Rectal hyposensitivity

American Journal of Gastroenterology  C 2006 by Am. Coll. of Gastroenterology Published by Blackwell Publishing

ISSN 0002-9270 doi: 10.1111/j.1572-0241.2006.00604.x

Rectal Hyposensitivity Marc A. Gladman, Ph.D., M.R.C.O.G., M.R.C.S.,1 Peter J. Lunniss, M.S., F.R.C.S.,1 S. M. Scott, Ph.D.,1 Michael Swash, M.D., F.R.C.P., M.R.C.P.2 1 Gastrointestinal Physiology Unit and 2 Department of Neurology, Barts and The London, Queen Mary’s School of Medicine and Dentistry, Whitechapel, London, United Kingdom

Rectal hyposensitivity (RH) relates to a diminished perception of rectal distension that is diagnosed during anorectal physiologic investigation. There have been few direct studies of this physiologic abnormality, and its contribution to the development of functional bowel disorders has been relatively neglected. However, it appears to be common in patients with such disorders, being most prevalent in patients with functional constipation with or without fecal incontinence. Indeed, it may be important in the etiology of symptoms in certain patients, given that it is the only “apparent” identifiable abnormality on physiologic testing. Currently, it is usually diagnosed on the basis of elevated sensory threshold volumes during balloon distension in clinical practice, although such a diagnosis may be susceptible to misinterpretation in the presence of altered rectal wall properties, and thus it is uncertain whether a diagnosis of RH reflects true impairment of afferent nerve function. Furthermore, the etiology of RH is unclear, although there is limited evidence to support the role of pelvic nerve injury and abnormal toilet behavior. The optimum treatment of patients with RH is yet to be established. The majority are managed symptomatically, although “sensory-retraining biofeedback” appears to be the most effective treatment, at least in the short term, and is associated with objective improvement in the rectal sensory function. Currently, fundamental questions relating to the contribution of this physiologic abnormality to the development of functional bowel disorders remain unanswered. Acknowledgment of the potential importance of RH is thus required by clinicians and researchers to determine its relevance. (Am J Gastroenterol 2006;101:1140–1151)

INTRODUCTION Functional bowel disorders are some of the most common and distressing disorders experienced in all ages of the population (1, 2), and are associated with significant impairment of quality of life (3). Abnormal visceral sensitivity is now widely considered to be important in the development of such disorders, and considerable attention has been dedicated to the study of visceral hypersensitivity (4), although the same cannot be said about the study of visceral insensitivity. In the rectum, perception of rectal filling is critical to normal function (5), i.e., the process of defecation and the maintenance of continence. A large body of work now exists evaluating rectal hypersensitivity (4, 6–9). However, rectal hyposensitivity (RH), which relates to insensitivity of the rectum, has been relatively neglected by both clinicians and researchers, and thus its relevance in patients with functional bowel disorders is unclear. Increasingly, appreciation of underlying pathophysiology is considered important in the treatment of patients with functional bowel disorders (10). It is conceivable, therefore, that the identification of those patients with RH may be crucial to successful management, potentially allowing rational, rather than empirical treatment. Consequently, an improved understanding and better characterization of RH is required. The aim of this review was to highlight the existence and clinical relevance of RH by describing its epidemiology, clinical

associations, and current treatment options, together with its etiology and the potential pathophysiologic mechanisms for its development, and thereby provide a basis for the future evaluation of the importance of RH in patients with functional bowel disorders.

SEARCH STRATEGY AND SELECTION CRITERIA Electronic searches were conducted of the MEDLINE (Pubmed) database, Cochrane library, EMBase, and Science Citation Index from the start of each of their time frames through to January 2006. Reference lists of all relevant articles were searched for further studies. Of the identified studies, only those articles published in the English language were selected. All studies were included irrespective of the quality of their evidence, since there have been very few direct studies of RH. In addition, much of the review is based on the extraction of relevant information from manuscripts that have evaluated patients with disorders of hindgut function, and that have reported RH in a proportion of patients studied.

DEFINITION AND DIAGNOSIS OF RH Definition RH describes a diminished perception of rectal distension (11). It was first objectively demonstrated using physiologic

1140

Rectal Hyposensitivity

investigations in 1940 in patients with neurogenic disturbances of the hindgut (12) and subsequently in patients with anorectal dysfunction (13), although the term “rectal hyposensitivity” was only adopted some years later (14). Patients with RH may complain of attenuation or loss of the “desire to defecate” (15–17), or of the “sensation of stool in the rectum” (18), although the abnormality is more accurately diagnosed during anorectal physiologic investigation (see below). NOMENCLATURE. In addition to RH, several terms have been used interchangeably in the literature to describe a “diminished perception of rectal distension.” Some adjectives describe rectal sensory function directly, e.g., impaired/diminished/blunted/deficient/reduced rectal sensation (5, 15–22), while others refer to the sensory thresholds obtained during sensory testing, e.g., increased conscious rectal sensitivity thresholds (23) or delayed rectal sensation (24). The use of such adjectives may lead to considerable confusion, as there is an inverse relationship between the results of rectal sensory testing and rectal sensory function itself, and thus the preferred term for “diminished perception of rectal distension” is rectal hyposensitivity, and this will be adopted for the remainder of this review. Diagnosis Assessment of rectal sensitivity is usually performed as part of the objective evaluation of anorectal function using physiological investigations, and is most commonly and conveniently performed in clinical practice by recording the threshold volumes required to elicit rectal sensations, namely, first sensation (FS), desire to defecate (DD), and maximum toleration (MT) during simple latex balloon distension with air (1, 25–28). Accordingly, RH should be diagnosed on the basis of elevated threshold volumes compared to the normal range (11, 19, 29, 30). However, there is no consensus in published studies as to which threshold should be used to make a diagnosis of RH (15, 20, 31, 32), although it seems appropriate to use elevation of any, or all, of the sensory thresholds, since clinical symptoms in patients with RH are similar irrespective of the number, or which of the sensory thresholds are elevated (33). It should be noted that differences in the methodology employed to perform rectal distension dictate that the actual volumes required to make a diagnosis of RH should not be “universally” applied, and it is recommended that individual units establish their own normal ranges (34), although threshold volumes for FS, DD, and MT greater than approximately 100, 200, and 300 mL, respectively, typically indicate the upper limit of normality (35), and thus are useful when making a diagnosis of RH (29). Previous studies evaluating rectal sensation have been restricted to symptomatic patients who seek help or relatively small numbers of healthy volunteers (35), and not those residing in the general “community,” and thus it remains to be established whether elevation of these sensory

1141

threshold volumes always translates into clinical symptoms. Similarly, it remains to be determined whether there is any correlation between the magnitude of the abnormal sensory threshold volumes and severity of clinical symptoms. With the advent of additional techniques to stimulate the rectum (e.g., distension using a barostat (16, 36, 37)/electrical or thermal stimulation (38, 39)) or to measure central response (cerebral evoked potentials (40)/functional magnetic resonance imaging (fMRI)/positron emission tomography (PET) scanning (41, 42)) it has become feasible to make a diagnosis of RH utilizing such techniques. However, none of these techniques has yet to find a place in the assessment of patients in routine clinical practice (1, 43). CLINICAL AND RESEARCH IMPLICATIONS 1. Rectal hyposensitivity is the preferred term to describe a diminished perception of rectal distension. 2. RH should be diagnosed on the basis of elevation of any of the rectal sensory thresholds during simple balloon distension with air. 3. The use of additional techniques to stimulate the rectum or measure central response cannot currently be recommended for diagnosis of RH in clinical practice. 4. Studies evaluating the use of alternative tests of rectal sensory function are required in patients with RH to evaluate the rectal afferent pathway in more detail.

