
==== Front
Saudi J Gastroenterol
Saudi J Gastroenterol
SJG
Saudi J Gastroenterol
Saudi Journal of Gastroenterology : Official Journal of the Saudi Gastroenterology Association
1319-3767
1998-4049
Wolters Kluwer - Medknow India

38497411
SJG-30-236
10.4103/sjg.sjg_407_23
Original Article
Sacral nerve stimulation effect on colonic motility in pediatric patients
Dorfman Lev 1*https://orcid.org/0000-0003-0427-2807

Sigal Anat 1*
El-Chammas Khalil 12
Mansi Sherief 12
Kaul Ajay 12
1 Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
2 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
* Author Lev Dorfman and author Anat Sigal contributed equally

Address for correspondence: Dr. Lev Dorfman, Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA. E-mail: levdorfman@gmail.com
Jul-Aug 2024
15 3 2024
30 4 236242
05 12 2023
21 2 2024
27 2 2024
Copyright: © 2024 Saudi Journal of Gastroenterology
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
Background:

Sacral nerve stimulation (SNS) is a minimally invasive surgical procedure used to treat refractory constipation in children. While its efficacy in improving symptoms has been studied, its effect on colonic motor function remains unclear. This case series explores SNS’s impact on colonic motor function in pediatric patients with idiopathic constipation, using high-resolution colonic manometry (HRCM).

Methods:

Four pediatric patients with chronic idiopathic constipation underwent SNS placement for intractable symptoms and were subsequently evaluated via HRCM. Clinical characteristics, comorbidities, treatment regimens, and outcomes were reviewed. HRCM was conducted during the SNS-off and SNS-on phases. The motility index (MI) was measured during the SNS-off (fasting and postprandial) and SNS-on phases.

Results:

Four pediatric patients aged 8 to 21 years met the inclusion criteria. In three patients, SNS-induced high-amplitude propagating contractions (HAPCs) were noted, and in one patient, low-amplitude propagating contractions (LAPCs) were noted. In one patient, propagating contractions were induced only when SNS was turned on. MI changes with SNS-on were variable among different patients with an increase in MI in two patients after turning SNS on and a decrease in the other two compared with baseline. Adverse effects following SNS placement remained minimal across all cases.

Conclusion:

This case series is the first to report SNS effects on colonic motility evaluated by HRCM in pediatrics. We demonstrate that propagating colonic contractions are promptly induced when SNS is turned on. Although the initial effects of SNS on colonic motility were observable, additional investigation is necessary to comprehend the fundamental mechanisms and long-term effectiveness of SNS in pediatric patients.

Colonic manometry
constipation
neuromodulation
pediatrics
sacral nerve stimulation
==== Body
pmcINTRODUCTION

Constipation is a common condition among children that can negatively impact their physical and social well-being and quality of life.[1] While most cases of idiopathic (functional) constipation respond to conventional and behavioral treatments, some children with intractable symptoms require an escalation in management, including surgical intervention. Sacral nerve stimulation (SNS) is a minimally invasive surgical procedure that is gaining popularity as a treatment for refractory constipation. SNS uses an electrode to provide direct electrical stimulation of the sacral nerves S2–S4. While SNS is considered a first-line surgical treatment for fecal incontinence refractory to conventional treatment in adults,[2] data regarding its long-term benefits in children with constipation, as well as fecal and urinary incontinence, remain limited.[34] Studies have been conducted to show the benefits and impact of SNS on various pediatric populations suffering from constipation. Lu et al. reported a significant decrease in fecal and urinary incontinence after SNS in children with functional constipation, as well as in those with constipation due to anorectal malformation, tethered spinal cord, and Hirschsprung’s disease.[5] Additionally, he reported a decrease of 20% in antegrade colonic enema (ACE) usage in those with a cecostomy. Comparing SNS with ACE, Vriesman et al.[6] reported SNS to be more effective for fecal incontinence treatment in children with severe functional constipation and fecal incontinence, while ACE was more effective in improving bowel movement (BM) frequency and abdominal pain. Other studies that were conducted on children with constipation associated with specific abnormalities, such as Hirschsprung’s disease and anorectal malformations, showed significant improvement in constipation after SNS placement.[7] However, the mechanism of action of SNS has yet to be fully understood, and its in vivo effect on colonic motor activity is still undetermined.[8] One way to study colonic motor responses to SNS is by measuring colonic motor patterns using high-resolution colonic manometry (HRCM). The parameters that are assessed during HRCM include the presence of low-amplitude propagating contractions (LAPCs) and high-amplitude propagating contractions (HAPCs) and the effect of SNS on the motility index (MI). The MI is calculated by measuring the area under the curve of pressure recordings, and it is used for the assessment of gastrocolic response, which is defined as an increase in MI by at least 15% from baseline.[910] Additionally, by examining a variety of colonic stimulus patterns, HRCM can be used to identify the ones that provide the best colonic response. In different studies conducted on adult patients with true fecal incontinence, anorectal manometry (ARM) was performed after a temporary or permanent SNS placement, and it showed an enhanced maximum anal squeeze pressure without an alteration of the resting anal pressure. In addition, rectal sensitivity to distension improved (decreased), without a change in rectal compliance.[11] No previous studies have assessed the effect of SNS on colonic motor function as measured by HRCM in pediatric patients. Therefore, our aim is to describe the effect of SNS on colonic motor function using HRCM in a case series of pediatric patients with constipation.

