How Can We Treat If We Do Not Measure: A Systematic Review of Neurogenic Bowel Objective Measures

Abstract

Background:

Guidelines fail to recommend objective measures to assist with treatment of neurogenic bowel dysfunction (NBD) in spinal cord injury (SCI).

Objectives:

The main objective was to review the literature to identify the objective measures used in all NBD populations and to present their results and any correlations performed to validated subjective measures.

Methods:

A systematic review of the literature was performed in accordance with PRISMA (2020) guidelines, including all records from January 2012 to May 2023 with MeSH terms like “neurogenic bowel” indexed in the following databases: PubMed, EMBASE, CINAHL, Cochrane Central Trials Register, and ClinicalTrials.gov. Abstracts were excluded if they did not include objective measures or if they only mentioned the esophagus, stomach, and/or small bowel. Records were screened independently by at least two collaborators, and differences were resolved by unanimous agreement.

Results:

There were 1290 records identified pertaining to NBD. After duplicates were removed, the remaining records were screened for a total of 49 records. Forty-one records (82%) included subjective measures. Two-thirds of the articles involved the population with SCI/disease (n = 552) and one-third were non-SCI NBD (n = 476). Objective measures were categorized as (1) transit time, (2) anorectal physiology testing, and (3) miscellaneous. Of the 38 articles presenting results, only 16 (42%) performed correlations of objective measures to subjective measures.

Conclusion:

There is an abundance of literature supporting the use of objective outcome measures for NBD in SCI. Strong correlations of subjective measures to objective outcome measures were generally lacking, supporting the need to use both measures to help with NBD management.

Introduction

Neurogenic bowel dysfunction (NBD) after spinal cord injury (SCI) is common, with the prevalence of chronic constipation (CC) and/or fecal incontinence (FI) ranging from 40% to 75%, and is often accompanied with abdominal distension, pain, and fecal impaction.^1,2 This prevalence is far greater than that of CC and FI in the general population (15%³ and 7%,⁴ respectively). Hemorrhoids, stercoral ulcers, pseudo-obstruction, volvulus, and rectal prolapse are some of the complications of NBD that may require surgery. CC and FI are also linked to autonomic dysreflexia. It is not surprising that the severity of NBD negatively impacts quality of life and has been identified as a top research priority for people living with SCI.^5,6 Yet, despite the importance of NBD, there is a paucity of evidence to guide clinicians on its management.⁷ Inherent to the problem is a lack of objective measures that are recommended for routine use in guiding NBD management and that are noticeably absent in the clinical practice guidelines.⁷

There are also other larger populations with central nervous system (CNS) disorders who suffer from NBD. In multiple sclerosis (MS), for example, the prevalence of CC and FI is around 40%, with nearly one in six people limiting their social activities or quitting work due to symptoms.⁸ The estimated prevalence of FI in other larger populations with CNS disorders include 68% in myelomeningocele (MM)⁹ and 15% in cerebrovascular accidents (CVA).¹⁰ CC and FI have also been seen in up to nearly 80% of patients with Parkinson’s disease (PD).¹¹ However, even in such considerably larger populations encompassing all diagnoses that can be associated with NBD, recommendations for the clinical management of NBD lack guidance on the routine use and utility of objective measures.¹²

Despite many advances in methods and techniques available for the assessment of gastrointestinal (GI) motor and sensory function, the clinical utility of these tests in NBD management is unclear. It is well known that clinical practice often lags behind advances in research.¹³ Are such objective measures in research failing to reach clinical practice? To help answer this question, we performed a systematic literature review to identify objective measures of function, symptoms, and/or treatment effects and to describe their use and association to clinical symptoms and features of NBD.

Methods

A systematic literature review was performed in accordance with PRISMA (2020) guidelines (Figure 1). The initial search was performed in July 2021 to identify relevant abstracts that included MeSH terms like “neurogenic bowel” indexed in the following databases: PubMed, EMBASE, CINAHL, Cochrane Central Trials Register, and ClinicalTrials.gov (eAppendix). In an effort to capture all of the available outcome measures used in research, we conducted a scoping review that was not limited to SCI and included trials and protocols that may not have results. After screening, the search was updated to include English language publications up to May 31, 2023. Due to the large number of records that were eligible (n = 153), we limited the review to those records published after 2011. Abstracts and manuscripts were screened independently by at least two of the collaborators (A. P., M. D., K. L., M. M., R. K., and A. S.), and differences were resolved by unanimous agreement.

Figure 1.

PRISMA flow diagram

The search strategy started with the definition of NBD, which has been described as FI and/or CC resulting from CNS disease or injury.¹⁴ Notably, we included the large diabetic population in an effort to capture as many objective measures as possible, because the vagus nerve is part of the CNS. We also focused on the colon, excluding abstracts that only mentioned the esophagus, stomach, and/or small bowel. Finally, if the abstracts did not mention objective measures, they were excluded. Articles that were not written in English were also excluded.

Articles were evaluated for type of study, population studied, number of subjects, the intervention (when applicable), the objective measures and their results, and subjective surveys or questionnaires with any correlations performed to the objective measures. Risk of bias was not performed because it is not relevant to this review, which sought to collect and report on the objective measures used in studies of NBD.

Results

There were 1290 records identified using our search terms pertaining to NBD (Figure 1). After duplicates were removed, the remaining records were screened and then limited to January 2012 to May 2023, for a total of 49 records reviewed: 39 were manuscripts (one protocol description) and 10 studies were found on clinicaltrials.gov with limited results reported. In the 38 manuscripts reporting results from completed studies, 23 were clinical trials and the remainder were observational trials. Only six were randomized control trials. Forty records (82%) included patient-reported outcome (PRO) measures. Of the 38 manuscripts presenting results, only 16 performed correlations of the objective measures to subjective measures.

Although details of the subjective measures found in this review are beyond the scope of this article, it is worthwhile to mention the more common ones that were associated with the objective outcome measures. The Bristol Stool Form Scale is a visual representation of stool consistency, hard to liquid, from 1 to 7, and has been used as a marker of transit time as well as for grouping subjects into categories, such as constipation.¹⁵ The Rome criteria are used to characterize and diagnose functional GI disorders and have updated their criteria four times at the time of writing this article.¹⁶ This measure was largely used to categorize people as having constipation. The Wexner constipation score is a detailed survey that scores the severity of symptoms that may occur with constipation.¹⁷ The Fecal Incontinence Severity Index provides a severity rating score for fecal incontinence, which has shown similar scores between patient self-report and scores from their clinicians.¹⁸ The Ten Question Bowel Survey was adapted from a larger questionnaire to characterize bowel function in SCI, although this has not been validated.¹⁹ Unlike the previously mentioned subjective measures, the Neurogenic Bowel Dysfunction score (NBDS) has been validated in the SCI population.²⁰ This self-report questionnaire surveys categories about fecal incontinence, constipation, obstructed defecation, and impacts on quality of life. The NBDS was the only self-reported measure of neurogenic bowel recommended for inclusion in the SCI common data elements (CDE).²¹

There were several populations with NBD included in this review of objective outcome measures (Table 1). Of the 38 manuscripts reporting results, 25 involved the population with SCI/disease, for a total of 552 people with SCI. The remaining studies included 476 people without SCI. The average number of subjects with SCI NBD reported in articles was 22 (range, 1-84). The average number of subjects in the other NBD populations was 37 (range, 16-66). We categorized the objective measures used in these studies into three main groups: (1) transit time, consisting of motility studies and time to evacuation; (2) anorectal physiology testing, consisting of anorectal manometry, electromyography, barostat, defecography, ultrasound, and impedance planimetry; (3) miscellaneous, including body weight before and after bowel movements, imaging of GI stool content, heart rate variability (HRV), and lesions found during colonoscopy.

Table 1.

