Single onabotulinumtoxinA 200U dose improved clinical symptoms but not urothelial dysfunction in neurogenic detrusor overactivity due to spinal cord injury

Abstract

Objective: To evaluate the changes in urothelial dysfunction protein expressions in bladder after onabotulinumtoxin injection and correlate that with clinical outcomes in spinal cord injury (SCI) patients. Methods: Twenty-six patients with neurogenic detrusor overactivity (NDO) and urinary incontinence due to suprasacral SCI were treated with onabotulinumtoxinA 200U detrusor injection. Urodynamic studies and bladder biopsies were obtained at baseline, 3, and 6 months after treatment. Biopsy tissues were investigated for E-cadherin, zonula occludens-1 (ZO-1), mast cell activity, and urothelial cell apoptosis, sensory protein expression including purinergic receptor P2X3, endothelial NOS, inducible NOS, β3-adrenoceptors, and muscarinic receptors M2 and M3. Differences in functional protein expression between controls and SCI patients and between successful and failed treatment groups were analyzed. Results: SCI patients had significantly lower E-cadherin, higher mast cell activity, increased apoptosis, decreased M3 and eNOS expressions than the controls at baseline. Of the 26 patients, 17 (65%) showed improvement in bladder capacity by >50% at 3 months; however, improvement declined by 6 months after treatment. The urothelial expression of E-cadherin and ZO-1 increased at 3 months but had declined at 6 months. The urothelial sensory protein expression did not change significantly after treatment. M3 receptor density was significantly decreased in SCI patients at baseline and patients with treatment success 3 months after injection (p = 0.01). Conclusion: A single injection of onabotulinumtoxinA 200U improved clinical symptoms but did not significantly alter urothelial sensory protein expression. The results imply that a single 200U onabotulinumtoxinA dose might not be adequate for urothelial dysfunction in NDO. IRB: TCGH 098-53. Keywords: Spinal cord injury, Neurogenic bladder, Sensory receptors, Urothelium