MATERIALS AND METHODS

We describe pediatric patients suffering from chronic idiopathic constipation, refractory to conventional treatment who underwent SNS placement and had HRCM after SNS placement. The indication for HRCM was persistent constipation and abdominal pain after SNS placement. Data were collected from electronic medical records, including basic clinical characteristics, past medical history, clinical and laboratory findings, constipation characteristics at diagnosis and during follow-up, patients’ comorbidities, treatment regimens in the past and present, their outcomes, and adverse effects. In addition, we documented patients’ stool patterns, presence or absence of accidents, and additional urinary symptoms pre- and post-SNS.

For all patients, SNS was conducted in two stages. The first-stage procedure included placing a temporary stimulator, after which symptoms were monitored for a 2-week period. If the patient’s constipation improved, the second-stage treatment was performed, which included the implantation of a permanent pulse generator. We documented patients’ clinical response to the procedure 6–12 months after the second-stage (permanent) placement.

HRCM was performed after SNS was turned off for 5 days before the study, using a water-perfused, 16-channel, 5-cm spaced colonic manometry catheter in accordance with the published minimum standards for performing CM in children.[12] All colonic manometry catheters were placed endoscopically under general anesthesia by a neurogastroenterologist at CCHMC. Laborie Medical System was used for the performance and analysis of the manometry data.

All studies were performed the following day after the endoscopic manometry catheter placement, to discount the effect of anesthesia on gut motility.[13] For the fed phase, a caloric intake of at least 20 kcal/kg was provided and consumed by the subjects.[12]

Recording of colonic manometry tracings and reporting were performed during fasting and postprandial periods with SNS off for 5 days and then with SNS turned on during the 6-hour study. Colonic stimulation was performed with bisacodyl [Figure 1]. The calculation of MI was performed by the proprietary motility software (Laborie Database Software, version 10.0a, Enschede, The Netherlands). MI was calculated during the fasting, postprandial, and SNS-on periods. Gastro-colonic response (GCR) was measured during the postprandial period.[10]

Figure 1 Protocol of high-resolution colonic manometry evaluation in patients with sacral nerve stimulation. Created with BioRender.com

High-resolution ARM was performed after SNS placement using the Medical Measurement System (Laborie Medical) imaging catheters, and the following parameters were evaluated: basal anal resting pressure (highest pressure with the patient relaxed), maximum anal squeeze pressure (highest pressure during voluntary contraction of the anal sphincter), conscious rectal sensitivity threshold (CRST), and recto-anal inhibitory reflex (RAIR).

The study was approved by the institutional review board on September 14, 2022.