Description of patient population and measures used for evaluation

Manuscript	Population	No. of subjects (NBD)	Category of objective measure(s)	Subjective measure(s)
Allen et al., 202251	Chronic SCI	80	TT	EQ-5D-5L, International SCI Bowel Function Basic DataSet Questionnaire, Visual Analog Scale, Bristol Stool Form Scale, Daily Bowel Management Diary
Khanna et al., 202243	MS	84	TT, APT	None measured.
Skjærbæk et al., 202236	PD	30	TT	SCOPA-AUT, Rome III, Munich Dysphagia Test-Parkinson's Disease, REM Sleep Behavior Disorder Screening Questionnaire
Bauman et al., 202138	Chronic SCI	6	TT, Miscellaneous	Nonvalidated: Ten Question Bowel Survey, adapted Treatment Satisfaction Questionnaire for Medications
Sangnes et al., 202150	DM	57	TT, Miscellaneous	GSRS
Vallès et al., 202122	Chronic SCI, Incomplete SCI	16	TT, APT	Rome III, Wexner incontinence score, ODSS, NBDS, diary, CVE-20, NRS
Albu et al., 202156	Chronic SCI, Complete SCI	10	APT	Rome III, Wexner incontinence score
Ibrahim et al., 202042	PD	27	TT	Garrigues Questionnaire, stool diary
Wegeberg et al., 202047	DM	24	TT	GCSI
De Pablo-Fernández et al., 201911	PD	42	TT, APT	GI symptoms from the Non-Motor Symptom Questionnaire, Patient Assessment of Constipation Symptoms Questionnaire, NBDS
Doi et al., 201925	PD	65	TT	None
Gourcerol et al., 201964	PD	16	APT	Constipation and fecal incontinence using 5-point Likertscoring scale
Knudsen et al., 201935	iRBD	22	TT	Rome III, Non-Motor Symptoms Questionnaire, MDS Unified Parkinson's disease Rating Scale part III
Paily et al., 201967	Supraconal SCI	35	APT	Wexner constipation and incontinence questionnaires
Putz et al., 202069	Complete SCI	20	APT	NBDS
Daeze et al., 201826	SB in pediatric population	22	TT, APT	Bristol Stool Scale, Rome III
Enevoldsen et al., 201828	Acquired brain injury	25	TT, Miscellaneous	NBDS
Sanagapalli et al., 201863	MS	33	APT	Wexner incontinence questionnaire, Rockwood score, Visual Analogue Scale, Bristol Stool Form Scale
Vaquero et al., 201859	Chronic SCI	6	APT	NBDS
Farmer et al., 201748	DM	48	TT	GCSI
Knudsen et al., 201733	PD	22	TT	Non-Motor Symptoms Questionnaire
Knudsen et al., 201734	PD	32	TT, Miscellaneous	Non-Motor Symptoms Questionnaire, Cleveland Clinic constipation score, Rome III
Putz et al., 201768	Complete SCI	20	APT	None measured
Sreepati & James-Stevenson, 201761	SB	1	APT	None measured
Ethans et al., 202237	Cauda equina syndrome	12	TT	Cleveland Clinic constipation score, St. Mark's fecal incontinence grading system, NBDS, modified AmericanSociety of Colon and Rectal Surgeons Fecal Incontinencescore, Self-rating of bowel function with Likert scales (overall bowel function, influence on daily activities, and general satisfaction)
Kim GW, et al., 201665	SCI	32	APT	NBDS
Kim JH, et al., 201623	Acute SCI, Subacute SCI	25	TT	Rome II, Bristol Stool Form Scale
Mazor et al., 201657	Chronic SCI, Motor incomplete SCI, Cauda equina syndrome	21	APT	Rome III, Hospital Anxiety and Depression Scale, SF-36, Stool diary, Knowles Constipation Questionnaire, Fecal Incontinence Severity Index, Visual Analogue Scale
Su et al., 201652	PD	66	TT, APT	Rome IV
Trivedi et al., 201658	SCI	37	APT	NBDS
Kwok et al., 201539	Chronic SCI, Complete SCI, Incomplete SCI	20	TT	NBDS, Cleveland Clinic constipation score, St. Mark's incontinence score, Spinal Cord Injury Spasticity Evaluation tool, Time to first stool, Time to complete bowel care
Rasmussen et al., 201527	Supraconal SCI	10	TT	NBDS, St. Marks Incontinence score, Cleveland Clinic constipation score
Awad et al., 201366	Complete SCI	20	APT	Pain measures, NBDS
Faaborg et al., 201329	SCI, CIC	21	TT	Cleveland Clinic constipation score, International Spinal Cord Injury Basic Bowel Function Data Set, Brief DanishPain Questionnaire
Marte & Borrelli, 201324	SB in pediatric population	16	TT	None measured
Rasmussen et al., 201331	SCI	15	TT, Miscellaneous	International Bowel Function basic and extended SCI data set, NBDS, St. Mark's incontinence score, Cleveland Clinic constipation score
Velde et al., 201330	SB in pediatric population	40	TT, APT	ROME III, Bristol Stool Scale, St. Mark's fecal incontinence grading system
Kajbafzadeh et al., 201262	SB in pediatric population	15	APT	Stool diary, form of stool and pain during defecation, NBDS
Rabadi & Vincent, 201273	SCI	71	Miscellaneous	None measured
Williams et al., 201249	Subacute and Chronic SCI	20	TT	None measured
Worsøe et al., 201270	Supraconal SCI, Complete SCI	7	APT	None measured
Bourbeau et al., ongoing	Neurogenic bowel using digital rectal stimulation for at least 6 months	2	APTT	None measured
Brigitte et al., ongoing	MS	92	APT	Wexner incontinence score, Cleveland Clinic constipation score, NBDS
Herrity et al., ongoing	Chronic SCI	36	TT, APT	Bowel diary, International Spinal Cord Injury Bowel Function Basic Data Set, SCI-QOL, interviews
Korsten et al., ongoing60	Chronic SCI	50	APT, TT, Miscellaneous	SCI Bowel Survey and Treatment Satisfaction Questionnaire
Krassioukov et al., ongoing	Chronic SCI, Complete SCI, Incomplete SCI	40	APT	Modified Wexner fecal incontinence score, NBDS
Manassero et al., ongoing	Neurogenic bowel with NBDS between 6-30	62	TT	NBDS, SF-36
McCaughey et al., ongoing	Chronic SCI	80	TT	EQ-5D-5L, International SCI Bowel Function Basic DataSet Questionnaire, Bristol Stool Scale, Diary
Street et al., ongoing	Chronic SCI	36	TT	NBDS

Note: APT = anorectal physiology; CIC = chronic idiopathic constipation; CVE-20 = 20-item quality of life in patients with constipation questionnaire; DM = diabetes mellitus; EQ-5D-5L = EuroQol-5 Dimension Health Questionnaire; GCSI = Gastroparesis Cardinal Symptom Index; GSRS = Gastrointestinal Symptom Rating Scale; iRBD = idiopathic REM sleep behavior disorder; MS = multiple sclerosis; NBD = neurogenic bowel dysfunction; NBDS = Neurogenic Bowel Dysfunction score; NRS = numerical rating scale; ODSS = Overall Disability Sum Score; PD = Parkinson’s disease; QOL = quality of life; REM = rapid eye movement; SB = spina bifida; SCI = spinal cord injury; SCOPA-AUT = Scales for Outcomes in Parkinson’s Disease - Autonomic Dysfunction; SF-36 = 36-Item Short Form Health Survey; TT = transit time.

Transit time

Transit time is broadly described as the transit of food through the stomach, small intestine, and colon (Table 2). For the purposes of this review, we focused on colonic transit time (CTT) and excluded articles that focused on the upper GI tract, such as studies only reporting esophageal motility, gastric emptying, and small intestinal motility. However, we included studies that captured the entirety of the GI transit time (whole gut transit time [WGTT]). Transit time was measured with the use of ingested radiopaque markers (ROMs), manually recording the time of bowel care, intestinal scintigraphy, and ingested wireless motility capsules (WMCs). Thirty-one (62%) of the records reviewed included objective measures related to transit time.

Table 2.