EPIDEMIOLOGY AND CLINICAL ASSOCIATIONS Epidemiology RH has been reported in 18–68% of patients with constipation (infrequency of, and/or obstructed defecation) (15, 19, 38, 44–47) and 10–18% of patients with fecal incontinence (32, 48). In the largest study to date, where RH was found to be present in 16% of 1,351 patients for physiologic assessment of hindgut dysfunction, it was present in 23% of patients with constipation alone, 10% of patients with incontinence alone, and 27% of patients with constipation and incontinence (29). By contrast, the prevalence of RH in the “community” remains unknown, as studies have only evaluated patients with symptoms who seek help. The gender prevalence of RH is equal (29), and it affects pediatric (49, 50) and elderly patients (51–53). Clinical Associations of RH RH appears most prevalent in patients with functional bowel disorders (29), where the cause-effect relationship is not entirely certain, although it has been suggested that RH is a major factor in the development of such disorders (33, 49). FUNCTIONAL CONSTIPATION. Constipated patients often report loss or attenuation of the “desire to defecate” (11, 15–17, 54). Objective evidence of RH on physiologic testing has commonly been reported in such patients (15, 19, 21, 46, 50, 55–57). Indeed, RH appears to be most prevalent

1142

Gladman et al.

in patients with constipation, with or without associated fecal incontinence (29). Furthermore, description of the largest of cohort of patients with RH in the literature to date (N = 261) revealed that the vast majority of such patients present with symptoms of constipation, most commonly obstructed defecation (33). RH has commonly been reported in association with other physiologic abnormalities in patients with constipation. Therefore, it is likely that it is not the only relevant physiologic abnormality, or indeed contributory toward symptoms in all patients. However, RH is the only demonstrable abnormality on physiologic testing in up to one-half of patients with constipation, suggesting that “apparent” isolated sensory impairment appears to be important in the pathophysiology of constipation in certain patients (33, 46). Indeed, together with colonic dysmotility and disordered pelvic floor function, RH has been classified as one of the three principal physiologic abnormalities in patients with functional constipation (19). IRRITABLE BOWEL SYNDROME. RH has previously been reported in certain patients with irritable bowel syndrome (IBS), particularly those with constipationpredominant IBS (C-IBS) (16, 37, 58, 59). However, it is conceivable that the observation of RH in patients with C-IBS merely describes the same cohort of patients with functional constipation, but that have been labeled differently, since it may be difficult, or even impossible, to differentiate these conditions as they share identical bowel symptoms (60). This may be a particular problem if the strict criteria of the Rome II working party relating to abdominal discomfort or pain are not adhered to when making a diagnosis of IBS (2) to differentiate it from the abdominal pain frequently experienced by patients with functional constipation (54). This problem is further confused by the tendency for the group of patients with chronic constipation with normal colonic transit and pelvic floor function to be considered as having IBS with constipation (61). FUNCTIONAL FECAL INCONTINENCE. RH has been reported in patients with fecal incontinence (FI). This is best documented in patients with diabetes mellitus (18) and multiple sclerosis (62), but may also be seen in other types of patients (1), including those with “idiopathic” FI (11, 20, 31, 32, 63). The incontinence in such patients should perhaps be more accurately described as “functional” rather than “idiopathic,” since many of the studies were performed before the advent of sonographic imaging of the sphincter muscles that would have been capable of revealing structural damage. Nevertheless, it does appear that isolated sensory impairment of the rectum may be important in the pathophysiology of FI in certain patients, since it is the only demonstrable abnormality in approximately one-third of patients with RH presenting with FI (33). Indeed, contemporary reviews of FI in the literature have acknowledged the importance of RH in the pathophysiology of incontinence (64, 65).

CLINICAL AND RESEARCH IMPLICATIONS. 1. RH is most prevalent in patients with constipation, although it is also important in patients with FI, especially in those with diabetes mellitus, or other neuropathic disorders. 2. Although it may be relevant to the etiology of symptoms in certain patients with RH, the exact cause-effect relationship remains to be determined.

PROPOSED MECHANISMS FOR THE DEVELOPMENT OF SYMPTOMS IN PATIENTS WITH RH Constipation Currently, the mechanism(s) for the development of constipation in patients with RH is not entirely clear. Indeed, it is possible that RH may merely be a consequence of functional constipation, rather than a cause of it, and thus may not be contributory to symptom development. Functional constipation may result from outlet obstruction and/or colonic dysmotility (66). Consequently, RH may result in, or contribute to, constipation via either of these mechanisms. Outlet obstruction may occur due to an inadequate increase in rectal pressure or inadequate reduction in anal pressure (“pelvic floor dyssynergia” (67)). An inadequate increase in rectal pressure during evacuation in patients with RH may occur either due to: (i) abnormal rectal motility/contractility in response to rectal distension (68, 69) (suggesting combined sensorimotor dysfunction of the rectum due to a neuropathic process) or (ii) “dispersal” of the expulsive forces that assist the evacuation of stools in the large cavity rectum in patients with RH and megarectum (see below) (66,70). An inadequate reduction in anal pressure in patients with RH appears to most commonly occur as a consequence of a failure of relaxation of the pelvic floor during evacuation (33, 71), which is proposed to occur secondary to blunting of the urge to defecate in patients with RH (68). Constipation may also result from colonic dysmotility. Delayed colonic transit has been noted in 31–77% of patients with RH (19, 33, 44), where the major site of holdup appears to be in the left colon and/or rectum (44, 72, 73). However, the mechanism for the delayed transit observed in patients with RH remains unclear. There is evidence that RH occurs as part of a neuropathic process affecting the rectum (and/or colon), given that a proportion of patients have evidence of motor dysfunction, as reflected by abnormalities of rectal tone, compliance and/or contractility (36, 56, 68, 69, 74–77). It is possible, therefore, that the delay in colonic transit in patients with RH reflects primary colonic dysmotility. Alternatively, given that RH may result in rectal outlet obstruction (see above), the delay in transit may occur secondary to rectal outlet obstruction (78), whereby chronic distension of the rectum leads to viscero-visceral reflex inhibition of proximal gut motor function (79, 80).

Rectal Hyposensitivity

Fecal Incontinence In normal subjects, conscious contraction of the external anal sphincter occurs in response to rectal distension, thus preventing incontinence of stool during reflex relaxation of the internal anal sphincter (52). This is crucially dependent on the perception of rectal distension (1, 32). It has been demonstrated that the threshold of internal sphincter relaxation occurs at lower distending volumes than that of the first perception of rectal distension in many patients with RH (20, 32, 48). Consequently, the presence of diminished perception of rectal distension allows fecal material to enter the rectum without conscious recognition, and thus conscious contraction of the external anal sphincter during reflex internal sphincter relaxation cannot occur (18,32). This results in a reduction in anal canal pressure, and allows stool to enter the anal canal, with the potential for passive leakage (24, 48). This may be a particular problem in patients with rectal reservoir dysfunction, resulting in an increased ability to store feces and fecal impaction, in whom it is increasingly recognized that the combination of RH and incomplete evacuation of rectal contents appears to play a significant role in the pathogenesis of fecal seepage (33, 81). In addition, the impaired perception of rectal distension also leads to a shorter “warning” between entry of stool into the rectum and impending defecation. This “late” recognition of volume in the rectum, or the passage of stool into the upper anal canal may account for the sudden, and apparently paradoxical, sense of extreme urgency experienced by some patients with RH (24, 82).

