Supra-sacral and infra-pontine spinal cord lesions, due to traumatic spinal cord injuries (SCI) or multiple sclerosis (MS), lead to the development of neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia. 

The neurogenic inflammation, caused by the spinal cord lesion, increases neurotrophic factors release which could be involved in the sensitization of the “silent C-fibers” innervating the bladder. These latter would be the trigger of an abnormal micturition reflex responsible for the emergence of NDO. NDO lead to urinary incontinence and to an increase the detrusor pressure, which could induce urological complications among which urinary tract infections, lithiasis and renal failure. Moreover, NDO decrease patients’ quality of life. 

To improve patient quality of life and preventing complications, the management of NDO is well standardized, based on antimuscarinics as first line and intradetrusor injection of botulinum toxin A (BTI) as second line before considering cystoplasty augmentation. All these strategies are associated with clean intermittent catheterization (CIC). However, BTI failure has been now characterized in SCI and MS patients. The severity of the disease appeared to be a risk factor for the therapeutic failure.
We hypothesized that the severity of the disease could result from an important neurogenic inflammation and that some extrinsic element could enhance this phenomenon. Recurrent urinary tract infections (UTI) could increase neurogenic inflammation and nerve ending sprouting via an increase in NGF [1] and pathogenic intra bladder bacteria could induce a sensitization of silent C-fibers nociceptors, leading to a mechanosensitive response of these fibers. As a result, the decrease of urinary tract infection (UTI) could impact the NDO severity. 

Among patients with NDO, some are treated for recurrent UTIs with weekly oral cycling antibiotic (WOCA) to prevent symptomatic and febrile UTI [2]. Thus, the aim of this study was to assess the impact of WOCA management on BTI failure among patients with NDO.

We performed a post-hoc study based on a cohort of patients with NDO treated with BTI between 2001 and 2013 [3]. This population was divided into two groups based on whether they were treated with WOCA or not (W/O WOCA). This study was conducted according to the legislation and conformed to Helsinki’s declaration principles.

The primary endpoint was the rate of BTI failure. BTI failures survival curves were calculated with a 95% confidence interval according to the Kaplan-Meier method and compared using the Mentel-Cox method. The hazard ratio was calculated using the Log rank method.

Two hundred and seventy-eight patients were included, with a mean age of 40.3 ± 13.3 years, of whom thirty had been treated with WOCA for recurrent UTIs. All of them were treated with BTI. BTI failure rate after 10 years of follow-up was 7,2% in the WOCA group versus 45% in the without WOCA (W/O WOCA) group, with an HR 0.2 IC95% [0,10 – 0,41], (p = 0,013). [Figure 1]

There is a statistically significant difference between the 2 groups supporting the hypothesis that WOCA helps to control the neurogenic inflammation and the subsequent C-fibers plasticity, extending the efficacy of TBI. It opens perspectives for better management of the neurogenic bladder, along with the management of others extrinsic factors of neurogenic inflammation. It would enable physicians and surgeons to postpone the cystoplasty augmentation.

However, the limits of this study, inherent to its methodology, oblige us to perform prospective studies to confirm the hypothesis and define the place of WOCA in the management of neurogenic bladder.

This study is in favor of significant decrease of BTI failure, among patients with NDO, when treated with WOCA.

Hayes BW, Choi HW, Rathore APS, Bao C, Shi J, Huh Y, Kim MW, Mencarelli A, Bist P, Ng LG, Shi C, Nho JH, Kim A, Yoon H, Lim D, Hannan JL, Purves JT, Hughes FM Jr, Ji RR, Abraham SN. Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity. Sci Immunol. 2024 Mar;9(93):eadi5578.
Dinh A, Hallouin-Bernard MC, Davido B, Lemaignen A, Bouchand F, Duran C, et al. Weekly Sequential Antibioprophylaxis for Recurrent Urinary Tract Infections Among Patients With Neurogenic Bladder: A Randomized Controlled Trial. Clin Infect Dis. 15 déc 2020;71(12):3128-35.
JoussainC, PopoffM, PhéV, EvenA, BossetPO, PottierS, et al. Long-termoutcomes and risks factors for failure of intradetrusor onabotulinumtoxin A injections for the treatment of refractory neurogenic detrusor overactivity. Neurourol Urodyn. févr 2018;37(2):799-806.