Munsat

CHAPTER 1

KEYPOINTS: à

The approach to each group is necessarily different. For those patients known to have neurological disease, it is important that the neurologist be aware of the likely problems and be familiar with management and treatment options.

In those in whom there is a question as to whether or not the complaint is part of a general neurological condition, the neurologist will need to know what investigations might be contributory.

à

Clustering of symptoms is important in trying to decide if pelvic organ complaints are due to ‘‘ordinary”, local pathology or are neurogenic.

à

The value of the clinical neurological examination is in recognizing co-existent general neurological problems. It is less useful in detecting defects of sacral innervation.

à

If the innervation of the bladder has been affected as part of a generalized neuropathy, there is usually evidence of extensive disease with a long history of neuropathic symptoms, including sensory changes in the feet and sometimes the hands, with loss of pain and temperature perception with or without positive symptoms, such as painful dysesthesia.

A NEUROLOGIST’S CLINICAL AND INVESTIGATIVE APPROACH TO PATIENTS WITH BLADDER, BOWEL AND SEXUAL DYSFUNCTION INTRODUCTION Neurologists encounter many patients with symptoms that may be due to disorders of sacral innervation. These are either patients with established neurological disease who commonly have complaints of urogenital dysfunction or patients of whom the question is being asked ‘‘is there a neurological basis for the patient’s complaints of bladder, sexual and sometimes bowel dysfunction?” The approach to each group is necessarily different. For those patients known to have neurological disease, it is important that the neurologist be aware of the likely problems and be familiar with management and treatment options. In those in whom there is a question as to whether or not the complaint is part of a general neurological condition, the neurologist will need to know what investigations might be contributory.

Later sections of this teaching course deal in detail with causes and investigation of specific complaints, i.e. urinary incontinence and retention, constipation and fecal incontinence and sexual dysfunction. However, at this stage, a broad understanding of the neurological control of pelvic organs and how this may be affected by disease is needed.

HISTORY Table 1 shows what symptoms might be expected from neurological disease at different levels. Clustering of symptoms is important in trying to decide if pelvic organ complaints are due to ‘‘ordinary”, local pathology or are neurogenic. For example, in a patient with spinal cord disease, bladder and sexual dysfunction are usually present together, whereas if bladder symptoms are due to prostatic outflow obstruction, sexual function is

preserved. Therefore, when taking the history, attention should focus on identifying whether a pelvic organ complaint is isolated or is part of a symptom complex.

CLINICAL NEUROLOGICAL EXAMINATION The value of the clinical neurological examination is in recognizing co-existent general neurological problems. It is less useful in detecting defects of sacral innervation. This is where clinical neurophysiological investigations might have been expected to provide important information, but in practice, with one or two notable exceptions (see Pullout 1), is disappointingly not the case.

If a focussed clinical examination fails to detect evidence of neurological disease, laboratory investigations rarely provide a diagnosis.

The following sections describe briefly what the typical history and clinical examination might reveal in each condition.

Peripheral neuropathy. The neurologist may be asked if a patient’s peripheral neuropathy is the cause of their bladder dysfunction. Many neuropathies are length dependent, the maximum deficit being evident in the longest fibers, whereas the nerve fibers to the bladder are relatively short. If the innervation of the bladder has been affected as part of a generalized neuropathy, there is usually evidence of extensive disease with a long history of neuropathic symptoms, including sensory changes in the feet and sometimes the hands, with loss of pain and temperature perception with or without positive symptoms, such as painful dysesthesia. On examination, both knee and ankle jerks will be absent and small fiber sensory impairment demonstrable to the level of the ankles.

1

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: Ă

It is exceptional for there to be single pelvic organ dysfunction due to a cauda equina lesion and corroborative evidence of other sacral root symptoms should be sought before, for example, attributing isolated bladder symptoms to a partial lesion.

TABLE 1

Conjunction of pelvic organ symptoms which may occur with neurological disease at different levels in the nervous system

Neurological lesion

Symptoms of pelvic organ dysfunction

Innervation within the pelvis

Bladder emptying difficulties ED, sometimes FSD

Peripheral neuropathy

ED (early) Bladder emptying difficulties (late) Diarrhea Postural hypotension

Cauda equina

Saddle sensory impairment Stress urinary incontinence Difficulty in initiation of micturition Urgency (occasionally) Sexual sensory loss ED, FSD Constipation Fecal incontinence/difficulty in evacuation

Spinal

Somatic sensory level Urinary urgency Incomplete bladder emptying ED, FSD Difficulty in bowel evacuation (in advanced disease)

Pontine (very rare)

Internuclear ophthalmoplegia Urinary retention

Extrapyramidal

Parkinsonism (advanced in IPD, minor in MSA) ED (early in MSA) Urinary incontinence (early in MSA) Constipation

Frontal

Personality change Urinary urge incontinence Fecal incontinence (exceptional)

ED, erectile dysfunction; FSD, female sexual dysfunction; IPD, idiopathic Parkinson’s disease, MSA, multiple system atrophy.

Bladder or bowel symptoms should not be attributed to peripheral neuropathy unless there are other features of autonomic involvement in diabetics. However, sexual dysfunction, particularly erectile failure, occurs early in diabetes and may in fact be a presenting symptom when there is little or no evidence of generalized neuropathy to find on examination.

Cauda equina. Cauda equina lesions are likely to cause bladder and sexual complaints as well as difficulties of defecation. It is exceptional for there to be single pelvic organ dysfunction due to a cauda equina lesion and corroborative evidence of other sacral root symptoms should be sought before, for example,

2

attributing isolated bladder symptoms to a partial lesion.

Cauda equina disease or damage that affects only S2-S4 will produce sensory loss restricted to the perineum and the back of the thighs. A lax anal sphincter may be demonstrable and sacral reflexes, such as the bulbocavernosus reflex, lost. However, even with extreme caudal spinal lesions, there are usually also neurological abnormalities in the lower limbs, and foot deformities due to weakness of the intrinsic muscles may be present if the problem is long standing.

Examination of the lower back and sacrum is very important in these cases.

PULLOUT 1

Clinical neurophysiological investigations of the pelvic floor

Bulbocavernosus reflex A neurophysiological method for recording the bulbocavernosus reflex, which had been clinically regarded to be of value in assessing patients with neurogenic bladder disorders, was first reported in 1967. Although abnormal in a proportion of patients with neurological disease causing pelvic organ dysfunction, the test was of little value when applied to patients with uncertain neurological lesions presenting with hypocontractile bladders or ED. The responses are mediated by large myelinated fibers and the small myelinated or unmyelinated fibers that either innervate the smooth muscle or constitute the functionally important afferent nerve supply of the region, are not tested.

The bulbocavernosus reflex was used extensively for the diagnosis of neurogenic erectile dysfunction. Elicited clinically by squeezing the glans penis and neurophysiologically by an electrical pulse to the dorsal penile nerve, a contraction of the bulbocavernosus muscle was observed or recorded electromyographically. The reflex tested the integrity of large myelinated nerve fibers in the S2-S4 segments. The minimum latency response was measured and values greater than 45 ms were considered abnormal. Although many patients with neurogenic ED due to either cauda equina or lower motor neuron lesions had abnormally prolonged or absent BCR responses, the test was not sensitive and some men with established cauda equina lesions or diabetic peripheral neuropathy had normal responses. Furthermore, the response was prolonged in some men with a demyelinating neuropathy who had unimpaired sexual function.

Terminal motor latency of the pudendal and perineal nerves Measurement of the terminal motor latency of the pudendal and perineal nerves (PTML) was a technique devised at St Mark’s Hospital, London. It has been used to demonstrate pathophysiological changes in these nerves in women with fecal, urinary or double incontinence.

The pudendal nerve is stimulated transrectally near the ischial spine through the wall of the rectum or vagina using an electrode mounted on the tip of the examiner’s finger. An electrode is mounted at the base of the finger which records from the anal sphincter and a ring electrode mounted on a Foley catheter can be used to record from the periurethral striated muscle. The latency of the response has been found to be prolonged in women with urinary stress incontinence following childbirth and women with fecal incontinence due to sphincter weakness. It is thought that stretching of the nerves during parturition and also with straining at defecation in chronic constipation results in pudendal nerve injury. Although of considerable research value, this test is not used in the routine assessment of women with urinary stress incontinence, nor has it proved to be as useful as electromyography of the anal sphincter in the assessment of fecal incontinence.

Pudendal evoked response The pudendal evoked potential (PEP) is easily recorded using a similar technique to that which is used for recording the tibial evoked potential, but with stimuli applied to the dorsal nerve of the penis or clitoris. The response has a similar waveform and even latency to that of the tibial evoked response — the slower conduction being due to the composition of the penile nerve being sensory only and lacking the fast conducting muscle afferent fibers of the tibial nerve.

At one time, it was recommended that the pudendal evoked response be included as part of screening tests in the investigation of erectile dysfunction. The PEP is abnormal in patients with spinal cord disease including MS, but is less sensitive in detecting spinal cord disease than is a comparison of the tibial evoked potentials recorded from both limbs.

Furthermore, spinal cord dysfunction is usually evident from clinical examination.

Pullout 1 continued

3

þ

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

Pullout 1 continued

þ

Anal or urethral sphincter EMG Recording from the striated muscle of the urethral sphincter or anal sphincter during cystometry was used as a means of detecting inappropriate sphincter contraction during detrusor contraction, the disorder known as detrusor sphincter dyssynergia. However, for several reasons, this type of kinesiological EMG recording is now little used, although sphincter EMG performed as a separate neurophysiological test remains a valuable investigation in some circumstances.

Needle electrode EMG of either the anal or urethral sphincter can be performed to show evidence of sacral segment or root damage in much the same way as EMG is used at somatic sites. However, because motor units in the sphincter fire tonically, it is difficult to recognize changes of denervation and most often changes of reinnervation are sought, based on the analysis of individual motor units captured using a trigger and delay line. In general, EMG is held to be the most valuable of the pelvic floor investigations to detect lower motor neuron damage. EMG of the striated musculature of the pelvic floor can demonstrate changes of denervation and chronic reinnervation in patients with cauda equina lesions as well those with suspected MSA. The striated muscles of the sphincters are innervated by anterior horn cells which lie in Onuf’s nucleus in the sacral part of the spinal cord and neuropathological studies showed loss of cells in Onuf’s nucleus in patients dying with Shy-Drager syndrome. These changes may be reflected by abnormalities of sphincter EMG in life. Changes of reinnervation in MSA are non-specific and some caution must be exercised in interpreting EMG findings in multiparous women or patients who have had extensive pelvic surgery. There is some debate as to the value of the test in distinguishing between MSA and IPD, but extreme prolongation of the mean of 10 motor units in a patient with minor parkinsonism and severe urinary incontinence and ED is strongly indicative of MSA. The other condition in which urethral sphincter EMG has proved to be of particular value is the investigation of young women in urinary retention.

Unfortunately, there is as yet no neurophysiological means of investigating detrusor smooth muscle function.

Autonomic function testing Using a combination of cardiovascular tests, generalized sympathetic and parasympathetic failure can be recognized, which may be associated with urogenital dysfunction.

Cardiovascular autonomic function tests measure changes in heart rate variability and blood pressure in response to deep breathing, changes in posture from lying to standing, cold stimuli, isometric exercise, sudden inspiratory gasps or Valsalva maneuver. These tests investigate only generalized cardiovascular autonomic failure and overlook possible focal or regional abnormalities in peripheral or central autonomic nerve function. It is not surprising, therefore, that normal cardiovascular results are found in some patients with abnormal erectile function and vice versa.

Sympathetic skin responses The changes in skin resistance that occur following various internally generated or externally applied arousal stimuli result from an increase in sweat gland activity mediated by the sympathetic nervous system, and lead to a changes in skin voltage that can be recorded using two surface electrodes. This response is called the sympathetic skin response (SSR) and is thought to originate from synchronized activation of sweat glands in response to a discharge of the efferent sympathetic nerve fibers. SSR responses recorded from the limbs can be used in the detection of mixed axonal neuropathies and have also been measured on the genital skin. The SSR could be recorded from the genitalia in normal subjects, but the response was absent in some diabetics with erectile dysfunction, both with and without a previously diagnosed neuropathy.

4

KEYPOINTS:

‘‘Corpus cavernosum EMG”

à

Because of the relative levels of innervation of the lower limbs and the pelvic organs, it is unusual to have a lesion between the pons and the sacral part of the cord giving rise to a neurogenic bladder or sexual dysfunction, that does not also produce signs of an upper motor neuron lesion in the lower limbs.

à

Various neurophysiological investigations of the pelvic floor and the sphincters have been developed and used over the years, but the current view is that few are of diagnostic value.

The electrical activity that can be recorded from the corpus cavernosum using either a concentric needle electrode or surface electrodes has been called ‘‘corpus cavernosum electromyography” (CC-EMG). Activity is recorded on a compressed time base with the subject at rest. Studies on ‘‘CC-EMG” have recognized that the recorded potentials are sympathetically mediated and that mental stimulation increased the frequency of the potentials. The similarity between ‘‘CC-EMG” and activity that can be recorded from surface electrodes placed on the limb of a patient using the set up as used to record SSR, but on a slow time base, suggests the two types of activity may have a common genesis, although there are some differences. In general, there is good evidence that these recordings represent some form of autonomic activity from the genitalia.

Spinal cord. Because of the relative levels of innervation of the lower limbs and the pelvic organs, it is unusual to have a lesion between the pons and the sacral part of the cord giving rise to a neurogenic bladder or sexual dysfunction that does not also produce signs of an upper motor neuron lesion in the lower limbs. This is undoubtedly the case in patients with multiple sclerosis (MS) but the rule appears to hold for most other instances of spinal pathology, unless the lesion is central, intramedullary and small.

The majority of men with spinal cord pathology causing bladder symptoms have impaired erectile function, but bowel complaints would not be an expected part of the picture, unless there is a marked neurological deficit. Symptoms and signs of a paraparesis of variable severity should also be expected.

Brainstem. Brainstem or pontine pathology usually causes marked neurological deficits, but occasionally a lesion can be sufficiently dorsal and discreet to produce predominantly a defect of bladder function. An internuclear ophthalmoplegia may be an accompanying sign in such cases, due to the proximity of the median longitudinal fasciculus.

Extrapyramidal. Parkinsonian features are marked in patients with long-standing Parkinson’s disease who develop genitourinary symptoms as part of the neurological picture.

Neurological abnormalities in patients with multiple system atrophy (MSA), however, may be subtle at a time when genitourinary symptoms present and it is important to examine for early cerebellar signs and also postural hypotension.

Supra pontine. The contribution of supra pontine pathology to neurogenic bladder dys-

function, with the exception of areas in the frontal lobes is poorly defined. Patients with frontal lobe incontinence may have neuropsychological impairment, such as a change of personality, but are not indifferent to their incontinence unless there has been extensive frontal lobe damage.

NEUROPHYSIOLOGICAL INVESTIGATIONS OF THE PELVIC FLOOR Various neurophysiological investigations of the pelvic floor and the sphincters have been developed and used over the years, but the current view is that few are of diagnostic value.

Although there have been many research papers reporting abnormalities of neurophysiological investigations in patients with established neurological disease, studies of the sensitivity of these compared with the neurological examination were rarely performed.

Exceptions are the use, but disputed value of, anal sphincter EMG to recognize changes of chronic reinnervation in multiple system atrophy and the use of urethral sphincter EMG to recognize a primary disorder of sphincter relaxation in young women with isolated urinary retention.

Because, historically, neurophysiological testing has been thought to be important in the past, a brief description is given here (Pullout 1). Greater detail can be found in a review articles [1, 2].

IMAGING OF THE NERVOUS SYSTEM Neurological imaging may be important if the patient had been referred from a urologist to a neurologist asking if the patient has a neurogenic basis for their symptoms. Imaging is

5

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: à

In a patient with bladder symptoms and established neurological disease, urodynamic investigations may be performed to understand the pathophysiological basis for the patient’s complaint and obtain information on which to base recomendations for management of incontinence.

à

A change in bowel habit unrelated to major changes in neurological condition or rectal bleeding always warrants investigation to exclude bowel malignancy.

à

Now that there are simple and effective symptomatic treatments for erectile dysfunction (ED), the emphasis has moved away from investigations that were carried out in former times to try and distinguish between organic and psychogenic causes of ED. In men with established neurological disease known to cause ED, laboratory investigation is not indicated, unless the response to treatment is poor.

particularly indicated to exclude a supra pontine abnormality or a sub-sacral lesion, and magnetic resonance imaging is now the investigation of choice.

Neurological imaging has no role in determining management of pelvic organ dysfunction in a patient with a known neurological diagnosis.

INVESTIGATIONS OF BLADDER SYMPTOMS Urodynamics. In a patient with bladder symptoms and established neurological disease, urodynamic investigations may be performed to understand the pathophysiological basis for the patient’s complaint and obtain information on which to base recommendations for management of incontinence. The term ‘‘urodynamics” encompasses any investigation of urinary tract function, although it is often used incorrectly as a synonym for cystometry.

The role of urodynamics in trying to decide if a patient has a neurogenic bladder disorder is limited. The majority of patients sent by urologists to neurologists have been demonstrated on filling cystometry to have bladder overactivity (see Chapter 2), and because there are non-neurogenic causes for this, the neurologist must try to confirm or refute that there is neurological basis for the problem. The clinical neurological examination is critical for this.

Ultrasound scanning of the urinary tract.

Ultrasound scanning has largely overtaken intravenous urography as the method of choice for examining the upper renal tract to detect dilatation, although urologists still prefer intravenous urography to look for ureteric stones.

The residual urine volume left after voiding is a critical factor in determining manage-

ment of neurogenic incontinence and can be measured by non-urologists using a small relatively inexpensive ultrasound scanner (see Chapter 2).

INVESTIGATION OF CONSTIPATION/ FECAL INCONTINENCE Bowel complaints do occur in patients with neurological disease which can mostly be managed symptomatically. However, the contribution of neurological disorders to bowel control is not an area that is well understood and investigations may be required in individual patients to define the pathophysiology of their symptoms as well as exclude non-neurological causes of fecal incontinence or co-incidental disease.

A change in bowel habit unrelated to major changes in neurological condition or rectal bleeding always warrants investigation to exclude bowel malignancy. A description is given in Chapter 3 of the various investigations that can be performed to study function and structure.

INVESTIGATION OF SEXUAL DYSFUNCTION Now that there are simple and effective symptomatic treatments for ED, the emphasis has moved away from investigations that were carried out in former times to try and distinguish between organic and psychogenic causes. In men with established neurological disease known to cause ED (see Table 1), laboratory investigation is not indicated, unless the response to treatment is poor.

In the general population, ED often has a significant vascular component. This type of problem may be investigated using a variety of techniques to study penile hemodynamics, as described in Chapter 4 (Pullout 2).

REFERENCES

6

[1]

Fowler CJ. The neurology of male sexual dysfunction and its investigation by neurophysiological methods. Br J Urol 1998;81:785-95.

[2]

Vodusek DB, Fowler CJ. Clinical neurophysiology. In: Fowler CJ, editor. Neurology of bladder, bowel, and sexual dysfunction. Boston: Butterworth Heinemann; 1999. pp. 109-43.

CHAPTER 2

KEYPOINTS:

URINARY INCONTINENCE AND RETENTION INTRODUCTION Loss of bladder control is a common problem for patients with neurological disease. Incontinence is likely to impose considerable extra burdens on a disabled person and their carers in terms of loss of quality of life, social embarrassment and expense and it is therefore important that the neurologist is aware of what treatments are available and the scientific basis for their effectiveness.

ANATOMY AND PHYSIOLOGY OF THE LOWER URINARY TRACT Physiological properties of the bladder enable the urine that is continuously produced to be stored at low pressure until such time as it is convenient and socially acceptable to void.

Normal voiding involves reflex detrusor contraction synchronized with voluntary sphincter relaxation to achieve complete bladder emptying.

Any pathology that affects the physiology of these processes will cause symptoms that can be divided into disorders of either storage or voiding (Table 1).

Storage. Whether voluntary or not, passage of urine through the urethra occurs when intravesical pressure exceeds intraurethral pressure. Reflex inhibition of the parasympathetic innervation of the detrusor during filling prevents its contraction and facilitates storage. Furthermore the bladder has viscoelastic properties that give it ‘‘compliance” so that as it fills, its internal pressure does not rise.

In the female urethra, the voluntary or ‘‘external” striated urethral sphincter is situated in the middle third of the urethra, whereas in males the striated sphincter is situated at the most inferior aspect of the prostate around the membranous urethra. Smooth muscle condensations in the region of the male bladder neck form the so-called ‘‘internal” sphincter, but the homologous structure

is less well developed in women. The internal and external sphincters remain closed during filling, but even though the internal sphincter is destroyed following transurethral resection of the prostate, incontinence very rarely occurs.

The pelvic floor, its overlying ‘‘endopelvic” fascia and the named ligamentous condensations of this fascia that are inserted into the anal sphincter, perineal body and lower vagina or membranous urethra in the male, constitute the mechanism of pelvic organ support. The pelvic floor muscles (levator ani and coccygeus), act like a hammock to maintain the position of the viscera in the pelvis which is important for continence (Figure 1).

Voiding. Voiding is initiated by inhibition of the striated sphincter and pelvic floor, followed some seconds later by a contraction of the detrusor muscle. To achieve complete bladder emptying sphincter activity must be inhibited throughout the cycle of detrusor contraction.

