Electrical stimulation of somatic afferent nerves in the foot increases bladder capacity in neurogenic bladder patients after sigmoid cystoplasty

In the current study all of the patients underwent sigmoid cystoplasties for 1–12 months (mean, 4.6 ± 1.2 months) because of a neurogenic bladder secondary to incomplete spinal cord injuries, meningoceles, or spina bifida. After recovering from surgery, the patients were asked to empty their bladders by CIC; however, the mean bladder capacity was only 280.5 ± 11.7 ml at early follow-up post-operatively based on urodynamic evaluation, which was unsatisfactory for those subjects who had undergone cystoplasty. In our previous research [1], we showed that the most common problem within 6 months post-operatively was incontinence, which might have resulted from the weakened function of the sphincter post-operatively. The presence of an indwelling urethral catheter for a long period could contribute to sphincter weakness because the maximal urethral pressure at rest was significantly decreased during the 6-month follow-up examination compared with the pre-operative pressure. Automatic contraction of the intestinal reservoir could also lead to pressure increase and incontinence. The residual detrusor also may maintain DO post-operatively. New bladder wall edema can result in reduced bladder compliance. The aforementioned four reasons can explain why the bladder capacity of the patients in the current study was not satisfactory at the early follow-up evaluation. The patients continued to use CIC combined with oral anti-cholinergic agents until the bladder capacity became larger 6 months post-operatively. The anti-cholinergic agents have some side effects, e.g., dry mouth, thus the patients cannot take the medications for a long time.

Previous studies in cats showed that transcutaneous electrical stimulation of somatic afferent nerves in the foot inhibits reflex micturition, significantly increases bladder capacity [5], and induces post-stimulation inhibition of reflex bladder activity that persists for 1–2 h [2]. Indeed, the same mechanisms might occur in healthy humans. It has been demonstrated that transcutaneous electrical stimulation of somatic afferent nerves in the foot can delay bladder filling sensations and significantly increase bladder capacity > 50% in healthy humans, and this technology has the potential to be an effective new treatment for patients with DO [3].

In our study, foot stimulation using skin surface electrodes also can delay the bladder filling sensation and significantly increase bladder capacity (Table 1 and Figure 1) in the patients after sigmoid cystoplasty. The volume per CIC was significantly increased compared with baseline, and this effect can last > 1 day.

The mechanism underlying foot stimulation is unknown, but may be mediated by the nerve in the foot [3]. The stimulation electrodes were placed on the skin surface rather than directly on the nerves. Which nerves were activated? The tibial nerve courses from the inner ankle inferiorly to the plantar surface of the foot and branches into the lateral and medial plantar nerves at the location of the electrodes. These nerves further branch into multiple small nerves that course toward the toes. Thus, it is highly likely that foot stimulation activates afferent branches of the tibial nerve in the lateral and medial plantar aspects of the foot.

The spinal segmental distribution of the stimulated somatic afferent pathways is an important factor in the efficacy of this type of neuromodulation [5]; however, inhibition at a supraspinal site cannot be excluded. A previous study in cats showed that the inhibitory effect on bladder activity elicited by electrical stimulation of the nerves from the hind limb muscles was lost after chronic spinal cord transection at the thoracic level, indicating a possible role of the supraspinal mechanisms in somato-vesical inhibition [6]. In the current study, all of the patients had incomplete spinal cord damage; therefore we cannot confirm whether or not foot stimulation has the same effects in patients with complete spinal cord damage. The Chen study [3] showed that some subjects voided a larger volume after only 30 minutes of stimulation, indicating that 30 minutes of stimulation might be sufficient to induce an inhibitory effect; thus, foot stimulation was applied for only 30 minutes in the current research.

In the Chen study [3], the average voided volume increased by > 50% or approximately 200 ml, which is more than the increase (approximately 30%) in volume per CIC in the current study. We calculated the mean volume per CIC in 24 hours after stimulation during the 3rd period, which was > 5 hours in the Chen study [3]. It is well known that the stimulation effect will weaken over time. Thus, if we also calculate the average volume per CIC 5 h after stimulation, the result may be close to the volume reported by Chen [3].

Although only a few subjects with neurogenic bladder secondary to incomplete spinal cord injuries, meningoceles, or spina bifida were tested in the study who used CIC to empty the bladder post-sigmoid cystoplasty, our results support proceeding with clinical trials involving foot stimulation in patients with OAB and other types of neurogenic bladder. Currently, CIC combined with an anti-cholinergic medication is the gold standard treatment for NDO; however, many patients are refractory to the medication or have dose-limiting side effects [7]. If foot stimulation can inhibit DO, improve bladder compliance, and increase bladder capacity in patients with neurogenic bladder, foot stimulation can be used to treat the patients instead of anti-cholinergic medications.

This is the first clinical trial in which electrical stimulation of the foot was used to treat patients. We want to determine whether or not this treatment can increase the bladder capacity in patients. Although a positive effect was shown in the current study, there were some flaws and limitations in the study. In the future, we need to conduct a randomized controlled trial to further elucidate and confirm our findings. First, the subjects in the current study all had meningoceles, incomplete spinal cord injuries, or spina bifida who had undergone sigmoid cystoplasties for 1–12 months and they do not represent all types of lower urinary tract disorders, thus we need to continue investigating patients with OAB and other types of neurogenic bladder. Second, we only focused on the changes of volume per CIC; CIC times and the urodynamic data after stimulation require study to verify the effect. Third, additional studies with a larger number of subjects are required to determine the optimal stimulation duration/pattern and further elucidate the post-stimulation effect. Fourth, the neobladder is composed of the residual bladder and sigmoid, still it is not known whether the capacity increased due to residual bladder or the sigmoid from the current data. It is difficult to prove in an augmentation model unless a pre-AE stim response is also recorded; alternatively, a similar study on orthotopic neobladder can also answer the question of whether detubularized bowel can respond to peripheral stimulation. However, no pre-augmentation stim was performed in this study. Though it is verified that neuromodulation is effective for both bladder and bowel dysfunction in previous literature [8], we still need to perform some studies to answer above-mentioned questions in the future. Fifth, all of the patients underwent this procedure at our medical center, but we are designing a portable bladder-pelvic stimulator so that patients can operate it in their own homes.