*3.4.2 Sexual function*

The effects of neuromodulation, particularly SNM, on improving sexual function among female patients, and male patients to an extent, are becoming more evident in the literature [114]. Dysfunction of the pudendal nerve, an important nerve in sexual stimulation, has been demonstrated in both refractory OAB and NOUR [115].

In a cohort of female patients who received SNM implants for OAB, urgencyfrequency syndrome or NOUR, improvements in both female sexual function index and quality of life indices were reported, though they were not correlated [116]. In another study on SCI female patients who had sexual dysfunction, there was a demonstratable improvement in the female sexual distress scale after neuromodulation therapy [117].

The argument is whether the improvements SNM provides with regards to urinary symptoms allows for a better sexual experience and confidence among patients or does SNM's effect on the pelvic floor musculature rejuvenise sexual function.

This argument is important in current applications and future considerations of neuromodulation for the treatment of sexual dysfunction. This was demonstrated in reviews of studies where sacral neuromodulation was employed in the treatment of neurogenic lower urinary tract symptoms and had demonstratable and maintainable improvements in erectile function indices to almost normal levels in a majority of patients after up to 3 years of follow-up [118].

On the contrary, another study assessing for pudendal nerve dysfunction in female patients who received SNM for refractory OAB or NOUR showed nonsignificant improvement in sexual dysfunction indices, and the authors found that these improvements as well as others in quality of life measures were in part due to improvements in urinary function; this finding was supported by a recent review [115, 119].

### *3.4.3 Neuromodulation in children and adolescents*

Scarce data, changing anatomy and somatic growth, physical activity, high reoperation rates, and neurologic instability and disease progression: all are valid arguments against application of SNM in children and adolescents. However, data is emerging on its off-label use, with modest responses. In a single center experience on eight children and adolescents with congenital lumbosacral and traumatic spinal cord defects and lower urinary tract dysfunction, the initial response rate to SNM application was 85%. This translated into a sustained efficacy in 50% of patients on 14-month follow-up, and three patients were able to abandon self-catheterization completely. These results, although on a heterogenous and small cohort of young patients, are promising and could defy the current status quo [120, 121].

Nevertheless, based on lack of evidence and limited studies, the ICS best practice statement stressed that the safety of SNM in this population cannot be established, highlighting the technical challenges associated with anatomical variations and difference in children and effects of somatic growth [4].

### **4. Future directions and research**

### **4.1 Further evaluation of effects of neuromodulation in urology**

Basic science research is still ongoing and perhaps still early in deciphering the exact mechanism of action of neuromodulation in restoring and normalizing bladder function. The different levels of speculated effect, in higher brain and spinal centers and in the more distal micturition pathways and reflex arcs make for a vast field of investigation, as well as the interplay of different neural and cellular messengers.

A better and clearer understanding of all factors involved would definitely allow for the optimization of patient outcomes, including most suitable candidates, duration of symptoms, and required concomitant medication, if any, that would maximize the benefit from different neuromodulation modalities. This is of particular importance when conflicting data on different effects on receptor pathways and modulated areas in the brain continue to emerge, and the definition and descriptions of the mechanisms of action are updated.

### **4.2 Rechargeable and MRI-compatible systems**

SNM, like any battery system, faces depletion. Thus, a rechargeable system is one of special appeal. Perhaps one of the most appealing arguments for upcoming

**233**

*Neuromodulation in Urology: Current Trends and Future Applications*

rechargeable systems is the fact it may potentially eliminate replacement surgery. The Relax-OAB study investigated the Axonics r-SNM system, a rechargeable SNM system granted post-marketing permission in Europe in 2016 and is under FDA assessment. Designed to last 15 years with charging requirements for 2 hours every 1–3 weeks, it has shown comparable objective improvements of up to 91% [83, 122, 123]. The Axonics system and the next generation InterStim Micro could revolutionize sacral