Innervation of the lower urinary tract.

Figure 2 shows the complex relationship between the somatic and autonomic innervation of the lower urinary tract.

Somatic. The motor neurons that innervate the urethral and anal sphincters lie in Onuf’s nucleus within the S2-4 sacral segments of

TABLE 1

à

Incontinence is likely to impose considerable extra burdens on a disabled person and their carers in terms of loss of quality of life, social embarrassment and expense and it is therefore important that the neurologist is aware of what treatments are available and the scientific basis for their effectiveness.

à

Whether voluntary or not, passage of urine through the urethra occurs when intravesical pressure exceeds intraurethral pressure.

Urinary symptoms may be related to either phase of bladder activity (i.e. storage or voiding)

Phase of bladder activity

Symptoms of dysfunction

Urine storage

Frequency, urgency, urge incontinence

Urine voiding

Hesitancy, intermittency, poor stream, terminal dribbling, incomplete emptying (+/- frequency and urgency)

7

NEUORLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

FIGURE 1

The muscles of the pelvic floor, which are part of the pelvic organ support mechanism in females.

From Dixon JS, Gosling JA. The anatomy of the bladder, urethra and pelvic floor. In: Mundy TP, Stephenson AR, Wein AJ, editors. Urodynamics, principles, practice and application, 2nd ed.

Churchill Livingstone; 1994. Reproduced with permission.

the spinal cord. The motor innervation passes through the pelvic and pudendal nerves to innervate the pelvic floor and striated urethral sphincter, respectively.

Parasympathetic. The principal autonomic innervation of the bladder is derived from cholinergic parasympathetic fibers that originate from the sacral cord. These pelvic parasympathetic preganglionic fibers are contained in the 2nd, 3rd and 4th sacral spinal nerve roots within the cauda equina, then peripherally in the pelvic nerves.

Sympathetic. The sympathetic innervation of the lower urinary tract arises in the lumbosacral sympathetic chain and passes to the bladder via the hypogastric and pelvic nerves. The sympathetic nerves to the bladder interact on parasympathetic ganglia that lie in the pelvic plexus on the bladder wall and may have an inhibitory effect during filling. Activation of α-adrenoceptors in the smooth muscle of the bladder neck and urethra causes contraction and prevents leakage during filling as well as closing the bladder neck during ejaculation.

8

Afferent. Sensory information concerning bladder filling is thought to arise from unmyelinated free ending nerves which lie in the suburothelium and is conveyed in sensory fibers which run with the parasympathetic, somatic and sympathetic innervation in the pelvic, hypogastric and pudendal nerves.

Based on data derived from animal experiments, information regarding detrusor muscle and urothelial derived sensation is thought to be conveyed via finely myelinated Aδ fibers and unmyelinated c-fibers, respectively. Some afferents in the suburothelium are sensitive to changes in the chemical composition of urine, for example changes in pH, osmolality or irritants, such as bacterially derived lipopolysaccharide. Many of the presumed sensory nerves contain vesicals of neurotransmitters, such as neurokinins, ATP or calcitonin gene related peptide which may exert paracrine effects. In addition, some afferent nerves have receptors for these substances resulting in a ‘‘chemical dialogue” at the interface of the urothelium, detrusor muscle and afferent

nerves. Afferent discharges that occur during detrusor contraction appear to reinforce the central drive that maintains a detrusor contraction. Afferent pathways from the bladder have been shown to terminate not in the pontine micturition center, but in the periaqueductal gray in cats [1].

Spinal interneurons. The afferent fibers synapse on secondorder spinal interneurons. These may act on preganglionic or motor nuclei or relay information to other regions of the spinal cord or higher centers. Interneuronal mechanisms play an important role in the integrated regulation of the lower urinary tract.

Neurological control of the bladder. A modern view of the control of the two mutually exclusive activities that the bladder performs, i.e. storage and voiding, is that neural programs for each process exist in the pons and that suprapontine influences act to switch from one state to the other. In both conditions, a reciprocal relationship is maintained between activity of the sphincter and the detrusor (Figure 3) [2].

In the late 1920s, Barrington Innervation of the male lower urinary tract.

FIGURE 2 demonstrated in the cat that there From Mundy AR. The structure and function of the lower urinary tract. In: Mundy AR, were areas in the pons that were Fitzpatrick JM, Neal DE, George NJ, editors. The scientific basis of urology. Isis Medical important for bladder control, Media; 1999. Reproduced with permission. such that section of the brainstem below a certain level left the experimental animal unable to void. An area in the pons was identified and proposed that the lateral region be regarded KEYPOINTS: subsequently became known as the pontine as important for continence and the medial micturition center (PMC) but is also known region, the site of activation for micturition à A modern view of the control of the two as ‘‘Barrington’s nucleus”. More recent animal [3]. mutually exclusive experiments have shown that there are two There in no direct afferent input from activities that the bladder performs, i.e. storseparate areas in the PMC. There is a lateral the bladder to the PMC, but instead, conage and voiding, is region which when stimulated, results in a nections between the periaqueductal gray that neural programs powerful contraction of the urethral sphinc- are thought to provide information as to the for each process exist ter, and a more medially placed region which state of fullness of the bladder [1]. in the pons and that when stimulated results in an immediate Recent studies of voiding using positron suprapontine influences act to switch decrease in urethral pressure and silence of emission tomography in male and female subfrom one state to the pelvic floor EMG signal, followed by a rise jects have demonstrated that the neurological other. in detrusor pressure. It has, therefore, been control of the bladder in man is essentially

9

NEUORLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

Urine storage and voiding. During urine storage, the detrusor muscle as it fills accommodates urine at a low pressure and does not contract — this involves the suppression of parasympathetic (motor) activity and the tonic contraction of the sphincters. Just prior to voiding, the intraurethral pressure falls as the sphincters relax and this if followed by detrusor contraction and voiding to completion.

FIGURE 3

KEYPOINTS: à

To effect both storage and voiding, higher centers as well as connections between the pons and the sacral spinal cord must be intact, and also the peripheral innervation that arises from the most caudal segments of the sacral cord. The innervation needed for physiological control of the bladder is extensive, so that urinary incontinence is a likely consequence of neurological disease.

similar to that which had been demonstrated in experimental animals. Right-handed volunteers were trained to void whilst lying in the scanner, but a proportion of the subjects were unable to do so. In those able to void, there was

FIGURE 4

Lateral and medial regions in the pontine micturition center. The lateral (L) region is important in the facilitation of urine storage whilst the medial (PMC) region is activated during voiding.

From Blok et al. [4]. Reproduced with permission.

10

activity in a region of the medioposterior pons, but in the ‘‘unsuccessful” voiders, a region in the ventrolateral pontine tegmentum was seen to be activated (Figure 4). It was proposed that these areas are homologous to those that had been shown to exist in the cat [4].

The neurological processes in man that determine when to switch from storage to voiding remain to be elucidated. The extent of bladder fullness is obviously a critical factor, as is the sense of urinary urgency that may not necessarily reflect the bladder volume. The importance of areas in the frontal regions have long been recognized [5], and it seems likely that frontal lobe input is involved in the inhibition of micturition until it is socially appropriate.

Thus to effect both storage and voiding, higher centers as well as connections between the pons and the sacral spinal cord must be intact, and also the peripheral innervation that arises from the most caudal segments of the sacral cord. The innervation needed for physiological control of the bladder is extensive, so that urinary incontinence is a likely consequence of neurological disease [6].

ties of the intrinsic innerva- KEYPOINTS: tion of the bladder [7].

In patients with à Incontinence is defined as the condition where neurological disease, the Woman Men ‘‘involuntary loss of same disorder of overacurine is objectively Age Age demonstrable and is a tive bladder function is Pregnancy Urinary symptoms social or hygienic probreferred to as ‘‘detrusor Childbirth Functional impairment lem”. hyperreflexia (DH).” It is Menopause Cognitive impairment not possible to distinguish à It is not possible to disHysterectomy Benign prostatic hypertrophy between DH and DI on tinguish between DH Obesity Postoperative and DI on cystometry cystometry (see Pullout 5) Urinary symptoms Urinary tract infection and the correct classiand the correct classificafication of a patient’s Functional impairment Medications (e.g. diuretics) tion of a patient’s bladder bladder disorder as DH Cognitive impairment disorder as DH depends depends on the clinical Urinary tract infection on the clinical recognition recognition of its neurological context. of its neurological context.

Medications (e.g. diuretics) (2) Genuine stress incontinence (GSI) is the involuntary loss of urine that folURINARY INCONTINENCE lows a rise in intra-abdomiIncontinence is defined as the condition nal pressure in the absence of a detrusor conwhere ‘‘involuntary loss of urine is objectively traction (Figure 5). Stress incontinence almost demonstrable and is a social or hygienic prob- exclusively affects women because parity is the lem” (International Continence Society). most important risk factor for the condition The prevalence of incontinence in the general — essentially, the support mechanisms and/or population is highly age dependent and in nerve supply of the pelvic floor may be damthose over the age of 65 years, as many as 10-20% are affected. The recognized risk factors associated with incontinence are listed in Table 2. In the community, many cases of incontinence have a multifactorial etiology.

Several different types of incontinence are recognized.

Types of incontinence.

(1) Urinary urge incontinence is the involuntary loss of urine that follows an uninitiated, uninhibitable detrusor contraction and is generally associated with a sensation of urinary urgency. There are several different causes of involuntary detrusor contraction, but the most common is the condition called ‘‘detrusor instability” FIGURE 5 In the bladder on the left, an increase in intraabdominal pressure (large (DI). The underlying pathophysarrows) is transmitted to the bladder. Stress urinary incontinence is prevented by numerous factors such as reflex contraction of the striated urethral sphincter. Pressure iology of DI is as yet unknown, increase is also transmitted to the intraabdominal urethra (small arrows) which also has but rival hypotheses suggest that the effect of preventing leakage. In the bladder on the right, the bladder neck is open and it is either myogenic and due to the sphincter is deficient resulting in stress urinary incontinence. an abnormality of the detrusor smooth muscle or that it is neuroFrom Versi E, Christmas TJ. Bladder. Health Press; 1998. Reproduced with permission. genic, resulting from abnormaliTABLE 2

General risk factors for incontinence

11

NEUORLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

Neurological causes of incontinence may be classified according to the level of the disease. The most common site at which damage to the nervous system causes bladder dysfunction is in the spinal cord, interrupting connections between the pons and the sacral cord and resulting in disorders of storage and emptying, together with other features of spinal cord disease.

Sub-sacral lesions may also affect both processes and cause dysfunction of other pelvic organs. Suprapontine, i.e. cortical disease can result in failure of appropriate ‘‘switching” so that unlike spinal cord disease the process of bladder emptying is normally co-ordinated, but occurs at an inappropriate time.

FIGURE 6

From Fowler CJ. Classification and investigation of neurovesical dysfunction. In: Whitehead HN, editor. A textbook of genitourinary surgery. Oxford: Blackwell Science; 1998. Reprinted with premission.

Redrawn from Comarr AE. Diagnosis of the traumatic cord bladder. In: Boyarsky S, Editor. The neurogenic bladder. Baltimore: Williams and Wilkins; 1967. pp. 147-52. Courtesy of D Slotton.

KEYPOINTS: à

Although there is a significant prevalence of incontinence in the general population, the prevalence is considerably higher in patients with neurological disease.

12

aged during pregnancy and parturition. In men, stress incontinence may occur following prostate surgery if there is inadvertent damage to the external sphincter or its innervation, since the bladder neck is incised during prostate resection and continence depends on an intact external urethral sphincter.

Stress incontinence may occur in women and men with neurological disease, such as cauda equina lesions, multiple system atrophy and neuropathies affecting the nerves that supply the continence mechanism [8].

(3) Mixed urinary incontinence is not uncommon in women and refers to co-existing stress and urge incontinence. Diagnosis and management can be difficult, but initial therapy is usually focused on the medical treatment of urgency, followed by the conservative management of stress incontinence (e.g. pelvic floor exercises).

(4) Other causes of urinary incontinence: Fistulae (e.g. vesicovaginal and uterovaginal and vesicovaginal fistulae) are seen following prolonged obstructed labor which is a problem in

parts of the world where medical resources are limited and transportation is poor [9]. Overflow incontinence may occur when there is an unrecognized disorder of bladder emptying and the capacity of an insensate, hypotonic bladder is exceeded.

Nocturnal enuresis in children rarely has a physical cause, but congenital anomalies (e.g. ectopic ureter) are encountered occasionally and should always be considered.

Neurogenic incontinence.

Although there is a significant prevalence of incontinence in the general population, the prevalence is considerably higher in patients with neurological disease. Neurological causes of incontinence are best classified with reference to the level of the pathology as suprapontine, pontine, spinal and subsacral (Figure 6).

Suprapontine pathology: The role of suprapontine input is to modulate the switching of storage and voiding. A failure of this will therefore present as a failure of storage and the various neurological causes of this type of bladder dysfunction are discussed in Chapters 8 and 9. Cortical causes of impaired initiation of micturition are rare, but may occur.

Spinal cord disease: Disruption of connections between the pontine micturition centers and the sacral cord is likely to result in both disorders of storage and of emptying. As explained earlier, the reciprocal activity of the sphincter and detrusor during voiding which ensures sphincter relaxation and detrusor contraction, is determined by the PMC. With disconnection from the pontine controlling center, the sphincter contracts with the detrusor resulting in the disorder of detrusor sphincter dyssynergia (DSD) (Figure 7).

Detrusor hyperreflexia following disconnection from the pons is thought to be due

Loss of the reciprocal inhibition of the sphincter and activation of the detrusor following disconnection from the pons results in detrusor sphincter dyssynergia (DSD).

FIGURE 7

to the emergence of a new segmental reflex. In health, the afferent unmyelinated fibers are relatively unimportant in the generation of detrusor contractions and the relevant sensory information is conveyed to the periaqueductal gray in small myelinated fibers.

However, with interruption of the physiological afferent spinal pathways, c-fiber afferents become the main initiators of detrusor contractions (Figure 8) [10].

The contractions so generated also may be poorly sustained.

The combination of a poorly sustained hyperreflexic bladder contraction and DSD lead to a raised post voiding residual (PVR), which will further exacerbate the The emergence of a segmental reflex (resulting in detrusor hyperreflexia), FIGURE 8 urgency associated with DH. the afferent limb of which is subserved by unmyelinated c-fibers following DH with DSD, is the most disruption of spinobulbar pathways by a spinal cord lesion. The administration of common abnormality that occurs intravesical vanilloids can alleviate symptoms through desensitization of the c-fibers. with a spinal cord lesion, accompanied by a variable degree of spastic paraparesis (see Chapter 5).

Sub-sacral: Cauda equina le-sions are the incomplete emptying and pelvic floor weakmain cause of sub-sacral injury to the inner- ness which results in severe incontinence. vation of the lower urinary tract (see ChapPeripheral neuropathy: The innervation of ter 6). Damage to the innervation of the blad- the bladder may be involved in the same der within the cauda equina is likely to affect neuropathic process as affects the innervation both the anterior and posterior sacral roots of the limbs in a peripheral neuropathy. The and therefore affect both the afferent and pelvic plexus can also be damaged by radical efferent innervation of the pelvic organs. The surgery within the pelvis resulting in bladder clinical picture is therefore typically of sen- dysfunction, usually impaired emptying, in sory loss because of damage to the S2-S4 roots the absence of somatic sensory loss. This is which innervate the back of the thighs, peri- discussed further in Chapter 7. anal and perineum region together with loss of voluntary control over both the anal Investigation of urinary incontinence. and urethral sphincter, as well as sexual Patients with neurological disease known responsiveness. However, the second order to cause bladder dysfunction. Basic investiparasympathetic innervation running to the gations and management of incontinence in detrusor from the spinal cord in the cauda patients with established neurological disequina terminates on the parasympathetic ease can be carried out by the neurologist ganglia that lie in the bladder wall. The detru- (Table 3). Of the various tests used in the sor is therefore not denervated, but ‘‘decen- assessment of incontinence (Pullouts 1-5), tralized”, and a range of bladder dysfunc- the most important is measurement of the tions has been described following cauda PVR. equina injury.

Although, in most instances, it may be With spinal dysraphism, there may be correctly deduced from a patient’s complaint both lower and upper motor neuron deficits of urinary urgency that there is underlying because of involvement of the conus, leading detrusor hyperreflexia, the extent of incomto a combination of detrusor hyperreflexia, plete bladder emptying cannot be reliably

13

NEUORLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS:

TABLE 3 à

à

à

Although, in most instances, it may be correctly deduced from a patient’s complaint of urinary urgency that there is underlying detrusor hyperreflexia, the extent of incomplete bladder emptying cannot be reliably ascertained from the history.

Measurement of the PVR is mandatory before commencing treatment with anticholinergic medication in a patient with known neurogenic bladder symptoms.

When a patient fails to respond to anticholinergics, it is advisable to re-assess the PVR and ensure this has not increased.

PULLOUT 1

Minimum urological investigations required

Patients with overt neurological disease þ

Typical lower urinary tract symptoms require: • Post void residual (PVR) measurement • Urinalysis/urine culture • Frequency volume chart

þ

When atypical lower urinary tract symptoms are present also include: • Urine cytology • Kidney, ureter, bladder X-ray • Urodynamics • Cystoscopy • Upper tract imaging (ultrasound or intravenous urogram)

ascertained from the history. If the PVR is raised, persistent urine in the bladder will stimulate hyperreflexic contractions and treatment with increasing doses of anticholinergic medication will not succeed unless some means of improved bladder emptying, namely clean intermittent self-catheterization (CISC) is also used. Furthermore, anticholinergic medication can impair already compromised bladder emptying, further exacerbating symptoms of detrusor hyperreflexia (Figure 9). For this reason, measurement of

Patients without overt neurological disease þ

All patients require: • Urinalysis/MSU • Urine cytology • Frequency volume chart • Post void residual • Urodynamics

þ

And refer to a urologist for: • Kidney, ureter, bladder X-ray • Cystoscopy • Upper tract imaging • Pad testing

the PVR is mandatory before commencing treatment with anticholinergic medication in a patient with known neurogenic bladder symptoms (Figure 10).

Urine microscopy and culture should also be done as recurrent urinary tract infections are common in patients with incomplete emptying, and will exacerbate symptoms considerably.

The need for full cystometry (Pullout 5) in patients with established neurological disease has been questioned. The investigation

Post void residual (PVR)

After the patient has voided normally, the PVR can be measured using ‘‘in-out” catheterization or ultrasound. It is important to ask the patient whether they use any special maneuvers to empty the bladder, such as abdominal straining, bending forward or applying direct pressure to the lower abdominal wall, since, if they do, the figure obtained for the PVR will not be a reflection of detrusor contractility.

When the bladder does not empty completely, the residual urine will exacerbate symptoms of storage dysfunction markedly in two ways. Firstly, it produces a sensation of incomplete bladder emptying, although this may be impaired in patients with neurological disease. Secondly, the time to reach bladder capacity is reduced as the PVR increases. Indeed, patients with neurogenic incontinence will very often have a decreased bladder capacity, so that the time taken to fill the bladder may be very short indeed. The end result is that frequency of micturition, urinary urgency and urge incontinence all worsen with increasing PVR. In addition, as the PVR increases, anticholinergic medications become less effective in controlling symptoms, and when the PVR is in excess of 100 ml, patients should be encouraged to do clean intermittent self-catheterization, if possible (Pullout 6). Measurement of the post micturition residual volume is also recommended before starting anticholinergic therapy, because these drugs decrease detrusor contractility, which adversely affects bladder emptying. When a patient fails to respond to anticholinergics, it is advisable to re-assess the PVR and ensure this has not increased (Figure 10).

Finally, residual urine is likely to become infected — a further reason for measuring the PVR and instituting CISC.

14

is indicated if there is uncertainty as to the pathophysiological basis of a patient’s bladder symptoms, but this is unlikely to be the case in a patient with, for example MS, in whom investigations should be focussed on symptom management. However, if the patient fails to respond to first-lines measures, cystometry may provide useful information regarding the properties of the bladder during filling and voiding.

Cystometry is essential following traumatic spinal cord injury and spina bifida where high resting intravesical pressure PULLOUT 2

Although anticholinergic medication can suppress detrusor hyperreflexia, it may also impair already compromised bladder emptying leading to an increasing post-void residual volume, which, in turn, may exacerbate symptoms of urgency and frequency.

FIGURE 9

might be expected. In these cases, there is a risk of silent chronic upper tract damage as the ureters are unable to empty into a

Frequencyvolume chart

A frequency-volume chart is a self-administered fluid-balance chart that provides an objective record of micturition pattern and is useful in the interpretation of symptoms of storage dysfunction.

Information recorded includes the time and volume of each drink and void and whether the void was preceded by urinary urgency or associated with incontinence (graded as “drops, moderate loss or flooding incontinence�). Pad or catheter usage should also be recorded along with the time of relevant medication (e.g. diuretics or anticholinergics).

15

NEUORLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

PULLOUT 3

Uroflowmetry

Uroflowmetry is a noninvasive test indicated in the assessment of voiding disorders. The patient is asked to void into a modified toilet and urine flow slows the speed of a motor driven spinning wheel in the base, from which the volume of urine voided per unit time (ml/s) is measured. In health, the normal void gives a bell-shaped curve on the uroflow graph (Figure A). The maximum flow rate (Qmax), mean flow (Qave) rate and volume voided (Vura) are assessed in conjunction the uroflow curve. It is not possible to distinguish between low flow secondary to detrusor failure and bladder outlet obstruction. To interpret a uroflow trace meaningfully, the total voided volume should be greater than 150 ml.