Description of objective and subjective measures used in transit time studies

Manuscript	Objective measure(s)	Objective measure results	Correlation of subjective and objective outcome measures*
Allen et al., 202251	CTT, WGTT	Pending	No correlations reported
Khanna et al., 202243	WGTT, 24 and 48 h scintigraphy images	7% of patients had delayed colonic transit at 24 h. 13% of MS with constipation had slow colonic transit.	No subjective measures reported
Skjærbæk et al., 202236	CTT	The total number of retained ROMs and corresponding CTTs were significantly higher in the PD group compared to controls.	There was no correlation between distal esophageal transit time and number of ROMs or symptoms of dysphagia. However, moderate positive correlations were seen between number ofROMs and RBDSQ score (r = 0.61) and Rome III (r = 0.4). Also, a significant correlation was found between the total number of ROMs and the total SCOPA-AUT score.
Bauman et al., 202138	Time to stool evacuation	Bowel session shortened to 107 ± 68 min vs. 41 ± 20 min Control vs. drug 42 to 88 min Decreased stool on X-ray	No correlations were reported. However, dual treatment showed improved Ten Question Bowel Survey.
Sangnes et al., 202150	CTT, WGTT	Faster colonic transit (18:37 vs. 54:25 h:min) Diarrhea had increased intraluminal pH in the entire colon (7.1 vs. 6.7, p = .05).	Colonic transit and cecal pH correlated with the GSRS score of diarrhea
Vallès et al., 202122	Total and segmental CTT	No change in CTT.	No correlations reported
Ibrahim et al., 202042	GTT	At 8 weeks, the mean GTT reduced significantly in the probiotic group compared to placebo (mean difference, 36.22 h). The mean change in GTT from baseline was more significant in the probiotic group compared to the placebo (mean difference, 37.32 h).	No correlations were reported. Although, self-reported bowel movements improved in the probiotic group compared to placebo group.
Wegeberg et al., 202047	Regional transit times and motility indexes using wireless motility capsule (SmartPill®, Medtronic, Minneapolis, MN)	Liraglutide treatment reduced large bowel transit time (31.7%) and decreased motility index (6.1%) compared to placebo. However, the groups did not differ in gastric emptying or small bowel transit times.	No correlations to large bowel transit time, only small bowel transit time
De Pablo-Fernández et al., 201911	CTT	Delayed colonic transit was found in a majority of the patients. Physiological findings were heterogenous including reduced colonic motility. CTT: Retention of more than the normal range for any one of the three sets of markers (<3 of day 1 markers, <5 of day 2 markers, and <11 of day 3 markers) was regarded as reflecting slow whole gut transit.	In those with less than 3 depositions per week or straining, 75% showed a delayed transit study. Of note, this investigation was abnormal in 1 patient who didn't fit the definition. There was no correlation between delayed transit and severity ofsymptoms.
Doi et al., 201925	CTT using radiopaque marker	The total CTT in DLB (74.9 ± 51.9 h) was longer than that in PD (59.5 ± 43.1 h), but the difference did not reach statistical significance.	No subjective measures reported
Knudsen et al., 201935	GITT, Colonic motility with 3D transit ambulatory system	The iRBD group showed a statistically significant increase in GITT, colonic volume, and CTT compared to controls. No difference was seen in these measures between iRBD and PD patients.	There were no correlations between subjective NMSQ total score or Rome III and objective measures of GITT, total volume, and total colonic 3D transit. 2. However, the Rome III 9 to 15 question constipation-specific subset scores correlated significantly with total number of retained ROM (r=0.459) and colonic 3D-Transit (r=0.481) but not total colonic volume.
Daeze et al., 201826	CTT, 6-day ROM	CTT: SB patients had a significant prolonged CTT compared to healthy controls. Of the patients with abnormal CTT, none of them developed fecal continence spontaneously, irrespective of the ARM result.	SB patients with constipation had a significant increase in their CTT compared to patients without constipation.
Enevoldsen et al., 201828	GITT	The mean GITT was significantly longer than in healthy controls (2.68 vs. 1.92 days).	No correlations reported
Farmer et al., 201748	Gastrointestinal motility test using wireless motility capsule (SmartPill)	Compared with healthy controls, patients showed prolonged gastric emptying (299 ± 289 vs. 179 ± 49 min), small bowel transit (289 ± 107 vs. 224 ± 63 min), colonic transit (2140 [1149-2799] min vs. 1087 [882-1650] min), and WGTT (2721 [1196-3541] min vs. 1475 [1278-2214] min). Patients also showed an increased drop in pH across the ileocecal junction (-1.8 ± 0.4 vs. -1.3 ± 0.4 pH) which was associated with prolonged colonic transit (r = 0.3).	There was an association between WGTT and GCSI when controlling for disease duration, sex and glycemic control (R2=0.27).
Knudsen et al., 201734	CTT	79% of PD patients displayed prolonged colonic transit time. 66% of patients had significantly increased colonic volume.	There was no correlation between the CTT and questionnaires (NMSQ and Rome). Rome questions 10 (hard stools) and 11 (straining) correlated to the ROM. The CSS total score correlated with total ROM.
Knudsen et al., 201733	GI motility using 3D-Transit system;GITT using radiopaque markers	Time to first mass and fast colonic movement were significantly increased in PD. Radiopaque marker GITT was significantly increased in the patient group whereas no difference was seen in scintigraphic gastric emptying time. Prevalence of constipation symptoms on the NMSQ was 41% in PD and 7% in controls. Using the 3D-Transit system, the patient group displayed significantly longer small intestinal and cecum-ascending transit times. No between-group difference was seen in gastric transit time.	Correlations with colonic transit were not tested, because only 24-h monitoring was performed. Nocorrelation was seen between constipation and small intestinal transit time.
Ethans et al., 202237	CTT using 3 Sitzmark capsules and abdominal X-ray	Not reported	No correlations reported
Kim JH, et al., 201623	CTT	CTT before and after PF administration was 57.41 ± 20.7 h and 41.2 ± 25.5 h for whole CTT, respectively, with the post administration decrease being significant. Transit time for each segment before and after PF administration was 14.4 ± 16.2 h and 10.1 ± 12.1 h in the right colon, 21.8 ± 12.3 h and 14.8 ± 11.8 h in the left colon, and 20.8 ± 12.1 h and 16.3 ± 14.2 h in the rectal colon, respectively. Statistical significance was seen in the right and left colon.	No correlations were reported. Although, constipation scores improved with PF.
Su et al., 201652	CTT	38% had normal CTT with median time of 43h. In 62% of the cohort with prolonged transit, the median CTT was 84.5h.	There was a significant relationship betweenconstipation scores and CTT.
Kwok et al., 201539	Time to first stool	The mean between-intervention difference for time to first stool (assessor determined) was 0 min showing no effect of standing on time to first stool.	No correlations reported
Rasmussen et al., 201527	Segmental colorectal transit times using radiopaque markers Evaluation of scintigraphic assessed colorectal emptying upon defecation Scintigraphic assessment of colorectal transport during stimulation of the reflex arch	Segmental colorectal transit times and rectal capacity did not change, and no change was seen in NBDS (median 13.5 [baseline] vs. 12.5 [follow-up]), St. Marks fecal incontinence score (4.5 vs. 5.0), and CSS score (6.0 vs. 8.0). No significant change was observed in colorectal emptying upon defecation (median 31% of the rectosigmoid at baseline vs. 75% at follow-up). No movement of colorectal contents was observed during stimulation of the reflex arch.	No correlations reported
Faaborg et al., 201329	GITT	There was no association between total GITT and average intensity of pain or unpleasantness in neither patients with SCI (r = .17) nor those with CIC (r = -.16). Likewise, there was no association between the CSS score and total GITT in neither SCI (r = 0.35) nor in CIC patients (r = 0.37).	There was no association between total GITT and average intensity of pain or unpleasantness in neither patients with SCI nor those with CIC. Similarly, there was no association between the CSS score and total GITT in neither SCI nor CIC patients.
Marte & Borrelli, 201324	Pre-post (72 h after ingestion) abdominal X-ray after 30 ROMs (10 circles, 10 cubes, and 10 cylinders) taken at intervals of 24 hours in the listed order	Before peristeen, all markers were present. After peristeen, the markers reduced from 30 ± 7.37 to 10.62 ± 6.29.	No subjective measures used
Rasmussen et al., 201331	Scintigraphic assessment of colorectal transport, bowel emptying	Median emptying at defecation was 31% of the rectosigmoid (range, 0% to complete emptying of the rectosigmoid and 49% of the descending colon) in subjects with SCI and 89% of the rectosigmoid (range, 53% to complete emptying of the rectosigmoid and the descending colon, and 3% of the transverse colon) in the control group. Colorectal emptying at defecation was associated with the St. Mark's fecal incontinence score but not with the CSS score, the NBDS, or GITT.	The scintigraphic defecation score was associated with the St. Mark's fecal incontinence score but notwith the NBDS and the CSS score. GITT was not associated with the St. Mark's fecal incontinence score, the NBDS, or the CSS score.
Velde et al., 201330	CTT	The total CTT was significantly prolonged in SB patients compared to the controls (median CTT 86.4 vs. 36 h). The CTT was significantly prolonged in constipated SB patients compared to nonconstipated SB patients (122.4 vs. 52.8 h).	Constipated SB patients had a significantly longer total CTT than nonconstipated patients. The NPV of an abnormal CTT to become spontaneously continent was 95 %. The PPV for being spontaneously continent was 100 % if both CTT and anal sphincter pressure were normal.
Williams et al., 201249	GITT using SmartPill (CTT, WGTT)	The SCI group had prolonged GET, CTT, and WGTT in comparison to the AB control group. Prolonged transit in SCI compared to AB: GET: 10.6 ± 7.2 vs. 3.5 ± 1.0 h; CTT: 52.3 ± 42.9 vs. 14.2 ± 7.6 h; WGTT: 3.3 ± 2.5 vs. 1.0 ± 0.7 days.	No subjective measures used
Herrity et al., ongoing	Wireless motility capsule (SmartPill)	Unknown	Unknown
Korsten et al., ongoing60	Time to bowel movement	Unknown	Unknown
Manassero et al., ongoing	Bowel transit time using radiopaque markers	Unknown	Unkown
McCaughey et al., ongoing	WGTT measured by SmartPill after eating a can of sweetcorn	Unknown	An exploratory analysis will be used to investigatethe effect of abdominal FES on quality of life and relations between bowel management (and medications) on CTT.
Street et al., ongoing	Time required for defecation	Ongoing trial	Ongoing trial