RESULTS

Four patients (three females) were included, aged 12, 13, 15, and 21 years. Their clinical characteristics are presented in Table 1. Three of the patients had additional comorbidities: Patient A had celiac disease, postural orthostatic tachycardia syndrome (POTS), dysphagia, chronic back pain, ankylosing spondylitis, and psoriasis; patient B suffered from idiopathic acute and chronic pancreatitis, vulvovaginitis, attention-deficit/hyperactivity disorder (ADHD), and asthma; and patient D had allergic conjunctivitis, eosinophilic esophagitis, oropharyngeal dysphagia, ADHD, Ehlers-Danlos syndrome (EDS), mast cell activation, speech and language disorder, anosmia, mild asthma, urticaria, autistic-like behaviors, and mild Chiari malformation. Two of the patients (B and C) had urinary symptoms: incontinence and recurrent urinary tract infections, and patient C had a loss of sensation of the urge to urinate. Besides constipation, we observed fecal incontinence in three of our patients (B, C, and D) and a loss of sensation of the urge to defecate in two of them (C and D). The stool consistency of the patients before SNS placement ranged from hard in three of the patients (A, B, and D) to soft with soiling in patient C. One patient had a cecostomy and was also performing antegrade enemas (patient B).

Table 1 Clinical characteristics

Patient	A	B	C	D	
Age (at CM)	21 YO	8 YO	10 YO	15 YO	
Sex	F	F	F	M	
Treatment trial (pre-SNS placement)	Low FODMAP diet, MiraLAX, lactulose, mineral oil, glycerin PR, milk of magnesia	MiraLAX, enema flush, Senna, lubiprostone, amitriptyline, hyoscyamine, MACE	Glycerin PR, MiraLAX, Senna Po, magnesium citrate, normal saline irrigations	Erythromycin, Senna and enema, MiraLAX, Nulytely, probiotics, Senna, bisacodyl, magnesium citrate	
Pre-SNS	Stool pattern	Frequency	Every 3–4 days	Every day (w/laxatives)	Every day (w/laxatives), bowel accidents 1–2/week	Every 1–2 days (w/laxatives)	
Consistency	Hard, rock-shaped	Hard, pebble-shaped	Soft (on laxatives)	Hard	
Soiling	No	Yes	Yes, no stool sensation	Yes, no stool sensation	
Urinary symptoms	No	Incontinence, enuresis, recurrent UTI	Incontinence, no sensation to urinate, recurrent UTI	No	
6–12 mo post-SNS	Stool pattern	Frequency	Every 3–4 days Less frequent cleanouts than before	Every 3–4 days No improvement, weight loss	Every day (w/laxatives)	Every 2 days Noncompliant with laxatives No longer required cleanouts	
	Consistency	Soft	Hard	Normal—loose	N/A	
	Soiling	No	Only after flushes	One bowel accident every 2 weeks	No	
	Urinary symptoms	No	No improvement	No improvement	No	

Furthermore, we documented the clinical response to the SNS placement at 6–12 months after permanent SNS placement. Two patients (A and C) experienced an improvement in their symptoms with more regular BMs (normal stool consistency, BMs every day/other day, no soiling, and no major complaints). Patient A had subsequent worsening symptoms with muscle weakness, difficulty in evacuation, and numbness in a perianal area with normal electromyography. One patient (B) had no improvement and continued to have constipation with hard stool, requiring flushes every 3–4 days, and abdominal pain with urinary and fecal incontinence. Patient D did not feel any improvement after SNS placement but was admitted due to noncompliance with his oral laxative regimen. At his 10-month follow-up after SNS placement, he had BMs every other day with no soiling.

In addition, there were no major adverse side effects of the SNS placement, except for incisional tenderness and occasional pain from the device’s wires in one child (A), as well as battery movement for which a revision of the subcutaneous battery pocket was performed. All patients had colonic manometry performed due to persistent symptoms of constipation despite being on a laxative regimen and SNS placement. SNS induced colonic motility in all patients—prompting HAPCs in three patients and LAPCs in one patient, HRCM findings are presented in Table 2 and manometry tracing of one of the patients is presented in Figure 2.

Table 2 Colonic manometry findings with SNS on and off

Patient	A	B	C	D	
HAPC	Fasting (SNS off)	Present	Absent	Absent	Absent	
Postprandial (SNS off)	Present	Absent	Absent	Absent	
Post-bisacodyl (SNS off)	Not performed	Absent	HAPCs present except distal 20 cm	Present (proximal 55 cm)	
SNS on	Present	Only in distal 30 cm	LAPCs	In proximal 30 cm	
GCR	Present	Present	Present	Present	
MI (mmHg)	Fasting (SNS off)	Proximal colon	0.9	5.5	2.00	2.53	
Distal colon	0.001	5.02	2.02	4.23	
Postprandial (SNS off)	Proximal colon	7.04	6.08	2.02	5.71	
Distal colon	1.08	7.49	3.27	5.48	
SNS on	Proximal colon	3.59	6.21	0.001	0.83	
	Distal colon	2.86	7.39	2.01	3.21	
HAPCs, high-amplitude propagated contractions; GCR, gastrocolic response; LAPCs, low-amplitude propagated contractions; MI, motility index; SNS, sacral nerve stimulation

Figure 2 High-resolution colonic manometry tracing showing high-amplitude propagating colonic contractions after SNS turned on

ARM was performed in all patients before and after SNS placement. In patients A, B, and C, ARM was performed with SNS off for 5 days and in patient D with SNS on [Table 3].