(A) Normal uroflow and complete emptying. The detrusor, like all smooth muscle, is unable to contract as rapidly as skeletal muscle, resulting in a smooth bell-shaped uroflow curve.

Therefore, it is generally possible to distinguish between a detrusor generated uroflow curve and one produced by abdominal straining, which undulates characteristically. The abrupt transient increase in flow recorded towards the end of the flow represents the voluntary contraction of the bulbospongiosus muscle, which empties the urethra of urine at the end of a void. Qura is the rate of urine flow in milliliters per second, Vura is the volume voided (547 ml), Qmax is the maximum urine flow in this trace (22.2 ml/s), Qave is the average flow rate (14.5 ml/s).

(B) This figure illustrates a uroflow trace and low urinary flow rate. It is not possible to distinguish whether the low flow rate is secondary to bladder outlet obstruction or detrusor failure. Bladder outlet obstruction can be caused by sphincteric dysfunction (e.g. DSD), benign prostatic obstruction or a urethral stricture. Maximum urinary flow rate (Qmax) is 7.9 ml/s, average urinary flow rate (Qave) is 3.8 ml/s in this patient. The total voided volume (Vura) is 164 ml.

(C) Intermittent and low uroflow trace due to abdominal straining. Note the typical abdominal straining pattern, generated by repeated voluntary contractions of skeletal muscle. Vura (total volume voided) is 415 ml, Qmax is 9.3 ml/s, Qave is 3.7 ml/s.

16

FIGURE 10

Algorithm for first-line treatment of bladder symptoms in a patient with neurological disease [11].

high-pressure bladder, resulting in obstructive uropathy. Cystometry combined with fluoroscopy (‘‘video urodynamics”) would be the investigation of choice in the diagnosis of DSD and ureteric reflux. It is unknown why obstructive uropathy in patients with MS is rare despite the fact that DSD, DH, a reduced bladder capacity and incomplete emptying are common findings in these patients.

Patients who do not respond to medical treatment or who have recurrent urinary tract infections should also have a urological evaluation to rule out conditions such as bladder calculi, ureteric reflux or carcinoma in situ.

Patients with neurological disease in whom the neurogenic basis for bladder dysfunction is uncertain. In patients with established neurological disease who develop urinary symptoms, the question may arise as to whether these new symptoms are part of the neurological condition or indicate a co-existing urological pathology. This can be particularly difficult if the neurological condition

is one that is known to be associated with a bladder disorder. The prime example of this situation is a man with long standing Parkinson’s disease who develops urinary frequency and urgency. It can be difficult to distinguish between a neurogenic and urological cause of bladder dysfunction. Voiding cystometry is indicated to attempt to identify the extent to which outflow obstruction is contributing to the bladder disorder, and referral to a urologist is therefore indicated (see Table 4).

Cystometry may also identify ‘‘sensory urgency” where symptoms of storage disorder are associated with bladder ‘‘hypersensitivity”. This is a disorder of bladder function which is not neurogenic, the etiology of which remains unknown, but can have symptoms somewhat similar to the neurogenic disorder of detrusor hyperreflexia.

Patients without known neurological disease and normal urological investigations.

Patients with marked urinary symptoms will have been thoroughly investigated by a urologist who, on discovering no structural cause, may refer the patient to a neurologist asking if there is an occult neurological basis for the bladder disorder. The clinical examination of such a case should focus particularly on whether or not there is an early spinal cord lesion — since most other causes of a neurogenic bladder are likely to be associated with clinically apparent neurological deficits.

Lower limb sensory evoked potentials are helpful in this respect, more so than the pudendal evoked potential. MR scanning of the cord is likely to be performed in these circumstances, although an abnormality is rarely found if the clinical examination and evoked potentials are all normal.

PULLOUT 4

KEYPOINTS: à

It is not possible to distinguish between low flow secondary to detrusor failure and bladder outlet obstruction on uroflowmetry.

à

Patients who do not respond to medical treatment or who have recurrent urinary tract infections should also have a urological evaluation to rule out conditions such as bladder calculi, ureteric reflux or carcinoma in situ.

à

Patients with marked urinary symptoms will have been thoroughly investigated by a urologist who, on discovering no structural cause, may refer the patient to a neurologist asking if there is an occult neurological basis for the bladder disorder.

Pad testing

A pad test may be performed to quantify objectively urine loss in cases of stress or urge incontinence. It is also useful in the pre-operative assessment of GSI and in assessing the response to anticholinergic therapy in mixed incontinence.

Pre-weighed incontinence pads are worn for intervals — the time over which data is collected varying from 20 minutes to 48 hours, depending on the protocol, during which patients may be asked to perform various exercises. The pads are then reweighed.

17

NEUORLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

TABLE 4

Investigations used in urological assessment of incontinence

Pelvic floor assessment/digital rectal examination of the prostate Frequency-volume chart Pad testing Uroflowmetry and postmicturition ultrasound Urodynamic studies (cystometry +/– fluoroscopy, urethral pressure profilometry) Cystoscopy Urine cytology

KEYPOINTS: à

M3 receptors appear to be more important in bladder contraction.

18

administration of anticholinergics, resulting in reduced frequency and urgency.

Oxybutynin is a tertiary amine with mixed pharmacological activity. In addition to its anticholinergic properties, oxybutynin also has smooth muscle relaxing (antispasmodic or musculotropic) effects. It also has anesthetic properties that may play a role in its reported intravesical action, but it is likely that when administered orally, its clinical effect is based upon its anticholinergic properties alone.

Dose-related side effects include a dry mouth, constipation and rarely blurring of vision and drowsiness. Dry mouth due to blockade of muscarinic receptors in the salivary glands resulting in decreased salivation, is the commonest reason for poor patient compliance. A sustained-release once-daily oral preparation of oxybutynin has recently become available which has a lower incidence of dry mouth, whilst maintaining stable and therapeutic levels of the medication.

Oxybutynin can be directly instilled into the bladder, which seems to lessen side effects, but this therapy has not yet gained universal acceptance, largely because of the inconvenience involved in preparing instillations regularly [13]. However, an intravesical slowrelease drug-delivery system has recently been developed which releases a constant dose of oxybutynin over a period of 1 month. Adequate plasma concentrations are

MANAGEMENT OF NEUROGENIC INCONTINENCE (TABLE 5) Oral therapy. Detrusor muscle contraction, whether physiological or pathological is mediated largely through parasympathetic cholinergic activation of muscarinic receptors. Thus the treatment of those symptoms resulting from detrusor hyperreflexia, such as urgency and frequency, are appropriately treated by antimuscarinic, anticholinergics.

There are five different subtypes of muscarinic receptors (M1-M5) present in different proportions in the end organs innervated by the parasympathetic nervous system, namely the smooth muscle of the cardiovascular, gastrointestinal, genitourinary and respiratory systems, the ciliary muscles and the salivary glands. Unwanted blockade of the cholinergic receptors in these target organs accounts for the side effects experienced with all TABLE 5 Management of neurogenic incontinence these drugs. M2 and M3 First-line treatment options receptors have been iden• Oral anticholinergics tified using molecular biological techniques in the • CISC (when PVR >100 ml) detrusor, with M2 receptors Second-line treatment options predominating (M2:M3 = • DDAVP 3:1). However, M3 receptors • Treatments under evaluation (intravesical oxybutynin, appear to be more imporresiniferatoxin, botulinum toxin) tant in bladder contraction.

It is likely that muscarinic Late treatment options receptor subtypes M1, M4 • Indwelling catheters (suprapubic vs. urethral drainage) and M5 are also present in • Pads the bladder. Contraction of • Surgery (e.g. augmentation cystoplasty or urinary diversion) the detrusor muscle is inhibin selected cases ited and bladder capacity increases following the

achieved, but the side effects are less than those that occur with comparable oral dosages, thought possibly to be due to lack of intestinal enzymatic conversion which is responsible for the formation of the metabolite causing side effects.

Oxybutynin has been found to be safe and effective for long-term use.

Tolterodine is an anticholinergic with similar efficacy to oxybutynin, but has less in the

PULLOUT 5

way of side effects, dry mouth, in particular.

This is thought to be because it has a greater affinity for detrusor than salivary gland muscarinic receptors.

Darafenacin is a highly selective M3 blocker currently undergoing clinical trials.

The activation of muscarinic receptors in the detrusor muscle results in both the influx of calcium and its release from intracellular stores — calcium channel blockade is, there-

KEYPOINTS: à

The detrusor pressure (Pdet) is derived by subtracting the intra-abdominal pressure (Pabd) from the intravesical pressure (Pves).

Cystometry

Cystometry [12] is an invasive test requiring urethral catheterization to measure intravesical pressure as well as measurement of intra-abdominal pressure via a fine intrarectal pressure line.

The test is divided into two phases: filling and voiding. After the patient has voided normally, a filling catheter and pressure recording line is passed into the bladder through the urethra and the PVR volume is recorded. The catheter is then connected to a manometer so that intravesical pressure can be measured (cm water). A catheter is also inserted into the rectum and connected to a manometer to measure the intra abdominal pressure. The detrusor pressure (Pdet) is derived by subtracting the intra-abdominal pressure (Pabd) from the intravesical pressure (Pves).

Cystometry may be performed in the lying, sitting or standing position. At the beginning of the test resting Pdet should be between 0 and 5 cm H2O and Pabd and Pves should be between 20 and 50 cm H2O. The Pabd and Pves will vary in relation to patient position — sitting or standing increases the weight of the abdominal viscera on the bladder. Ideally, the filling phase should be performed with the patient in the lying position, and prior to voiding, the patient is repositioned into either the standing or sitting position, although this is often difficult in patients with poor mobility and detrusor hyperreflexia.

The bladder is filled with warmed saline at slow-, medium- or fast-fill rates. Slow-fill rates (i.e. less than 20 ml/min) are preferred in patients with neurogenic bladder problems because unstable contractions can be provoked by fast-fill rates. The patient is instructed to communicate any bladder sensations to the investigator. Valsalva straining and coughing at regular intervals during filling is used to assess urethral competency. Whenever the patient feels as if he or she would normally void, the pump is stopped, the filling catheter is removed and the patient voids into a uroflowmeter with the pressure lines in situ. Thus information on bladder storage functions, namely sensation, capacity, detrusor compliance and stability as well as urethral competency is provided in the filling phase.

During cystometry, the patient must not try to suppress an urge or the pump stopped in order to allow the urge to settle. It must be accepted that certain artifacts will limit the result, but the investigator should aim to reproduce the patient’s troublesome symptoms.

(A) A cystometric trace demonstrating normal bladder filling. The patient was filled in the standing position with 0.9% saline at a rate of 30 ml/s and the point of first sensation of filling (FD) is marked on the trace. The pump was stopped when he had a normal desire to void (ND) and the total volume infused (Vinfus) was 254 ml.

The patient was asked to cough at regular intervals to check the accuracy of the pressure recordings (c = cough).

19

NEUORLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

Pullout 5 continued

þ

(B) The patient (in A) is now ready to void. The bladder filling catheter is removed prior to voiding, but both pressure recording catheters are left in place. Urine flow (Qura) is recorded by a uroflowmeter and during the flow, the detrusor pressure (Pdet) is observed.

Any abdominal straining during the flow can be identified and quantified.

Qmax was 20.5 ml/s, Pdet at Qmax was 49 cm/H2O in cases of bladder outlet obstruction this pressure would be much higher, until decompensation of the detrusor occurs. This is a normal study.

(C) Cystometrogram trace demonstrating detrusor hyperreflexia (DH) and urge incontinence. After 118 ml had been instilled (Vinfus), the patient experienced urgency (UR) that was associated with an uninitiated, uninhibitable detrusor contraction (Pdet) and involuntary leakage of urine occurred (Qura).

Pves, intravesical pressure; Pabd, intraabdominal pressure; Pdet, detrusor pressure; Qura, urine flow.

KEYPOINTS: à

CISC has transformed the uroneurological care of patients with all types of neurogenic bladder dysfunction.

20

fore, another potential target for pharmacological intervention in the treatment of DH. Propiverine is a recently introduced drug that has both anticholinergic and calcium channel blocking properties.

In patients with typical symptoms of storage dysfunction and a PVR less than 100 ml, anticholinergic drug therapy may be commenced see Figure 10 [14].

Clean intermittent self-catheterization.

CISC was introduced in 1972 and has been shown to be safe and effective method of emptying the bladder in patients who have a raised PVR. Efforts to treat detrusor hyperreflexia with anticholinergics or other treatments are unlikely to succeed when the PVR is in excess of 100 ml, since residual urine reduces the interval between unstable bladder contractions. Draining a residual will therefore help to reduce symptoms of frequency

and urgency (see Pullout 1). It is true to say that CISC has transformed the uroneurological care of patients with all types of neurogenic bladder dysfunction (see Pullout 6 and Table 6) as formerly these patients would have been offered continuous catheter drainage.

The commencement of a CISC regimen is a significant intrusion into a patient’s daily routine, but many patients adapt well to it because of the improvement in symptoms it may afford. The required frequency of catheterization is largely determined by symptoms.

For example, many patients will not empty well after the first void in the morning and will benefit from catheterization at this time.

Likewise, they should perform CISC before going to bed as nocturnal frequency may so be greatly reduced. Catheterization at variable times during the day, such as prior to leaving

home or before a meeting or social event, may also help control symptoms.

Importantly, in addition to alleviating bladder symptoms, CISC may help reduce the risk of urinary tract infection, acquired ureteric reflux and obstructive uropathy, all of which are associated with high PVR (see Pullouts 1 and 6). There is, however, an accepted risk of urinary tract infection from using the technique [15].

Desmopressin. A common problem is nocturnal frequency and nocturnal incontinence secondary to severe DH. Despite use of anticholinergic agents, some patients may continue to be woken by urinary urgency. An effective agent for treatment of nocturia is desmopressin (DDAVP), which is an analog of the posterior pituitary hormone, antidiuretic hormone (ADH) (see Pullout 7).

Future treatments. Animal experimental studies on the mechanism of DH following spinal cord injury have shown that the neural mechanism for this appears some weeks after acute spinal cord transection and is due to the emergence of a new functional pathway which operates at a sacral segmental level rather

PULLOUT 6

TABLE 6

Advantages of CISC over indwelling catheterization

Bladder capacity can be better preserved The patient is independent to empty the bladder There is no permanent catheter (which requires continuous care) Bladder neck erosion and prostatitis are avoided Interference with sexual function is avoided Urethral trauma/strictures/diverticuli and fistulae are avoided Catheter blockage and bypassing (leakage around the catheter) are avoided Catheter-related calculi are avoided The incidence of urinary tract infection/epididymo-orchitis and septic episodes is less than in those on CISC There is probably a decreased risk of long-term, catheter associated bladder cancer

than trans-spinally (Figure 8). This led to the therapeutic use of the selective c-fiber neurotoxin, capsaicin to ‘‘de-afferent” the detrusor muscle in cases of spinal hyperreflexia [16].

Early reports of the success of resiniferatoxin (RTX), an analogue of capsaicin to treat detru-

Clean intermittent self-catheterization (CISC)

The rationale of CISC should be explained and the importance of adhering to proper hygienic (but not sterile) technique. Patients must also be assured that there is no risk of damage to the external urethral sphincter by passing a catheter or ultimate ‘‘dependence” on the catheter to void — two common patient concerns. Urethral false passages and bladder perforation are extremely rare complications. Introducing infection may also be a problem but the benefits of regular CISC far outweigh the complications of its use.

A dedicated nurse who will teach CISC and provide follow-up for advice and assistance is critical to success with teaching CISC. The patient must also be motivated to perform it regularly. Hygiene is especially important — the patient must have access to a supply of clean tap water for hand washing and preparation and cleansing of the catheters before and after use.

The patient gently cleanses the external urethral meatus and slowly advances the lubricated catheter into the bladder to drain the urine. Patients get used to passing catheters, although the time this takes depends on many factors including the patient’s manual dexterity, eyesight and also attitude.

Catheter size varies in length (according to sex) and diameter (10-14 Ch are most commonly used). Catheters suitable for children are also available. Smaller sized catheters will drain urine more slowly and some patients therefore prefer a larger diameter. Catheters may be single-use or reusable: reusable catheters are rinsed under a tap before use and coated with a water-based lubricant (e.g. ‘‘KY Jelly”). Single-use catheters have a hydrophilic coating that is activated on contact with tap water and which acts as a lubricant. There is no evidence to suggest that there is an increased risk of infection when reusable catheters are used instead of the single-use variety.

Many patients with neurological disease will simply be unable to catheterize due to decreased manual dexterity, leg spasms or mobility and their carer may then be taught the technique. Some patients will not have carers who are prepared to do this and some patients may be unwilling to do self-catheterization because of a dislike of the principal. Attitude is clearly very important in determining the success of this form of management.

21

NEUORLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

PULLOUT 7

Desmopressin (DDAVP)

Desmopressin promotes increased water reabsorption at the collecting tubule of the kidney, resulting in reduced nocturnal urine production. The use of DDAVP can result in hyponatremia and should be used with great caution in the elderly. All patients should be warned that if they develop headache, general malaise or swelling of the face or ankles they should discontinue the medication and serum sodium should be checked. DDAVP is suitable for use in younger patients, including children with DH. Whilst DDAVP is not intended for use during the day, patients with DH may occasionally use the drug prior to meetings or social events, when they wish to have the added security of being free from urinary urgency. It is, however, important to stress that DDAVP should only be used once in 24 hours.

sor hyperreflexia have promising implications for development of therapies in the future (see Pullout 8). It may well be that treatments based on this principle of ‘‘de-afferentation” will only be effective in detrusor hyperreflexia of spinal origin and not for DH of suprapontine origin or in cases of detrusor instability [17].

Reports of intravesical injections of botulinum toxin in patients with severe DH are showing interesting results.

Indwelling catheters. With progression of a disabling, neurological disease, decreased mobility and cognitive decline may make the combination of anticholinergics and CISC no longer possible. At this point, long-term catheterization is unavoidable.

PULLOUT 8

Patients may have either a urethral catheter or suprapubic catheter. It is not unreasonable to insert a urethral catheter initially and if and when any of the common complications of urethral catheterization arise, arrange for a urologist to insert a suprapubic catheter. Problems associated with indwelling urethral catheters include catheter blockage and ‘‘bypassing” (leakage around the catheter secondary to a detrusor contraction, which generally occurs when the catheter is blocked). Catheter blockage is caused by encrustation of the catheter by crystals present in the urine, that adhere to any foreign body (the catheter). In addition, solutes in the urine can precipitate out of solution forming calculi, given certain physiological circumstances (e.g. urine pH or osmolality); and the presence of a foreign body is an important factor in this process. Bypassing is best managed by changing the catheter more frequently and may require the prescription of anticholinergics.

Urethral catheters may cause bladder neck erosion, sphincter damage and urethral trauma, which are difficult problems to manage in debilitated women.

A further disadvantage of urethral catheters is that they interfere with sexual function which is especially important for younger patients, and this must be taken into consideration.

Suprapubic catheterization involves the insertion of a catheter into the bladder directly through a small surgical incision in the lower

Intravesical vanilloids

The intravesical administration of vanilloids (capsaicin and RTX) in patients with spinal DH results in a reduction of suburothelial nerve densities and ultrastructural changes in unmyelinated C-fibers of the bladder. The vanilloid receptor (VR) is a non-selective cation channel present on unmyelinated afferent nerves. The VR integrates noxious stimuli at a cellular level and thus, in vitro, the action of the VR is facilitated by changes in acidity, rapid changes in temperature, bacterial lipopolysaccharide and the vanillyl-containing molecules, including capsaicin and RTX. RTX has 1000 times greater affinity for the vanilloid receptor and has less initial side effects compared to capsaicin (e.g. suprapubic pain or burning urethra).

Capsaicin is derived from the capsicum red hot chilli pepper and RTX from the dried resin of the cactus Euphorbia resinifera.

Clinically, intravesical instillation of vanilloids is associated with an increase in bladder capacity and an improvement in the symptoms of spinal DH — frequency, urgency and urge incontinence. The effect of intravesical vanilloid treatment lasts for a variable length of time, usually 3-6 months. Early phase clinical trials of RTX are currently in progress.

22

abdominal wall. This short procedure is performed under cystoscopic control and requires a brief general, spinal or local anesthetic.

Patients often find suprapubic catheters easier to manage and many of the long-term complications seem less. The incidence of urine infection is probably equal with both methods of drainage.

In those where catheterization has been used for 5 years or more, annual cystoscopy is advised to exclude squamous cell carcinoma [18].

Surgical options. A urinary diversion procedure may be required in certain patients.

An incontinent vesicostomy involves the construction of a stoma on the lower abdomen from a segment of ileum that is connected to the bladder, enabling free drainage of urine into a urostomy bag. Catheterizable stomas can be surgically fashioned in patients who are able to perform catheterization. This procedure has the advantage in that it preserves the bladder and the ureterovesical junction.

When the bladder cannot be used (e.g. the small shrunken bladder as may occur in spina bifida or co-existing genuine stress urinary incontinence), an ileal conduit urinary diversion is an alternative. This involves the construction of a stoma and intra-abdominal reservoir made of ileum, into which the ureters drain directly [19]. A urostomy bag is required to collect the free draining urine.

