Constipation is one of the most common gastrointestinal (GI) complaints of patients presenting to medical attention. Between 1958 and 1986, an estimated 25 million annual physician visits resulted from constipation and related complaints (1). In pediatrics, 3% of all primary care visits and up to 25% of visits to gastroenterologists result from complaints related to constipation (2,3). The worldwide prevalence of childhood constipation has been estimated to be between 1% and 30% (3). The pervasive nature of this problem is reflected in the health care resources that are devoted to it. In the United States, $3.9 billion per year are spent treating childhood constipation (4). The vast majority of patients with constipation will improve with routine care, a subset go on to develop chronic complaints (5). Most of these patients have idiopathic or functional constipation; however, organic, and potentially treatable, causes of chronic constipation do exist and can at times be missed.
Spinal cord abnormalities have been described as a potentially treatable cause of constipation (6). A recent study by Bekkali et al (7) in an unselected population of children with constipation that underwent magnetic resonance imaging (MRI) found a 3% prevalence of spinal abnormalities. In our study of children with intractable constipation, we found that among patients who underwent MRI, 10% had spinal abnormalities (8).
It is important to be able to identify those children in whom intractable defecation disorders are a manifestation of spinal cord abnormalities. Surgical intervention in correctable abnormalities (tethered cord syndrome) may lead to resolution of complaints. Conversely, a delay in identification and treatment may lead to irreversible nerve damage (9).
MRI of the spine is necessary to diagnose these spinal problems; however, performing MRI in every child with intractable constipation is certainly not an optimal screening modality because of the cost and risk of sedation in younger children. Therefore, it would be desirable to find other tools that could better select the patients with intractable constipation that ought to have MRI to determine whether they have a tethered cord or other spinal abnormality, and ultimately may be amenable to neurosurgical correction.
Physical examination is not always a reliable screen in their identification. In our previous study, we found that none of the children with intractable constipation, who had an abnormal spinal MRI, had lower extremity neurologic deficits, and only one-third had abnormalities of the cremasteric reflex, anal wink, or anal tone (8). Anorectal manometry is a well-established modality in the evaluation of lower GI tract physiology (10). There are discrete manometric patterns that have been identified in patients with certain spinal cord injuries (11) and well-defined neuropathies (12). We hypothesized that children with intractable constipation and spinal cord problems may have reproducible aberrations in anorectal function that may differentiate them from patients who do not have spinal problems. We therefore conducted the present study to determine whether constipated children with spinal cord abnormalities had patterns on anorectal manometry that could be used to predict which constipated patients should receive MRI.
PATIENTS AND METHODS
A retrospective case-control study was designed using the anorectal manometry tracings of patients with intractable constipation who were found to have abnormal spinal MRI and comparing them with the tracings of age-matched controls with intractable constipation who had a normal spinal MRI. All spinal MRIs and anorectal manometries were requested by the primary gastroenterologist caring for the patients. Intractable constipation was defined, as previously published (8), as <2 bowel movements per week for >3 months that did not respond to laxative treatment, including osmotic and stimulant laxatives in addition to enemas and suppositories. Patients with abnormal MRIs who had undergone an anorectal manometry as part of their evaluation were identified. Our age-matched controls were children of the same age who had undergone an anorectal manometry and had a normal MRI within 2 months of the case patients. Controls had similar clinical histories and physical examinations as the patients. No patient or control had any other medical conditions except for chronic constipation. Patients with anorectal malformations, history of trauma, painful anal lesions, myelomeningocele, or other neurologic disorders were excluded.
All anorectal manometries were performed by a single experienced investigator (S.N.). The anorectal manometry tracings were deidentified and reviewed by 2 independent investigators unaware of the MRI findings. All of the MRIs were reviewed by a neuroradiologist during routine clinical examination. The neuroradiologist was unaware of the manometry findings. The study was approved by the institutional review board of Children's Hospital Boston.