Table 3 Anorectal manometry data pre- and post-SNS placement

Patient	A	B	C	D*	
				
Pre-SNS	Post-SNS	Pre-SNS	Post-SNS	Pre-SNS	Post-SNS	Pre-SNS	Post-SNS	
Basal anal resting pressure (mmHg)	Normal (55)	Hypotonic (19)	Normal (62)	High (101)	High (85)	Normal (63)	Normal (73)	Normal (45)	
RAIR	Present	Present	Present	Equivocal (squeezing and crying)	Present	Present	Present	Present	
CRST (ml)	No data	300 (high)	Sedated	10 (normal)	No data	20 (normal)	50–60 (borderline high)	40 (Normal)	
Squeeze pressure (mmHg)	Weak (65)	Weak (25)	Sedated	Normal (288)	Normal (185)	Normal (190)	Normal (153)	Normal (107)	
*Patient D—ARM was performed with SNS on—all others with SNS off

DISCUSSION

In our case series, we present four pediatric patients with idiopathic constipation who underwent SNS placement and had HRCM studies with SNS being turned on at the final phase of the study. The response to SNS was not similar among the patients: In two patients (A and B), MI increased from baseline, with a more prominent increase in MI in the distal colon, and in the other two patients (C and D) MI was lower compared with baseline, but higher MI was noted in the distal colon. Higher MI in the distal colon is in line with the fact that the distal colon has dual spinal innervation via both the lumbar splanchnic nerve and sacral pelvic nerves, while the proximal colon is innervated by the thoracic and lumbar spinal cords via the lumbar splanchnic nerve.[1415] Interestingly, unlike the description of Dinning et al.[816] in an adult population with constipation, in our series turning SNS on caused an increase in MI in just two cases, while in the other two it caused a decrease in colonic MI.

All patients showed propagating contractions after SNS was turned on. In patient A, HAPCs were noted along the entire length of the colon before and after turning SNS on. In patient B, no propagated contractions were noted before the SNS was turned on, despite bisacodyl stimulation; after turning SNS on, HAPCs were noted in distal 30 cm of the descending colon. In patients C and D, HAPCs were noted throughout the colon, except in distal 20–30 cm, only after bisacodyl stimulation before turning SNS on; after turning SNS on, patient C had LAPCs throughout the colon, while patient D had HAPCs in the proximal colon only. Patient B was the only one not to have any propagated contractions at all, even with bisacodyl stimulation, with SNS off. This patient did not have a dilated colon on contrast enema to explain this finding. These results are concordant with Patton et al.,[17] who showed that SNS placement increases the frequency of propagating sequences throughout the colon in adult patients with fecal incontinence. This effect was prominent in a later study in patients with slow-transit constipation, where suprasensory SNS stimulation (0.5–2 V) significantly increased the frequency of propagating sequences compared with subsensory stimulation (0.2 V below sensory threshold).[18] Unlike the description by Dinning et al.,[16] not all our patients had a pan colonic response and retrograde propagating contractions were not noted.

Additionally, on rectal manometry results post-SNS, we observed various changes, ranging from a decrease in anal resting pressure and no change in RAIR or squeeze pressure in two patients, to an increase in resting anal pressure in one patient. While expecting an increase in rectal tone after SNS placement as described in previous studies,[19] our results are comparable to the findings of Jarrett et al.[20] on the effect of SNS on distal colonic motility in patients with fecal incontinence, which showed no significant changes in the anal resting or squeeze pressures compared with the baseline measurements. They showed a variable effect of SNS on anal pressures among individuals, so that no correlation was observed between the manometric data and clinical outcome. Patient A’s lower anal tone observed in the repeated ARM study remains unexplained as she had no documented neuromuscular spinal abnormality.