Where surgery is being considered, a number of factors including disability, urological status and life expectancy should be carefully considered.

In those with outlet obstruction from DSD who cannot perform CISC, surgical sphincterotomy or the placement of sphincteric stents are options. However, these procedures require adequate detrusor contraction to facilitate emptying. Urethral sphincterotomy involves the endoscopic ablation of the voluntary urethral sphincter, which allows enhanced emptying and lower bladder pressures, but is rarely performed nowadays as CISC should be possible in most cases. A sphincteric stent maintains urethral patency and adequate urine flow. Male patients will subsequently require the use of a condom catheter because of persistent leakage, whereas women will require pads or diapers.

Artificial urinary sphincters (AUS) are used in selected patients with incontinence secondary to sphincteric weakness (e.g. spina bifida).

Following either a trans perineal or suprapubic surgical approach, an inflatable cuff is placed around the urethra. A reservoir, containing fluid and a pump are attached to the cuff, which is then filled and drained to maintain continence and empty the bladder as required.

The complications of these devices include infection, erosion and mechanical failure. It is, however, contraindicated to insert an artificial sphincter in the presence of marked vesicoureteric reflux, which is a common problem in those with spinal dysraphism [20]. Whilst the AUS is a frequently used surgical option in patients with spina bifida, the procedure has not gained much popularity in the adult neurogenic bladder population.

Carefully selected patients with non-progressive neurological disease and low-capacity, neurogenic bladders may benefit from augmentation cystoplasty both symptomatically and with regard to preservation of upper tract function. This procedure involves increasing the bladder capacity using a patch made from ileocecum, ileum, colon, or stomach and thus decreasing intravesical pressure. This is a major operation with significant short- and long-term complications and should not be considered in those who are deteriorating neurologically. Because impaired emptying is likely to ensue, the patient must be warned that CISC is likely to be necessary [21].

URINARY RETENTION Urinary retention may be due either to mechanical obstruction, failure of the bladder neck or sphincter to relax, or failure of the detrusor to contract. Urinary retention may be either complete or partial and may be acute or chronic in onset.

Complete urinary retention. The most common causes of complete urinary retention are urological and it is unlikely a neurologist will be asked to see a patient in complete urinary retention who has not undergone urethrocystoscopy to exclude a local urological lesion. Acute urinary retention from a urological cause is usually painful, whereas a neurological lesion should be suspected if acute complete retention is painless. The common gen-

23

NEUORLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

TABLE 7

Causes of complete urinary retention

General •

Constipation

•

Postoperative — (general and epidural anesthesia)

•

Drug-induced (tricyclic antidepressants, anticholinergics, ganglionic blocking agents)

Urological •

Benign prostatic hyperplasia

•

Carcinoma of the prostate

•

Urethral stricture

•

Clot retention Calculus

Neurological •

Acute spinal shock phase — spinal cord injury or transverse myelitis

•

Spina bifida, myelodysplasia, sacral agenesis

•

Cauda equina lesion

•

Herpes zoster

•

Diabetic neuropathy and other small fiber neuropathies

•

Tabes dorsalis

•

Pontine pathology (rare)

•

Cerebral disease (rare)

•

Multiple system atrophy

•

Fowler’s syndrome (isolated urinary retention in young women)

the young women also have polycystic ovaries. The onset of retention may follow an operation, not necessarily performed in the pelvis, or childbirth, and spontaneous recovery is not common. The diagnosis necessitates examining the striated urethral sphincter with a concentric needle electrode (see Chapter 1) although other investigations, such as a raised urethral pressure profile, may also indicate a local sphincter abnormality.

Other causes of urinary retention have yet to be explained and non-urological retention in young men who have preserved sexual function (and some young women who do not have the sphincter EMG abnormality) remains an enigma. Imaging and neurophysiological investigations fail to reveal an abnormality in these patients and it is assumed the problem must be either in the detrusor muscle or its innervation.

Partial urinary retention (or incomplete emptying). Partial urinary retention or incomplete bladder emptying, is a common feature of the neurogenic bladder and Table 8 lists those neurological conditions in which a raised postmicturition residual volume is often found.

The importance of recognizing incomplete emptying has already been stressed (see Pullout 1) since, if this occurs in combination with detrusor hyperreflexia, the symptoms of urgency and urge incontinence can be resistant to treatment until some means of effectively emptying the bladder is found.

eral, non-neurological and neurological causes of complete retention are listed in Table 7.

It will be evident from Table 7 that other accompanying neurological symptoms and signs would be expected if the problem were neurogenic. The exception to this is the acute onset Neurological disorders commonly TABLE 8 of urinary retention in a young associated with incomplete bladder emptying women. Fowler and colleagues recognized a syndrome affecting Post-traumatic spinal cord disease young women who presented with Progressive spinal cord disease, e.g. multiple sclerosis massive, painless urinary retention Peripheral neuropathy (small fiber) in whom sphincter EMG showed there was a myotonic-like activity Cauda equina lesion [22]. It was postulated that the disMultiple system atrophy order caused a primary failure of sphincter relaxation and many of

24

REFERENCES [1]

Blok B, Weer H, Holstege G. Ultrastructural evidence for a paucity of projections from the lumbosacral cord to the pontine micturition centre or M-region in the cat: a new concept for the organization of the micturition reflex with the periaqueductal gray as central relay. J Comp Neurol 1995;359:300-9.

Experimental study of afferent innervation of bladder in cat.

[2]

de Groat W. Central neural control of the lower urinary tract. In: Bock G, Whelan J, editors.

Neurobiology of incontinence. Chichester: Wiley; 1990. p. 27-56.

Review chapter summarizing current concepts of neurology of bladder control.

[3]

Holstege G, Griffiths D, de Wall H, Dalm E. Anatomical and physiological observations on supraspinal control of bladder and urethral sphincter muscles in the cat. J Comp Neurol 1986;250:449-61.

Experimental studies in the cat showing two separate centres for bladder control in pons.

[4]

Blok B, Willemsen T, Holstege G. A PET study of brain control of micturition in humans. Brain 1997;120:111-21.

First study using PET to study micturition in healthy male volunteers.

[5]

Andrew J, Nathan PW. Lesions of the anterior frontal lobes and disturbances of micturition and defaecation. Brain 1964;87:233-62.

Study of frontal lobe lesions causing bladder disorders.

[6]

Fowler CJ. Neurological disorders of micturition and their treatment. Brain 1999;122:1213-31.

Review of neurological causes of bladder dysfunction.

[7]

de Groat W. A neurologic basis for the overactive bladder. Urology 1997;50,S6A:36-52.

Recent review of causes of bladder overactivity.

[8]

DeLancey JOL, Fowler CJ, Keane D, Macarak E, Mostwin J, Elbadawi A et al. Pathophysiology. In: P Abrams P, Wein A, editors. Incontinence. Health Publication Ltd; 1999. p. 227-94.

Chapter on the causes of incontinence with contributions from multi-expert team, prepared after the first WHO meeting on Incontinence held in Monaco in 1998.

[9]

Danso KA, Martey JO, Wall JJ, Elkins TE. The epidemiology of genito-urinary fistulae in Kumasi, Ghana, 1977-1992. Int Urogynecol J 1996;7:117-20.

An important cause of incontinence following obstructed labor.

[10] de Groat W, Kawatani T, Hisamitsu T, Cheng C, Ma C, Thor K et al. Mechanisms underlying the recovery of urinary bladder function following spinal cord injury. J Auton Nerv Syst 1990;30:S71-8.

Emergence of C mediated reflex initiating bladder contractions in chronic spinal cats.

[11] Fowler CJ. Investigation of the neurogenic bladder. J Neurol Neurosurg Psychiatry 1996;60:6-13.

Importance of measuring post micturition residual volume in patients with neurogenic incontinence.

[12] Abrams P, Blaivas J, Stanton S, Anderson J. The standardisation of terminology of lower urinary tract function. Scand J Urol Nephrol 1988;114(Supplement).

[13] Madersbacher H, Knoll M. Intravesical application of oxybutynin: mode of action controlling detrusor hyperreflexia. Eur Urol 1995;28:340-4.

[14] Wein A. Neuromuscular dysfunction of the lower urinary tract and its treatment. In: Walsh PC, Darracott AR, Vaughan E, Wein AJ, editors. Campbell’s urology: Saunders; 1998. p. 953-1006.

References continued

25

Ăž

NEUORLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

References continued

Ăž

[15] Bakke A, Irgens L, Malt U, Hoisaeter P. Clean intermittent catherisation performing abilities, aversive experiences and distress. Paraplegia 1993;31:288-97.

A large study of patients on CISC. [16] De Ridder D, Chandiramani V, Dasgupta P, Van Poppel H, Baert L, Fowler CJ. Intravesical capsaicin as a treatment for refractory detrusor hyperreflexia: a dual centre study with long-term followup. J Urol 1997;158:2087-92.

[17] Cruz F, Guimaraes M, Silva C, Reis M. Suppression of bladder hyperreflexia by intravesical resiniferatoxin. Lancet 1997;350:640-1.

[18] Hackler RN. Long-term suprapubic cystostomy drainage in spinal cord injury patients. Br J Urol 1982;54:54-120.

[19] Woodhouse CRJ, Reilly JM, Strachan J, Malone PR. The Mitrofanoff principle for continent urinary diversion. Br J Urol 1989;63:53-7.

Surgery for chronic retention.

[20] Scott FB, Fishman IJ, Shabsigh R. The impact of the artificial urinary sphincter in the neurogenic bladder on the upper urinary tracts. J Urol 1986;136:636-42.

[21] Mundy AR, Stephenson TP. Clam ileocystoplasty for the treatment of refractory urge incontinence. Br J Urol 1985;57:641-6.

[22] Fowler CJ, Christmas TJ, Chapple CR, Fitzmaurice PH, Kirby RS, Jacobs HS. Abnormal electromyographic activity of the urethral sphincter, voiding dysfunction, and polycystic ovaries: a new syndrome? Br J Med 1988;297:1436-8.

Proposed explanation for urinary retention and obstructed voiding in neurologically normal young women.

26

CHAPTER 3

KEYPOINTS:

CONSTIPATION AND FECAL INCONTINENCE INTRODUCTION The distal colon, rectum and anus together serve to store and eliminate feces. In neurological disease either of these functions may be affected independently causing constipation, fecal incontinence or a combination of both problems. Constipation is a decreased frequency of bowel actions (less than one every 3 days) that may also be associated with excessive straining during the passage of stool. Fecal incontinence is the involuntary or inappropriate passage of stool; the term ‘‘anal incontinence” includes incontinence of flatus also.

Lack of bowel control can have devastating effects upon the individual, lowering their self-esteem and confidence. Patients who have this problem may restrict their lives and become socially isolated. Constipation and fecal incontinence can be a cause of considerable morbidity (e.g. fecal impaction or skin excoriation) and can present a significant challenge to the healthcare team, both in terms of nursing issues and therapeutic strategy.

From the diagnostic viewpoint, it can be difficult to distinguish between the impact of neurological diseases on bowel function and other contributing factors, such as side effects of medication or chronic immobility. Whilst some data exist relating to the prevalence and pathophysiology of bowel dysfunction in neurological disorders, there have been few trials on practical management issues.

PREVALENCE Constipation is a common complaint affecting approximately 5% of Western populations.

Fecal incontinence affects men and women of all ages, but increases with age. Daily or weekly episodes of incontinence occur in about 2% of the adult population and in about 7% of healthy independent adults over the age of 65. The incidence of the problem increases with infirmity and a third of elderly people in hospital or residential care are incontinent of stool [1].

The incidence of bowel symptoms in neurological patients is considerably higher than in the general population as shown in Table 1.

Chapters 5-9 describe bowel disorders in specific neurological disorders and this topic is also reviewed in a recent chapter by Norton and Henry [2].

Confusingly, in the colorectal literature, the term ‘‘neurogenic incontinence” is often used to describe fecal incontinence secondary to pudendal nerve damage following childbirth, rather than secondary to major neurological disease.

à

The distal colon, rectum and anus together serve to store and eliminate feces.

à

Whilst some data exist relating to the prevalence and pathophysiology of bowel dysfunction in neurological disorders, there have been few trials on practical management issues.

ANATOMY The gastrointestinal tract may be viewed as a continuity of organ systems with specific functions (i.e. mouth, esophagus, stomach, paraintestinal organs, small and large bowel and anus). The striking homogeny in innervation and vascular supply that transcends these specific functions is related to its embryological development.

Pelvic floor. The anatomy of the pelvic floor musculature, and its importance in the support of the pelvic organs is discussed in detail in Chapter 2. Puborectalis, which is one of the named muscles that comprise the pelvic floor, plays an important role in both fecal continence and defecation. The muscle

TABLE 1

Incidence of bowel dysfunction in patients with neurological disease Constipation

Cerebro-vascular accidents

Fecal incontinence 30-40% at admission 9% at 6 months [3]

Parkinson’s disease

50% [4]

Multiple sclerosis

43% [5]

51% [5]

Spinal cord injury

17% [6]

11% weekly 50% occasionally [6]

27

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

FIGURE 1

The internal and external anal sphincters.

From Bendall MJ. Fecal incontinence. In: The Wallace Teaching Pack for Continence Advisors, Wallace; 1989. Reproduced with permission.

KEYPOINTS: à

The tone of the puborectalis maintains the so-called ‘‘anorectal angle” which is vital for continence.

Full relaxation of the puborectalis is necessary for normal bowel emptying.

28

originates at the pubis and passes posteriorly on either side of the pelvic viscera, to wrap around the junction of the lower one third of the rectum and the anal canal, and is closely related to the external (voluntary) anal sphincter (Figure 1) [7]. The tone of the puborectalis maintains the so-called ‘‘anorectal angle” which is vital for continence. Full relaxation of the puborectalis is necessary for normal bowel emptying. The perineal body consists of fibromuscular tissue and marks the point of insertion of most of the pelvic floor muscles. In the female, the perineal body lies between the vagina and anus and is anterior to the anus in the male. Damage to this structure (which occurs during parturition) is associated with fecal incontinence.

Anal sphincters. The anus is made up of internal (involuntary) and external sphincters (voluntary). The internal sphincter is comprised of smooth muscle, arranged in inner circular and outer longitudinal layers. The external sphincter is comprised of striated, volun-

tary muscle closely related to the puborectalis muscle (Figure 1).

PHYSIOLOGY Colonic function. The large intestine starts at the ileocecal valve and consists of the cecum, colon and rectum. The principal role of the proximal half of the colon is the absorption of water and electrolytes. Approximately 2 liters of fluid daily passes into the colon from the small intestine and absorption takes place mainly in the right colon so that only 150 ml of fluid is lost in the feces each day.

The muscle wall of the large intestine consists of an inner circular and incomplete outer longitudinal layer (tenia). Parallel bundles of individual muscle cells are connected by gap junctions that facilitate the transmission of impulses in all directions, but more rapidly in the orientation of the bundles. Thus each muscle layer acts as a syncytium. Two distinct types of colonic contraction occur: mixing movements and mass movements. Mixing movements are

powerful contractions of both the outer longitudinal and inner circular muscle layers and serve to facilitate absorption and stool formation by repetitive moulding of the semi-solid feces. Mixing movements are not peristaltic, although some anal-ward movement of the fecal material does occur, particularly in the

proximal colon. Colonic ‘‘mass movements” are peristaltic contractions that propel the feces towards the rectum and are predominate from the transverse colon onwards.

Defecation (Figure 2) [8]. Fecal material stored in the colon is propelled past the rectosigmoid sphincter, a so-called ‘‘physiologi-

KEYPOINTS: à

Two distinct types of colonic contraction occur: mixing movements and mass movements.

Control of the anorectum during continence and defecation. Until the act of defecation begins, the rectum is kept empty by tonic concentration of the rectal wall and the rectosigmoid sphincter. Thus intrarectal pressure is higher than the intrasigmoid pressure and the rectal material remains in the sigmoid colon. The rectum also exhibits retropulsive peristaltic activity to return feces back into the colon. Rectal filling eventually occurs when a series of powerful colonic mass movements propel the feces distally into the rectum. There is an awareness of the need to defecate when the rectum is distended to approximately 150 ml, at which time the intrarectal pressure is approximately 25 cm H2O. At this stage, continence is maintained by the anorectal angle, formed by the puborectalis muscular sling, and the internal and external anal sphincters. Continued distension of the rectum initiates the rectoanal inhibitory reflex, which results in internal sphincter relaxation and opening of the proximal anal canal, with a consequent drop in intra anal pressure. Reflex contraction of the rectum is then combined with voluntary Valsalva straining and relaxation of the puborectalis muscle and external sphincter. The traces demonstrate recordings of pressures in the colon, rectum and anus during the events described above.

FIGURE 2

From Craggs MD, Vaizey CJ. Neurophysiology of the bladder and bowel. In: Fowler CJ, editor.

Neurology of bladder, bowel and sexual dysfunction. Butterworth Heinemann; 1999. Reproduced with permission.

29

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: à

Distension of the distal rectum initiates afferent signals that are associated with a conscious sensation of needing to defecate (at a volume of 150 ml).

à

The rectoanal inhibitory reflex results in internal anal sphincter relaxation (a decrease in anal canal pressure is observed on manometry) and voluntary relaxation of the external sphincteric and pubococcygeal muscles.

à

Stimulation of the enteric plexi by parasympathetic fibers increases the overall activity of the gastrointestinal tract by promoting peristalsis and increasing local blood flow and intestinal secretion.

cal sphincter” into the normally empty rectum by colonic mass movements prior to defecation. Distension of the distal rectum initiates afferent signals that are associated with a conscious sensation of needing to defecate (at a volume of 150 ml, Figure 3) [7]. These afferent signals also spread through the myenteric plexus to initiate further contractions of the descending and sigmoid colon and rectum. If it is judged to be appropriate, a final series of neurologically controlled events are initiated and defecation occurs. Using volitional Valsalva straining, an increase in intraabdominal pressure is produced, which is followed by pelvic floor descent and the rectoanal inhibition reflex is initiated. The rectoanal inhibitory reflex results in internal anal sphincter relaxation (a decrease in anal canal pressure is observed on manometry) and voluntary relaxation of the external sphincteric and pubococcygeal muscles. When pubococcygeal relaxation occurs, the anorectal angle increases, thus facilitating the passage of stool. Defe-

The effect of progressive rectal distension on sphincter closing pressure. In this example, rectal distension to 50 ml is accompanied by an initial rise in sphincter tone. However, the rectoanal reflex results in partial relaxation of the internal sphincter, when a decrease in sphincter closing pressure (intra anal pressure) is observed.

Distension to 100 ml provokes even stronger sphincteric contraction, with higher sphincter closing pressure, to maintain continence. Despite these high pressures, the rectoanal inhibitory reflex again causes internal anal sphincter relaxation. Note also that sphincter tone does not return to previous levels. When a critical volume of 150 ml is reached, the reflex causes complete relaxation of the internal anal sphincter. Continence at this point depends primarily on external anal sphincter tone.

FIGURE 3

From Bendall MJ. Fecal incontinence. In: The teaching pack for continence advisors, vol I. Portex, Kent: SIMS; 1987-1991. Reproduced with permission.

30

cation can be delayed by contraction of the external anal sphincter and the urge to defecate gradually decreases in intensity over a period of minutes.

NEUROLOGICAL AND HORMONAL CONTROL OF THE GASTROINTESTINAL TRACT Enteric innervation. The gastrointestinal tract has its own intrinsic innervation, the enteric nervous system, which is comprised of an outer myenteric plexus and an inner submucosal plexus. The former regulates smooth muscle activity, whilst the latter influences the secretory and absorptive functions of the mucosa as well as local blood flow. The enteric nervous system can function in isolation, but some modulation by both the parasympathetic and the sympathetic nervous systems occurs.

Afferent nerves that originate in the epithelium and gut wall are also connected to the enteric nervous system, the prevertebral ganglia and the vagus nerve. The afferent nerves are stimulated by mucosal irritation, gut distension and specific chemicals in the gut (e.g. cholecystokinin) and can elicit local reflexes or convey information to other centers [9].

The secretion of hormones (e.g. thyroxin) and parahormones (e.g. vasoactive intestinal polypeptide), which follows various stimuli, has a significant effect on bowel function.

Parasympathetic innervation. The parasympathetic innervation of the colon is divided into cranial (vagus nerve) and sacral (pelvic nerves) divisions. The vagus nerve innervates the foregut and midgut, ending at the splenic flexure. The pelvic nerves originate from the second, third and fourth divisions of the sacral parasympathetic outflow and innervate the hindgut (descending and sigmoid colon and the anorectum). The density of parasympathetic innervation is greater for the sacral division compared to the cranial outflow. Stimulation of the enteric plexi by parasympathetic fibers increases the overall activity of the gastrointestinal tract by promoting peristalsis and increasing local blood flow and intestinal secretion. The parasympathetic nervous system is also an integral component of the defecation reflex.

Sympathetic innervation. The sympathetic innervation of the gastrointestinal tract originates in the thoracolumbar outflow (T5-L2).

After leaving the spinal cord, the sympathetic fibers pass through the paravertebral ganglia to relay in the celiac and mesenteric ganglia.

Postganglionic sympathetic fibers terminate principally on the enteric nervous system.

Contraction of the internal anal sphincter is responsible for resting anal pressure and is probably regulated by the sympathetic nervous system. The sympathetic nervous system inhibits the gastrointestinal tract through the inhibitory effect of noradrenaline on the enteric nerves and also causes vasoconstriction when appropriate.

