complete mechanism through which BoNTA acts and loses its efficacy in the detrusor is still unclear. Recent studies and a recent review by Apostolidis et al proposed a mechanism of BoNTA action that involved a primary effect on the release of acetylcholine and a secondary effect on bladder afferent pathways, by reducing sensory receptors in the sub-urothelium, and a central desensitisation through a decrease in central uptake of substance P [9], [10], [11]. The result is a long-lasting inhibition of afferent and efferent mechanisms on the basis of DO. But the exact mechanism of action on the afferent pathways remains unknown.
The use of BoNTA in the treatment of neurogenic DO (NDO) is increasing as well as the years of follow-up and consequently the number of retreatments. But only few studies in the literature consider the possible development of drug resistance in patients who have undergone multiple treatments [12], [13], [14]. Moreover, these few studies had a relatively short follow-up. A recent study by Compérat and colleagues, who looked at histologic features, demonstrated that there were no differences in inflammatory infiltration and oedema in the bladder wall of patients who received BoNTA injections and those who did not. There was major fibrosis in the non-injected patients compared with injected patients, but in their study there were only two patients with four and three injections, respectively [15]. So the long-term effects of chronic treatment with botulinum toxin and its efficacy and safety after repeated injections remain unknown. Most patients might require retreatment, but the effects of multiple injections have not been clearly evaluated in a long-term prospective study.
In this retrospective study, we present our experience with a large homogeneous population treated in a single centre with botulinum toxin type A (Dysport®) for NDO, to detect a possible reduction of BoNTA efficacy and duration and to evaluate the long-term efficacy and safety of toxin after repeated injections.
Section snippets
Procedure
Since 1999, we have treated about 50 neurogenic patients per year with Botox® or Dysport® for NDO. Between September 1999 and December 2005, we treated 199 patients with spinal cord lesions (SCLs) with NDO, resistant to conventional antimuscarinic therapy, with Dysport injections only. All patients had a clinical examination, urinalysis, and a urodynamic study at baseline and 3, 6, and 12 mo after each treatment as well as a visual analogue scale (VAS; range scale: 0–10) and a bladder diary
Results
All patients presented an SCL (American Spinal Injury Association [ASIA] A-D). Thirty-nine of 199 who had an SCL above T5, ASIA A-B, presented a clinically significant autonomic dysreflexia due to neurologic bladder dysfunction. In all patients, the dysreflexia disappeared within 3 d after injection.
The mean patient age was 42.5 yr (median: 45.5 yr; range: 18–74 yr) and mean follow-up was 48 mo (median: 52 mo; range: 16–91 mo). The effect of BoNTA injection on bladder function was observed
Discussion
Data have been published in the last 5 yr about BoNTA treatment for neurogenic lower urinary tract dysfunctions [15]. In the neurourologic field, for SCL patients, we indicate a lifelong treatment especially for young people without clear data on long-term clinical results and toxin impact on the detrusor muscle. A recent review demonstrated that there are few studies with a reasonable number of patients that can achieve a real statistical significance. The only one with 200 patients was a
Conclusions
There are few studies reporting data about the English toxin. We have demonstrated the long-term efficacy and safety and high level of patient satisfaction using Dysport. Moreover, this efficacy is maintained throughout. Our study outlined the importance of correct bladder management after BoNTA injections, which should influence the efficacy duration of the treatment. Prospective studies with long follow-up periods are necessary in patients on maintenance therapy to define clinical benefits as
Conflicts of interest
The authors have nothing to disclose.
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