PATHOPHYSIOLOGIC MECHANISMS AND ETIOLOGY Pathophysiologic Mechanisms of RH The pathophysiologic mechanisms of RH are unknown (55). Traditionally, it has been widely considered that diminished perception of rectal distension, as detected by increased sensory threshold volumes, reflects impaired afferent nerve function. However, sensory assessment using simple balloon distension may not be reliable in the presence of rectal dilatation (“megarectum”) (4, 83, 84), as greater volumes will be required to distend and stimulate the rectum, and thus the elevated sensory threshold volumes may reflect inadequate stimulation rather than dysfunction of the rectal afferent pathway. Consequently, RH may be due to (i) “impaired afferent pathway function” and/or (ii) the presence of abnormal rectal wall properties, e.g., megarectum (15, 16, 18, 55, 77), where it may not necessarily reflect impairment of the afferent nerve pathway. Each of these mechanisms, and their potential causes will be discussed below. Although fundamental, this distinction between RH reflecting a disorder of the rectum, or its afferent pathway, has largely been ignored by clinicians and researchers, and thus the relative importance of each of these mechanisms is currently unknown. IMPAIRED RECTAL AFFERENT PATHWAY FUNCTION. Perception of rectal stimuli depends on stimulation of termi-

1143

nal afferents (mechanoreceptors) in the rectal wall and transduction and transformation of the stimulus into an electrical signal, which is transmitted along the afferent pathway up to the cerebral cortex where it is “processed” (11, 40). Abnormalities of visceral afferent nerve sensitivity may, therefore, result from disruption to any of the following levels of the brain-gut axis (Fig. 1) (85): 1. Receptor: impaired transduction/transformation of stimulus (downregulation/receptor insensitivity); 2. Afferent nerve sensitivity: impaired transmission of signal (peripheral or central); 3. Defective central processing. It is unknown whether “true” dysfunction of the rectal afferent pathway leading to RH is caused by an increased threshold of rectal mechanoreceptors, abnormal impulse conduction, or altered processing of information in the central nervous system (49). Transmission of sensory information from the rectum may be disrupted due to “direct injury” at the level of the peripheral afferent neuron or at the level of the central nervous system (Fig. 1), and due to coexisting neuropathic disorders. Observational evidence in support of each of these mechanisms is presented below. Furthermore, it has been suggested that alterations in the central processing of afferent information from the rectum, such as activation of pain inhibitory systems or attenuation of central arousal systems, may lead to the development of RH (16, 86). The use of spinal monitoring and brain imaging techniques may ultimately enable the discrimination of those patients who have problems at the level of the primary afferent neurons and/or the spinal cord from those who have aberrant brain processing of sensation (87). Indeed, cortical representation of rectal sensation may be evaluated using PET and fMRI scanning (41). Such techniques have confirmed that cortical representation may be altered in patients with abnormal visceral sensitivity (41). However, cortical representation has never been evaluated in patients with RH to determine whether there is a reduced signal between the periphery and the central nervous system, or an alteration of central response to normal stimuli. ABNORMAL RECTAL WALL PROPERTIES. In addition, RH may reflect a disorder of the rectum itself, occurring due to the presence of abnormal rectal wall properties in that greater volumes are required to elicit sensory thresholds (Fig. 2). Clinically, this is most commonly seen in patients with dilatation of the rectum, or megarectum (88). Indeed, sensory threshold volumes during simple balloon distension are significantly elevated in patients with megarectum (19, 89). However, it is unclear whether the results reflect impaired afferent nerve function, or merely the degree of rectal dilatation (15, 51, 90). RH may also occur in the presence of alterations of rectal compliance and tone, and spontaneous relaxation. Recently, such biomechanic properties were systematically studied in constipated patients using the barostat, where 47% of patients with RH were found to have increased rectal

1144

Gladman et al.

Figure 1. Schematic representation of the rectal afferent pathway. Sensory information from the rectum is transmitted through a “three-order neuron chain,” and thus RH may theoretically result from disruption at any level of this chain (Reprinted from Gastroenterology Clinics of North America, vol. 25, Camilleri, M, et al., Gastrointestinal sensation: Mechanisms and relation to functional gastrointestinal disorders. c 1996, with permission from Elsevier). 247–58. 

compliance (i.e., excessive laxity of the rectum), although other rectal biomechanic properties were similar to asymptomatic volunteers (77). This study highlights the fact that RH diagnosed during simple balloon distension may occur, at least in part, in the presence of abnormal rectal biomechanic properties, rather than changes in afferent nerve sensitivity. It should be noted, however, that rectal wall properties were normal in the remaining 53% of patients, suggesting that elevation of sensory threshold volumes was not related to altered rectal biomechanics in this subgroup of patients with RH (77). “Potential” Causes of RH Although the exact cause(s) of RH are unknown, it has frequently been noted in certain groups of patients, or in association with or following certain interventions and dis-

eases (Table 1), although causality has not been definitively established. CONGENITAL FACTORS. RH has been reported in patents with congenital abnormalities of the rectal afferent pathway, most commonly seen in association with sacral agenesis (91), and a failure of closure of the neural tube, i.e., spina bifida/myelomeningocele (92–95). In addition, secondary distension of the proximal bowel (megarectum), may occur due to congenital disorders of anorectum development, Table 1. Potential Etiologic Factors of RH According to Likely Mechanism Congenital Factors Defect of afferent pathway Rectal abnormalities

Peripheral

Sacral agenesis

Central Megarectum

Neural tube disorders Anorectal malformations

Acquired Factors Disruption of Peripheral afferent pathway

Figure 2. Impact of rectal size on sensory threshold volumes. Greater volumes are required to initiate distension, and thus elicit rectal sensations during balloon distension in patients with megarectum (A), compared to those with “normal” rectal capacity (B) (modc 1990 ified from: Madoff et al. Int J Colorectal Dis 1990;5:37–40  Springer Verlag, reprinted with kind permission of Springer Science and Business Media).

Rectal abnormalities

Aganglionosis Resection of pelvic nerves

Resection of sacral nerves Pelvic surgery Central Cauda equine syndrome Conus medullaris lesions Supraconal lesions Demyelination/ Multiple sclerosis degeneration Tabes dorsalis Subacute combined Degeneration of the cord Parkinson’s disease Neuropathies Diabetes mellitus Psychosocial Behavioral disorders Megarectum Neuronal degeneration Obstructive Endocrine Central nervous system Psychiatric Idiopathic

Rectal Hyposensitivity

such as a failure of the rectum to develop (agenesis/atresia/stenosis), which creates a physical barrier to the passage of intestinal content (96), or due to a failure of relaxation of the aganglionic segment in patients with Hirschsprung’s disease, which results in a functional obstruction (97). ACQUIRED FACTORS Defect of rectal afferent pathway. Peripheral or central interruption of the rectal afferent pathway, together with the effect of various neuropathic disorders, may lead to RH (Table 1). Peripheral disruption: The exact neuroanatomy of afferent pathways from the rectum remains to be determined in humans, but rectal afferent fibers appear to pass through the pelvic plexus and with the nervi erigentes (pelvic splanchnic nerves) to enter sacral segments 2, 3, and 4 of the spinal cord (98–100). Consequently, disruption to the pelvic (101) or sacral nerves (12, 102–105) may result in RH. It is also possible that RH may occur secondary to peripheral nerve injury during pelvic surgery (85,106), particularly hysterectomy (where division of the uterine-supporting ligaments may result in nerve injury as confirmed by the demonstration of sensory and autonomic nerves in the resected specimens (107), and the procedures involving rectal mobilization (where afferent fibers are susceptible when the lateral ligaments are divided (108). Indeed, in a study of 261 patients with RH, 38% had a history of previous pelvic surgery (33). Central disruption: Central nervous system lesions at all levels of the spinal cord (low, high, and mixed), or within the brain itself are associated with RH (12, 82, 109–113). However, it appears that there is no difference in rectal sensitivity between these three groups (110). Indeed, it has been proposed that the finding of RH in combination with absent conscious contraction of the external anal sphincter strongly suggests a spinal lesion (110). Spinal trauma (surgery or lower back injury with confirmed disc pathology) has been noted in 18% of patients with RH (33). Demyelinating/neurodegenerative disorders: RH has been objectively demonstrated in patients with multiple sclerosis compared to asymptomatic controls (62, 114), being more severely impaired in incontinent than in continent patients (62). It has also been reported in patients with the neurosyphilitic syndrome tabes dorsalis (12), characterized by demyelination of the intraspinal portion of sensory nerves in the dorsal roots. Patients with subacute combined degeneration of the posterior and lateral columns of the cord secondary to vitamin B12 deficiency may also develop RH (12), as may patients with Parkinson’s disease (115). Neuropathies: Peripheral neuropathy resulting in generalized derangements of multiple peripheral nerves, most commonly seen as a complication of diabetes mellitus, may lead to RH (25, 113), where it is most commonly observed in patients with FI. Indeed, RH is suggested to be of importance in the etiology of such symptoms in such