The growing need for MR-compatible systems is not a wishful thought, but in the face of evolving biomechanical technology and a growing population that needs both SNM and regular MRI assessment, it seems sensible that the development of

Casually described as a system that "listens to the patient" closed-loop or functional stimulation is a mode of conditional electrical stimulation that is being investigated as a potential neuro-prosthesis that senses bladder fullness, detects bladder contractions, and eventually modulates an electrical response "blindly" without the patient having to actively control their micturition habits. To date there are a number of animal and limited human trials on a set of intelligent electrodes specifically designed to fulfill this purpose. The advantages of such a system are numerous, mainly bypassing chronic stimulation and subsequent bladder muscle fatigue through improvements in warning time for impending bladder contractions, as well as a more natural control on voiding and improved SNM battery life [83]. Many investigators have also looked into improved neurological and bladder pres-

Thirty years into its first reintroduction, it is still surprising how limited the indications for SNM in particular remain in the face of accumulating evidence, albeit from small trials restricted by a small pool of patients and candidates. Off-label use of SNM in chronic pelvic pain syndromes, pregnant women, children and neurogenic bladder patients should be the priority of authoritarian bodies to promote research and insight especially when treatment of such conditions could

Though an existing technology, this direct PNS variation has further potential to modulate the combined sacral nerve roots that the former effects without the need of a sacral lead. Utilizing a percutaneous prepubic electrode placed on the clitoris to temporarily deliver electric stimulation and subsequently modulate the dorsal genital nerve, the anterior terminal branch of the pudendal nerve, this technology

Hypothesized to exert its effect through inhibition of bladder efferents, particularly parasympathetic pathways via vesical ganglia and detrusor smooth muscle, the dorsal genital nerve is stimulated using an external pulse generator, and has been shown to reduce urgency incontinence episodes in a number of patient cohorts. However, the device is still not appealing due to lead migration and difficult controls, improvements on which would surely stir further interest

*DOI: http://dx.doi.org/10.5772/intechopen.92287*

such devices is just a matter of time [14].

sure sensors as a modality for functional stimulation.

**4.5 Dorsal genital nerve stimulation**

among physicians and patients alike [82].

**4.4 Expanding indications and revisiting limited applications**

have remarkable effects on the quality of life of those affected [124].

has been tested in small scale trials with promising results.

**4.3 Closed-loop neuromodulation**

neuromodulation durability.

*Neuromodulation in Urology: Current Trends and Future Applications DOI: http://dx.doi.org/10.5772/intechopen.92287*

rechargeable systems is the fact it may potentially eliminate replacement surgery. The Relax-OAB study investigated the Axonics r-SNM system, a rechargeable SNM system granted post-marketing permission in Europe in 2016 and is under FDA assessment. Designed to last 15 years with charging requirements for 2 hours every 1–3 weeks, it has shown comparable objective improvements of up to 91% [83, 122, 123]. The Axonics system and the next generation InterStim Micro could revolutionize sacral neuromodulation durability.

The growing need for MR-compatible systems is not a wishful thought, but in the face of evolving biomechanical technology and a growing population that needs both SNM and regular MRI assessment, it seems sensible that the development of such devices is just a matter of time [14].

### **4.3 Closed-loop neuromodulation**

*Neurostimulation and Neuromodulation in Contemporary Therapeutic Practice*

of patients after up to 3 years of follow-up [118].

*3.4.3 Neuromodulation in children and adolescents*

difference in children and effects of somatic growth [4].

descriptions of the mechanisms of action are updated.

