June 21, 2009 -
PRLog -- Many millions of people worldwide suffer from ‘overactive bladder’, a condition characterised by extremely frequent urination and the inability to retain urine, resulting in frequent leaks. An overactive bladder is usually caused by unwanted contraction of the muscle that controls the bladder and BTX-A is effective as it blocks the signals that tell this muscle to contract, but leaves the surrounding muscles able to function properly. In recent studies, researchers have shown that injection of Botox into the bladder muscle prevents these contractions, improving bladder function for over 80% of patients treated. Although I have endevoured to make this series non-academic, the use of BTX-A in Uroogy has largely happened within the 21st century and any worthwhile evaluation of its influence means evaluating this data. To be historically correct, I must say that Urologists actually started exploring the use of botulinum toxin type A in the late 1980’s to treat spinal cord injured patients who suffered from detrusor external sphincter dyssynergia (DESD) Dykstra DD, Sidi AA, Scott AB, Pagel JM, Goldish GD: Effects of botulinum A toxin on detrusor-sphincter dyssyngeria in spinal cord injury patients. J Urol.988; 139: 919. The researchers noted that BTX-A acted at the neuromuscular junction of the external sphincter to block vesicle transport of acetylcholine;
in essence, producing a chemical denervation and the clinical effects began within 2-3 days and were reversible. This effect was noted to be related to terminal nerve sprouting, which occured within 3-6 months. Injection of BTX-A into the sternomastoid muscle of mice also was shown to induce the formation of terminal nerve sprouts from the parent terminal de Paiva A, Meunier FA, Molgo J, Aoki KR, Dolly JO: 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. 1999; 96: 3200-5. The sprouts form functional synapses with the muscle, but eventually regress at a time when the parent nerve terminal regains the ability to release neurotransmitters. These papers are mentioned as the researchers relate to new nerve generation rather than the BTX-A losing its effect. Since this early work, there has been a recent almost exponential interest in the use of BTX-A in urology. Most recently, Schurch et al. have successfully treated spinal cord injured patients with detrusor hyperreflexia using intravesical BTX-A injections at multiple sites Schurch B, Stohrer M, Kramer G, Schmid DM, Gaul G, Hauri D: Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: A new alternative to anticholinergic drugs? Preliminary results. J Urol. 2000; 164: 692-7.
A follow-up long-term study completed by the same investigators (in 87 patients with detrusor hyperreflexia)
corroborated the efficacy of intravesical botulinum toxin injection presented in their earlier work. In this paper, detrusor muscle injections were performed in over 30 sites, with either 300 units of Botox® or 500-750 units of Dysport® with the trigone spared, (presumably, to avoid the potential complication of vesicoureteral reflux). The researchers reported clinical responses lasted 4-14 months, and observed no adverse effects with treatment. (Schurch B, Stöhrer M, Kramer G, Grosse J, Schmid D, Hauri D: Botulinum Toxin-A to treat detrusor hyperreflexia in spinal cord injured patients. Neurourology & Urodynamics. 2001; 20: 521-2). I should possibly mention that Del Popolo et al noted hyposthenia in 5/61 patients treated with high-dose intravesical BTXA injections (300u of Botox® or 1,000u Dysport®) Del Popolo G: Botulinum-A toxin in the treatment of detrusor hyperreflexia Neurourology & Urodynamics. 2001; 20: 522-4, Abstract. We can assume that the dose and the volume injected appear to play a significant role in inducing systemic toxicity with BTX-A. These effects are significant, but I expect that the main disadvantage of intravesical BTX-A injections for many urologists (especially those working in public hospitals) will be the repeated cystoscopies and toxin injections that are necessary to maintain clinical results. More recently, BTX-A injections have extended beyond the realm of neurogenic bladders to patients with nonneurogenic voiding and storage disorders. Radziszewski et al. published a paper on the effects of intravesical BTX-A injections in a pilot study of patients with either idiopathic bladder overactivity or functional outlet obstruction. Radziszewski P, Dobronski P, Borkowski A: Treatment of the non-neurogenic storage and voiding disorders with the chemical denervation caused by botulinum toxin type A- A pilot study. Neurourology & Urodynamics. 2001; 20: 410-2, Abstract. Following intravesical or sphincteric BTX-A injections, patients demonstrated resolution of incontinence and improved voiding efficiency, respectively. Zermann et al. injected 7 patients with severe urgency-frequency syndrome (who were refractory to anticholinergic therapy or electrical stimulation with intravesical BTX-A) and noted that 4 of them responded to treatment with decreases in frequency and increased bladder capacity. Zermann DH, Ishigooka M, Schubert J, Schmidt RA: Trigonum and bladder base injection of botulinum toxin A (BTX) in patients with severe urgency-frequency-
syndrome refractory to conservative medical treatment and electrical stimulation. Neurourology & Urodynamics. 2001; 20: 412-3, Abstract.
Even more recently, Professor Michael Chancellor, a urologist from the University of Pittsburgh, presented a paper to the American Urological Association i nhte summer of 2002, detailing research of 50 patients (age range 31-84) injected with botulinum toxin into the bladder or urethra.between October of 1998 and October 2001. The patient’s voiding dysfunctions were a result of both neurogenic and non-neurogenic conditions and included: multiple sclerosis, spinal cord injury, cerebral vascular accident, overactive bladder, interstitial cystitis, and dysfunctional voiding and in each case they were suffering from involuntary contractions of the bladder muscle, which caused incontinence, or an inability to completely empty the bladder. Analysis of the 50 patients indicated that 41 of 50 patients (82%) reported a decrease or absence of incontinence as well as a significant decrease in voiding symptoms. The improvement was seen within seven days of the injection and symptoms were alleviated for approximately six months. None of the patients experienced long-term complications from the treatment.. Sleep quantity and quality increased in more than 50% of patients. (Chancellor MB, Smith CP: One surgeon’s experience in 50 patients with botulinum toxin injection into the bladder and urethra. J Urol. 2002; 167: 249). These patients were followed up and it was shown that the effects lasted up to 12 months and no patient developed stress incontinence or urinary retention. This effect is not limited to adults as children with neuropathic bladders may also benefit from BTX- A injections. In a study of 17 children with myelomeningocele, Schulte-Baukloh et al studied the efficacy of different doses of BTX-A given into 30 to 40 sites in the detrusor muscle to improve bladder compliance. Urodynamic studies showed a 112.1% increase in mean reflex volume and maximal bladder capacity increased by 56.5%.. There is little doubt as urologists find more and more clinical success with urethral and bladder BTX-A injections in the treatment of everything from DESD, non-neurogenic pelvic floor spasticity, and refractory overactive bladder that our medical colleagues of the future will soon see BTX-A in much the same way that our medical colleagues of the past viewed the wonders of antibiotics. We are living in an interesting age!
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