1145

patients (18, 62), since improvements in bowel continence can be achieved by improving rectal sensitivity (i.e., reducing sensory threshold volumes) using biofeedback therapy (18). RH has also been reported in continent diabetic patients without other gastrointestinal symptoms (116), where it was not related to the presence of autonomic neuropathy or duration of disease, leading to the proposition that involvement of rectal afferent neurons occurs early in the disease (116). Psychosocial disorders: It is also possible that psychosocial factors may act at a central level, resulting in RH (55). Of particular relevance in relation to RH is behavior relating to defecation, since it is widely believed that the voluntary withdrawal of attention from rectal sensations and/or habitual suppression of the desire to defecate may lead to RH (14, 16, 30, 50, 85, 117). In addition, a history of severe sexual/physical abuse may be associated with RH, where it may reflect altered central processing of afferent information as a “psychological defense mechanism” of dissociation in response to (painful) rectal stimuli (118).

Abnormal anatomic or biomechanic properties of the rectum. The only clinically important condition characterized by altered rectal properties is persistent dilatation of the rectum, or megarectum. Megarectum may occur secondary to the conditions listed in Table 1, but in the absence of an organic cause it is termed, idiopathic megarectum ( 88, 97). CLINICAL AND RESEARCH IMPLICATIONS 1. The distinction between RH due to impaired afferent nerve function and abnormal rectal wall properties is fundamental, as it will allow management to be directed accordingly, although it is currently unclear how such distinction can be made in clinical practice. 2. RH is commonly seen in association with neuropathic disorders, particularly as a complication of diabetes mellitus, and following pelvic surgery, and thus the presence of such “potential risk factors” in patients with functional bowel disorders should alert the clinician to the possibility of a diagnosis of RH. 3. Prospective studies are required to determine the relative importance of afferent nerve dysfunction and abnormal rectal wall properties in patients with RH, employing the use of clinically applicable methodology so that the distinction can be made in everyday practice by clinicians. 4. Such studies should involve the assessment of rectal size, and afferent nerve function using alternative techniques to stimulate the rectum (e.g., electrical/thermal stimulation), as these potentially provide a more accurate assessment of “true” nerve function, since they are not influenced by rectal wall properties. 5. Studies using spinal monitoring and brain imaging techniques may enable the discrimination of those patients who have problems at the level of the primary afferent

1146

Gladman et al.

neurons and/or the spinal cord from those who have aberrant brain processing of sensation.

TREATMENT Empiric (Symptomatic) Therapy The majority of patients with RH are managed empirically. Treatments employed merely address the clinical manifestation (e.g., constipation, FI, etc.) of the underlying functional disturbance, and are not specifically designed to directly address the abnormality of rectal sensitivity. Several detailed accounts of the empirical management of functional disorders such as constipation, IBS, and incontinence are available in the literature (30, 66, 119, 120), and a detailed discussion of such management options is beyond the scope of this review. Direct Therapy There are limited studies in the literature that have directly evaluated various treatment modalities that specifically address the underlying physiologic abnormality in patients with RH. However, the results of such studies must be interpreted with considerable caution as the available evidence is generally of low quality obtained from case series, and not controlled with respect to the outcome from other medical interventions or no treatment. Furthermore, the studies usually involved small numbers of patients, with short-term followup. Moreover, such studies have usually employed various modalities as a component of a more complex treatment strategy (e.g., medical therapy/bowel retraining/psychology therapy in combination), and have not specifically evaluated the individual components in isolation. BEHAVIORAL RETRAINING TECHNIQUES/BIOFEEDBACK. The largest body of work relating to treatment of patients with RH involves the application of behavioral retraining techniques incorporating biofeedback. Increasingly, such techniques have been employed to treat functional bowel disorders (121–124), particularly in patients with FI and constipation associated with pelvic floor dysfunction (121). The following account will concentrate on those studies that have specifically sought to correct the sensory dysfunction in patients with RH. Under such circumstances, biofeedback incorporates “sensory retraining” to improve the perception of rectal distension (125), in addition to standard maneuvers employed to improve rectoanal coordination and evacuatory function (121). Constipation: Clinical improvement appears to occur in 58–87% of chronically constipated patients with RH following behavioral retraining with or without biofeedback, although patient numbers studied were small and follow-up limited to the short term (15, 125, 126). Furthermore, rectal sensitivity, objectively assessed during physiologic evaluation, improves (frequently falling to within normal limits) in

65–92% of patients, although this is not the case in nonresponders (15, 125, 126) Fecal incontinence: Sensory (and sphincter strength) retraining biofeedback was successful in reducing episodes of FI in 60–94% of incontinent patients with RH (18, 24, 127– 130). Furthermore, biofeedback led to improvement or normalization of sensory threshold volumes in 58–92% of patients (18, 24, 127–130). The improvements in function and rectal sensitivity were maintained for up to 12–30 months of follow-up after completion of therapy (18, 129, 130). In a randomized, crossover study evaluating active sensory retraining biofeedback, significant improvements in clinical symptoms and rectal sensory function were noted compared to a control group undergoing “sham” retraining, although it should be noted that not all patients with improved sensation had improved continence (130). Indeed, the only significant change in objective anorectal function following completion of the entire program was improvement in the perception of rectal distension, while sphincter pressures remained unchanged. Similarly, responders to treatment were all noted to have normal threshold volumes for first sensation at the end of treatment in one study, whereas five of the six nonresponders failed to improve to this level (128). Consequently, it has been proposed that sensory retraining is critical to the success of biofeedback, and that patients with more severely impaired rectal sensitivity are less likely to improve their sensory function enough to recover continence (128). Summary: Despite the growing use of behavioral retraining techniques and biofeedback in recent years, and reports of positive results following treatment, quality evidence to demonstrate their efficacy and support their use in clinical practice is lacking (131, 132). Nevertheless, such techniques offer promise in the treatment of patients with RH, at least in the short term, where it appears that the single most important component of biofeedback training for FI is an improved ability to detect rectal distension (18, 24, 127–130), although they, as with many other studies evaluating the efficacy of biofeedback (131), are open to criticism due to lack of control groups, randomization, and adequate statistical power, and are subject to potential “order effects” in trials with “crossover” design (132). Furthermore, it has been suggested that the success of behavioral retraining techniques is a consequence of the close interaction between the patient and therapist, and could thus lend itself to a placebo effect (125). A recent study appears to support this concept, since pelvic floor exercises and biofeedback yielded no greater benefit than standard therapy for FI (133), although that study has been criticized for being inadequately powered (134). Moreover, the efficacy of the individual components of the package that comprise “behavioral retraining techniques” (e.g., the use of laxatives alone) have not been adequately evaluated.