Manometric studies were performed with a multilumen polyvinyl catheter continuously perfused by a low-compliance pneumohydraulic pump (Model ARM2, Arndorfer Medical Specialties Inc, Greendale, WI), as previously described (12). The catheter contained 4 distal recording ports at 1-cm intervals arrayed at 90° angles from one another. The most distal recording port was situated 3 cm from the tip of the catheter, where a nonlatex balloon was attached. The balloon was connected to the recording system so that the time of balloon distention could be recorded. Baseline measurements were set at atmospheric pressure. To evaluate conscious sensation, the rectum was distended while the balloon was situated 10 cm above the anal verge. The balloon was rapidly inflated at serial volumes of 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, and 120 mL. The balloon inflations were done with a 60-mL syringe that was connected to the balloon with a stopcock, which allowed the administration of larger balloon volumes. The volume at which sensation of fullness was reported was identified. The catheter was then withdrawn in 0.5-cm increments, and the area of maximum internal anal sphincter (IAS) resting pressure was identified. The manometry catheter was left in position with at least 2 pressure ports in the area of maximum pressure and the most distal port in the rectum. Thus, the balloon was positioned 4 cm proximal to the high-pressure zone. The balloon was again rapidly inflated and deflated at the series of volumes mentioned previously and the following measurements were obtained at each volume: mean intra-anal pressure, characteristics of the IAS relaxation or rectoanal inhibitory reflex (RAIR), mean latency of relaxation (time between balloon distention and start of relaxation), and duration of relaxation. After the rapid inflations, the balloon was left inflated for 1 minute at each volume, and the percentage of relaxation, duration of relaxation, and the final sphincter pressure were measured. We also measured threshold of relaxation (minimum volume that produced a 10% relaxation) (12), constant relaxation volume (balloon volume that produced no recovery during 1-minute stimulus), threshold of sensation (minimum balloon volume that could be felt 2 of 3 trials), and mean voluntary squeeze pressure (measured above baseline pressure). The presence of internal anal sphincter spasms was recorded. This was diagnosed when there was an increase in intra-anal pressure after balloon distention that was not associated with external anal sphincter contraction. External sphincter activity was always monitored by placing a finger in direct contact with the external sphincter while holding the manometry catheter. This is a method that allows the detection of external sphincter contractions. Increases in intra-anal or rectal pressure that were associated with external sphincter contraction were considered to be squeezes and those occurring without any activity in the external anal sphincter were considered to be involuntary spasms. We also had different transducers in the anal canal, and when spasms occurred, they were seen only in the proximal transducers, whereas the distal transducer showed no change, indicating there was no external anal sphincter activity.
Data are reported as mean ± standard error of the mean, except for patient characteristics, which are reported as standard deviations. Statistical significance was assessed using χ2 analysis or Student t test. A P value of <0.05 was considered to be statistically significant. All of the analyses were performed using SPSS version 16.0 (SPSS Inc, Chicago, IL).
A total of 10 patients and 10 controls were identified. Their main characteristics are shown in Table 1. Lower extremity neurologic examination as conducted by a pediatric gastroenterologist was normal in all of the patients. One patient was noted to have a shallow sacral dimple, and 1 patient had an absent anal wink. All of the patients had a guaiac-negative stool and no hemorrhoids, fissures, or other anorectal lesions. The MRI abnormalities found were as follows: tethered cord (low conus and fatty filum) (n = 3), isolated fatty filum (n = 3), spinal lipoma (n = 2), fatty filum with spinal lipoma (n = 1), and impinging arachnoid cyst on sacral roots (n = 1). Nine of the patients decided to proceed with surgical correction. Of these, 4 reported partial resolution of symptoms, 3 had complete resolution, and 2 were lost to follow-up. The patient who did not have surgery continued to have the same symptoms.
When we compared anorectal manometry parameters between both groups, we found that a significant difference existed between cases and controls in the volume that achieved maximum internal anal sphincter relaxation and in the presence of internal anal sphincter spasms (P < 0.05) (Table 1, Figs. 1 and 2). None of the patients without spinal cord lesions had anal spasms with balloon distention, whereas 60% of our patients with spinal cord lesions had anal spasms during anorectal manometry (P = 0.003) (Figs. 1 and 2).
When looking at manometric parameters with serial balloon distention, we noted that there was an overall shift in the curve of percentage of relaxation to the left in the group with spinal problems (Figs. 1 and 2). This was consistent with our finding that maximum relaxation occurred at lower volumes in patients with spinal cord abnormalities (controls: 60 ± 22.6 vs 35 ± 19.6 mL in patients with spinal lesions [P = 0.02]). No significant differences were noted in mean latency time for relaxation, mean duration of relaxation after a short balloon distention, and mean duration of relaxation with prolonged balloon distention (1 minute) (Fig. 2)
We found discrete anorectal manometry changes that seem to occur more frequently in constipated children who have spinal abnormalities uncovered by MRI. These findings were a shift in the RAIR dose-response curve upon balloon distention to the left and the presence of anal spasms upon balloon distension. These preliminary findings suggest that given that in patients with spinal cord lesions there may be anorectal manometry abnormalities, anorectal manometry may be a good test to indicate which children with intractable constipation may have spinal abnormalities and may need MRI of the spine. Until more information is available, however, the anorectal manometry cannot be used as the sole screening test to decide which children with constipation need MRI.
