Elsevier

European Urology

Volume 45, Issue 4, April 2004, Pages 510-515
European Urology

European Experience of 200 Cases Treated with Botulinum-A Toxin Injections into the Detrusor Muscle for Urinary Incontinence due to Neurogenic Detrusor Overactivity

https://doi.org/10.1016/j.eururo.2003.12.004Get rights and content

Abstract

Objectives: To present a comprehensive experience with botulinum-A toxin (BTA) injected into the detrusor muscle in patients with spinal cord injuries/diseases causing neurogenic incontinence.

Methods: Ten European medical centers provided the results of 231 patients with neurogenic detrusor overactivity who were treated with BTA. 300 units of Botox® (Allergan Inc.) were injected cystoscopically into the detrusor muscle at 30 different locations, while sparing the trigonum. Urinary continence status, concomitant anticholinergic medication use and patient satisfaction were recorded. Key urodynamic parameters (reflex volume, maximum detrusor pressure during voiding, detrusor compliance and maximum cystometric bladder capacity) at baseline and at the first and second urodynamic follow-up examinations were analyzed.

Results: By the time of the initial (mean 12 weeks after injection) as well as at the second urodynamic follow-up examinations (mean 36 weeks after injection), the mean cystometric bladder capacity (p<0.0001) and the mean reflex volume (p<0.01) increased significantly, while the mean voiding pressure (p<0.0001) decreased significantly. The mean bladder compliance had increased significantly (p<0.0001) by the first follow-up examination and non-significantly by the time of the second follow-up. No injection related complications or toxin related side effects were reported. The patients considerably reduced or even stopped taking anticholinergic drugs without recurrence of reflex incontinence and were satisfied with the treatment.

Conclusions: This retrospective European multicenter study presents the most extensive experience to date with BTA injections into the detrusor muscle to treat neurogenic incontinence due to detrusor overactivity and confirms that this new treatment is safe and valuable. Significant improvement of bladder function corresponds with continence and the subjective satisfaction indicated by the treated patients.

Introduction

Botulinum neurotoxin type A (BTA) synthesized in Clostridium botulinum is the disease agent for botulism and most potent natural poison. From the structural point of view the toxin is a 150 kD amino acid di-chain molecule consisting of a light (50 kD) and a heavy chain (100 kD) which are linked by a disulfide bond [1]. The toxicity of the BTA is a result of a multi-step mechanism [2]. The neurotoxin binds to the pre-synaptic nerve endings of cholinergic neurons and enters the neuron by receptor mediated endocytosis. There the catalytic domain specifically cleaves the SNAP-25 protein essential for normal synaptic vesical fusion. This cleavage results in the inhibition of neuronal acetylcholine secretion, ultimately leading to a temporary chemodenervation and the loss or reduction of neuronal activity at the target organs [1], [3]. In general, this chemodenervation is fully reversible. Regeneration process relies on the formation of functional neuronal sprouts that reconnect pre-synaptic nerve endings with their target organs (muscles or glands) [4].

The first therapeutic applications were reported in patients with strabismus and blepharospasmus [5], [6]. Currently, the toxin is a safe and highly effective therapeutic agent for numerous indications including cervical dystonia [7], juvenile cerebral palsy [8], focal spasticity [9], hyperhidrosis [10] and detrusor-sphincter dyssynergia [11], [12], [13], [14]. Also disorders of smooth muscle systems such as achalasia [15] and anal fissure [16] have been successfully treated with BTA. Recently, the efficiency of BTA injections into the detrusor smooth muscle to treat major detrusor overactivity and neurogenic incontinence has been proven [17], [18], [19], [20]. This minimally invasive procedure offers a new therapeutic option between ineffective or incompatible anticholinergic drug therapy and surgery like enterocystoplasty.

This study provides a comprehensive European experience with BTA injections into the detrusor muscle in patients with neurogenic incontinence due to detrusor overactivity.

Section snippets

Patients and methods

According to a protocol first introduced in 1999 [17] in total 231 patients with neurogenic detrusor overactivity and incontinence due to spinal cord injuries, multiple sclerosis, spina bifida or myelomeningocele were treated with BTA injected into the detrusor muscle (for details see Fig. 1). This retrospective study involves the data provided by a total of ten European medical centers found in Germany, Italy, France, Austria, and Switzerland. A survey form was developed to collect all

Results

All patients presented with neurogenic detrusor overactivity, and in 92 cases this was accompanied by detrusor sphincter dyssynergia. Before injection, 163 patients were on anticholinergic drugs. 86 took oxybutynin (80 orally and 6 using intravesical instillation), 33 took trospium chloride, 26 tolterodine, 6 propiverin and 12 took a combination of oxybutynin and trospium chloride (see Fig. 2, Fig. 3). The injection appeared as an easy and minimally invasive procedure. For the injection

Discussion

The physiologic alterations that accompany spinal cord injury (SCI), myelomeningocele (MMC) or multiple sclerosis (MS) can lead to significant bladder dysfunction. These disturbances are known to have a major impact on overall morbidity and patient’s quality of life. In the majority of SCI, MMC and MS patients bladder dysfunction can be categorized as upper motor neuron (UMN) dysfunction. The UMN syndrome presents as a disruption of the descending pathways providing the inhibitory input to the

Conclusion

This retrospective European multicenter study presents the most extensive experience to date with BTA injected into the detrusor muscle to treat neurogenic incontinence due to detrusor overactivity and confirms that this new approach is a safe and valuable therapy. Significant improved bladder function corresponds with continence and subjective satisfaction as indicated by the treated patients.

Acknowledgements

The authors are grateful to Mr. Peter Knapp for the excellent technical and scientific support and thank Mr. Huub van Hedel for statistical assistance. This study was supported by the Swiss National Foundation (Grant No. 32.52562.97).

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