PSYCHOLOGIC THERAPY. Two separate studies performed by the same group have demonstrated a trend toward normalization of rectal sensitivity in patients with RH and

Rectal Hyposensitivity

C-IBS following hypnotherapy (37, 135). In both studies the number of patients with RH studied was small, and the reduction in sensory thresholds failed to reach statistical significance, although normalization of such thresholds did occur in a proportion of patients (37, 135) and was not associated with alterations in rectal compliance (37, 135) and thus most likely reflects changes in actual afferent pathway function. The mechanism by which hypnotherapy normalized afferent function in patients with either RH or C-IBS could not be determined by the study, although it was proposed that it may be due to alteration in the processing of information by the central nervous system (37). ELECTRICAL STIMULATION. Sacral nerve electrical stimulation (SNS) offers promising short-term results in patients with FI (136) and functional constipation (137–139). Recently, a noninvasive form of electrical stimulation has been applied to a group of constipated patients, all of whom had RH, using an anal plug with pulse generator (44, 140). This study represents the only interventional study in a homogeneous cohort of patients with RH. In the setting of a randomized trial, clinical improvement and enhancement of rectal sensitivity on physiologic testing were observed in patients receiving electrical stimulation therapy, but not in those undergoing biofeedback therapy (44). It has been suggested by some investigators that improvement in rectal sensitivity may be a mechanism by which symptoms improve following SNS (136–141), although direct evidence of this is currently lacking. SURGERY. Surgery may be employed to remove the insensitive, and potentially dysfunctional rectum, following failure of conservative measures. However, an alternative approach involves surgical alteration of abnormal rectal properties in an attempt to reestablish normal physiological function. Recently, a novel procedure, the vertical reduction rectoplasty, has been designed based on the premise that reducing rectal capacity and compliance would restore the perception of rectal fullness and improve rectal sensory and evacuatory function in patients with RH and megarectum (142), and has been shown to be successful in achieving and maintaining correction of rectal diameter, compliance, and sensory function in most patients, and that this is translated into clinical benefit that is sustained in the medium term (143). Impact of RH on Treatment Outcomes The finding of RH in patients with functional bowel disorders may be a poor prognostic indicator following conservative and surgical intervention. RH appears to be a predictor of poor outcome following biofeedback for treatment of FI (128, 144) and outlet obstruction (145), with nonresponders having significantly higher rectal sensory threshold volumes. In addition, poor outcomes have been reported in patients with RH following anal sphincter repair or reconstruction (146, 147) and segmental (148) or subtotal colectomy (149, 150) for

1147

constipation. Despite these observations, the presence of RH is not normally considered when selecting patients with functional bowel disorders for such interventions at the present time. CLINICAL AND RESEARCH IMPLICATIONS. 1. The optimum treatment of patients with RH is currently unclear, and the majority are managed symptomatically. 2. Behavioral retraining techniques incorporating biofeedback are successful in the majority of patients with constipation or incontinence, at least in the short term. 3. Electrical stimulation may have a role in the treatment of patients with RH, although adequately designed randomized trials are currently lacking. 4. Surgical alteration of rectal wall properties is an option in patients with RH in the presence of rectal dilatation, when conservative measures are ineffective. 5. Appropriately designed prospective studies including only patients with RH are required to individually evaluate the efficacy of symptomatic therapy, biofeedback therapy, and electrical stimulation in the treatment of functional bowel disorders.

CONCLUSIONS The contribution of RH to the development of functional bowel disorders has been relatively neglected, despite it being prevalent in patients with such disorders. It is unclear whether RH precedes or follows symptoms, and thus the cause-effect relationship is yet to be determined, although there is some evidence to suggest that it may be important in the etiology of symptoms, given that it is the only apparent identifiable abnormality on physiologic testing in certain patients. This suggests that further evaluation of this physiologic abnormality is warranted, given the frequency with which functional bowel disorders are encountered in clinical practice. Many questions remain unaddressed. Of particular importance is how to make the distinction between patients with RH due to afferent nerve dysfunction and those with RH due to abnormal rectal wall properties, since rational treatment of symptoms will only be possible following identification of underlying mechanisms in individual patients. Ultimately, improved understanding and better characterization of patients with RH may be important in the management of functional bowel disorders, and thus appropriately designed controlled trials, including homogenous populations of patients with RH are needed. Whether identification of patients with RH influences the outcomes of treatments for functional bowel disorders remains to be determined. Reprint requests and correspondence: Marc A. Gladman, Clinical Research Fellow, GI Physiology Unit, 3rd Floor Alexandra Wing, The Royal London Hospital, Whitechapel, London E1 1BB, UK. Received December 4, 2005; accepted January 17, 2006.

1148

Gladman et al.

REFERENCES 1. Diamant NE, Kamm MA, Wald A, et al. AGA technical review on anorectal testing techniques. Gastroenterology 1999;116:735–60. 2. Thompson WG, Longstreth GF, Drossman DA, et al. Functional bowel disorders and functional abdominal pain. Gut 1999;45(suppl 2):II43–7. 3. Halder SL, Locke GR 3rd, Talley NJ, et al. Impact of functional gastrointestinal disorders on health-related quality of life: A population-based case-control study. Aliment Pharmacol Ther 2004;19:233–42. 4. Camilleri M. Testing the sensitivity hypothesis in practice: Tools and methods, assumptions and pitfalls. Gut 2002;51(suppl 1):i34–40. 5. Crowell MD. Pathogenesis of slow transit and pelvic floor dysfunction: From bench to bedside. Rev Gastroenterol Disord 2004;4(suppl 2):S17–27. 6. Mayer EA, Raybould HE. Role of visceral afferent mechanisms in functional bowel disorders. Gastroenterology 1990;99:1688–704. 7. Whitehead WE, Holtkotter B, Enck P, et al. Tolerance for rectosigmoid distention in irritable bowel syndrome. Gastroenterology 1990;98:1187–92. 8. Mertz H, Naliboff B, Munakata J, et al. Altered rectal perception is a biological marker of patients with irritable bowel syndrome. Gastroenterology 1995;109:40–52. 9. Talley NJ, Spiller R. Irritable bowel syndrome: A little understood organic bowel disease? Lancet 2002;360:555– 64. 10. Camilleri M, Talley NJ. Pathophysiology as a basis for understanding symptom complexes and therapeutic targets. Neurogastroenterol Motil 2004;16:135–42. 11. Azpiroz F, Enck P, Whitehead WE. Anorectal functional testing: Review of collective experience. Am J Gastroenterol 2002;97:232–40. 12. White JC, Verlot MG, Ehrentheil O. Neurogenic disturbances of the colon and their investigation by the colonmetrogram. Ann Surg 1940;112:1042–57. 13. Goligher JC, Hughes ES. Sensibility of the rectum and colon: Its role in anal incontinence. Lancet 1951;2:543–8. 14. Devadhar DS. Surgical correction of rectal procidentia. Surgery 1967;62:847–52. 15. De Medici A, Badiali D, Corazziari E, et al. Rectal sensitivity in chronic constipation. Dig Dis Sci 1989;34:747–53. 16. Harraf F, Schmulson M, Saba L, et al. Subtypes of constipation predominant irritable bowel syndrome based on rectal perception. Gut 1998;43:388–94. 17. Gosselink MJ, Schouten WR. Rectal sensory perception in females with obstructed defecation. Dis Colon Rectum 2001;44:1337–44. 18. Wald A, Tunuguntla AK. Anorectal sensorimotor dysfunction in fecal incontinence and diabetes mellitus. Modification with biofeedback therapy. N Engl J Med 1984;310:1282–7. 19. Shouler P, Keighley MR. Changes in colorectal function in severe idiopathic chronic constipation. Gastroenterology 1986;90:414–20. 20. Hancke E, Schurholz M. Impaired rectal sensation in idiopathic faecal incontinence. Int J Colorectal Dis 1987;2:146–8. 21. Varma JS, Smith AN. Neurophysiological dysfunction in young women with intractable constipation. Gut 1988;29:963–8. 22. Smith AN, Varma JS, Binnie NR, et al. Disordered colorectal motility in intractable constipation following hysterectomy. Br J Surg 1990;77:1361–5.