Somatic innervation. The innervation of the external sphincter is via the pudendal nerve (S2 [3,4]). Cutaneous sensation from the perianal area and perineum is carried in branches of the pudendal nerves, whereas sensations related to tension and stretch in the rectal wall and proximal part of the anal canal is carried in the pelvic nerves.

Central nervous system. The medial prefrontal area and the anterior cingulate gyrus appear to represent two important higher centers that contribute to the regulation of bowel function. It is thought that these centers are involved in the timing and initiation of defecation with their effects over voluntary control being mediated through spinal pathways.

CONSTIPATION Constipation is a common condition for which there are many different causes and assocations (Table 2). Elderly people are most commonly affected because other factors, such as immobility, are likely to worsen the situation.

Discrete pathophysiological mechanisms for constipation have not generally been identified; however, two broad categories of constipation have been described — a decreased colonic transit time (colonic inertia) and outlet obstruction. Colonic inertia results in a slow transit of feces and is thought to be secondary to a defect in the smooth muscle, its innervation or other stimuli of contractions. In outlet obstruction, there is difficulty evacuating the rectum completely, due to a failure of relaxation of the pelvic floor or anus during defecation [1].

People with simple constipation occasionally present with abdominal pain and investigations generally do not detect any abnormality. Based on history alone, it can be very diffi-

cult for the physician to differentiate between slow colonic transit time and outlet obstruction. Severe cases of constipation secondary to slow colonic transit can present with decreased appetite and uncommonly with nausea and vomiting. Patients who have difficulty in evacuating the rectum generally have outlet type obstruction, and constipation occurs because the feces desiccate and harden in the rectum causing fecal impaction. This acts like a mass causing abdominal discomfort, bleeding, and ‘‘overflow” incontinence when liquid stool bypasses the hard mass in the colon. The majority of colorectal fecal impactions occur in the rectum. In patients with high spinal lesions, impaction can precipitate autonomic dysreflexia.

In patients with severe constipation and difficulty with defecation it is important to exclude intussusception as a remedial cause of intrarectal obstruction. Intussusception occurs when a segment of intestine involutes into the section immediately distal to it and can result from chronic straining and hard stools. A rec-

TABLE 2

KEYPOINTS: à

The sympathetic nervous system inhibits the gastrointestinal tract through the inhibitory effect of noradrenaline on the enteric nerves and also causes vasoconstriction when appropriate

à

Discrete pathophysiological mechanisms for constipation have not generally been identified; however, two broad categories of constipation have been described — a decreased colonic transit time (colonic inertia) and outlet obstruction.

Conditions that cause or are associated with constipation

General • Irregular bowel habit (ignoring call to stool) • Simple (low fiber diet) Drugs • Opiates, aluminum antacids, antidepressants, iron, anticholinergics, diuretics Hormonal/metabolic • Hypothyroidism, hyperparathyroidism, Addison’s disease Neurological diseases • Communication and/or mobility problems (e.g. dementia, post CVA) • Multiple sclerosis • Parkinson’s disease • Spinal cord injury • Cauda equina injury • Diabetic neuropathy Other • Increased ileal segmental contractions or decreased colonic mass movements of unknown etiology • Failure of relaxation of the pelvic floor muscles and/or sphincters during defecation of unknown etiology • Abnormal rectal enteric innervation (e.g. congenital megarectum) • Post operative ileus (abdominal or other surgery) • Colonic disease (e.g. diverticulosis, carcinoma) • Painful anal conditions (e.g. hemorrhoids, anal fissure) • Rectocele, intussusception or rectal prolapse

31

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: à

Complete bowel emptying at an appropriate time and place requires the culmination of multiple, interdependent physiological and psychosocial events.

à

Damage to the anal sphincters or their innervation can result in incontinence, and obstetric injury is the commonest cause of these defects.

TABLE 3

tocele occurs when the anterior wall of the rectum prolapses forwards, creating a bulge or pouch in the posterior vagina. It is a condition which is caused by weakened posterior vaginal tissues and is generally seen in older women. Most rectoceles are asymptomatic, but sometimes can cause incomplete emptying so that patients have to reduce their rectocele in order to facilitate the process of bowel emptying.

FECAL INCONTINENCE Complete bowel emptying at an appropriate time and place requires the culmination of multiple, interdependent physiological and psychosocial events. When the integrity of this chain of events is disrupted at any point, fecal incontinence can occur. However, in most cases, numerous dysfunctions combine so that fecal incontinence has a multifactorial etiology (Table 3).

Fecal incontinence in non-neurological patients may be a significant problem in the

Conditions that cause or are associated with fecal incontinence

Anal sphincter/pelvic floor incompetence • Obstetric injury to the anal sphincter • Age-associated decrease in anal sphincter squeeze pressure • Pudendal neuropathy (following pregnancy) • Traction neuropathy (associated with chronic constipation) • Denervation atrophy following pudendal nerve injury • Post surgery (e.g. following anal stretch for recurrent anal fissure or low anterior resection for rectal carcinoma) Diarrhea • “Overflow” incontinence in patients with fecal impaction • Infection • Medication (e.g. antimicrobials, excessive laxatives) • Post radiation therapy • Colonic disorders (inflammatory bowel disease, diverticulosis, colorectal carcinoma) Neurological diseases • Communication and/or mobility problems (e.g. dementia, post CVA) • Spinal cord injury • Cauda equina injury • Multiple sclerosis • Parkinson’s disease • Absent or decreased sensation of rectal filling (e.g. diabetic neuropathy) Others • Reduced rectal compliance • Rectal prolapse

32

elderly. The principal causes of incontinence in these patients are fecal impaction with overflow diarrhea, anal sphincteric incompe-tence and diarrhea from other causes. Dietary factors can cause either excessively loose stools or constipation with impaction and overflow incontinence.

An institutionalized patient with poor mobility can become incontinent of feces simply due to inadequate care or facilities and those with cognitive decline or decreased communication abilities (e.g. post CVA) can suffer from incontinence, despite having an intact sphincter mechanism.

Damage to the anal sphincters or their innervation can result in incontinence, and obstetric injury is the commonest cause of these defects [10]. Fecal leakage without awareness causing soiling is usually associated with dysfunction of the smooth muscle of the internal sphincter or impacted stool in the rectum. Fecal urgency

TABLE 4

Questions in the assessment of bowel function

Bowel habit and stools • Diet • Usual bowel pattern • Usual stool consistency • Blood and/or mucus • Use of medications Sensation • Sensation of bowel fullness • Urgency, ability to defer defecation and urge incontinence • Ability to distinguish flatus from stool • Pain prior to or with defecation • Ability to control flatus • Passive soiling (loss of stool without a prior urge to defecate) Defecation • Straining • Digital stimulation or extraction of stool • Use of suppositories, enemas • Sensation of incomplete emptying General • Obstetric history • Urological history • Use of pads • Ability to use toilet independently • Toilet adaptations • Attitude and availability of carers • Effect on lifestyle and relationships • Psychological factors (e.g. depression)

and urge incontinence are generally related to dysfunction of the striated external anal sphincter or to high bowel pressures and a normal sphincter as may occur with diarrhea.

Sensory defects can result in impaired sensation of rectal fullness or an inability to distinguish between feces or flatus.

HISTORY AND EXAMINATION. The assessment of bowel symptoms should include questions relating to ability of toileting and the availability of carers. The most important areas for assessment are listed in Table 4.

Physical examination should focus on pelvic floor assessment, in particular looking for rectocele, anal tone and signs of damage to support structures (e.g. perineal body) or the anal canal (e.g. obstetric injury). Digital rectal examination will identify fecal impaction or an ano-rectal mass. Neurological examination should include a full assessment of the lower limbs and perineal sensation.

INVESTIGATIONS Anorectal physiology and radiology tests used in the assessment of bowel function are outlined in Tables 5 and 6. The technique of anal manometry is described in Pullout 1.

TABLE 5

Non-neurological causes of fecal incontinence or constipation can affect anyone. A sudden change in bowel habit or rectal bleeding always warrants assessment of the large bowel by colonoscopy and/or barium enema to exclude malignancy (bowel cancer being the second most common malignancy in the developed world).

MANAGEMENT OF BOWEL DISORDERS General measures and advice. The practicalities of bowel management can be difficult for anyone with a physical impairment to manage independently. Patients with bowel problems often need considerable psychological support, together with information on the normal workings of the bowel and an explanation of the underlying mechanism of their problem.

Solutions often need to be imaginative and creative, tailored to the individual’s abilities, lifestyle, physical environment and the availability of help at appropriate times [2]. There are a large variety of adaptations that can be made to a toilet to facilitate access and stability in use. The use of a footstool while sitting on the toilet can increase the ano-rectal angle and thereby facilitate evacuation. Biofeedback and bowel training programs may

KEYPOINTS: à

A sudden change in bowel habit or rectal bleeding always warrants assessment of the large bowel by colonoscopy and/or barium enema to exclude malignancy (bowel cancer being the second most common malignancy in the developed world).

à

Patients with bowel problems often need considerable psychological support, together with information on the normal workings of the bowel and an explanation of the underlying mechanism of their problem.

Ano-rectal physiology tests used in the assessment of fecal incontinence and constipation

Test

Method

What it tests

Anal manometry

See Pullout 1.

Resting pressure (internal sphincter contractile activity) and squeeze pressure are measured.

Balloon distension

A rectal balloon is slowly filled with air or water and first sensation, urge and maximum tolerated volumes are recorded.

Sensitivity of the rectum to distension is measured and the presence of a megarectum can be excluded.

Recto-anal inhibitory reflex

An anal balloon is quickly filled with air and the consequent drop in anal pressure is measured.

Absence of the reflex is diagnostic of Hirschsprung’s disease, but the reflex can be impaired in neurological conditions.

Balloon expulsion test

Rectal balloon and surface EMG electrodes.

Pelvic floor co-ordination on attempted defecation.

Saline retention test

A fixed volume of saline is instilled into the rectum.

Continence and rectal compliance to distension.

Electrosensitivity threshold

Sensation to electrical stimulation in the anus and rectum is measured.

Hindgut denervation can be identified.

Pudendal terminal motor latency

See Chapter 1.

Prolongation in conductance of distal pudendal nerve.

Anal sphincter EMG

See Chapter 1, Pullout 1.

Denervation and reinnervation of external anal sphincter.

33

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

PULLOUT 1

Anorectal manometry

Anorectal manometry is used to determine rectal sensation and anal sphincter competency and function. The test is generally performed after a cleansing enema. A 4-mm-diameter catheter with four lumens is used for recording pressures. Each lumen has a distal side opening, spaced 5 mm apart from the next. Distilled water is continuously perfused into the rectum at a rate of 0.5 ml/min through three of the lumens, which are connected to external pressure transducers. A latex balloon, 6.5 cm long and 4 cm wide with a capacity of 50 ml is attached to the tip of the catheter and covers the fourth lumen. Intraluminal-balloon pressures are transmitted to a fourth transducer.

With the subject in the left lateral position, the catheter is introduced into the rectum so that all recording holes are positioned within the distal rectum. The balloon is then filled with water or inflated and the volume at which various sensations (e.g. normal desire to defecate or fecal urgency) are recorded. The patient can be instructed to expel the balloon or the rectal catheter can be withdrawn through the anal canal, with the recordings taken at fixed distances from the anal verge. Voluntary anal sphincter squeeze and abdominal straining pressures are also recorded.

TABLE 6 Test

Method

What it tests

Transit studies

Radio-opaque markers are ingested on 3 successive days and plain a abdominal X-ray is taken after five days.

Slow transit constipation/inefficient evacuation.

Evacuating proctography

Barium paste is filled into the rectum and the patient is asked to defecate.

Ability of the rectum to retain the paste, integrity of the sphincters, co-ordination of pelvic floor relaxation with attempted emptying, megarectum, prolapse, rectocele or intussusception are identified.

Anal ultrasound

An intra-anal ultrasound probe is inserted into the anal canal.

Structural integrity of the internal and external anal sphincters.

TABLE 7

34

Radiology tests used in the assessment of fecal incontinence and constipation

Commonly used medications used in the treatment of constipation

Category

Examples

Bulking agents

Natural bran Ispaghula husk Sterculia

Stool softeners

Castor oil Docusate sodium (osmotic also)

Osmotic

Magnesium salts Lactulose Dioctyl (softener also)

Colonic stimulants

Senna Bisacodyl

Rectal stimulants

Suppositories (e.g. glycerin, bisacodyl) Enemas (e.g. phosphate, sodium-based micro-enemas)

have a role in certain neurological patients, especially those with non-progressive neurological lesions.

Constipation (see algorithm for fecal loading, Figure 4) [11].

Dietary advice. Adequate fluid intake should be recommended for all patients, irrespective of the presence of constipation. The diet should contain daily portions of fruits and vegetables along with insoluble fibers. Normal daily stool weight in the UK average 50-300 g whereas in developing countries with a higher fiber intake, average stool weight is 500 g or more with two or three bowel actions per day.

Patients should be educated about the gastrocolic reflex and be encouraged to identify those times during the day when the urge to defecate following meals is greatest (‘‘timed bowel movements”).

ommended. Bulk-forming laxatives stimulate peristalsis by maintainFaecal loading? ing hydration and thereYes fore size of the stool.

These are useful in those Incontinent? with an inadequate oral No diet. Many of the bulkYes ing agents available conDiscomfort tain psyllium, an insoluble form of fiber. HowEnemas Yes No ever, bulking agents can Ineffective Effective be counter-productive if Stool consistency? peristalsis is impaired Hard Soft and can contribute to impaction in immobile Osmotic laxative Stimulant laxative individuals.

Stool softening agents.

Effective Effective Ineffective Ineffective Stool softeners may help where the main problem Enemas Add stimulant laxative is difficult evacuation or use combined product and agents such as dioctyl sodium sulfasuccinate can also improve intesEffective Effective Ineffective Ineffective tinal function. Hyperosmotic agents, typically Ineffective sugar solutions, can be effective in promoting Hard bowel movements when Soft fiber supplementation Manual evacuation Drastic treatment and hydration strategies (Picosulphate, Picolax fail.

Golytely) Colonic stimulants.

Colonic stimulants may help with slow transit.

FIGURE 4 Algorithm for the management of fecal loading [11].

Mineral and other types of oils can soften the stool From Edwards C. An overview of adult constipaton and faecal and promote motility. incontinence. In: Getliffe K, Dolman M, editors. Promoting continence.

For patients with more Bailliere Tindall; 1997. Reproduced with permission. severe problems, laxatives (e.g. bisacodyl) can be employed, but should Drug treatment. Table 7 summarizes the be restricted to occasional use in order to most widely used preparations used in the avoid dependency. Stimulant laxatives should treatment of constipation. Different ap- be used with extreme caution if it is suspected proaches are indicated for different types of that the patient is fecally impacted. constipation. Little work on the effects of variRectal stimulation. Rectal stimulation facilious treatments of constipation and fecal incon- tates evacuation. Glycerin suppositories protinence in specific neurological conditions has vide a source of lubrication, while the act of been carried out. rectal insertion can promote sphincteric relaxBulking agents. When simple measures ation and thereby promote evacuation. Other of diet change fail to resolve constipation, suppositories available provide similar actions fiber supplements (bulking agents) are rec- along with the added feature of a chemical

KEYPOINTS: à

Bulk-forming laxatives stimulate peristalsis by maintaining hydration and therefore size of the stool.

à

Stool softeners may help where the main problem is difficult evacuation and agents such as dioctyl sodium sulfasuccinate can also improve intestinal function.

à

Colonic stimulants may help with slow transit.

à

Rectal stimulation facilitates evacuation.

35

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: à

Patients who experience incontinence of feces associated with loose stool or who have a passive anal seepage of soft stool may benefit from low dose constipating medication, although there are no data on use specifically in patients with neurological problems.

à

A stoma can bring a significant improvement in quality of life in selected patients.

à

Good results can be achieved with repair of the sphincter ring.

bowel stimulant. A variety of enema solutions can also be employed to promote defecation, but can potentially predispose the patients to electrolyte losses. Therefore ‘‘mini-dose” enemas (e.g. liquefied glycerin with docusate) provide a simplified enema strategy that is effective in many patients.

Bowel washout regimes. An enema may assist in clearing the rectum and if given in the morning may reduce the risk of fecal incontinence occurring at some other time during the day. The response to rectal washouts is variable and depends on the content, volume and temperature of the instillate.

Manual evacuation. There is no evidence that regular manual evacuation of feces is harmful. Patients with little or no reflex activity in the lower colon who cannot stimulate peristalsis have to use manual evacuation of their bowels.

MANAGEMENT OF INCONTINENCE Patients can adjust their diet, fluid intake and medications in order to have a harder stool, as this facilitates bowel control whilst taking care to avoid troublesome constipation.

Constipating agents. Patients who experience incontinence of feces associated with loose stool or who have a passive anal seepage of soft stool may benefit from low-dose constipating medication, although there are no data on use specifically in patients with neurological problems. Loperamide or Codeine phosphate reduce fecal incontinence, and improve stool consistency. These medications need to be taken prior to eating, and the dose individually titrated. Some patients may choose to effectively stop spontaneous evacuation by using these agents and are able to plan evacuation at a convenient time, using suppositories or a micro-enema. Such a regime can give an element of control and predictability to bowel function, but risks the development of side effects of constipation.

Managing intractable fecal incontinence.

Other than pads, very few products have been designed specifically for fecal leakage. Disposable anal plugs, placed either inside the rectum or in the anal canal, are available but can be uncomfortable and give a constant sensation of rectal fullness.

36

SURGERY Stoma. A stoma can bring a significant improvement in quality of life in selected patients. People with severe physical disabilities often find that inability to cope independently with toileting severely restricts their scope for social, work and personal activities.

It is very difficult for a person in a wheelchair to manage an episode of fecal incontinence, or even defecation, alone in a public toilet. A stoma is much more accessible. When bowel function remains unpredictable and uncontrollable or for those with fecal incontinence a stoma will permit social continence.

Anal sphincter repair. Anal ultrasonography can identify damage to the external anal sphincteric ring, which generally follows obstetric injury and causes incontinence. Good results can be achieved with repair of the sphincter ring.

Post anal repair. Patients with fecal incontinence whose sphincter ring is intact but denervated can expect some improvement in anal function with this procedure. The puborectalis muscle is sutured so that the anorectal angle is decreased and the length of the anal canal is increased.

Antegrade continence enema (ACE). This procedure is mainly used in children with spina bifida. The appendix is brought onto the abdominal surface as a small continent catheterizable stoma which enables antegrade irrigation and evacuation of the colon. The aim is to washout the entire contents of the colon while sitting on the toilet, thus facilitating continence.

Dynamic graciloplasty. In specialized centers, over 75% of carefully selected non-neurological patients have had good results with this technique, which involves the reconstruction of a damaged or absent anal sphincter using a gracilis muscle flap and electrostimulation.

Artificial bowel sphincter. The artificial urinary sphincter is now a recognized option in the management of some cases of urinary incontinence. It has recently been modified and enlarged for use as an artificial anal sphincter, but long-term results of its use are awaited.

REFERENCES [1]

Kamm M. Faecal incontinence. Br Med J 1998;316:528-32.

A comprehensive and up to date review of the prevalence, etiology and management of fecal incontinence.

[2]

Norton C, Henry M. Investigation and treatment of bowel problems. In: Fowler CJ, editor.

Neurology of bladder, bowel and sexual dysfunction. Newton, MA: Butterworth Heinemann; 1999.

A review chapter with particular emphasis on management options.

[3]

Nakayama H, Jorgensen H, Pedersen P, et al. Prevalence and risk factors of incontinence after stroke: The Copenhagen Stroke Study. Stroke 1997;28:58-62.

This study of 935 acute stroke patients determined the prevalence of fecal and urinary incontinence on admission and after 6 months.

[4]

Edwards L, Quigley E, Pfeiffer R. Gastrointestinal dysfunction in Parkinson’s disease: frequency and pathophysiology. Neurology 1992; 42:726-32.

A review article on the prevalence and etiology of gastrointestinal symptoms in Parkinson’s disease.

[5]

Hinds J, Eidelman B, Wald A. Prevalence of bowel dysfunction in multiple sclerosis. A population survey. Gastroenterology 1990;98:1538-42.

[6]

Glickman S, Kamm M. Bowel dysfunction in spinal cord injury patients. Lancet 1996;347:1651-53.

This study on 115 patients determined the prevalence, nature and effects of spinal cord injury on bowel function.

[7]

Bendall MJ. Faecal incontinence. In: The teaching pack for continence advisors, vol I. Portex, Kent, UK: SIMS. 1987-1991.

Two volumes on all aspects of urinary and fecal incontinence with useful educational information.

[8]

Craggs MD, Vaizey CJ. Neurophysiology of the bladder and bowel. In: Fowler CJ, editor. Neurology of bladder, bowel and sexual dysfunction. Newton, MA: Butterworth Heinemann; 1999.

[9]

Kunze WAA, Furness JB. The enteric nervous system and regulation of intestinal motility. Annu Rev Physiol 1999;61:117-42.

This is a “state of the art” review of the intrinsic nerve circuits that control mixing and propulsion in the intestine.

[10] Sultan AH, Kamm MD, Hudson CN, Thomas JM, Barthram CI. Anal-sphincter disruption during vaginal delivery. New Engl J Med 1993;329:1905-11.