Note: 3D-Transit system, Motilis Medica SA, Lausanne, Switzerland; SmartPill®, Medtronic, Minneapolis, MN. AB = able-bodied; ARM = anorectal manometry; CIC = chronic idiopathic constipation; CTT = colonic transit time; CSS = Cleveland Constipation Scoring System; DLB = dementia with Lewy bodies; FES = functional electrical stimulation; GET = gastric emptying time; GTT = gut transit time; GITT = gastrointestinal transit time; GCSI = Gastroparesis Cardinal Symptom Index; GSRS = Gastrointestinal Symptom Rating Scale; iRBD = idiopathic REM sleep behavior disorder; MS = multiple sclerosis; NBDS = Neurogenic Bowel Dysfunction score; NMSQ = Non-Motor Symptoms Questionnaire; NPV = negative predictive value; PD = Parkinson’s disease; PF = Poncirus fructus; PPV = positive predictive value; RBDSQ = REM Sleep Behavior Disorder Screening Questionnaire; ROM = radiopaque markers; SB = spina bifida; SCOPA-AUT = Scales for Outcomes in Parkinson’s Disease - Autonomic Dysfunction; WGTT = whole gut transit time.

^*All outcomes are significant with p < .05 unless otherwise noted.

Radiopaque markers

Generally, ROMs are ingested at a known time, and then abdominal imaging is performed at a later time to calculate the transit time based on the presence or absence of the ROMs on imaging. There were several ROM protocols used in the NBD studies. One method relied on ingesting distinct groups of ROMs three times at 24-hour intervals and then performing abdominal imaging at some point days later.^11,22-24 The timing of abdominal X-rays after ingestion varied, from 120 hours after ingestion of the first set and defined slow WGTT based on retention of the groups of ROMs (≥3 of day 1 markers, ≥5 of day 2 markers, and ≥11 of day 3 markers)¹¹ to serial abdominal X-rays taken on days 4, 7, and 10 after ingestion.²² In the repetitive ingestion method protocol, subjects ingested a small test capsule that contained 20 ROMs (Sitzmarks^®) once a day for 6 days after breakfast. An abdominal X-ray was taken 1 week later.²⁵ A similar protocol involved 6 days of ingestion of a capsule containing 10 ROMs; on day 7, an abdominal X-ray^26-32 or CT scan with or without intravenous contrast medium was performed.^33-36 Yet another study protocol utilized Sitzmarks capsules ingested daily for days 1 to 3, with abdominal X-rays taken on days 4 and 7.³⁷ All of the protocols required dietary modifications before ingesting the ROMs. Seventeen records (55%) measuring transit time used or proposed techniques utilizing abdominal imaging and ROMs.

ROMs were informative in NBD. In subjects with PD, idiopathic REM sleep behavior disorder, and Lewy body disease, ROMs were able to detect longer CTT and WGTT compared to controls.^25,34-36 However, ROMs could not distinguish between PD with and without constipation based on subjective reporting.¹¹ The Rome III constipation-specific subset scores from questions 9 to 15 demonstrated a moderate correlation to the total number of retained ROMs (r = 0.459, p = .037).³⁵ Moderate positive correlations were seen between total number of ROMs and the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) score (r = 0.61, p = .0003) and the Rome III functional constipation score (r = 0.4, p = .029).³⁶

In people with acquired brain injury (ABI), WGTT was significantly longer than in control subjects (2.7 days, 95% CI 2.7-3.2 vs. 1.9 days, 95% CI 1.6-2.22; p = .011).²⁸ Despite significantly longer WGTT, the subjects with ABI had NBD scores of “no” or “little” impact on quality of life, with one scoring in the “moderate” range. Age was also associated with a longer WGTT in their model (0.04 years, 95% CI 0.008-0.062).

In the pediatric population with spina bifida (SB), ROMs showed significantly increased CTT compared to controls.²⁶ ROMs could distinguish between SB patients who met Rome III criteria for constipation compared to those who did not.²⁶ Furthermore, there was evidence of prognostic value with transit time ROM measures. All children who achieved bowel continence had similar CTT to the controls.

In SCI, ROM measures of CTT were sensitive to changes after a bowel intervention, corresponding to a significant improvement in constipation scores from the Rome II criteria.²³ In another study of subjects with SCI in whom no significant difference was seen post intervention, there were no changes in the WGTT and subjective questionaires.²⁷

In summary, ROMs have a variety of ingesting and imaging protocols, and they have been shown to correlate with subjective outcome measures in the NBD population. Noteworthy, ROMs were also sensitive to change after intervention in the SCI population.

Recording time

Four studies measuring transit time relied on manually recording aspects of time for a bowel movement, including the time to stool evacuation,³⁸ time to first stool,³⁹ time required for defecation,⁴⁰ and time to complete bowel care.^39,41 In the two completed studies, no correlations of recording times to subjective measures were performed.^38,39 One study measured transit time by having subjects ingest four red carmine capsules, which are nonabsorbable, nontoxic colorants of the stool. The time to have a red-colored stool from ingestion time was calculated as the WGTT.⁴² Subgroup analysis of those who had improved WGTT using the red carmine capsule method was correlated to validated PD questionnaires that included measures of GI symptoms.⁴²

Intestinal scintigraphy

Intestinal scintigraphy involves ingesting a radioactive tracer to evaluate transit time and requires nuclear medicine collaboration. Two studies performed scintigraphic evaluation of colorectal emptying during defecation.^27,43 One protocol involved swallowing two doses of ¹¹¹In-coated resin pellets several days prior (based upon prior knowledge of the subjects’ WGTT) to arriving to a nuclear medicine facility for scintigraphy.²⁷ Subjects were asked to hold medications that might affect motility 24 hours before the study, fast overnight prior to arrival, and refrain from a morning bowel care routine. Their study did not show a change before or after the intervention, and this was similar to the lack of change in the NBD, St. Marks incontinence, and Cleveland Clinic constipation scores.²⁷ The other study referenced a protocol that they modified from 1997 in which a capsule with activated charcoal dosed with diethylenetriaminepentaacetic (DTPA) and radiolabeled ion exchange pellets were swallowed along with a standard meal, with images taken serially up to 48 hours after ingesting the pellet.^43,44 CTTs were measured at 24 and 48 hours. In their study of 84 people with MS, the authors found that only 7% had delayed CTT at 24 hours and 13% who were complaining of constipation had slow CTT.⁴³

Wireless motility capsules

WMCs are ingested to provide transit time to a wearable external device by measuring pressure, pH, and temperature along the way, providing gastric emptying time, small intestinal and colonic transit time, WGTT, and pressure patterns. A portable receiver records data from the capsule over 5 days, depending on the time of expulsion of the WMC from the body. These study protocols involve discontinuation of proton pump inhibitors (PPIs) to avoid pH alterations and other agents affecting motility. In addition to discontinuation of PPIs (that affect gastric pH), the SmartPill™ (Medtronic, Minneapolis, Minnesota) protocols include ingesting a standardized meal consisting of a Smartbar (Medtronic) and 50 mL of water. Ten records (32%) measured transit time using ingested wireless capsules. Seven studies measured WGTT using WMC.^45-52