23. Molnar D, Taitz LS, Urwin OM, et al. Anorectal manometry results in defecation disorders. Arch Dis Child 1983;58:257–61. 24. Buser WD, Miner PB Jr. Delayed rectal sensation with fecal incontinence. Successful treatment using anorectal manometry. Gastroenterology 1986;91:1186–91. 25. Whitehead WE, Schuster MM. Anorectal physiology and pathophysiology. Am J Gastroenterol 1987;82:487–97. 26. Keighley MR, Henry MM, Bartolo DC, et al. Anorectal physiology measurement: Report of a working party. Br J Surg 1989;76:356–7. 27. Lowry AC, Simmang CL, Boulos P, et al. Consensus statement of definitions for anorectal physiology and rectal cancer: Report of the Tripartite Consensus Conference on Definitions for Anorectal Physiology and Rectal Cancer. Dis Colon Rectum 2001;44:915–9. 28. Rao SS, Azpiroz F, Diamant N, et al. Minimum standards of anorectal manometry. Neurogastroenterol Motil 2002;14:553–9. 29. Gladman MA, Scott SM, Chan CLH, et al. Rectal hyposensitivity: The prevalence and clinical impact in patients with intractable constipation and fecal incontinence. Dis Colon Rectum 2003;46:238–46. 30. Rao SS. Diagnosis and management of fecal incontinence. American College of Gastroenterology Practice Parameters Committee. Am J Gastroenterol 2004;99:1585–604. 31. Lubowski DZ, Nicholls RJ. Faecal incontinence associated with reduced pelvic sensation. Br J Surg 1988;75:1086–8. 32. Sun WM, Read NW, Miner PB. Relation between rectal sensation and anal function in normal subjects and patients with faecal incontinence. Gut 1990;31:1056–61. 33. Gladman MA, Scott SM, Williams NS, et al. Clinical and physiological findings, and possible aetiological factors of rectal hyposensitivity. Br J Surg 2003;90:860–6. 34. Felt-Bersma RJ, Gort G, Meuwissen SG. Normal values in anal manometry and rectal sensation: A problem of range. Hepatogastroenterology 1991;38:444–9. 35. Jameson JS, Chia YW, Kamm MA, et al. Effect of age, sex and parity on anorectal function. Br J Surg 1994;81:1689– 92. 36. Gosselink MJ, Hop WC, Schouten WR. Rectal tone in response to bisacodyl in women with obstructed defecation. Int J Colorectal Dis 2000;15:297–302. 37. Lea R, Houghton LA, Calvert EL, et al. Gut-focused hypnotherapy normalizes disordered rectal sensitivity in patients with irritable bowel syndrome. Aliment Pharmacol Ther 2003;17:635–42. 38. Kamm MA, Lennard-Jones JE. Rectal mucosal electrosensory testing-evidence for a rectal sensory neuropathy in idiopathic constipation. Dis Colon Rectum 1990;33:419– 23. 39. Chan CL, Scott SM, Birch MJ, et al. Rectal heat thresholds: A novel test of the sensory afferent pathway. Dis Colon Rectum 2003;46:590–5. 40. Speakman CT, Kamm MA, Swash M. Rectal sensory evoked potentials: An assessment of their clinical value. Int J Colorectal Dis 1993;8:23–8. 41. Mertz H, Morgan V, Tanner G, et al. Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention. Gastroenterology 2000;118:842–8. 42. Hobday DI, Aziz Q, Thacker N, et al. A study of the cortical processing of ano-rectal sensation using functional MRI. Brain 2001;124:361–8. 43. van der Schaar PJ, Lamers CB, Masclee AA. The role of the barostat in human research and clinical practice. Scand J Gastroenterol 1999;34(suppl 230):52–63.

Rectal Hyposensitivity

44. Chang HS, Myung SJ, Yang SK, et al. Effect of electrical stimulation in constipated patients with impaired rectal sensation. Int J Colorectal Dis 2003;18:433–8. 45. Karlbom U, Lundin E, Graf W, et al. Anorectal physiology in relation to clinical subgroups of patients with severe constipation. Colorectal Dis 2004;6:343–9. 46. Meunier P. Physiologic study of the terminal digestive tract in chronic painful constipation. Gut 1986;27:1018– 24. 47. Bharucha AE, Fletcher JG, Seide B, et al. Phenotypic variation in functional disorders of defecation. Gastroenterology 2005;128:1199–210. 48. Sun WM, Donnelly TC, Read NW. Utility of a combined test of anorectal manometry, electromyography, and sensation in determining the mechanism of ’idiopathic’ faecal incontinence. Gut 1992;33:807–13. 49. Loening-Baucke V, Yamada T. Cerebral potentials evoked by rectal distention in humans. Electroencephalogr Clin Neurophysiol 1993;88:447–52. 50. Di Lorenzo C, Benninga MA. Pathophysiology of pediatric fecal incontinence. Gastroenterology 2004;126(suppl 1):S33–40. 51. Read NW, Abouzekry L, Read MG, et al. Anorectal function in elderly patients with fecal impaction. Gastroenterology 1985;89:959–66. 52. Read NW, Abouzekry L. Why do patients with faecal impaction have faecal incontinence. Gut 1986;27:283–7. 53. Varma JS, Bradnock J, Smith RG, et al. Constipation in the elderly. A physiologic study. Dis Colon Rectum 1988;31:111–5. 54. Preston DM, Lennard-Jones JE. Severe chronic constipation of young women: ’Idiopathic slow transit constipation’. Gut 1986;27:41–8. 55. Baldi F, Ferrarini F, Corinaldesi R, et al. Function of the internal anal sphincter and rectal sensitivity in idiopathic constipation. Digestion 1982;24:14–22. 56. Roe AM, Bartolo DC, Mortensen NJ. Slow transit constipation. Comparison between patients with or without previous hysterectomy. Dig Dis Sci 1988;33:1159–63. 57. Wald A, Hinds JP, Caruana BJ. Psychological and physiological characteristics of patients with severe idiopathic constipation. Gastroenterology 1989;97:932–7. 58. Prior A, Maxton DG, Whorwell PJ. Anorectal manometry in irritable bowel syndrome: Differences between diarrhoea and constipation predominant subjects. Gut 1990;31:458–62. 59. Steens J, Van Der Schaar PJ, Penning C, et al. Compliance, tone and sensitivity of the rectum in different subtypes of irritable bowel syndrome. Neurogastroenterol Motil 2002;14:241–7. 60. Corazziari E. Definition and epidemiology of functional gastrointestinal disorders. Best Pract Res Clin Gastroenterol 2004;18:613–31. 61. Prather CM. Subtypes of constipation: Sorting out the confusion. Rev Gastroenterol Disord 2004;4(suppl 2):S11–6. 62. Caruana BJ, Wald A, Hinds JP, et al. Anorectal sensory and motor function in neurogenic fecal incontinence. Comparison between multiple sclerosis and diabetes mellitus. Gastroenterology 1991;100:465–70. 63. Hoffmann BA, Timmcke AE, Gathright JB Jr, et al. Fecal seepage and soiling: A problem of rectal sensation. Dis Colon Rectum 1995;38:746–8. 64. Lamah M, Kumar D. Fecal incontinence. Dig Dis Sci 1999;44:2488–99. 65. Cheung O, Wald A. Review article: The management of pelvic floor disorders. Aliment Pharmacol Ther 2004;19:481–95.