Interestingly, both patients with urinary symptoms did not show improvement with SNS, which was initially introduced as a possible treatment for urinary incontinence. These results might be secondary to the small sample size of our group.

While we observed only minimal adverse effects of the SNS placement in our study, such as incisional tenderness and pain from the device’s wires in one child (A), as well as battery movement, it is important to take into consideration the complications of SNS placement, which were reported by some other groups.[521] In the study conducted by Lu et al., six of 25 patients (24%) who received SNS for constipation and fecal incontinence experienced complications that required further surgery.[5] These included local infections (four patients), lead displacement or malfunction (two patients), numbness and discomfort with sitting (one patient), and symptom relapse requiring additional surgery (one patient). In addition, one patient from the same study required two SNS removals due to infection and did not have the device replaced after the second removal. Similarly, one of our patients experienced worsening constipation symptoms in the follow-up, and his SNS was removed as well. While the current case series provides insight into the physiologic effects of SNS on colonic motor activity in pediatric patients with constipation, larger studies are needed to confirm its efficacy and long-term safety in this population.

Our case series has shown that SNS induced propagating colonic contractions in all cases (HAPCs in three patients and LAPC in one patient), with a more prominent distal colonic response as expected. However, the change in MI, as measured by real-time HRCM, was inconsistent. While the mechanism of action of SNS is not completely understood,[22] our series shows that SNS has not only long-term beneficial effect on colonic motility but also an immediate effect, which can be detected on colonic manometry. The effectiveness of SNS might not be related to the underlying colonic motor activity before SNS is turned on. This is demonstrated by the fact that the patient who had no propagated contractions before turning SNS on showed them to be present after turning it on. Conversely, the patient who had HAPCs before turning SNS on had only LAPCs after turning it on.

These findings support our recently presented data, showing that colonic manometry did not predict SNS outcomes and support the stepwise SNS placement approach with the 2-week trial of temporary SNS before permanent SNS placement.[23]

Our findings support previously described findings in adults, but future research is needed to better understand the mechanism underlying the effect of SNS on colonic motor function.

There are several limitations to this study. First, the 5 days of turning off the SNS before HRCM used in our protocol may not have been sufficient to fully eliminate the effects of prior neuromodulation, a mechanism that has been discussed in previous studies.[2425] While it is possible that extending the period of the SNS being turned off would have yielded different results, it is important to consider the potential impact of discontinuing SNS use before the study on the study participants. In addition, it is important to note that our patients had different underlying comorbidities, which may have influenced the results.

This case series is the first to report SNS effects on colonic motility evaluated by HRCM in pediatric patients. We demonstrate that propagating colonic contractions are promptly induced by SNS, providing valuable insights into the evaluation and management of patients with refractory symptoms related to constipation treated with SNS. Although the initial effects of SNS on colonic motility were observable, additional investigation is necessary to comprehend the fundamental mechanisms and long-term effectiveness of SNS in pediatric patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.
==== Refs
REFERENCES