The SmartPill has been shown to detect differences between people with NBD and healthy controls. Williams et al. compared 20 subjects with SCI-related NBD to 10 subjects without SCI and found several differences. Pertinent to this review, CTT (52.3 ± 42.9 vs. 14.2 ± 7.6 hours; p = .01) and WGTT (3.3 ± 2.5 vs. 1.0 ± 0.7 days; p < .01) were significantly prolonged compared to the non-NBD controls.⁴⁹ Similarly, Farmer et al. compared 48 subjects with type 1 diabetes and distal symmetric polyneuropathy to 41 healthy participants from an established normal cohort, and they found several differences.⁴⁸ The NBD group had significantly prolonged minutes of WGTT (2721 vs. 1475; p < .001) and CTT (2140 vs. 1087; p < .001). However, in people with PD and constipation based on Rome IV criteria (n = 53), only 33 (66%) of the subjects demonstrated prolonged CTT (median, 84.5 hours) while 20 (38%) had CTT considered normal.⁵² There was a weak correlation between Rome IV scores and CTT (r = 0.32, p = .01).⁵² The SmartPill was also responsive to measuring changes with treatment. Wegeberg et al. showed that a drug intervention could reduce CTT by 31.7% (p = .04) compared to placebo in 48 subjects with type 1 diabetes and distal peripheral neuropathy (DSPN).⁴⁷ In the experimental group, they performed correlations to GI symptoms of nausea and vomiting, postprandial fullness, and bloating, and they did not find a significant association to large bowel transit. In another study of people with diabetes gastroenteropathy (n = 57), CTT was increased in patients who were defined as having diarrhea based on the Gastrointestinal Symptom Rating Scale (GSRS) of ≥4 versus those with DM who did not have diarrhea (18:37 vs. 54:25 hours:minutes; p < .001).⁵⁰ People with diabetic diarrhea also had increased intraluminal pH in the entire colon (7.1 vs. 6.7; p = .05).⁵⁰

Knudsen et al. used another wireless capsule called the 3D-Transit ambulatory system (Motilis Medica SA, Lausanne, Switzerland), which provides the capsule position by converting the electromagnetic field into space-time coordinates.³³ They compared people with PD to healthy controls and found a highly significant increase in proximal CTT in PD. No correlations were performed to the subjective NonMotor Symptoms Questionnaire (NMSQuest).

In summary, WMCs were able to detect transit time differences between groups based on subjective reported outcomes and diagnoses as well as response to treatment. Correlations to subjective outcomes were generally inconsistent.

Anorectal physiology tests

Anorectal physiology tests (APTs) are primarily indicated to evaluate functional anorectal abnormalities that could result in CC and/or FI.⁵³ These tests include anorectal manometry (ARM), electromyography, and defecography. There were 25 records that included anorectal physiology measures, of which 20 had published results and five were ongoing studies (Table 3).

Table 3.

Description of objective measures and subjective correlations used in anorectal physiology studies