1149

66. Locke GR 3rd, Pemberton JH, Phillips SF. AGA technical review on constipation. American Gastroenterological Association. Gastroenterology 2000;119:1766–78. 67. Whitehead WE, Wald A, Diamant NE, et al. Functional disorders of the anus and rectum. Gut 1999;45(suppl 2):II55– 9. 68. Read NW, Timms JM, Barfield LJ, et al. Impairment of defecation in young women with severe constipation. Gastroenterology 1986;90:53–60. 69. Schouten WR, Gosselink MJ, Boerma MO, et al. Rectal wall contractility in response to an evoked urge to defecate in patients with obstructed defecation. Dis Colon Rectum 1998;41:473–9. 70. Wald A. Outlet dysfunction constipation. Curr Treat Options Gastroenterol 2001;4:293–7. 71. Chan CL, Scott SM, Knowles CH, et al. Exaggerated rectal adaptation-another cause of outlet obstruction. Colorectal Dis 2001;3:141–2. 72. Gladman MA, Scott SM, Khela MK, et al. Impaired rectal sensation appears to influence the pattern of abnormal transit in patients with slow-transit constipation (STC). Gastroenterology 2003;124(suppl 1):A686. 73. Verduron A, Devroede G, Bouchoucha M, et al. Megarectum. Dig Dis Sci 1988;33:1164–74. 74. Bassotti G, Chiarioni G, Vantini I, et al. Anorectal manometric abnormalities and colonic propulsive impairment in patients with severe chronic idiopathic constipation. Dig Dis Sci 1994;39:1558–64. 75. Solana A, Roig JV, Villoslada C, et al. Anorectal sensitivity in patients with obstructed defaecation. Int J Colorectal Dis 1996;11:65–70. 76. Bannister JJ, Timms JM, Barfield LJ, et al. Physiological studies in young women with chronic constipation. Int J Colorectal Dis 1986;1:175–82. 77. Gladman MA, Dvorkin LS, Lunniss PJ, et al. Rectal hyposensitivity: A disorder of the rectal wall or the afferent pathway? An assessment using the barostat. Am J Gastroenterol 2005;100:106–14. 78. Maurer AH, Krevsky B. Whole-gut transit scintigraphy in the evaluation of small-bowel and colon transit disorders. Semin Nucl Med 1995;25:326–38. 79. Camilleri M, Ford MJ. Review article: Colonic sensorimotor physiology in health, and its alteration in constipation and diarrhoeal disorders. Aliment Pharmacol Ther 1998;12:287–302. 80. Law NM, Bharucha AE, Zinsmeister AR. Rectal and colonic distension elicit viscerovisceral reflexes in humans. Am J Physiol Gastrointest Liver Physiol 2002;283:G384– 9. 81. Rao SS. Pathophysiology of adult fecal incontinence. Gastroenterology 2004;126(suppl 1):S14–22. 82. Smith AN, Binnie NR. Neurological disorders. In: Kumar D, Waldron DJ, Williams NS, eds. Clinical measurement in coloproctology. London: Springer-Verlag, 1991:124– 39. 83. Madoff RD, Orrom WJ, Rothenberger DA, et al. Rectal compliance: A critical reappraisal. Int J Colorectal Dis 1990;5:37–40. 84. Lagier E, Delvaux M, Vellas B, et al. Influence of age on rectal tone and sensitivity to distension in healthy subjects. Neurogastroenterol Motil 1999;11:101–7. 85. Wingate D, Hongo M, Kellow J, et al. Disorders of gastrointestinal motility: Towards a new classification. J Gastroenterol Hepatol 2002;17:S1–14. 86. Houghton LA. Sensory dysfunction and the irritable bowel syndrome. Baillieres Best Pract Res Clin Gastroenterol 1999;13:415–27.

1150

Gladman et al.

87. Aziz Q, Thompson DG. Brain-gut axis in health and disease. Gastroenterology 1998;114:559–78. 88. Todd IP. Discussion on megacolon and megarectum with the emphasis on conditions other than Hirschsprung’s disease. Proc R Soc Med 1961;54:1035–40. 89. Gattuso JM, Kamm MA. Clinical features of idiopathic megarectum and idiopathic megacolon. Gut 1997;41:93– 9. 90. Taylor I, Hammond P, Darby C. An assessment of anorectal motility in the management of adult megacolon. Br J Surg 1980;67:754–6. 91. Morera C, Nurko S. Rectal manometry in patients with isolated sacral agenesis. J Pediatr Gastroenterol Nutr 2003;37:47–52. 92. Wald A. Use of biofeedback in treatment of fecal incontinence in patients with meningomyelocele. Pediatrics 1981;68:45–9. 93. Loening-Baucke V, Desch L, Wolraich M. Biofeedback training for patients with myelomeningocele and fecal incontinence. Dev Med Child Neurol 1988;30:781–90. 94. Agnarsson U, Warde C, McCarthy G, et al. Anorectal function of children with neurological problems. I: Spina bifida. Dev Med Child Neurol 1993;35:893–902. 95. Verity C, Firth H, ffrench-Constant C. Congenital abnormalities of the central nervous system. J Neurol Neurosurg Psychiatry 2003;74(suppl 1):i3–8. 96. Hrabovszky Z, Dewan PA. Revision anorectoplasty in the management of anorectal anomalies. Pediatr Surg Int 2002;18:269–72. 97. Ehrenpreis T. Megacolon and megarectum in older children and young adults. Classification and terminology. Proc R Soc Med 1967;60:799–801. 98. McMinn RMH. Last’s anatomy regional and applied (9th Ed). London: Churchill Livingstone, 1994. 99. Knowles CH, Scott SM, Lunniss PJ. Slow transit constipation: A disorder of pelvic autonomic nerves? Dig Dis Sci 2001;46:389–401. 100. Kaiser AM, Ortega AE. Anorectal anatomy. Surg Clin North Am 2002;82:1125–38, 101. Devroede G, Lamarche J. Functional importance of extrinsic parasympathetic innervation to the distal colon and rectum in man. Gastroenterology 1974;66:273–80. 102. Gunterberg B, Kewenter J, Petersen I, et al. Anorectal function after major resections of the sacrum with bilateral or unilateral sacrifice of sacral nerves. Br J Surg 1976;63:546– 54. 103. Nakahara S, Itoh H, Mibu R, et al. Anorectal function after high sacrectomy with bilateral resection of S2-S5 nerves. Report of a case. Dis Colon Rectum 1986;29:271–4. 104. Nakai S, Yoshizawa H, Kobayashi S, et al. Anorectal and bladder function after sacrifice of the sacral nerves. Spine 2000;25:2234–9. 105. Sun WM, MacDonagh R, Forster D, et al. Anorectal function in patients with complete spinal transection before and after sacral posterior rhizotomy. Gastroenterology 1995;108:990–8. 106. Pescatori M. Colporectopexy for obstructed defecation. Do we need anorectal physiology studies? Dis Colon Rectum 2003;46:838. 107. Butler-Manuel SA, Buttery LD, A’Hern RP, et al. Pelvic nerve plexus trauma at radical hysterectomy and simple hysterectomy: The nerve content of the uterine supporting ligaments. Cancer 2000;89:834–41. 108. Speakman CT, Madden MV, Nicholls RJ, et al. Lateral ligament division during rectopexy causes constipation but prevents recurrence: Results of a prospective randomized study. Br J Surg 1991;78:1431–3.