1 Van Ginkel R Reitsma JB Büller HA Van Wijk MP Taminiau JAJM Benninga MA Childhood constipation: Longitudinal follow-up beyond puberty Gastroenterology 2003 125 357 63 12891536
2 Falletto E Brown S Gagliardi G Sacral nerve stimulation for faecal incontinence and constipation in adults Tech Coloproctol 2018 22 125 7 29313166
3 Dewberry L Trecartin A Peña A Pierre MS Bischoff A Systematic Review: Sacral Nerve Stimulation in the Treatment of Constipation and Fecal Incontinence in Children with Emphasis in Anorectal Malformation Springer Berlin Heidelberg 2019 1009 12
4 Fox JA Reinberg YE Incontinence. Pediatric sacral neuromodulation for refractory incontinence Nat Rev Urol 2010 7 482 3 20818324
5 Lu PL Koppen IJN Orsagh-Yentis DK Leonhart K Ambeba EJ Deans KJ Sacral nerve stimulation for constipation and fecal incontinence in children: Long-term outcomes, patient benefit, and parent satisfaction Neurogastroenterol Motil 2018 30 doi:10.1111/nmo. 13184
6 Vriesman MH Wang L Park C Diefenbach KA Levitt MA Wood RJ Comparison of antegrade continence enema treatment and sacral nerve stimulation for children with severe functional constipation and fecal incontinence Neurogastroenterol Motil 2020 32 e13809 32017325
7 Ladi-Seyedian SS Sharifi-Rad L Manouchehri N Ashjaei B A comparative study of transcutaneous interferential electrical stimulation plus behavioral therapy and behavioral therapy alone on constipation in postoperative Hirschsprung disease children J Pediatr Surg 2017 52 177 83 27524737
8 Dinning PG Colonic manometry and sacral nerve stimulation in patients with severe constipation Pelviperineology 2007 26 113 6
9 Dorfman L Wongteerasut A El-Chammas K Sahay R Fei L Kaul A Can sight or smell of food induce gastrocolonic response? NASPGHAN 2022 Annual Meeting Orlando, FL 2022
10 Dorfman L El-Chammas K Mansi S Kaul A Gastrocolonic response Curr Gastroenterol Rep 2022 24 137 44 36324042
11 Vaizey CJ Kamm MA Turner IC Nicholls RJ Woloszko J Effects of short term sacral nerve stimulation on anal and rectal function in patients with anal incontinence 1999 407 12
12 Rodriguez L Sood M Di Lorenzo C Saps M An ANMS-NASPGHAN consensus document on anorectal and colonic manometry in children Neurogastroenterol Motil 2017 29 doi:10.1111/nmo. 12944
13 Arbizu RA Nurko S Heinz N Amicangelo M Rodriguez L Prospective evaluation of same day versus next day colon manometry results in children with medical refractory constipation Neurogastroenterol Motil 2017 29 doi:10.1111/nmo. 13050
14 Markovic F Ratcliffe EM Development of the enteric neuromuscular system Faure C Thapar N Di Lorenzo C Pediatric Neurogastroenterology: Gastrointestinal Motility Disorders and Disorders of Gut Brain Interaction in Children Cham Springer International Publishing 2022 11 9
15 Harrington AM Castro J Erickson A Grundy L Brierley SM Chapter 17-Extrinsic sensory afferent nerves innervating the gastrointestinal tract in health and disease Said HM Physiology of the Gastrointestinal Tract 6th ed Academic Press 2018 387 418
16 Dinning PG Fuentealba SE Kennedy ML Lubowski DZ Cook IJ Sacral nerve stimulation induces pan-colonic propagating pressure waves and increases defecation frequency in patients with slow-transit constipation Colorectal Dis 2007 9 123 32 17223936
17 Patton V Wiklendt L Arkwright JW Lubowski DZ Dinning PG The effect of sacral nerve stimulation on distal colonic motility in patients with faecal incontinence Br J Surg 2013 100 959 68 23536312
18 Dinning PG Hunt LM Arkwright JW Patton V Szczesniak MM Wiklendt L Pancolonic motor response to subsensory and suprasensory sacral nerve stimulation in patients with slow-transit constipation Br J Surg 2012 99 1002 10 22556131
19 Matzel KE Stadelmaier U Hohenfellner M Gall FP Electrical stimulation of sacral spinal nerves for treatment of faecal incontinence Lancet 1995 346 1124 7 7475602
20 Jarrett ME Matzel KE Christiansen J Baeten CG Rosen H Bittorf B Sacral nerve stimulation for faecal incontinence in patients with previous partial spinal injury including disc prolapse Br J Surg 2005 92 734 9 15838899
21 Bielefeldt K Adverse events of sacral neuromodulation for fecal incontinence reported to the federal drug administration World J Gastrointest Pharmacol Ther 2016 7 294 305 27158546
22 El-Chammas K Santucci N Mansi S Kaul A Pediatric gastrointestinal neuromodulation: A review Saudi J Gastroenterol 2022 28 403 12 35418002
23 Dorfman L El-Chammas K Singh A Mansi S Santucci NR Kaul A Mo2004 efficacy of sacral nerve stimulation in children with refractory idiopathic constipation Gastroenterology 2023 164 S 950
24 Koch SM van Gemert WG Baeten CG Determination of therapeutic threshold in sacral nerve modulation for faecal incontinence Br J Surg 2005 92 83 7 15584063
25 Janknegt RA Weil EH Eerdmans PH Improving neuromodulation technique for refractory voiding dysfunctions: Two-stage implant Urology 1997 49 358 62 9123698