Manuscript	Objective measure(s)	Objective measure results	Correlation of subjective and objective outcome measures
Khanna et al., 202243	ARM and balloon expulsion	Resting anal sphincter pressure in MS with constipation only was 65.2 mm Hg; in constipation + FI, it was 49.3 mm Hg. 18% of MS with constipation had anal sphincter pressure >90 mm Hg.	No subjective measures used
Vallès et al., 202122	ARM, EAS EMG	EAS voluntary contraction pressure decreased at 3 months after BTX-A infiltration as compared to baseline and when both groups were compared.	No correlations were performed. Although, BTX-A treatment showed improved level of satisfaction related to bowel function at 1 month and in the ODSS at 3 months compared to baseline, and constipation severity improved at 1 and 3 months with Rome III and NBS at 3 months.
Albu et al., 202156	ARM	There were no significant changes in the ARM parameters after MSC or placebo intervention.	No changes in bowel function, quality of life or independence measures were observed.
De Pablo-Fernández et al., 201911	ARM, MR defecography	Anorectal dysfunction was more prevalent than isolated slow transit constipation. Physiological findings were heterogenous including rectal hyposensitivity, defecatory dyssynergia, and poor motor rectal function.	No association was found between severity of constipation and abnormal anorectal function on ARM. MR defecography was the only investigation correlated with severity of constipation measured byPACSYM and NBD questionnaires.
Gourcerol et al., 201964	ARM	STN-DBS increased maximal amplitude of anal squeezing pressure (OFF: 85.7 ±14.5 vs. ON: 108.4 ±21.0 cmH2O), with no significant difference in the duration. No other significant difference was found between stimulation conditions (OFF vs. ON) for anal resting pressure (OFF: 72.5 8.6 cmH2O vs. ON: 71.7 9.0 cmH2O), RAIR, maximal tolerable rectal volume (OFF: 231 24 mL vs. ON: 241 26 mL), or anal pressure during defecation effort with a similar rate of ano-rectal dyssynergia (7/16 and 8/16 with and without STN-DBS, respectively). No order effect (ON-OFF vs. OFF-ON) was observed.	No correlations performed
Paily et al., 201967	ARM	Resting, squeeze, and cough pressures did not change after antimuscarinic treatment. Rectal compliance was significantly higher after antimuscarinic treatment. The percent amplitude of maximal sphincter relaxation of the RAIR was decreased, and excitation latency was increased. There was no significant change in the duration of recovery of the RAIR. Additionally, there were no changes in ARM or rectal compliance in those who received Mirabegron.	There was a significant correlation between change in rectal compliance and change in Wexner constipationscore.
Putz et al., 202069	MR defecography	The significantly higher values for the anorectal angle at rest and hiatal descent (M-line) at rest in participants with SCI correlated with the clinical assessment of bowel incontinence. Furthermore, in nearly half of the investigated SCI cohort, the results suggested pelvic floor dyssynergia as a potential mechanism underlying constipation in people with complete SCI.	Study correlated MR defecography to NBD.
Daeze et al., 201826	ARM	The median resting pressure in SB patients was 39 mm Hg (12-83 mm Hg). Median first sensation was 20 mL (10-90 mL). Median maximum tolerable volume was 90 mL (20-240 mL). Nine out of 17 patients (52.9%) had an abnormally low resting pressure.	There was no significant difference in resting pressureaccording to fecal continence status. The patients with spontaneous fecal continence tended to have a higher resting pressure. The 3 children with abnormal low resting pressure remained incontinent.
Sanagapalli et al., 201863	Anorectal physiology test, Endoanal ultrasound	Responders (79%) demonstrated improvement in at least some objective outcome measures related to their FI; conversely, nonresponders did not demonstrate any significant improvement in any parameters and in fact exhibited worsening in most of these outcomes.	No correlations were performed. Twenty-six patients (79%) were classified as responders by the predetermined Wexner incontinence score criteria, while 7 (21%) were nonresponders. The mean Wexner score among responders reduced from 13.56 ± 3.8 at baseline to 7.06 ± 2.8 after PTNS therapy, whereas in nonresponders it rose slightly from 13.46 ± 3.9 to13.96 ± 3.1.
Vaquero et al., 201859	ARM	Four patients showed improvement either in sensitivity (first sensation at filling) or in achieving a higher pressure in anal contraction or higher pressure of rectal sphincter at rest.	No correlations performed, but 4 patients had an improvement in NBD score at follow-up.
Putz et al., 201768	MR defecography	Measurement results for anorectal angle, anorectal descent, hiatal width (H-line), and hiatal descent (M-line) deviate significantly from reference values in the literature in asymptomatic subjects without SCI. The overall mean values in the study for SCI patients were anorectal angle (rest) 127.3°, anorectal angle (evacuation) 137.6°, anorectal descent (rest) 2.4 cm, anorectal descent (evacuation) 4.0 cm, H-line (rest) 7.6 cm, H-line (evacuation) 8.1 cm, M-line (rest) 2.6 cm, M-line (evacuation) 4.2 cm.	No subjective measures reported.
Sreepati & James-Stevenson T, 201761	ARM, Defecography	ARM showed a normal resting pressure with no augmentation of squeeze pressure. This was consistent with a weak EAS. Following a successful trial of temporary SNS with improvement in FI symptoms by 75%, the patient had a permanent SNS placed. One year later, the patient reports sustained improvement in constipation and FI symptoms. Baseline: A defecography suggested atrophy of the puborectalis and poor squeeze with EAS muscle atrophy.	No subjective measures reported
Kim GW, et al., 201665	Ultrasonic measurement of rectal diameter	After defecation, those in the UMNB group had smaller rectal diameters and areas than those in the LMNB group. Significant reduction of rectal diameter and area was observed after defecation as well. The LMNB groupshowed slightly increased rectal area after defecation, which was not statistically significant.	No correlations performed
Mazor et al., 201657	Anorectal function studies: resting and squeeze anal sphincter pressure, cough pressure, sustained squeeze, straining rectal pressure, concomitant anal relaxation or paradoxical contraction, perineal descent, rectal sensitivity thresholds up to 300 mL	Patients with SCI and NBD exhibited a reduction in their first sensation threshold.	Improvement in balloon expulsion time strongly correlated with improvement in both Fecal Incontinence Severity Index and constipation scores.
Su et al., 201652	High-resolution ARM and balloon expulsion	Sixty-six patients with chronic constipation; 9 patients (14%) had normal defecatory coordination. Type II dyssynergia was the most common (n = 27, 41%), followed by type IV (n = 26, 39%), and type III (n = 4, 6%).	There was a significant relationship between constipation scores and colonic transit times (r = 0.32). However, the Parkinson's disease scores and duration were not correlated with the manometric ortransit findings.
Trivedi et al., 201658	ARM, Rectal compliance	One SCI subject had a higher RC (17.0 ± 1.9 vs. 10.7 ± 0.5 mL/mm Hg, p < .05) and SC (8.5 ± 0.6 vs. 5.2 ± 0.5 mL/mm Hg). LMN-SCI subjects had a lower RC (7.3 ± 0.7 mL/mm Hg) while SC was unchanged (8.3 ± 2.2 mL/mm Hg). Anal resting pressure was decreased in SCI (55 ± 5 vs. 79 ± 7 cm H2O). Anal squeeze pressure was decreased in LMN-SCI (76 ± 13 vs. 154 ± 21 cm H2O). In SCI and LMN-SCI, the amplitude reduction of the RAIR was greater (62±4% and 70±6% vs. 44±3%).	No correlations performed
Awad et al., 201366	Rectal sensitivity with barostat	IOP was higher in SCI patients (12 ± 2 mm Hg, CI: 11–13) compared with HS (9.5 ± 2 mm Hg, CI: 8–10). Fasting and PP rectal mean bag volume and rectal compliance (mL per mm Hg) were similar in both SCI patients and HS. In SCI patients, rectal tone decreased after food compared with their own fasting values. The SCI patients had higher first sensation thresholds compared with the HS. Fasting rectal bag volume was positively correlated with the time used for each defecation (r = 0.5009) and negatively correlated with flatus incontinence (r = 0.5429). PP rectal bag volume was positively correlated with the frequency of FI (r = 0.54) and negatively correlated with flatus incontinence (r = -0.587). None of the symptoms were correlated with any of the sensitivity parameters.	Fasting pain sensation was similar in both groups; however, SCI patients reported PP pain sensation at lower pressure than controls. One of the seven cervical SCI patients reported pain sensation. Compared with their own fasting values there was no significant change in the PP threshold for noxiousand nonnoxious stimuli in both groups, except for the PP urge to defecate sensation, which was felt at a lower pressure for the SCI patients compared to HS.
Velde et al., 201330	ARM	The median resting pressure was 45 mm Hg (10-62 mm Hg); the median squeeze pressure was 43 mm Hg (15-134 mm Hg); 12/19 patients have dyssynergia.	Both resting and squeeze pressures were significantlyhigher in the spontaneously continent compared to the incontinent and pseudo-continent SB patients. Of the 19 patients, 42% had normal resting pressure. From the 19 patients, 8 (42 %) had a normal resting pressure.
Kajbafzadeh et al., 201262	ARM, RAIR, sphincter pressure	In the treatment group, sphincter pressure and RAIR significantly improved compared with sham stimulation and pretreatment measures. Frequency of defecation increased statistically significant from 2.5 ± 1.1 per week before treatment to 4.7 ± 2.3 per week after treatment.	No correlations to ARM, but subjective pain and NBDS were improved.
Worsøe et al., 201270	Rectal CSA measured using impedance planimetry and manometry	Median stimulation amplitude was 51 mA (range, 30-64). CSA was smaller during stimulation, and differences reached statistical significance at distension pressures of 20 cm H2O (average decrease 9%) and 30 cm H2O (average decrease 4%) above resting rectal pressure. Rectal pressure-CSA relation was significantly reduced during stimulation at 20 and 30 cm H2O distension. Even though a reduction in CSA during stimulation was seen in all patients, the changes were relatively small. It was shown that acute DGN stimulation in subjects with supraconal SCI results in reduced rectal compliance CSA.	No subjective measures used
Bourbeau et al., ongoing	Compare changes in colonic pressure (cm H2O) over baseline in response to electrical rectal stimulation versus mechanical rectal distension	Unknown	Unknown
Brigitte et al., ongoing	AP parameters (no details provided)	Unknown	Unknown
Herrity et al., ongoing	ARM	Unknown	Unknown
Korsten et al., ongoing60	High-resolution manometry [maximum sphincter pressure (resting and squeezing pressure), mean sphincter pressure, residual anal and intrarectal pressure (high pressure zone), and recto-anal pressure differential (difference of intrarectal and residual anal pressures)]; Changes to the sensitivity and strength of response of the RAIR in response to rectal distention.	Unknown	Unknown
Krassioukov et al., ongoing	Mean maximum resting anorectal pressure will be measured using ARM both without and with TCSCS.	Unknown	Unknown

Note: AP = anorectal physiology; ARM = anorectal manometry; BTX-A = botulinum toxin type A; CI = confidence interval; CSA = cross-sectional area; DGN = dorsal genital nerve; EAS = external anal sphincter; EMG = electromyography; FI = fecal incontinence; HS = healthy subjects; IOP = individual operating pressure; ODSS = Overall Disability Sum Score; LMN = lower motor neuron; LMNB = lower motor neuron neurogenic bowel; MR = magnetic resonance; MS = multiple sclerosis; MSC = mesenchymal stroma cell; NBD = neurogenic bowel dysfunction; NBS = neurogenic bowel dysfunction; NBDS = Neurogenic Bowel Dysfunction score; PACSYM, Patient Assessment of Constipation-Symptoms questionnaire; PP = postprandial; PTNS = posterior tibial nerve stimulation; RAIR = recto-anal inhibitory reflex; RC = rectal compliance; SC = sigmoid compliance; SB = spina bifida; SCI = spinal cord injury; SNS = sacral nerve stimulation; STN-DBS = subthalamic nuclei deep brain stimulation; TCSCS = transcutaneous spinal cord stimulation; UMNB = upper motor neuron neurogenic bowel.

