European Experience of 200 Cases Treated with Botulinum-A Toxin Injections into the Detrusor Muscle for Urinary Incontinence due to Neurogenic Detrusor Overactivity
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).
References (30)
Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery
Ophthalmology
(1980)- et al.
Effects of botulinum A toxin on detrusor-sphincter dyssynergia in spinal cord injury patients
J Urol
(1988) - et al.
Botulinum-A toxin as a treatment of detrusor-sphincter dyssynergia: a prospective study in 24 spinal cord injury patients
J Urol
(1996) - et al.
Treatment of detrusor sphincter dyssynergia by transperineal injection of botulinum toxin
Arch Phys Med Rehabil
(1998) - et al.
Botulinum toxin for achalasia
Lancet
(1993) - et al.
Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results
J Urol
(2000) - et al.
Efficacy of botulinum-a toxin in children with detrusor hyperreflexia due to myelomeningocele: preliminary results
Urology
(2002) - et al.
Structure and function of tetanus and botulinum neurotoxins
Q Rev Biophys
(1995) Kinetic studies on the interaction between botulinum toxin type A and the cholinergic neuromuscular junction
J Pharmacol Exp Ther
(1980)- et al.
Crystal structure of botulinum neurotoxin type A and implications for toxicity
Nat Struct Biol
(1998)
Functional repair of motor endplates after botulinum neurotoxin type A poisoning: biphasic switch of synaptic activity between nerve sprouts and their parent terminals
Proc Natl Acad Sci USA
Botulinum A toxin injection as a treatment for blepharospasm
Arch Ophthalmol
Therapeutic uses of botulinum toxin
N Engl J Med
Management of spasticity in cerebral palsy with botulinum-A toxin: report of a preliminary, randomized, double-blind trial
J Pediatr Orthop
Treatment of spasticity with botulinum toxin: a double-blind study
Ann Neurol
Cited by (377)
Current and Emerging Pharmacological Targets and Treatments of Urinary Incontinence and Related Disorders
2023, Pharmacological ReviewsDrug Treatment of Lower Urinary Tract Dysfunction in Women
2023, Textbook of Female Urology and Urogynecology: Clinical PerspectivesBotulinum Toxin Treatment of Neurogenic Detrusor Overactivity and Overactive Bladder
2023, Textbook of Female Urology and Urogynecology: Clinical Perspectives