In this paper, 202 consecutive women were studied before and after delivery to determine the incidence of damage to the anal sphincter and the relation of injury to symptoms, anorectal physiologic function and the mode of delivery.

[11] Edwards C. An overview of adult constipation and faecal incontinence. In: Getliffe K, Dolman M, editors. Promoting continence. Bailliere Tindall. 1997.

This chapter contains much practical advice for carers of patients with constipation and fecal incontinence.

37

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

à

Although the number of men in an ED prevalence study who have neurological disease will be low, the incidence of ED and other types of sexual dysfunction in men with neurological disease is very high.

38

CHAPTER 4

NEUROGENIC SEXUAL DYSFUNCTION IN MEN AND WOMEN INTRODUCTION Physiological sexual function depends on both central and peripheral neurological pathways.

Neurological disease of many different types can, therefore, adversely affect function in both men and women.

In general terms, sexual libido and arousal depend upon psychological factors and on the integrity of higher brain centers, whereas function of the spinal cord and peripheral pathways is essential for effecting sexual responsiveness. Central centers which determine drive include the basal hypothalamus and limbic system, and the frontal and fronto-temporal regions where testosterone, dihydrotestosterone and estrogen may have important modulatory effects. Spinal pathways and the peripheral nervous system conveying efferent and afferent activity to pelvic parasympathetic, sympathetic and somatic innervated structures are critical for the voluntary and autonomically mediated aspects of genital responses.

Study of male sexual function and the many disorders, both neurological and nonneurological, which can affect it, is a relatively new medical subject, little being known, researched or discussed before the mid 1970s.

The change in public attitude towards sexuality which occurred in Europe and the US at that time, together with the appearance of some effective therapies, has altered the situation, and male sexual dysfunction is now an area of intense research and active treatment.

Female sexual dysfunction (FSD) is only just beginning to be scientifically studied, driven by the hope that some of the therapies which have proved to be so effective in men might be extended to women. Still much less is now known and possible therapies lag significantly behind.

The focus of treatment of sexual dysfunction so far has been the treatment of erectile dysfunction (ED). This chapter follows the

traditional approach and deals first with male sexual dysfunction, ED in particular, before covering the lesser studied topic of FSD. ERECTILE DYSFUNCTION A definition of ED is the persistent inability to develop and maintain an erection sufficient for satisfactory sexual activity [1]. The term ‘‘impotence” should now be avoided because of its broader, negative connotations.

General prevalence. In the late 1980s, a large study was carried out of men aged 40-70 years living around Boston, USA which showed that ED was a common problem and that its incidence increased with age [2]. More than 1000 men completed a self-administered questionnaire which asked, if they had impotence, to rate the problem. Their ED was then categorized as ‘‘minimal”, ‘‘moderate” or ‘‘complete”. The combined prevalence of all categories of ED was 52%. Figure 1 shows a break down of severity with aging. Other general associated factors were identified, which are summarized in Table 1.

80

Prevalence (%)

KEYPOINTS:

Complete ED Moderate ED Minimal ED

67% 57%

60 48%

40

39%

20 0

40

50

60

70

Age (yrs) FIGURE 1

Association between age and prevalence of erectile dysfunction.

From the Massachusetts Male Aging Study (n=1290) [2].

posterior urethra, closure of KEYPOINTS: the bladder neck and rhythmic contractions of the ischio- Ă Smooth muscle relaxation of the traAging cavernosus and bulbocaverbecular smooth muscle (as shown in Figure 1 [2]) nosus. Bladder neck closure in this vascular system Chronic illness is mediated by the and emission are under symAtherosclerosis, diabetes, cardiovascular disease, release of nitric oxide pathetic control from the thorenal disease, hepatic failure, depression, endocrine from the vascular racolumbar sympathetic outdisorders and neurological disease endothelium in flow, whereas the contraction response to pelvic Surgery and trauma of the pelvic floor muscles is parasympathetic activSpinal cord injury, pelvic injury/surgery, prostatectomy ity. under somatic nerve control.

Drug and other modifiable factors Following orgasm and Alcohol, tobacco, medication (antihypertensives, antiejaculation, sympathetic tone à Visual, olfactory, audidepressants, hormones, tranquilizers, H2 antagonists, tory, tactile and imagireturns and causes the cavernonsteroidal anti-inflammatory drugs native stimuli are intenosal and helicine arteries to grated in the medial pre-optic area (MPOA), contract, restricting blood flow but there is no direct into the lacunar spaces. The fallconnection demonstraBecause the subject population of the ing intralacunar pressure then decompresses ble between this strucMassachusetts study was racially unmixed the subtunical venules and allows increased ture and the spinal and unusually well educated, further venous outflow so that detumescence occurs. cord. The paravenepidemiological studies are now being carried tricular nucleus (PVN) Neurological control of male sexual funcis the origin of out to reassess the prevalence of ED globally. tion and penile erection. Central control of descending, oxytocinEarly results are producing figures of the sexual response is currently an area of intense ergic autonomic pathsame order of magnitude as those of the research and animal experiments, often in ways to the sacral cord Massachusetts study, although there are some the rat, have now defined the importance of which mediate erectile regional differences. responses and this regions in the hypothalamus. Visual, olfacreceives input from the Prevalence of ED in neurological disease. tory, auditory, tactile and imaginative stimuli MPOA. Although the number of men in an ED prev- are integrated in the medial pre-optic area alence study who have neurological disease (MPOA), but there is no direct connection will be low, the incidence of ED and other demonstrable between this structure and types of sexual dysfunction in men with neu- the spinal cord. The paraventricular nucleus rological disease is very high. The data are (PVN) is the origin of descending, oxytocinsparse, but Table 2 gives some published inci- ergic autonomic pathways to the sacral cord dences from various small studies of specific which mediate erectile responses and this neurological illnesses. receives input from the MPOA. Dopaminergic Physiology of penile erection and receptors, probably D2 receptors in the PVN ejaculation. Erection results from filling of the paired corpora cavernosa with blood at TABLE 2 Incidence of sexual dysfunction, including ED, in systolic pressure. The lacunar spaces within neurological disease the corpora are fed by the numerous helicine arteries which branch off the cavernosal Hypothalamic-pituitary disorders 78% [3] arteries. Smooth muscle relaxation of the Parkinson’s disease 60% [4] trabecular smooth muscle in this vascular MSA 98% [5] system is mediated by the release of nitric 1 Spinal cord injury 25-95% [6] oxide from the vascular endothelium in MS 62-83% [7-9] response to pelvic parasympathetic activity.

Reduction of corporeal venous drainage is Diabetic neuropathy approx. 100% 2 critical in the erectile response and occurs 1 as a result of compression of the subtunical Depending on level and completeness of lesion. draining veins against the rigid tunica 2 The extent to which micro-vascular disease and metabolic factors albuginea (Figure 2). contribute to the common problem of ED in diabetics is uncertain, but a man with diabetic neuropathy is highly likely to have ED. Ejaculation involves emission of semen from the vas and seminal vesicles into the TABLE 1

General factors known to predispose to ED

39

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

FIGURE 2

Physiology of penile erection.

From [24].

induce erection in animals, which is the rationale for the therapeutic use of apomorphine (a mainly D2 agonist) as an erectogenic agent.

FIGURE 3

Diagram showing the peripheral innervation of the male and female sexual organs.

Reproduced by courtesy of Petter Hedlund and Axel Brattberg.

40

Many inhibitory, mainly serotoninergic, pathways have also been identified within the diencephalon.

tory spinal input. Very little is known about the neurophysiology of orgasm — the senCentral input sation is blocked by bilateral anterolateral (i.e. spinothalPsychogenic amic tracts) cordotomy. A erection SPECT study showed an increase in activity in the right Sympathetic (thoraco-lumbar) frontal lobe region during ejaculation in healthy male Peripheral subjects, but no focal activainnervation tion in the medial anterior parietal lobe corresponding Reflex erection Penis to somatosensory cortex of the genital projection area.

This was interpreted as FIGURE 4 Neurological pathways involved in erectile implying that the right preresponse. frontal cortex is important for the emotional responses of male sexuality.

The parasympathetic innervation travels to Neurological diseases causing ED. Figure the genital region in the pelvic nerves, the so 5 and Table 3 show the various different neucalled ‘‘nervi erigentes” and pudendal nerves. rological diseases that may adversely affect Sympathetic innervation of the genital region sexual function, penile erection, in particular. originates in the thoracolumbar chain (T11-L2) A detailed description of what is known about and travels in the hypogastric nerves to the sexual dysfunction in both sexes with each confluence of neural tissue which lies either disease is given under the appropriate headside of the rectum and the lower urinary ings of Chapters 5-9. tract — the pelvic plexus. This also receives History in men with neurogenic ED. In input from the pelvic nerves and it is from men with established neurological disease and the pelvic plexus that the very fine cavernous ED, laboratory investigations are rarely indinerves pass to innervate the corpora caver- cated. It is usually clear from the history how nosa (Figure 3). the onset of ED relates to the development of There are essentially two neurological their neurological disability. pathways for erection: a sacral segmental pathway which subserves reflex erections and a spinal pathway which is necessary for TABLE 3 Neurological causes of ED psychogenic erections (Figure 4). Reflex erections result from cutaneous genital stimulaTemporal lobe epilepsy tion with afferent impulses conveyed in the Hypothalamic pituitary disorders pudendal nerve to S2- S4 the efferent activParkinson’s disease ity travelling through the same-level sacral Multiple system atrophy roots. Psychogenic erection requires cortical Spinal cord injury activation of erectogenic pathways via the spinal cord and the sometimes preservation Multiple sclerosis of this type of responsiveness in men with Spina bifida low spinal cord lesions suggests that it may Cauda equina be mediated by sympathetic pathways. In Peripheral neuropathy (especially health, psychogenic and reflex erections reinsmall fiber) force one another.

Surgical damage to cavernosal Ejaculation depends on descending spinal innervation pathways which are predominantly excitatory, although there may also be an inhibi-

KEYPOINTS: à

There are essentially two neurological pathways for erection: a sacral segmental pathway which subserves reflex erections and a spinal pathway which is necessary for psychogenic erections.

à

In men with established neurological disease and ED, laboratory investigations are rarely indicated.

41

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

Temporal lobe Hypothalamic-pituitary Parkinson’s Disease MSA

Central input

Trauma MS Spina bifida

Sympathetic (thoraco-lumbar) Cauda equina Small fibre neuropathy Cavernosal n. damage

Peripheral innervation Penis

FIGURE 5

KEYPOINTS: à

The sexual function deficit resulting from spinal cord disease (either traumatic or MS) depends on the level and extent of the lesion: typically, a man with a cervical or high thoracic lesion will have preserved reflex erections, but not be able to sustain erection for penetrative intercourse.

à

Bladder dysfunction occurs considerably later and evidence of relevant neuropathy is best detected by testing small fiber function in the feet, since many of the small fiber neuropathies are lengthdependent.

à

In the general population, ED often has a significant vascular component.

42

Sites at which neurological disease can affect pathways necessary for erectile response.

Temporal lobe disease and hypothalamicpituitary disease often causes loss of desire as an early symptom, which the patient may not complain of, although ED can occur with preserved libido with pathology at those sites.

The sexual function deficit resulting from spinal cord disease (either traumatic or multiple sclerosis (MS)) depends on the level and extent of the lesion: typically, a man with a cervical or high thoracic lesion will have preserved reflex erections, but not be able to sustain erection for penetrative intercourse. The teaching that if a man had nocturnal penile erections or reflex erections, but could not sustain an erection for intercourse, his impotence was psychogenic, is no longer thought to be correct, particularly in the case of spinal cord disease.

Ejaculation and orgasm are likely to be affected by spinal cord lesions. ED is very rarely the only symptom and the complaint is usually part of a symptom complex accompanied by a spastic paraparesis and neurogenic bladder dysfunction.

If ED occurs as a result of a cauda equina lesion, somatic sensation in the S2-S4 dermatomes is also likely to be impaired. Small fiber peripheral neuropathies, i.e. diabetes and amyloid disease, are particularly likely to cause ED, and this may occur early in the condition without disturbances of ejaculation.

Bladder dysfunction occurs considerably later,

and evidence of relevant neuropathy is best detected by testing small fiber function in the feet, since many of the small fiber neuropathies are length-dependent.

Following pelvic trauma or surgery which injures the pelvic nerves or cavernosal nerves, ED occurs, but with preservation of somatic sensation, unless the pudendal nerve is also damaged.

Clinical examination. Following a careful history, clinical examination focussing on the points shown in Table 4 will identify concomitant spinal cord disease, root lesions or peripheral neuropathy. In general, if a clinical neurological examination fails to discover evidence of neurological disease, sophisticated neurophysiological investigations are unlikely to be contributory.

Investigations. Now that there are simple and effective symptomatic treatments for ED, the emphasis on investigations has shifted. In former times, these were carried out to establish whether the problem was psychogenic or organic and, if organic, whether surgical intervention was indicated.

In the general population, ED often has a significant vascular component. A history of coronary or peripheral vascular disease suggests a vascular cause. This may be is investigated by andrologists using a variety of techniques including color Doppler ultrasonography imaging with intracavernosal injections, cavernosometry and cavernosography if surgery is being considered. A brief description of these investigations of penile hemodynamics, usually only performed in non-neurogenic ED, is given in Pullout 1.

Useful insight as to the cause of ED in a patient comes from observing their response to intracavernosal injection of an erectogenic agent, such as prostaglandin E1.

A good response from a low-dose injection suggests the cause is likely to be neurogenic,

TABLE 4

Clinical neurological examination for ED

Lower limb reflexes Plantar responses Sensation (thermal testing) of feet

psychogenic or endocrine, whilst a poor response using a high dose suggests there may be a vascular cause and those investigations described in Pullout 1 may be indicated.

However, false-negatives with this test do occur as the psychological inhibition caused by the anxiety of a penile injection in an impersonal setting, such as at a hospital clinic, may inhibit the response to intracavernosal injection.

There is continuing discussion as to the minimum biochemical investigations necessary, and some authorities recommend measurement of serum total and free testoster-

PULLOUT 1

one, prolactin, glucose and cholesterol [10]. If there is reason to suspect a hypothalamic-pituitary lesion, measurement of hormone levels is mandatory.

The use of neurophysiological tests to investigate genital innervation has been advocated in the past, but none of them is now used routinely. The various tests are described in Chapter 1, (Pullout 1) since many of them were promoted as being appropriate for investigating pelvic organ dysfunctions other than ED. Evaluation of the test specific for ED, socalled ‘‘corpus cavernosum EMG” is still ongoing, and although it may prove to be of

KEYPOINTS: à

If there is reason to suspect a hypothalamic-pituitary lesion, measurement of hormone levels is mandatory.

Investigation of penile hemodynamics

These investigations are sometimes requested by urologists and andrologists when a vascular cause for ED is suspected and they may be particularly indicated in patients who have not responded to oral agents.

Methods of investigating arterial supply Color Doppler ultrasonography (CDU) is considered to be an ideal screening method for both functional and anatomic evaluation of penile arterial blood flow. Following intracavernosal injection, components of the penis, including the corpora cavernosa, corpus spongiosum, septum, urethra, cavernous artery, and dorsal vein, can be visualized. Cavernosal artery diameter and peak systolic arterial velocity can be measured, although there is no general agreement as to what is regarded as normal, partly due to lack of control data in healthy volunteers and partly because arterial inflow is dependent on the degree of smooth muscle relaxation which may be determined by factors such as patient’s anxiety.

Selective pudendal arteriography is technically difficult and invasive and is rarely used, except in men with erectile failure secondary to pelvic trauma in whom pudendal arterial reconstruction is being considered.

Methods of investigating venous leakage Failure of the veno-occlusive mechanism to trap arterial blood within the penis results in ED. The underlying etiology, diagnosis and treatment of venous leakage remains controversial, but many different pathological processes have been described. The majority of patients with “venous leak” have normal venous anatomy, but fail to compress the emissary veins as they exit from the cavernosal bodies.

CDU, cavernosometry and cavernosography are all used in the diagnosis of venous leak. Following an intracavernosal injection of a vasodilator, flow should stop in diastole or even reverse if the veno-occlusive mechanism is functioning adequately. Excessive forward flow in the cavernosal arteries during diastole with failure to obtain a firm erection is taken as evidence for a venous leak.

Cavernosometry is the technique whereby intracavernosal pressure is measured in response to corporeal perfusion and cavernosography is the technique whereby abnormal venous outflow is seen radiologically following perfusion of contrast.

Smooth muscle degeneration, as occurs in diabetes, may result in inadequate sinusoidal relaxation with inadequate inflow and failure of the intracavernosal pressure to rise sufficiently to occlude the emissary veins. A healthy tunica albuginea that stretches and kinks the emerging emissary veins as the penis engorges is also necessary for venoocclusion. In Peyronie’s disease, firm fibrous plaques form at random on the tunica preventing full elongation of the penis with consequent penile curvature and venous leak in some patients. The treatment of erectile dysfunction secondary to venous leak is not straightforward as the underlying pathogenesis is often unclear. Attempts to reduce leakage by dividing draining veins have some short-term success, but the longer term results are poor.

43

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

value in assessing penile autonomic innervation, it is unlikely to assume importance as anything other than a research investigation.

Treatment. With the introduction of the orally active agent sildenafil (Viagra®, Pfizer) in 1998, the treatment of ED was transformed.

Prior to then, intracavernosal injection pharmacotherapy was the most used treatment, usually administered by urologists or andrologists. Before that, what help that was available was the provenance of psychotherapists or those surgeons who implanted penile prostheses. An effective oral treatment has meant that treatment of ED can now be offered by primary care physicians as well as specialists not previously therapeutically empowered, such as neurologists.

Oral medication: Sildenafil citrate (Viagra®) is a potent and highly selective inhibitor of type 5 cGMP phosphodiesterase (PDE5). Its action is to augment nitric oxide-mediated relaxation pathways in penile tissues by increasing available cGMP in the corpus cavernosum (Figure 6). The effect of the medication is therefore not to cause erection, but to enhance the response to sexual arousal. Sildenafil is rapidly absorbed with a maximal plasma concentration occurring within 1 hour, so that it

KEYPOINTS: à

An effective oral treatment has meant that treatment of ED can now be offered by primary care physicians as well as specialists not previously therapeutically empowered, such as neurologists.

NANC neurons

Endothelial cells

Nitric Oxide

+ Guanylate cyclase

Smooth Muscle Relaxation

+ cGMP

GTP

Sildenafil Citrate

_ PDE 5

Penile erection

+

GMP

Nitric oxide-cGMP mechanism of corpus cavernosal smooth muscle relaxation and penile erection. Sexual stimulation results in the release of nitric oxide from corporal vascular endothelium and nonadrenergic-noncholinergic (NANC neurons). PDE 5 = cGMP-specific phosphodiesterase type 5.

FIGURE 6

44

is necessary for it to be taken about 1 hour before intended sexual activity.

More than 6000 men with many different causes of ED have now participated in placebo-controlled trials of sildenafil citrate, and the medication was demonstrated to be effective, with few side effects or adverse events.

The pivotal study was a large placebo-controlled, flexible dose-escalation study with an open label extension in men with organic, psychogenic or mixed etiology ED [11]. Efficacy was assessed using the self-administered International Index of Erectile Function (IIEF) questionnaire which showed significantly higher mean scores for frequency of penetration and maintenance of erection in the sildenafil-treated group compared with men receiving placebo. Sexual desire was not increased in the active agent-treated group, but the scores for orgasmic function, intercourse satisfaction and overall satisfaction were all better. Adverse effects were headache, flushing, dyspepsia, nasal stuffiness and visual disturbances, but these were usually mild and were dose-related. Only 2% withdrew from the open-label study because of adverse effects. Similar findings for efficacy have been demonstrated since in other studies, although the response rate is variable, being less good in vasculopaths and diabetics and better in patients with neurogenic ED. The side-effect profile has also been consistent, with few patients discontinuing medication because of adverse reactions.

However, initially, there was public concern about the medication’s safety prompted by reports of death following the use of Viagra®, as monitored by ‘‘spontaneous” reports to the US Food and Drug Administration. This anxiety has now lessened and studies have shown that although the cardiovascular risk profile for myocardial infarction is similar to that which predisposes to ED, there has not been a higher rate of serious cardiovascular events in the treated groups than in the placebo groups in controlled studies. Epidemiological studies have shown that the incidence of serious events has been consistent with the expected background frequency in the treated population [12], and there is no evidence that sildenafil adds to the overall risk in patients with or without cardiovascular disease [13]. Sildenafil is contraindicated with concurrent use of

nitrates as it interacts to cause severe acute hypotension. Sildenafil is contraindicated in severe hepatic impairment and in conditions that predispose to priapism and bleeding disorders.

The efficacy of sildenafil in several neurological conditions has now been demonstrated. Following spinal cord injury, reflex erections may be preserved, but these are often not suitable for satisfactory sexual activity. In a placebo-controlled, cross-over study, 76% of 168 patients who had had traumatic spinal cord injury, reported improved erections and a preference for sildenafil [14]. The majority of the subjects had some residual erectile function, although in 25 of those who did not, sildenafil also improved erections in 16.

Preliminary analysis of a placebo-controlled trial of sildenafil in 217 men with MS has likewise demonstrated excellent efficacy, with 90% of 104 patients on sildenafil and 24% of 113 patients on placebo, reporting improved erections [15] as well as a measurable improvement in quality of life. A placebo-controlled trial in eight men with spina bifida showed improved erectile function in 63% [16]. Thus, the present evidence points to this form of treatment being particularly effective in men with ED caused by spinal pathology. Any pre-existing neurological difficulty with ejaculation, however, persists.