Anorectal manometry

When performed according to guidelines, ARM consists of placing a flexible catheter, with a deflated balloon at the end, into the rectum while the patient is in a left lateral position.⁵⁴ The ARM test protocol consists of measuring the rectal pressures after several voluntary short squeezes and a long squeeze and then several pushes to simulate defecation and then performing rectal sensory testing by inflating the balloon and prompting for subjective sensation (rectal sensation test [RST]), the recto-anal inhibitory reflex testing (RAIR), and the balloon expulsion test (BET).⁵⁴ The RAIR test is performed by rapidly inflating the balloon to measure the expected reflex decreased anal pressure.⁵⁴ Finally, the BET is the procedure that measures the ability, based on time taken, for a subject to expel the inflated balloon from the rectum.⁵⁴ The complete battery of ARM tests should take 15 to 20 minutes.⁵⁴ Advances in technology have led to high-resolution or high-definition ARM (HR-ARM), which provides greater information and several novel parameters that have yet to be fully validated.⁵⁵

There were 20 records that included ARM measures, of which 16 had published results. Seventeen records (85%) included SCI patients, and the remaining three records evaluated patients with PD. In one SCI study, dyssynergic defecation (DD) type I, defined as a rise in intrabdominal pressure with a paradoxical increase in the anal sphincter, was seen in all subjects at baseline.²² In another study of people with chronic SCI in which all subjects lacked voluntary anal contraction, the RAIR was observed in all subjects, and the recto-anal excitatory reflex (RAER), defined as an increase in pressure of 2 SD above the preinflation resting pressure upon balloon inflation, was present in 50% of subjects.⁵⁶ ARM measures could distinguish between SCI-associated and functional anorectal disorders, with the former having lower anal squeeze pressures and lower success rates in BET.⁵⁷ Based on anal resting pressure and anal squeeze pressure, ARM measures could distinguish between supraconal SCI and lower motor neuron SCI.⁵⁸ The ARM protocol could also detect a significant change in external anal sphincter (EAS) voluntary contraction pressure in the intervention group, which corroborated with improved scores on the obstructed defecation scoring system (ODS), although no correlations were performed.²² In a small observational study using mesenchymal stromal cell implantations into the syrinx formed after SCI, there was some evidence of improved ARM measures of rectal sensitivity and pressures 6 months after implantation.⁵⁹ One study had results posted on clinicaltrials.gov without statistical analyses or explanation of results.⁶⁰

In children with SB who were being observed before starting a bowel program with the goal of gaining fecal continence, all patients with normal ARM and normal CTT developed continence, but no other correlations to CTT or continence status were seen by ARM.²⁶ Noteworthy, all 17 subjects exhibited RAIR.²⁶ In a case study of an adult with SB and mixed CC and FI, baseline ARM measures were consistent with a weak EAS, intact RAIR, and DD.⁶¹ In an interventional study of interferential electric stimulation, the treatment group showed improved RAIR and sphincter pressure compared to controls and pretreatment measures and corroborated the improved NBD scores and defecation frequency.⁶²

In contrast, in adults with MS undergoing posterior tibial nerve stimulation, responders (based on improved Wexner incontinence questionnaire) did not show differences in ARM measures.⁶³ In a large retrospective study of patients with MS, there was no difference seen in ARM measures when grouped by constipation, slow CTT, delayed gastric emptying, and CC with fecal incontinence.⁴³

In PD, HR-ARM was abnormal in 70% of subjects with constipation, with the most common findings of rectal hyposensitivity (65%) and decreased EAS function (30%).¹¹ No association was found between severity of constipation as measured by the Patient Assessment of Constipation Symptoms (PAC-SYM) and NBD questionnaires and ARM measures.¹¹ In another study of PD patients with CC (n = 66), nine patients (14%) had normal defecatory coordination, while the remainder had dyssynergia type II (n = 27, 41%), type IV (n = 26, 39%), and type III (n = 4, 6%).⁵² Noteworthy, in this study, CTT measured by WMC was normal in 38% of the subjects and prolonged in 66%.⁵² Same-day ARM measures were responsive to changes seen in PD between the “on” and “off” conditions of deep brain stimulation of the subthalamic nucleus.⁶⁴

In summary, ARM can diagnose dyssynergic defecation and abnormal RAIR reflexes in people with SCI. ARM can also help differentiate between people with SCI based on upper and lower motor neuron bowel. Finally, ARM showed responsiveness to treatment in most NBD population and could prognosticate bowel elimination outcomes in SB.

Ultrasound

Endo-anal ultrasound is used to visualize anal muscular anatomy. The ultrasound probe is inserted into the rectum with the patient in the left lateral decubitus position. Defects in sphincter integrity are considered hyper- or hypoechoic disruptions of at least 5-mm thickness. In people with MS and fecal incontinence who were responsive to posterior tibial nerve stimulation based on an improved Wexner incontinence score, sphincter integrity was not related to treatment outcomes.⁶³ Another study measured the rectum by placing the probe on the pubic symphysis.⁶⁵ They were able to see a difference in SCI with upper and lower motor neuron bowel by rectum size, based on measurements before and after defecation.⁶⁵

Barostat

To measure rectal compliance, a mechanical barostat has been used, which, like ARM, involves inserting a catheter with a balloon into the rectum. The other end of the catheter is connected to a barostat to measure pressure during a sequence of fixed distensions at 4 mm Hg increments. Compliance is calculated using the volume and pressure readings. Compared to non-SCI controls, the baseline rectal tone was higher in SCI with complete injury,⁶⁶ the mean rectal compliance was significantly higher in supraconal SCI, and significantly lower in lower motor neuron SCI.⁵⁸ In another study, 3 months after initiation of anti-muscarinic bladder therapy, rectal compliance was significantly raised, while no changes were seen by conventional ARM (not high resolution).⁶⁷ Increasing compliance of the rectum was associated with worsening constipation, based on changes in the Wexner constipation score.⁶⁷ In SCI with complete injury, symptoms moderately correlated to barostat measurements of rectal tone, such as the time used for defecation, flatus incontinence, and frequency of fecal incontinence based on the NBDS.⁶⁶

One study included sigmoid compliance, which positions the barostat catheter at least 30 cm from the anal verge.⁵⁸ Sigmoid compliance was significantly higher in supraconal SCI compared to controls.⁵⁸ Correlations to GI symptoms were not performed in this study.

Defecography

Defecography allows for the measurement of anorectal function at rest or during defecation and can detect uncoordinated pelvic floor/anal sphincter muscle contraction and relaxation. Prior to the procedure, subjects are asked to have a bowel movement using a suppository to empty the rectum of fecal contents. Ultrasound gel or barium paste is introduced into the rectum via syringe for magnetic resonance (MR) defecography and fluoroscopic defecography, respectively. Imaging is performed during maximum strain and maximum contraction (omitted in SCI studies with absent motor control) and during evacuation. MR defecography was performed in three studies and barium defecography in another. Dyssynergia, defined as evidence of failure of relaxation or descent of puborectalis during attempted evacuation, was found in six (67%) subjects with PD.¹¹ This was correlated with severity of constipation measured by PAC-SYM and NBD questionnaires.¹¹ In people with chronic SCI, pelvic floor measurements at rest and defecation were significantly different from non-SCI controls,⁶⁸ and they were correlated to incontinence episodes based on the NBDS.⁶⁹ In an adult with SB, fluoroscopic X-ray defecography was consistent with ARM in diagnosing DD.⁶¹

Impedance planimetry

One study used rectal impedance planimetry,⁷⁰ which involves inserting a probe with electrodes, surrounded by a saline-filled balloon, into the rectum. The potential difference of the current is the calculated rectal cross-sectional area (CSA), determined by the detection electrodes that are also on the probe within the rectal saline balloon.⁷¹ Anal and rectal pressure were simultaneously measured. In the trial in people with SCI testing dorsal genital nerve (DGN) stimulation, the authors were able to detect a reduction in rectal CSA during DGN stimulation at different rectal distention pressures.⁷⁰

Miscellaneous

There were eight records that utilized miscellaneous objective measurements of NBD (Table 4). Two records (one article) proposed using body weight and abdominal radiography to measure changes that reflect stool volume.^38,72 In people with chronic SCI after 2 weeks of a bowel intervention, body weight and retained stool seen on abdominal X-ray were improved compared to baseline.³⁸ Using dedicated software to assemble three-dimensional volumes of interest of the colon with computed tomography (CT), a significant difference was seen between patients with PD and healthy controls.³⁴ Noteworthy, CT colonic volume was associated to ROMs to measure transit time, as well as Rome III criteria and NMSQuest.³⁴ Two studies utilized autonomic function tests to assess neurogenic bowel.^28,50 One study included 24-hour HRV as a noninvasive measure of autonomic function in order to compare it to measures of WGTT by ROM in ABI.²⁸ In this small study (n = 25), no correlations were found between HRV and WGTT.²⁸ Another study utilized both HRV and orthostatic hypotension testing and only found a weak correlation with the initial drop in diastolic blood pressure and CTT (r = -0.34, p = .04).⁵⁰ Finally, in an observational study of veterans with SCI, lesion counts from colonoscopy were associated to duration of SCI (p < .001) but had significantly less lesions compared to age-, sex-, and race/ethnicity-matched Veterans without SCI.⁷³ No relationship was found between colonoscopic lesion type or count and SCI lesion location or severity.

Table 4.