Previous authors also have described unique manometric characteristics in adults and children with various levels and types of spinal cord injury, mostly spinal cord transection (11,13–15). Most of the authors have described abnormal sphincter relaxation, with exaggerated responses to small balloon volumes. We also have described specific alterations in patients with sacral agenesis (12), showing that sacral nerve agenesis results in a lack of dose-response curve to balloon distention. Therefore, it is not surprising that children with tethered cord also may have specific sphincter abnormalities and that they may resemble the ones seen in sacral lesions. In a small study, Kayaba et al (16) noted similar sphincter changes in adult patients with tethered cord.
The postulated mechanism of injury in patients with tethered cord syndrome is prolonged ischemia and disruption of the neuronal mitochondrial electron transport chain, secondary to traction upon the sacral roots caused by the tethered cord (9). Patients with spinal masses often have symptoms of tethered cord syndrome, because the mass also serves to add traction to the spinal cord. In all of these patients, the actual location of injury is somewhat variable, but it is thought to be above the tethering site and below the counteracting site at the lowest dentate ligament (T12-L1). As patients grow and cord traction increases, they develop progressive symptomatology related to sacral nerve dysfunction. Their complaints include lower limb sensory deficits, lower urinary tract dysfunction (usually in the form of incontinence), and anorectal dysfunction; therefore, the abnormalities seen in the anorectal manometry are probably explained in part by this injury.
We noted a shift in the RAIR dose-response curve to the left. The exact mechanisms responsible for this increase in IAS relaxation are not understood. We know that the presence of the rectoanal inhibitory reflex is independent of the spine; however, its characteristics may be modulated by the spine (12). Previous studies of patients with spinal cord injury have shown that when spinal transection spares the sympathetic and parasympathetic centers or destroys only the sympathetic center, there is still a normal dose-response curve to balloon distention; however, the graded response to distension is absent in transection patients if the parasympathetic center is affected (17). In patients with sacral agenesis, we also have shown this lack of dose-response curve, with the relaxation curve shifted to the left (12). Thus, the abnormal response of the IAS to balloon distention appears to result from some abnormality of extrinsic nervous modulation.
In this series, we also found that 60% of our cases had transient internal anal sphincter spasms in response to rectal distension. To our knowledge, the relation between anal spasms and spinal lesions has not been described in the literature. The exact mechanism of this relation is unclear. The internal anal sphincter receives extrinsic innervation from both the parasympathetic and sympathetic nervous systems (18). In normal subjects, there seems to be a tonic excitatory sympathetic discharge, which in patients with tethered cord may be exacerbated by the traction injury below the lowest dentate ligament (T12-L1), causing transient hyperactivity of the sympathetic nerves that originate from there (L1-L3). It also is possible that disruption of sensory afferent nerves may cause loss of a yet undefined negative feedback loop. A similar phenomenon of rectal hypereflexia in 2 of 5 patients with tethered cord syndrome was described by Kayaba et al (16).
One limitation of the study is that we did not perform electromyography during our anorectal manometry, so we have no electromyographic way to ensure that there were no external anal sphincter contractions at the time of the spasms. In our experience, having a finger at the anal verge during the procedure allows the detection of external anal sphincter contraction, and it has been a reliable way to differentiate squeezing or external sphincter contractions from the IAS contractions seen during a spasm. Also, the spasms were usually noted in the most proximal transducers, with no changes in those transducers that were closer to the anal verge. If there was EAS contraction, then we would have expected the opposite. We therefore believe that the phenomenon we observed was not external sphincter contraction.
Another limitation to consider is that there may be a selection bias. The children studied had intractable constipation and reached our tertiary center after being treated by a pediatrician and a pediatric gastroenterologist. The cases of abnormal MRI were randomly chosen without any knowledge of the manometric findings, and the controls were age matched, also without any knowledge of the findings of their anorectal manometry. Furthermore, this study was not intented to determine the prevalence of spinal cord problems in children with constipation, but to evaluate manometric findings of children with spinal problems. This is a preliminary observation in which we have shown that children with spinal cord problems may have anorectal manometry abnormalities; however, to adequately assess the utility of manometry as a screening test, additional studies with larger numbers of nonselected patients are needed.
In summary, anorectal manometry may be a viable tool to identify spinal lesions in children with refractory constipation. Children with spinal lesions had the presence of anal spasms and required decreased volume to achieve maximal relaxation during anorectal manometry. Our findings are important because they suggest that it may be possible to detect those patients with intractable constipation who are more likely to have spinal abnormalities, therefore targeting the performance of MRI to those children with anorectal manometry abnormalities.
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