Abstract reports of an open label study of men with Parkinson’s disease have also shown sildenafil to be effective [17], although this study showed that in men with parkinsonism due to multiple system atrophy (MSA) who had ED and either symptomatic or asymptomatic autonomic failure, hypotension was significantly exacerbated by sildenafil. It is therefore important to check for postural hypotension in men with parkinsonism before prescribing sildenafil.

The efficacy of sildenafil in treating ED in diabetics is less than in most other patient groups with ED. In a study of 131 diabetics, 56% reported improved erections on active treatment compared with 10% of 127 in the placebo group [18]. The peripheral vascular component as well as the effect of advanced glycosylated end products which decrease nitric oxide activity are thought to be contribute to the severity and relative intractability of ED in diabetics.

In men who have ED following radical prostatectomy, sildenafil is ineffective in those in whom it was not possible to carry out a nerve-sparing procedure on either side [19].

At the time of writing, sildenafil is the only available orally active erectogenic agent, but preliminary studies have demonstrated an erectogenic effect with oral apomorphine [20], although nausea is a frequent side effect, particularly in those using higher dosages. However, it is certain that in the near future, other orally active treatments for ED will become available, either other phosphodiesterase inhibitors or agents which act on some other stage of the process of the erectile response.

Intracavernosal pharmacotherapy: Prior to the availability of an orally active treatment, injection of medication into the corpus cavernosum was the preferred treatment. The first used agent was papaverine, but this was subsequently replaced by alprostadil [21], a prostaglandin PGE1. Various combinations of injectable agents have also been tried.

The main side effect of alprostadil is penile pain, which occurs in about half of the patients. Priapism is characterized by a persistent erection that generally lasts 4-6 hours and can be associated with severe pain. When this condition occurs, it should be considered a medical emergency as permanent damage can be sustained after 12 hours of persistent erection. Treatment involves immediate injection of phenylephrine hydrochloride at 500 µg into the corpora cavernosum. This administration can be repeated at 20-minute intervals. Alternately, blood can be aspirated from the corpora via a 23-gauge butterfly needle along with α-adrenergic irrigation (1 mg phenylephrine HCl to 1 liter of normal saline). The main late complication is the appearance of fibrotic nodules or scarring within the corpora, but in most cases, these disappear after temporary discontinuation of the treatment.

Intracavernosal injection therapy still has a continuing role in treatment of patients who do not respond to sildenafil, although the determining features for responsiveness are not yet known. Patients with neurogenic ED responded well to low doses of alprostadil therapy, while those with vascular disease required higher doses.

KEYPOINTS: à

It is therefore important to check for postural hypotension in men with parkinsonism before prescribing sildenafil.

à

Patients with neurogenic ED responded well to low doses of alprostadil therapy, while those with vascular disease required higher doses.

45

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: à

Similar erection mechanisms to those that occur in men also operate in women, including NO- and cGMP-mediated vascular events.

à

The clitoris is homologous to the glans penis and is the most densely innervated area of the skin with an innervation density, approximately twice that of the male dorsal penile nerve, so that clitoral sensory thresholds are lower than that of the glans penis.

A high attrition rate for using the treatment was found in several studies, thought to be due to dislike of injections, the artificiality of the therapy and the practical difficulties preparing and administering the solution.

In order to overcome some of these problems, several easy self-injection devices have been manufactured.

Intraurethral pharmacotherapy and topical creams: Although intraurethral administration of alprostadil as a medicated pellet (MUSE®), which obviated the need for injection, was theoretically an attractive option, the efficacy of the preparation is much less, despite higher doses. Its use in clinical practice has been somewhat disappointing.

Topically acting vasodilator creams have been developed, some with a mixture including nitric oxide donors [22].

Vacuum devices: A vacuum device consists of a vacuum chamber, a vacuum pump that creates negative pressure within the chamber, and a constrictor or tension band that is applied to the base of the penis after the erection is achieved. Vacuum-induced erections are due to venous turgidity and the penis is only rigid distal to the constricting band. These devices have been successfully used in older men and have the advantage of having limited side effects, although these may include pain, hematoma, petichiae, and numbness. The use of this device is contraindicated in patients with bleeding disorders, Peyronie’s disease, and in those with intracavernosal scarring.

Vacuum devices may also be useful to enhance the effects other treatment modalities (intracavernosal, intraurethral).

Penile prosthesis: Penile prostheses are generally much less used nowadays. The complication rate in men with spinal cord disease was higher than in other patients, and, in general, a prosthesis is not suitable for a man who has progressive neurological disease.

FEMALE SEXUAL DYSFUNCTION Similar erection mechanisms to those that occur in men also operate in women, including NO- and cGMP-mediated vascular events.

Arousal and hyperalgesia of the genital tissues can be provoked by imagery and fantasy, or by stimulation of vaginal or cervical tissues or of other erogenous zones. During this process, blood flow is increased to the

46

vagina which results in lubrication and erection of the female cavernous tissues and clitoris. Women experience a period of REM-sleepassociated augmentation of vaginal blood flow and increased lubrication, analogous to male nocturnal tumescence.

Lubrication is derived mainly from a transudate from the vaginal tissues, although secretion from Bartholin’s glands, the cervix, and uterus also contribute [23]. Diminished lubrication can impair sexual function and can be caused by estrogen deficiency states, pituitary insufficiency, antiestrogen therapy, and anticholinergic agents.

Neurological control of sexual function in women. The clitoris is homologous to the glans penis and is the most densely innervated area of the skin with an innervation density approximately twice that of the male dorsal penile nerve, so that clitoral sensory thresholds are lower than that of the glans penis.

The clitoris contains three different types of nerve endings, including free endings that mediate response to pain, submucosal fibers that respond to pressure and movement, and onion bulbs that are involved in sensing pressure and vigorous movements. These latter two types of nerve endings are localized in close proximity to cavernous tissue and are thereby stimulated during the phase of vascular engorgement. The clitoral nerves join the pudendal nerves, which ultimately transmit information to the sacral spinal cord.

Two clitoral reflexes characterize the neurophysiology of the clitoris. The bulbocavernosus reflex is a phasic response that can be triggered by pinching the clitoris and involves contraction of the bulbocavernosus muscle and the external anal sphincter. Vibratory stimulation evokes a tonic reflex involving sustained contraction of the pelvic floor musculature. The bulbocavernosus muscles surround the vaginal introitus and insert on the dorsal surface of the clitoris forming an anatomical sling. During the process of muscle contraction, the dorsal vein is compressed and the cavernous tissue becomes engorged with blood, leading to clitoral erection.

In addition to the clitoris, there are areas on the anterior vaginal wall which respond to sexual stimulation, and some have claimed the existence of a highly localized area, the socalled ‘‘Grafenberg spot” (G-spot).

TABLE 5

Types of female orgasm

Clitoral or vulval Uterine or vaginal Blended Anal Erogenous zones (breasts/neck/hands) Psychogenic

With appropriate stimulation and rising sexual excitement, orgasm may be reached.

The female orgasm is characterized by the experience of a spreading sensation of warmth followed by up to 20 synchronous contractions of the vaginal musculature and sphincters lasting for 10-50 seconds. There are several forms of female orgasm, which provides for a broad diversity of stimulation sites (Table 5). Some women can experience multiple orgasms in sequence in response to repeated or persistent sexual stimulation.

Neurological causes of FSD. Much less is known about neurogenic FSD than is known about male sexual dysfunction and, furthermore, most female patients are still very much more reticent about discussing sexual problems, although that may change. However, based on considerations of the homologous nature of neurological control of sexual responses, it is reasonable to assume that the diseases shown in Figure 5 and listed in Table 3 adversely affected women in much the same way as men. Each of these and what therapy is available is discussed in the appropriate chapters (Chapters 5-9).

SEXUAL HEALTH AND REHABILITATION The ready availability of simple, effective treatment for ED has made both patients and their doctors more willing to talk about sexual dysfunction. The high incidence of ED in neurological disease (Table 2) means that every neurologist is taking care of many patients who have sexual dysfunction amongst their complaints. Ignoring this aspect of the patient’s health should be regarded as being as neglectful as failure by the physician to attend to some other major neurological dysfunction.

In treating sexual dysfunction, irrespective of the cause, the physician may or may not become involved in the extent to which the problem has affected partner relationships. In progressive neurological disease, the disease itself may have a considerable impact on a relationship, and restoring erectile function may have complicated repercussions when a patient’s partner has become their carer.

Following traumatic spinal cord injury, the problems are quite different and may include sexual rehabilitation of an otherwise fit young man, so that he is able to enjoy a full dyadic relationship.

A sympathetic and encouraging approach of enquiry is necessary, with the level of detail of discussion determined by the extent to which patient and doctor feel comfortable with the topic. Often the subject can be easily introduced following discussion of neurogenic bladder dysfunction, pointing out to the patient that, as is often the case, the same parts of the nervous system are needed for control of the bladder and sexual function. The neurologist must be sensitive to the patients’ situation and be nonjudgmental. Provided this approach is taken, the successful treatment of

KEYPOINTS: à

The high incidence of ED in neurological disease means that every neurologist is taking care of many patients who have sexual dysfunction amongst their complaints.

REFERENCES [1]

Impotence. National Institutes of Health Consensus Statement. December 1992. p. 10.

Early meeting of officially convened group to discuss the medical consequences of ED.

[2]

Feldman H, Goldstein I, Hatzichristou D, Krane R, McKinlay J. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994;151:54-61.

First large scale study of a population to look at the prevalence of ED.

References continued ►

47

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

References continued ►

[3]

Lundberg P, Hulter B. Sexual dysfunction in patients with hypothalamo-pituitary disorders. Exp Clin Endocrinol 1991;98:81-8.

Effect of pituitary tumors on sexual function — a Swedish study from a sexology unit receiving referrals from a regional neurosurgical unit.

[4]

Singer C, Weiner WJ, Sanchez-Ramos JR, Ackerman M. Sexual dysfunction in men with Parkinson’s Disease. J Neurol Rehabil 1989;3:199-204.

An early study of sexual dysfunction in Parkinson’s disease.

[5]

Beck RO, Betts CD, Fowler CJ. Genito-urinary dysfunction in multiple system atrophy: clinical features and treatment in 62 cases. J Urol 1994;151:1336-41.

Retrospective study of urinary symptoms in MSA: ED was found to be the earliest symptoms of the disease.

[6]

Bors E, Comarr A. Neurological disturbances of sexual function with special references to 529 patients with spinal cord injury. Urol Surv 1960;10:191-222.

First study of sexual dysfunction following SCI in a large cohort being rehabilitated.

[7]

Lilius HG, Valtonen EJ, Eikstrom J. Sexual problems in patients suffering from multiple sclerosis.

Scand J Soc Med 1976;4:41-4.

[8]

Minderhoud JM, Leemhuis JG, Kremer J, Laban E, Smits PML. Sexual disturbances arising from multiple sclerosis. Acta Neurol Scand 1984;70:299-306.

[9]

Valleroy ML, Kraft GH. Sexual dysfunction in multiple sclerosis. Arch Phys Med Rehabil 1984;65:125-8.

References 7, 8 and 9, questionnaire surveys of sexual problems sent to patients with MS.

[10] Morgentaler A. Male impotence. Lancet 1999;354:1713-18.

Recent review looking at current, i.e. post Viagra, management of ED. [11] Goldstein I, Lue T, Padma-Nathan H, Rosen R, Steers W, Wicker P, et al. Oral sildenafil in the treatment of erectile dysfunction. New Engl J Med 1998;338:1397-1404.

First published results of sildenafil in a large unselected population of men.

[12] Zusman R, Morales A, Glasser D, Osterloh I. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol 1999;83:35C-44C. [13] Jackson G, Betteridge J, Dean J, Hall R, Holdright D, Holmes S, et al. A systemic approach to erectile dysfunction in the cardiovascular patient: a consensus statement. Int J Clin Pract 1999;53:445-51.

Reference 12 from US, this from UK concluding lack of cardiovascular risk in treatment with sildenafil.

[14] Giuliano F, Hultling C, Masry E. Randomized trial of sildenafil for the treatment of erectile dysfunction in spinal cord injury. Ann Neurol 1999;46:15-21.

Large study showing efficacy of sildenafil in men with SCI. [15] Fowler CJ, Miller J, Sharief M. Viagra (sildenafil citrate) for the treatment of erectile dysfunction in men with multiple sclerosis. Ann Neurol 1999;46:497.

Abstract — result of multicenter study showing efficacy of sildenafil in men with MS. [16] Palmer J, Kaplan W, Firlit C. Erectile dysfunction in spina bifida is treatable. Lancet 1999;354:125-6.

Small group of men with spina bifida successfully treated with sildenafil.

48

[17] Hussain IF, Brady C, Swinn MJ, Mathias CJ, Fowler CJ. Exacerbation of orthostatic hypotension with sildenafil citrate (Viagra) in patients with autonomic failure due to MSA , submitted.

Small group of men with parkinsonism treated with sildenafil — those with Parkinson’s disease responded well; 3 out of 6 with MSA developed severe hypotension.

[18] Rendell M, Rajfer J, Wicker P, Smith M, Group ftSDS. Sildenafil for treatment of erectile dysfunction in men with diabetes. J Am Med Assoc. 1999;281:421-6.

Large study of diabetics.

[19] Lowentritt B, Scardino P, Miles B, Orejela F, Schatte E, Slawin K et al. Sildenafil citrate after radical retropubic prostatectomy. J Urol 1999;162:1614-17.

Poor response of men who have had bilateral nerve involvement.

[20] Heaton J, Morales A, Adams M, Johnston B, El-Rashidy R. Recovery of erectile function by the oral administration of apomorphine. Urology 1995;45:200-6.

Early study looking at the effect of apomorphine on erectile function.

[21] Linet O, Ogring F, Group ftAS. Efficacy and safety of intracavernosal alprostadil in men with erectile dysfunction. New Engl J Med 1996;334:873-7.

Formal study of intracavernosal alprostadil — prior to then papaverine made up by local pharmacy departments was used for cavernosal injection.

[22] Gomaa A, Shalaby M, Osman M, Eissa M, Eizat A, Mahmoud M et al. Topical treatment of erectile dysfunction: randomised double blind placebo controlled trial of cream containing aminophylline isosorbide dinitrate, and co-dergocrine mesylate. Br Med J 1996;312:1512-15.

A mixture of nitric oxide releasing creams assists ED applied topically.

[23] Lundberg P. Physiology of female sexual function and how it is affected in neurological disease. In: Fowler CJ, editor. Neurology of bladder, bowel and sexual dysfunction. Newton, MA: Butterworth Heinemann; 1999, pp. 33-46.

Excellent review of neurology of female sexual function.

[24] Krane R, Goldstein I, Saenz de Tejada I. Impotence. New Engl J Med 1989;321:1648-59.

Early research review of pathophysiology of ED.

49

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: à

à

Although genito-urinary tract abnormalities represent some of the most demoralizing and disabling manifestations of MS, there continues to be a lamentable code of silence between physicians and patients concerning these important issues.

Abnormalities of the lower urinary tract (bladder and urethra) will be experienced by at least 96% of MS patients after 10 years of disease activity.

CHAPTER 5

MULTIPLE SCLEROSIS (MS), OTHER MYELOPATHIES AND SPINAL CORD INJURY (SCI) INTRODUCTION A comprehensive assessment and treatment strategy for bowel, bladder, and sexual dysfunction in a patient with multiple sclerosis (MS), other myelopathies, or spinal cord injury (SCI) requires a co-ordinated approach based on a knowledge of the patient’s disease course, iatrogenic factors, concomitant symptomatic complaints, as well as a knowledge of their social and psychological factors. A multidisciplinary team is often required involving neurologists, urologists, gynecologists, rehabilitation specialists, nurses, and primary care physicians. Through their efforts, the function and quality of the patient’s life can be significantly improved.

MULTIPLE SCLEROSIS (MS) Although genito-urinary tract abnormalities represent some of the most demoralizing and disabling manifestations of MS, there continues to be a lamentable code of silence between physicians and patients concerning these important issues. Without exception, patients should be asked about bladder, bowel, and sexual function. A comprehensive exploration into the problems can facilitate the diagnosis and treatment of such ailments. A greater understanding of the pathophysiology, diagnostic techniques, and treatment interventions for genitourinary dysfunction will equip the neurologist to manage patients with MS more effectively.

BLADDER DYSFUNCTION A set of questions should be used to elicit information from the patient (Table 1). Furthermore, an interdisciplinary strategy of assessment and intervention that emphasizes the collaboration between the neurologist and urologist optimizes the broadest range of treatment

50

options and enhances the chances for successful management of the MS patient with genitourinary tract dysfunction.

Abnormalities of the lower urinary tract (bladder and urethra) will be experienced by at least 96% of MS patients after 10 years of disease activity. Bladder dysfunction can produce a diversity of symptomatic complaints that are differentiated on the basis of whether they relate to storage or emptying deficits. The most common complaints relating to bladder dysfunction in patients with MS are urgency, frequency, and urge incontinence, all of which are related to detrusor hyperreflexia. Others include hesitancy, interrupted stream, incomplete emptying, double voiding, nocturia, and enuresis.

While MRI imaging has substantially advanced our ability to diagnose patients with MS and follow disease activity, there has been no recognized correlation between the number of lesions or atrophy and any specific urodynamic parameter or bladder dysfunction [1].

TABLE 1

Question set for evaluating bladder dysfunction

1.

Frequency

2.

Urgency

3.

Urge incontinence

4.

Frank incontinence

5.

Stress incontinence

6.

History of obstetrical injury or genitourinary surgery

7.

Hesitancy

8.

Double voiding

9.

Nocturia and/or enuresis

10. Iatrogenic agents

However, a number of features of the clinical examination appear to correlate with lower urinary tract dysfunction and lower extremity motor dysfunction seems to be the best predictor of bladder dysfunction. In a study with 170 MS patients and bladder symptoms, only four did not have symptoms and signs of pyramidal abnormalities [2]. Extensor plantar responses (Babinski’s sign) are evident in 70-95% of patients with bladder dysfunction and in 70% with detrusor sphincter dyssynergia (DSD). This strong positive relationship between bladder abnormalities and pyramidal dysfunction in the lower extremities is not surprising considering the neuroanatomical juxtaposition of these distinctive pathways, with the ‘legs above the bladder’ (Figure 1).

Other features include hyperreflexia, clonus, spasticity, pyramidal distribution weakness, and a sensory level (all suggestive of a myelopathy). There is also a correlation between urinary symptoms and lesions with the midbrain and pons [3-5]. In particular, specific brainstem syndromes are associated with a higher risk of bladder dysfunction, especially DSD. The most notable of these syndromes is internuclear ophthalmoplegia, a neuro-ophthalmologic hallmark of MS. While detrusor hyperreflexia with synergic voiding is the most common pattern of bladder dysfunction in MS, the incidence of DSD has been estimated to range from 18 to 66%. The uncoordinated dyssynergia is believed to result from an interruption in the descending regulatory pathways from the pontine micturition center such that there is simultaneous contraction of the detrusor

KEYPOINTS: à

Strong positive relationship between bladder abnormalities and pyramidal dysfunction in the lower extremities is not surprising considering the neuroanatomical juxtaposition of these distinctive pathways, with the ‘legs above the bladder’.

The relative levels of segmental innervation of the lower limbs and urogenital tract make it highly likely that a patient with a paraparesis will also have bladder and sexual dysfunction.

FIGURE 1

muscles and the urethral sphincters. The consequences of DSD can include a high post voiding residual (PVR), increased bladder pressures, a higher risk of urinary infections and urinary tract calculi, and upper tract disease — principally hydronephrosis, in occasional patients.

CASE 1: BLADDER DYSFUNCTION ML is a 41-year-old female patient with a 5-year history of relapsing-remitting MS. She has evidence of diffuse hyperreflexia, mild lower extremity pasticity, bilateral extensor plantar responses and subtle but definite bilateral internuclear ophthalmoplegia. She complains of frequency, hesitancy, urgency, and urge incontinence with two-time nocturia.

Treatment considerations 1.

2.

3.

4.

Measure a PVR, urinalysis, urine culture and sensitivity, BUN, creatinine, blood glucose, renal ultrasound.

If the PVR is less than 100 ml, treat with anticholinergic agent and repeat the PVR in 1-2 weeks.

If the PVR is greater than 100 ml and not reduced with double voiding or the application of a hand-held vibrator applied to the lower abdomen, begin intermittent catheterization and add anticholinergic agents for urgent bladder symptoms. Consider referral to a urologist for urodynamics.

If nocturia is not improved with the above measures, consider adding nighttime DDAVP.

51

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: à

à

à

à

It is important not to rely on the history in order to ascertain whether voiding dysfunction is present. For instance, in one study, only 47% of patients with an elevated PVR had a sensation of incomplete emptying [2]. However, of those who claimed to empty their bladders completely, 53% were incorrect.

For the majority of patients with MS that a general neurologist will evaluate, a PVR is often the only assessment that is necessary.

The emergence of effective treatment strategies for sexual dysfunction provides compelling justification to overcome the reluctance to explore these issues in a sensitive and objective manner.

Estimates suggest that the incidence of sexual dysfunction in MS ranges from 62 to 83%.