Description of miscellaneous objective measures and subjective correlations

Manuscript	Objective measure(s)	Objective measure results	Correlation of subjective and objective outcome measures
Bauman et al., 202138	Body weight, Abdominal XR	There was a reduction of body weight, which was confirmed by abdominal XR.	No relevant correlations
Sangnes et al., 202150	Autonomic function tests - HRV and orthostatic hypotension	No significant differences between DM with diarrhea versus no diarrhea based on autonomic tests.	Initial diastolic blood pressure drop during orthostatic testing is weakly correlated with CTT (r = -0.34).
Enevoldsen et al., 201828	HRV	No correlation was found between HRV and GITT.	No correlations performed
Knudsen et al., 201734	CT-based volume	66% of patients had significantly increased colonic volume.	No correlation between colonic volume and both UPDRS and disease duration. Colonic volume was positively associated to retained ROM, Rome III, and NMSQuest total score.
Rabadi & Vincent, 201273	Lesions	No relationship was found between colonoscopic lesion type and SCI lesion location or severity. A relationship was found between total colonoscopic lesions and duration of SCI. When adjusted for age, no difference was seen between lesion counts in SCI and non-SCI.	No subjective measures used
Korsten et al., ongoing	Body weight Abdominal XR	No analyses provided on clinicaltrials.gov	Unknown
Kim JH, et al., 201623	Abdominal XR	Stool retention score significantly decreased after PF administration, from 7.25 ± 1.60 to 6.46 ± 1.53 Leech points.	No correlations performed
Knudsen et al., 201935	CT-based volume	Total colonic volume was significantly increased in iRBD patients compared to controls but not in comparison to PD patients.	No correlations were seen between NMSQuest total score,Rome III, and total volume.

Note: CT = computed tomography; CTT = colonic transit time; DM = diabetes mellitus; GITT = gastrointestinal transit time; HRV = heart rate variability; iRBD = idiopathic REM sleep behavior disorder; PD = Parkinson’s disease; ROM = radiopaque marker; NMSQuest = Non-Motor Symptoms Questionnaire; PF = Poncirus fructus; NMSQuest = Non-Motor Symptoms Questionnaire; SCI = spinal cord injury; UPDRS = Unified Parkinson’s Disease Rating Scale; XR = X-ray.

Discussion

The goal of this systematic review of the literature was to identify objective measures of NBD and their relative utilities and to ultimately determine their role in the management of symptomatic patients with SCI. Despite the lack of recommendations for objective measures in clinical guidelines, there is an abundance of literature supporting their use. There is evidence that they can distinguish between upper motor and lower motor neuron, differences based on etiology of neurogenic bowel, and response to treatment. Unfortunately, less than half of the studies with objective measures were correlated to the validated subjective measures used in the vast majority of studies, adding to the challenge of finding clinical utility from these measures.

Subjective measures varied across studies, with over a dozen different surveys and questionnaires used. Even within the same neurologic population, there is no clear consensus as to which questionnaires can be used to categorize NBD, severity of symptoms, and response to treatment. Not surprisingly, when correlations of these subjective measures were made to objective measures, many did not show an association, and only one was strongly correlated: in motor incomplete SCI, improvement in the balloon expulsion time strongly correlated with improvement in both Fecal Incontinence Severity Index and constipation scores (r = 0.91 and 0.90, respectively; p < .05).⁵⁷ Although a strong correlation to an objective measure would be ideal, objective and subjective measures are not necessarily aligned, which suggests that they are both needed to help with management.

The variety of measures that exist lend themselves to several different approaches. For patients who have difficulty returning for serial visits, ARM can be performed as a dedicated clinic visit, and there are motility testing protocols available that require just one visit for imaging. The opportunity exists to mail ROMs to patients and have imaging performed in clinic. Also, the measures allow clinicians to explore inexpensive options (carmine capsules), use existing equipment (ultrasound, X-ray, fluoroscopy, CT, MRI), or even consider purchase of specialized equipment (HR-ARM). It is apparent from this literature review that many opportunities exist to measure NBD.

It is important to recognize that the experience of GI disorders in individuals with neurogenic bowel can be highly variable. Some may maintain relatively stable GI function, whereas others may encounter more significant challenges over time. The use of GI physiologic tests at baseline is pivotal for assessing the degree of functional and sensorimotor dysfunction. The results of these tests inform the treatment plan. For example, identifying abnormal anorectal sensory and motor function through ARM may guide pelvic floor retraining programs, and recognizing motility patterns via manometry can lead to the use of prokinetic medications. Furthermore, understanding the specific abnormalities in GI function allows for the development of more personalized treatment plans. Instead of a one-size-fits-all approach, health care providers can tailor interventions to address each patient’s unique needs and issues, which is especially important given that proper management can help mitigate the progression and severity of GI disorders in SCI patients. These test results also serve to educate patients about the nature and severity of their condition, enhancing patient compliance with treatment plans and providing reassurance about their symptoms.

Another important aspect of GI function tests is their ability to monitor disease progression and the response to treatment. Specifically, in addition to the level and severity of the SCI, the duration of the injury plays a significant role in the progression of GI disorders. Regular monitoring through GI physiologic testing can be an integral part of the management plan aimed at preventing complications. Although traumatic SCI is considered a static injury, the sequelae progress over time. Changes over time have been described in the autonomic system,⁷⁴ neurogenic bladder,⁷⁵ and bone density.⁷⁶ Similarly, NBD symptoms progress over time with SCI, yet only 70% of people with SCI reported changing any aspect of their bowel management over a 5-year period.⁷⁷ Furthermore, aging and changes in life for nonneurologic reasons, such as parity/delivery in women, could impact the NBD. As much as there is a need to create survey tools to monitor effectiveness of treatment response in SCI NBD, objective measures are a necessary complement, as highlighted in this systematic review.

A single test to understand the nuances of NBD in SCI does not exist, as evidenced by the multitude of objective measures we have reported on. Clearly, the routine digital rectal exam is not sufficiently informative about anorectal physiology and does not provide any information relating to transit time. The ideal test would capture both anorectal physiology and transit time. In this idealistic reality, testing would begin early after SCI to establish baseline bowel function. Then, as the duration of injury progresses and changes in NBD management are needed, the test could be repeated to evaluate the changes and determine the necessary adjustments to the bowel program accordingly. The ideal management of NBD in SCI would also include an objective test that could be performed at home to help with bowel management. Finally, these tests would be responsive to treatment, would be correlated to patient-reported outcomes, and would be ubiquitous, universally covered by insurance. However, we should not let this ideal stand in the way of moving forward.

Herein, we argue that incorporating objective measures of NBD would improve the long-term management of patients with SCI. Given the multitude of available tests, SCI health care providers can be selective, depending on individual patient needs. Simple tests, like measuring patients’ weight or performing an abdominal radiograph, can be performed. We have found that such radiographic assessment of stool burden is a simple and effective tool that can be performed in clinic and is reimbursed by all insurances in our region. A large stool burden seen on abdominal X-ray can help explain to patients the need to optimize their bowel program to prevent symptoms, like distention, abdominal and/or lower extremity spasticity due to constipation, or overflow incontinence. Plain X-rays of the abdomen, albeit useful in the context of NBD, carry the risk of radiation injury long-term. Point of care (portable) ultrasound, if validated, would be a better option with the potential to be performed at home.⁷⁸

Regardless of the objective measure used, it is up to the SCI health care providers to develop a protocol with scientific rigor to demonstrate clinical utility and practicality. Herein lies the challenge, and the reader is directed to recommendations from an expert panel on evaluations of NBD after SCI/disease.²¹ As a comparison, neurogenic bladder, like NBD, is a top research priority for people living with SCI.^5,6 Subjective measures from surveys, questionnaires, and diaries and objective measures from urodynamic studies are recommended to assess the function of the lower urinary tract.⁷⁹ With the wide variety of tests available to measure NBD, the opportunity exists to develop an equivalent recommendation for people with SCI and disease.

In summary, these tests play a pivotal role in the management of patients with GI disorders by providing accurate diagnoses, guiding treatment decisions, and allowing for individualized care plans. It is worth noting that they are often underutilized in patients with NBD. Given the serious complications of unmanaged GI disorders such as FI and autonomic dysreflexia, the importance of proper testing in determining effective management and early intervention cannot be overstated. These measures are crucial in preventing and mitigating complications associated with GI disorders, and their routine use in the population with SCI is needed to mitigate morbidity and ultimately improve outcomes and quality of life.