109. Weber J, Denis P, Mihout B, et al. Effect of brain-stem lesion on colonic and anorectal motility. Study of three patients. Dig Dis Sci 1985;30:419–25. 110. Sun WM, Read NW, Donnelly TC. Anorectal function in incontinent patients with cerebrospinal disease. Gastroenterology 1990;99:1372–9. 111. MacDonagh R, Sun WM, Thomas DG, et al. Anorectal function in patients with complete supraconal spinal cord lesions. Gut 1992;33:1532–8. 112. Greving I, Tegenthoff M, Nedjat S, et al. Anorectal functions in patients with spinal cord injury. Neurogastroenterol Motil 1998;10:509–15. 113. Krogh K, Christensen P, Laurberg S. Colorectal symptoms in patients with neurological diseases. Acta Neurol Scand 2001;103:335–43. 114. Nordenbo AM, Andersen JR, Andersen JT. Disturbances of ano-rectal function in multiple sclerosis. J Neurol 1996;243:445–51. 115. Bassotti G, Maggio D, Battaglia E, et al. Manometric investigation of anorectal function in early and late stage Parkinson’s disease. J Neurol Neurosurg Psychiatry 2000;68:768–70. 116. Cozzolino D, Salvatore T, Giugliano D, et al. Sensorimotor evaluation of ano-rectal complex in diabetes mellitus. Diabete Metab 1991;17:520–4. 117. Mimura T, Nicholls T, Storrie JB, et al. Treatment of constipation in adults associated with idiopathic megarectum by behavioural retraining including biofeedback. Colorectal Dis 2002;4:477–82. 118. Ringel Y, Whitehead WE, Toner BB, et al. Sexual and physical abuse are not associated with rectal hypersensitivity in patients with irritable bowel syndrome. Gut 2004;53:838–42. 119. Schiller LR. Review article: The therapy of constipation. Aliment Pharmacol Ther 2001;15:749–63. 120. De Giorgio R, Barbara G, Stanghellini V, et al. Diagnosis and therapy of irritable bowel syndrome. Aliment Pharmacol Ther 2004;20:10–22. 121. Rao SS, Enck P, Loening-Baucke V. Biofeedback therapy for defecation disorders. Dig Dis 1997;15:78–92. 122. Enck P, Musial F. Biofeedback in pelvic floor disorders. In: Pemberton J, Swash M, Henry MM, eds. The pelvic floor: Its function and disorders. London: WB Saunders, 2002:393–404. 123. Kamm MA. Constipation and its management. BMJ 2003;327:459–60. 124. Palsson OS, Heymen S, Whitehead WE. Biofeedback treatment for functional anorectal disorders: A comprehensive efficacy review. Appl Psychophysiol Biofeedback 2004;29:153–74. 125. Rao SS, Welcher KD, Pelsang RE. Effects of biofeedback therapy on anorectal function in obstructive defecation. Dig Dis Sci 1997;42:2197–205. 126. Peticca L, Pescatori M. Outlet obstruction due to anismus and rectal hyposensation: Effect of biofeedback training. Colorectal Dis 2002;4:67. 127. Latimer PR, Campbell D, Kasperski J. A components analysis of biofeedback in the treatment of fecal incontinence. Biofeedback Self Regul 1984;9:311–24. 128. Chiarioni G, Bassotti G, Stanganini S, et al. Sensory retraining is key to biofeedback therapy for formed stool fecal incontinence. Am J Gastroenterol 2002;97:109– 17. 129. Ozturk R, Niazi S, Stessman M, et al. Long-term outcome and objective changes of anorectal function after biofeedback therapy for faecal incontinence. Aliment Pharmacol Ther 2004;20:667–74.

Rectal Hyposensitivity

130. Miner PB, Donnelly TC, Read NW. Investigation of mode of action of biofeedback in treatment of fecal incontinence. Dig Dis Sci 1990;35:1291–8. 131. Coulter ID, Favreau JT, Hardy ML, et al. Biofeedback interventions for gastrointestinal conditions: A systematic review. Altern Ther Health Med 2002;8:76–83. 132. Heymen S, Jones KR, Ringel Y, et al. Biofeedback treatment of fecal incontinence: A critical review. Dis Colon Rectum 2001;44:728–36. 133. Norton C, Chelvanayagam S, Wilson-Barnett J, et al. Randomized controlled trial of biofeedback for fecal incontinence. Gastroenterology 2003;125:1320–9. 134. Schott AM, Damon H, Mion F, et al. A randomized controlled trial of biofeedback that does not have the power to conclude. Gastroenterology 2004;126:1496–7. 135. Prior A, Colgan SM, Whorwell PJ. Changes in rectal sensitivity after hypnotherapy in patients with irritable bowel syndrome. Gut 1990;31:896–8. 136. Jarrett ME, Mowatt G, Glazener CM, et al. Systematic review of sacral nerve stimulation for faecal incontinence and constipation. Br J Surg 2004;91:1559– 69. 137. Malouf AJ, Wiesel PH, Nicholls T, et al. Short-term effects of sacral nerve stimulation for idiopathic slow transit constipation. World J Surg 2002;26:166–70. 138. Kenefick NJ, Nicholls RJ, Cohen RG, et al. Permanent sacral nerve stimulation for treatment of idiopathic constipation. Br J Surg 2002;89:882–8. 139. Ganio E, Masin A, Ratto C, et al. Short-term sacral nerve stimulation for functional anorectal and urinary disturbances: Results in 40 patients: Evaluation of a new option for anorectal functional disorders. Dis Colon Rectum 2001;44:1261–7. 140. Chang HS, Myung SJ, Yang SK, et al. Functional constipation with impaired rectal sensation improved by electrical stimulation therapy: Report of a case. Dis Colon Rectum 2004;47:933–6.

1151

141. Ganio E, Luc AR, Clerico G, et al. Sacral nerve stimulation for treatment of fecal incontinence: A novel approach for intractable fecal incontinence. Dis Colon Rectum 2001;44:619–29. 142. Williams NS, Fajobi OA, Lunniss PJ, et al. Vertical reduction rectoplasty: A new treatment for idiopathic megarectum. Br J Surg 2000;87:1203–8. 143. Gladman MA, Williams NS, Ogunbiyi OA, et al. Mediumterm results of vertical reduction rectoplasty and sigmoid colectomy for idiopathic megarectum. Br J Surg 2005;92:624–30. 144. Wald A. Biofeedback therapy for fecal incontinence. Ann Intern Med 1981;95:146–9. 145. McKee RF, McEnroe L, Anderson JH, et al. Identification of patients likely to benefit from biofeedback for outlet obstruction constipation. Br J Surg 1999;86:355–9. 146. Cohen M, Rosen L, Khubchandani I, et al. Rationale for medical or surgical therapy in anal incontinence. Dis Colon Rectum 1986;29:120–2. 147. Geerdes BP, Heineman E, Konsten J, et al. Dynamic graciloplasty. Complications and management. Dis Colon Rectum 1996;39:912–7. 148. Lundin E, Karlbom U, Pahlman L, et al. Outcome of segmental colonic resection for slow-transit constipation. Br J Surg 2002;89:1270–4. 149. Pluta H, Bowes KL, Jewell LD. Long-term results of total abdominal colectomy for chronic idiopathic constipation. Value of preoperative assessment. Dis Colon Rectum 1996;39:160–6. 150. Akervall S, Fasth S, Nordgren S, et al. The functional results after colectomy and ileorectal anastomosis for severe constipation (Arbuthnot Lane’s disease) as related to rectal sensory function. Int J Colorectal Dis 1988;3:96–101.

The authors declared no conflicts of interest.