Clinical Efficacy and Changes of Urothelial Dysfunction after Repeated Detrusor Botulinum Toxin A Injections in Chronic Spinal Cord-Injured Bladder

Chornic spinal cord injury (SCI) will induce bladder urothelium dysfunction. This study investigated the therapeutic effects on urothelial dysfunction after repeated detrusor injections of onabotulinumtoxinA (BoNT-A) in SCI patients with neurogenic detrusor overactivity (NDO). Twenty chronic suprasacral SCI patients with NDO were enrolled. The patients received 300 U BoNT-A injection into the detrusor every six months. The urothelium was assessed by cystoscopic biopsy at baseline and six months after each BoNT-A treatment. Immunofluorescence staining for urothelial dysfunction, including E-cadherin, zonula occludens-1 (ZO-1), tryptase for mast cell activity, and urothelial apoptosis were investigated. The outcome of urothelial dysfunction parameters after BoNT-A injection were compared between baseline and six months after each treatment. Repeated 300 U BoNT-A injections showed a sustained decrease of detrusor pressure compared with baseline. After three repeated BoNT-A detrusor injections, significantly greater distributions of E-cadherin (p = 0.042) and ZO-1 (p = 0.003) expressions, but no significant changes, of urothelial apoptosis and mast cell activation were found after repeated BoNT-A therapy. Urothelial dysfunction, such as adhesive and junction protein concentrations in SCI patients' bladders, recovered after three repeated cycles of BoNT-A treatment. The therapeutic effects sustained. However, urothelial inflammation and apoptosis after SCI were not significantly improved after three repeated BoNT-A injections.