Botulinum neurotoxins

Botulinum neurotoxin A (BoNT-A) is derived from the Gram-negative anaerobic bacterium Clostridium botulinum (Brubaker et al. 2008). The end-organ effects of BoNTs are mediated at the parasympathetic presynaptic nerve terminal. Efferents affect much of the clinical efficacy of BoNT mediated by direct inhibition of acetylcholine and adenosine-5-triphosphate release from presynaptic cholinergic nerve terminals, resulting in reversible chemodenervation and flaccid muscle paralysis (Anger et al. 2010). The onset of action typically occurs within 48–72 h and can last between 6 and 9 months. This reversibility of clinical response is secondary to axonal regeneration and nerve sprouting, which leads to attenuation of clinical effect and the need for repeated injections (Simpson 2004).

Most studies have injected BoNT directly into the detrusor muscle (Sahai et al. 2009; Brubaker et al. 2008). Adverse effects of BoNT-A include gross haematuria, injection site pain, urinary tract infection and post-void reflux and urinary retention (Simpson 2004). Thus, the ability and the willingness to perform clean intermittent catheterisation (CISC) following BoNT-A injections should be mandatory (Sahai et al. 2009).

Brubaker et al. (2008) reported on a population of women with refractory idiopathic UUI randomised to BoNT-A vs placebo. Patient Global Impression of Improvement scores at 2 months were significantly better in the treatment group (p = 0.003) and 60% of the women achieved a clinical response (p = 0.0001). There was a highly significant reduction in daily incontinence episodes in the BoNT-A group (p = 0.0001). Furthermore, perception of bladder control was greater in the BoNT-A cohort (p = 0.0001). However, reported adverse effects included urinary tract infections and increased post-void residual urine in the BoNT-A arm (Brubaker et al. 2008). Sahai and colleagues (2009) randomised 16 patients to 200 U of BoNT-A and 18 patients to placebo and noted a significant improvement in the primary outcome measure of maximum cystometric capacity at 4 weeks and 12 weeks. There were also significant improvements in frequency, urgency and UUI episodes and QoL scores. These effects were maintained at 24 weeks follow-up.

* 출처: http://informahealthcare.com/doi/abs/10.3109/01443615.2011.649317