**4.2 Rechargeable and MRI-compatible systems**

**4.1 Further evaluation of effects of neuromodulation in urology**

Basic science research is still ongoing and perhaps still early in deciphering the exact mechanism of action of neuromodulation in restoring and normalizing bladder function. The different levels of speculated effect, in higher brain and spinal centers and in the more distal micturition pathways and reflex arcs make for a vast field of investigation, as well as the interplay of different neural and

A better and clearer understanding of all factors involved would definitely allow for the optimization of patient outcomes, including most suitable candidates, duration of symptoms, and required concomitant medication, if any, that would maximize the benefit from different neuromodulation modalities. This is of particular importance when conflicting data on different effects on receptor pathways and modulated areas in the brain continue to emerge, and the definition and

SNM, like any battery system, faces depletion. Thus, a rechargeable system is one of special appeal. Perhaps one of the most appealing arguments for upcoming

**4. Future directions and research**

cellular messengers.

This argument is important in current applications and future considerations of neuromodulation for the treatment of sexual dysfunction. This was demonstrated in reviews of studies where sacral neuromodulation was employed in the treatment of neurogenic lower urinary tract symptoms and had demonstratable and maintainable improvements in erectile function indices to almost normal levels in a majority

On the contrary, another study assessing for pudendal nerve dysfunction in female patients who received SNM for refractory OAB or NOUR showed nonsignificant improvement in sexual dysfunction indices, and the authors found that these improvements as well as others in quality of life measures were in part due to improvements in urinary function; this finding was supported by a recent review [115, 119].

Scarce data, changing anatomy and somatic growth, physical activity, high reoperation rates, and neurologic instability and disease progression: all are valid arguments against application of SNM in children and adolescents. However, data is emerging on its off-label use, with modest responses. In a single center experience on eight children and adolescents with congenital lumbosacral and traumatic spinal cord defects and lower urinary tract dysfunction, the initial response rate to SNM application was 85%. This translated into a sustained efficacy in 50% of patients on 14-month follow-up, and three patients were able to abandon self-catheterization completely. These results, although on a heterogenous and small cohort of young patients, are promising and could defy the current status quo [120, 121]. Nevertheless, based on lack of evidence and limited studies, the ICS best practice statement stressed that the safety of SNM in this population cannot be established, highlighting the technical challenges associated with anatomical variations and

**232**

Casually described as a system that "listens to the patient" closed-loop or functional stimulation is a mode of conditional electrical stimulation that is being investigated as a potential neuro-prosthesis that senses bladder fullness, detects bladder contractions, and eventually modulates an electrical response "blindly" without the patient having to actively control their micturition habits. To date there are a number of animal and limited human trials on a set of intelligent electrodes specifically designed to fulfill this purpose. The advantages of such a system are numerous, mainly bypassing chronic stimulation and subsequent bladder muscle fatigue through improvements in warning time for impending bladder contractions, as well as a more natural control on voiding and improved SNM battery life [83]. Many investigators have also looked into improved neurological and bladder pressure sensors as a modality for functional stimulation.

### **4.4 Expanding indications and revisiting limited applications**

Thirty years into its first reintroduction, it is still surprising how limited the indications for SNM in particular remain in the face of accumulating evidence, albeit from small trials restricted by a small pool of patients and candidates. Off-label use of SNM in chronic pelvic pain syndromes, pregnant women, children and neurogenic bladder patients should be the priority of authoritarian bodies to promote research and insight especially when treatment of such conditions could have remarkable effects on the quality of life of those affected [124].

### **4.5 Dorsal genital nerve stimulation**

Though an existing technology, this direct PNS variation has further potential to modulate the combined sacral nerve roots that the former effects without the need of a sacral lead. Utilizing a percutaneous prepubic electrode placed on the clitoris to temporarily deliver electric stimulation and subsequently modulate the dorsal genital nerve, the anterior terminal branch of the pudendal nerve, this technology has been tested in small scale trials with promising results.

Hypothesized to exert its effect through inhibition of bladder efferents, particularly parasympathetic pathways via vesical ganglia and detrusor smooth muscle, the dorsal genital nerve is stimulated using an external pulse generator, and has been shown to reduce urgency incontinence episodes in a number of patient cohorts. However, the device is still not appealing due to lead migration and difficult controls, improvements on which would surely stir further interest among physicians and patients alike [82].