In a smaller percentage of patients, detrusor hypocontractility and areflexia can occur in association with large PVRs. This pattern may result from loss of cortical facilitation, from cerebellar lesions, or from lesions below the sacral cord.

It is important not to rely on the history in order to ascertain whether voiding dysfunction is present. For instance, in one study, only 47% of patients with an elevated PVR had a sensation of incomplete emptying [2]. However, of those who claimed to empty their bladders completely, 53% were incorrect [2].

Because of the effect of a raised post void residual volume on bladder function it is essential to measure the PVR before prescribing anticholinergic medication, as emphasized in Chapter 2.

Upper tract disease is exceptional in MS and is linked to predictable risk factors including DSD and the presence of an indwelling catheter. This is in marked contrast to those with spinal cord injury who are very much at risk of developing upper urinary tract complications. The reason for this difference is not known since MS can be associated with just as severe lower limb spasticity as may occur following SCI. For the majority of patients with MS that a general neurologist will evaluate, a PVR is often the only assessment that is necessary. However, in selected patients, urodynamic evaluation, as discussed in Chapter 2, can facilitate the proper identification of bladder and sphincteric abnormalities. This assessment can also provide compelling evidence to suggest upper motor neuron dysfunction in patients with a suspected CNS process such as MS. When no formal urinary investigation is completed, 73% of MS patients are treated inappropriately [6]. At a minimum, a PVR should be completed in all patients with MS on a periodic basis in order to capture evidence of voiding dysfunction.

SEXUAL DYSFUNCTION While sexual abnormalities represent some of the most distressing features of MS, they are often not discussed by patients with their physicians during the process of medical care. In a study involving 47 women with MS and sexual dysfunction, the majority had never

52

TABLE 2

Question set for evaluation of sexual dysfunction

1. Sexually active either with partner or by self stimulation 2. Communication with sexual partner 3. Interest in sex (libido) 4. Arousal 5. Sensation 6. Ability to achieve orgasm 7. Erection 8. Lubrication 9. Pain 10. Fatigue 11. Sexual practices and positions 12. Spasticity and its impact 13. Bladder dysfunction during sex

been asked to discuss their sexuality in relation to their disease [7].

The emergence of effective treatment strategies for sexual dysfunction provides compelling justification to overcome the reluctance to explore these issues in a sensitive and objective manner. A comprehensive assessment of the patient’s various symptomatic complaints is imperative in order to maximize sexual functioning (Table 2).

Chapter 4 discusses in general the various options for treating neurogenic sexual dysfunction. Specifically in MS, the therapy for fatigue, spasticity, pain, bowel and bladder dysfunction, and mood disorders should be optimized, as these various factors can directly impair sexual functioning. Even if therapeutic strategies are not effective in individual patients, the process of open and honest exploration of these issues can be an important and meaningful experience for both the patient and physician. A number of myths and misconceptions often serve as a powerful obstacle to pursuing education and treatment of sexual disorders (Table 3).

Estimates suggest that the incidence of sexual dysfunction in MS ranges from 62 to 83% [8-10].

Concomitant conditions such as diabetes and atherosclerosis can more strongly predispose patients to develop a sexual disturbance.

patients with MS and urinary dysfunction, there is a strong correspondence between ED and pyramidal dysfunction in the 1. I have MS and sexual dysfunction is the least of my lower extremities. Although concerns there has been an interest in the 2. Disabled patients have no sexual needs relationship between sexual dys3. My physician is not interested in hearing about sexual function in MS and neuroendodysfunction crine changes such as testoster4. It is not appropriate to discuss sexual dysfunction one deficiency, a correlation has with my doctor not been confirmed.

5. Sex must culminate in orgasm Men with MS may still expe6. Sex must involve intercourse rience spontaneous erections, 7. Physical contact must involve sexual activity particularly at night i.e. noc8. People should instinctively be sexually competent turnal penile tumescence, but 9. Patients should not masturbate or use fantasy the presence of nocturnal erections does not indicate that their problem is psychiatric, as was perhaps formerly thought. The Sexual dysfunction in men with MS. ability to sustain an erection adequately for Patients with MS will commonly experience intercourse depends largely on psychogenic sexual dysfunction, often in combination with erectile drive which is impaired by spinal cord urinary abnormalities. The initial assessment disease. should include a search for factors that potenA variety of neurophysiological tests have tially contribute to sexual abnormalities (Table been used to assess ED in MS, including the 4). Erectile dysfunction (ED) will occur in about pudendal evoked potential (see Chapters 1 70% of men with MS [11-13]. The mean time and 4). However, the current view is that these between the onset of neurological symptoms do not contribute to understanding the comand the emergence of ED in MS patients is plaint of ED in a man with MS who on clinical about 9 years: sexual dysfunction is rarely a examination has evidence of spinal cord dispresenting manifestation of MS [13,14]. As with ease.

TABLE 3

Myths and misconceptions of sexual dysfunction in MS

KEYPOINTS: Ă

As with patients with MS and urinary dysfunction, there is a strong correspondence between ED and pyramidal dysfunction in the lower extremities.

Ă

Men with MS may still experience spontaneous erections, particularly at night i.e. nocturnal penile tumescence but the presence of nocturnal erections does not indicate that their problem is psychiatric, as was perhaps formerly thought.

CASE 2: MALE SEXUAL DYSFUNCTION IN MS SL is a 35-year-old man with clinically definite secondary progressive MS with ongoing relapses. His clinical course has been stabilized with interferon therapy. He has mild spastic paraparesis and complains of sexual dysfunction characterized by decreased ability to achieve and maintain erection, difficulty achieving orgasm, chronic fatigue, and frequent extensor and adductor spasms during sexual intercourse. His wife is concerned that her husband no longer finds her attractive. Their primary sexual activity has consisted of intercourse.

Treatment considerations 1.

2.

3.

4.

5.

6.

7.

8.

9.

Begin a broad discussion about sexual dysfunction in MS with the patient and his wife.

Encourage more communication between the husband and wife.

Assess for any iatrogenic causes.

Optimize treatment for spasticity, especially before sexual activity.

Evaluate sleep hygiene and treat nocturnal spasms and nocturia if present.

If there are no contraindications, consider treating erectile dysfunction with sildenafil.

If sildenafil is ineffective, consider alternative treatment, such as intracorporeal alprostadil.

If orgasm is still difficult to achieve, suggest that vibrator stimulation be applied to the ventral surface of the glans penis (at the frenulum).

Emphasize the value of energy-conserving sexual positions and encourage alternative sexual practices other than intercourse.

53

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

TABLE 4

Factors that influence sexual dysfunction in MS and SCI

1. Dysfunction can fluctuate with disease activity 2. Reduced sensory responsiveness 3. Psychological factors and depression 4. Pain and paresthesias 5. Bowel and bladder dysfunction 6. Spasticity 7. Fatigue 8. Iatrogenic causes (e.g. SSRIs, tricyclic antidepressants) 9. Relationship discord 10. Physician neglect (‘code of silence’) 11. Preoccupied with misconceptions 12. Alteration of body image

Oral therapy for MED in MS. While a variety of therapeutic options are currently available for men with ED, oral agents have clearly eclipsed all other therapies in terms of popularity and effectiveness. Along this line, the most significant advance has been the development of oral sildenafil citrate (Viagra®) (see Chapter 4). The response of men with MS to treatment with this agent has been excellent [15]: comparisons across

studies showing a particular efficacy in this patient group. Ejaculatory difficulties may, however, persist.

Sexual dysfunction in women with MS. Women with MS will frequently experience sexual dysfunction, either related to the disease process or secondary to other factors that similarly affect males (Table 4). Diminished lubrication can be improved by the liberal use of lubricating agents that are now widely available. Some women will experience sensory disturbances during sexual activity that can often be treated effectively with membrane stabilizing medication such as gabapentin, carbamazepine, and similar agents.

In those who experience vaginal hypesthesia, most often secondary to sensory myelitis, vibratory stimulation of the clitoris and vaginal tissues can lead to pleasurable sensations and even orgasm.

Given the similarities between male and female sexual responses, there is rationale to study the potential role of agents such as sildenafil in the treatment of female sexual dysfunction. We are currently completing a randomized, double-blind, placebo-controlled cross-over study of sildenafil in women with MS and sexual dysfunction.

CASE 3: SEXUAL DYSFUNCTION IN A WOMAN WITH MS GN is a 58-year-old post-menopausal woman with secondary progressive MS. She complains of lower extremity spasticity, chronic fatigue, depression, and bladder urgency. There has been difficulty with diminished sexual arousal, numbness in the vaginal region, poor lubrication, painful sensations on attempted intercourse, and difficulty achieving orgasm. During sexual activity she experiences involuntary leg spasms with associated bladder urgency and urge incontinence. Her depression is well treated with fluoxetine.

Treatment considerations 1.

2.

3.

4.

5.

6.

7.

8.

9.

54

Strongly consider discontinuation of fluoxetine and treating her depression with an alternative agent that is less associated with sexual dysfunction (e.g. trazodone, venlafaxine).

Assess sleep hygiene and treat nocturnal motor spasms and bladder dysfunction if present.

Optimally treat spasticity.

Treat bladder urgency and urge incontinence, especially before sexual activity (void before sex and use anticholinergic agents for bladder relaxation).

Encourage the use of lubricating agents.

Treat painful sensations (consider a tricyclic antidepressant, which may be helpful for pain, depression, and bladder urgency).

Refer to gynecologist for possible hormone replacement therapy.

Encourage energy-conserving positions.

Emphasize the benefits of good communication with partner concerning problems and potential solutions.

BOWEL DYSFUNCTION Bowel dysfunction occurs in many patients with MS at some point during the course of the illness and can persist as a chronic manifestation of the disease [16,17]. Although there is a predilection for bowel dysfunction to occur in those patients with bladder complaints, in a study of patients with MS attending a clinic for treatment of urinary symptoms, one third did not have bowel problems [17].

A number of factors contribute to the onset of bowel dysfunction that must be recognized by the treating physician so that a strategic therapeutic plan can be formulated. The assessment of bowel abnormalities must begin with an inquiry about bowel symptoms and complaints (Table 5).

The most frequent abnormalities of bowel dysfunction are constipation, impaction, and incontinence, but by far the most common problem is constipation. Unlike the high frequency of bladder incontinence that occurs in MS patients, regular bowel incontinence is less common.

Constipation. The contributing factors that result in constipation are manifold (Table 6).

A reduction in neuro-gastrointestinal signaling through the autonomic nervous system has been advanced as a hypothesis on how MS can lead to a slowing in intestinal transit time [18].

MS patients can experience difficulty with voluntary transitions from the storage to defecation process in response to a full rectum.

Inadequate relaxation of the pubococcygeus and sphincter muscles can prohibit defecation despite the patient’s perception of bowel urgency and the performance of the Valsalva

TABLE 6

Constipation: contributing factors

1. Reduced neurogastrointestinal signaling 2. Reduced gastrocolic reflex 3. Pelvic floor muscular spasticity 4. Inadequate hydration 5. Drugs (e.g. anticholinergic agents) 6. Immobility 7. Lack of physical conditioning 8. Weak abdominal muscles

maneuver. AbdomiTABLE 5 Question set for evaluating nal muscle contracbowel dysfunction tions facilitate the process of fecal evac1. Problems with constipation uation. These mus2. Problems with diarrhea cles are innervated 3. Alternating bouts of constipation and

by T6-T12 spinal cord diarrhea segments and disease 4. Problems with incontinence activity within the 5. Bowel urgency spinal cord at these 6. Urgency with difficulty evacuating levels can lead to an rectum increase in abdomi7. Hard painful stools nal compliance.

8. Adequate hydration and fiber Following the 9. Iatrogenic agents ingestion of a meal, especially in the morning, many individuals experience the perceived need to defecate. This process is KEYPOINTS: recognized as the gastrocolic reflex, but it may be blunted in patients with MS. Nevertheless, à A number of factors contribute to the onset patients should be encouraged to identify the of bowel dysfunction time of day where the post-meal urge to defthat must be recognized by the treatecate is strongest. ing physician so that Inadequate fluid hydration is a major cona strategic therapeutic tributor to bowel constipation in MS patients. plan can be formuMany patients recognize that fluid intake can lated. provoke bladder urgency and urge incontinence and will therefore restrict their fluid à The most frequent abnormalities of bowel intake. It is crucial that an integrated treatdysfunction are constiment plan be formulated for each patient pation, impaction, and that takes into consideration the interaction incontinence, but by between bowel and bladder pathophysiologifar the most common problem is constipacal mechanisms. tion.

Other factors that contribute to constipation include iatrogenic causes, primarily from medications, inadequate dietary or supplemental fiber, immobility, and inadequate exercise. The most common agents that can cause or exacerbate constipation in MS patients include antihypertensive agents, anticholinergics (commonly used for bladder urgency), sedative-hypnotic agents, calcium supplements and aluminum containing antacids, tricyclic antidepressants, narcotic analgesics, diuretics, and iron supplements.

When constipation is prolonged, bowel incontinence or impaction can ensue. Treatment of impaction involves the use of hyperosmotic agents, enemas, and typically disimpaction. During this time, bulking agents should be discontinued until the colon is evacuated.

55

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: Ă

Fecal incontinence in MS is relatively uncommon and generally is associated with poorly treated constipation.

Isolated bowel incontinence should be investigated separately.

More severe consequences can occur and include intestinal obstruction, intussusception, and rectocele. Chronic straining can cause intussusception and intrarectal obstruction leading to severe difficulty with rectal emptying or a constant sensation of incomplete rectal emptying and the need to defecate. Patients with such complaints should be referred to a colo-rectal specialist.

Fecal incontinence. When fecal incontinence occurs, a number of factors may be responsible and include reduced sensation of rectal filling, poor voluntary contraction of the anal sphincter and pelvic floor musculature (poor voluntary squeeze pressure), and reduced rectal compliance.

Fecal incontinence in MS is relatively uncommon and generally is associated with poorly treated constipation. Isolated bowel incontinence should be investigated separately. The institution of a formal bowel program for treatment of constipation (see Chapter 3) will generally reduce the risk of incontinence. Furthermore, it is important to identify provocative factors (e.g. irritants, such as caffeine and alcohol) that can be altered to reduce the incidence of incontinence episodes.

In some patients with severe spinal cord dysfunction and loss of voluntary control, frequent episodes of fecal incontinence will mandate the use of protective pants and timed

elimination periods by the use of scheduled suppository treatment to establish a program of reliable bowel movements. The predictability of this regimen is of great benefit to both those demoralized by the experience of bowel accidents and their carers.

The general treatment of constipation and fecal incontinence is described in Chapter 3.

OTHER MYELOPATHIES INCLUDING HUMAN T-LYMPHOTROPIC VIRUS-1 ASSOCIATED MYELOPATHY (HAM) Various causes of myelopathy are given in Table 7. The approach to pelvic organ dysfunction in myelopathic disorders that cause upper motor neuron bladder dysfunction is the same as that detailed above.

One example of a condition that produces similar genitourinary dysfunction to that of MS is HAM, also known as tropical spastic paraparesis (TSP) [19]. This condition is caused by a retrovirus which has an expanding worldwide distribution. The risk factors for transmission include i.v. drug abuse, blood transfusion, and sexual intercourse. The virus can also be transmitted vertically from mother to infant during breast-feeding. The diagnosis of TSP can be made by a number of molecular techniques including immunofluorescence, ELISA, Western blot, with CSF antibodies, and

by PCR.

CASE 4: BOWEL DYSFUNCTION IN MS JH is a 30-year-old nurse with a history of clinically definite relapsing-remitting MS. She presents for a follow-up clinic visit complaining of severe constipation. She previosly would have daily bowel movements in the morning after breakfast. She now works the morning shift and often skips her morning meal. She has stopped her previous vigorous exercise routine and has gained 10 kg. It is clear that she has had some degree of abdominal distention secondary to her weight gain and poor abdominal muscle tone. The patient is well known to restrict fluids secondary to severe bladder urgency and a history of urge incontinence while at work. In addition, she is being treated with amitriptyline for depression and migraine headache prophylaxis. She has used laxatives and digital stimulation to promote bowel movements.

Treatment considerations 1.

2.

3.

4.

5.

6.

7.

56

Resume a regular exercise program to include abdominal muscle exercises.

Begin a weight loss program.

Perform a PVR and if less than 100 ml implement anticholinergic therapy in order to reduce bladder urgency and urge incontinence. Subsequently repeat the PVR to exclude anticholinergic induced urinary retention.

Strongly emphasize the importance of adequate fluid hydration of at least 2000 ml/day.

Increase dietary fiber and begin a bulking agent.

Suggest the use of glycerin or other suppositories if pelvic floor and spincteric muscular spasticity is suspected.

Alternative agents for depression and migraine could be considered.

TSP is characterized pathologically by a chronic inflammatory process primarily affecting the spinal cord white matter. Evidence of demyelination with axonal sparing in association with macrophage activation and oligodendrocyte apoptosis reminiscent of the pathology in MS. However, in TSP there is an additional component of pathology within the bladder lamina propria in conjunction with thickened neurons which assume the appearance of ‘sausage rolls’ [19]. These histopathological features are distinctive to TSP and have not been observed in other myelopathies that produce bladder dysfunction.

Assessment and management of genitourinary dysfunction in patients with TSP is similar to that of other myelopathies, as outlined in Chapter 2.

Bladder dysfunction occurs in 75-100% of infected individuals with the most common patterns being detrusor hyperreflexia and DSD. Approximately 60% of TSP patients will require the use of CIC at some point during the illness [19]. Occasional patients will exhibit evidence of decreased detrusor activity, which would appear to result from disease involvement of the posterior and anterior nerve roots in addition to Onuf’s nucleus. Similar to MS, upper tract disease is distinctly uncommon.

SPINAL CORD INJURY (SCI) Bladder dysfunction. In those patients who experience spinal cord injury (SCI), there is an initial period of cessation of spinal reflexes including bladder areflexia. This typically lasts for days to weeks during which the bladder requires continuous drainage, either by a urethral or suprapubic catheter.

Many of the same assessment and treatment strategies outlined for myelopathies as described in Chapter 2 can be applied to those with SCI. However, there are major urological differences between those with progressive spinal cord disease and the spinal cord injured. The former are usually not suitable to undergo urological surgery, whereas those with SCI are otherwise fit and need a definitive solution to their bladder dysfunction, and furthermore, because they are at risk of renal failure, they should remain under urological supervision.

The risk of renal failure is due to three principal disorders: obstruction; vesicoure-

TABLE 7

Causes of myelopathy

þ

Spinal cord injury

þ

Compressive-disc disease/spondylosis/chiari malformation

þ

Metastatic lesions

þ

Spinal cord tumors (glioma, lymphoma, etc.)

þ

Multiple sclerosis (MS)

þ

Post infectious or post vaccinal myelitis

þ

Idiopathic transverse myelitis

þ

Neuromyelitis optica (Devic’s syndrome)

þ

Neurosarcoidosis

þ

Amyotrophic lateral sclerosis (ALS)

þ

Primary lateral sclerosis (PLS) (bladder dysfunction exceptional)

þ

HIV (vacuolar myelopathy)

þ

HTLV-1 associated myelopathy (tropical spastic paraparesis)

þ

Leukodystrophy (e.g. adrenomyeloneuropathy)

þ

Nutritional causes (e.g. Vitamin B-12 deficiency)

þ

Hereditary myelopathies

teric reflux; and the formation of calculi. Urinary obstruction leads to an increase in bladder pressures and a thickened trabeculated bladder wall. Vesicoureteric reflux occurs secondary to elevated detrusor pressures and requires intervention with bladder drainage and the use of anticholinergic agents. Urinary tract calculi occur more commonly in those who are immobilized for prolonged periods.

Stone formation can serve as a nidus for recurrent urinary tract infections. In those with chronic indwelling catheters, the balloon can be the site for the formation of eggshell calcification ultimately leading to sloughing and the formation of bladder stones. Treatments for calculi include lithotripsy, percutaneous nephrolithotomy, and ureterorenoscopy. Chronic catheterization can be associated with a small risk of squamous cell carcinoma that is substantially higher than that seen in the general population and because of this, periodic cystoscopy is recommended. While renal failure was previously responsible for significant amount of mortality in those with SCI, new management strategies have substantially reduced morbidity and mortality. An important review on this subject has recently been published [20].

In some individuals, implantation of a Brindley sacral root stimulator may be appro-

KEYPOINTS: à

There are major urological differences between those with progressive spinal cord disease and the spinal cord injured. The former are usually not suitable to undergo urological surgery, whereas those with SCI are otherwise fit and need a definitive solution to their bladder dysfunction, and furthermore, because they are at risk of renal failure, they should remain under urological supervision.

57

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: Ă

Ninety-five percent of SCI patients required at least one therapeutic method to initiate defecation and half of them became dependent on others for toileting.

Ă

Most men following SCI are able to obtain reflex erections, but these are not usually adequate for intercourse and few experience psychogenic erections.

58

priate. The procedure requires sacral deafferentation causing loss of reflex detrusor and erectile function and is therefore only indicated in those with a complete cord lesion.

Stimulating electrodes are placed on the anterior roots of S2-S4 and a radioreceiver is placed in the lower anterior chest. Micturition can be initiated by the application of a mirror-image radio transmitter over the receiver. Following a defined period of stimulation the current is terminated. During this phase, the sphincter will relax rapidly, while the detrusor contraction does so more slowly. It is during this phase of dyssynergic muscle relaxation that effective voiding occurs.

A distinctive abnormality that occurs in those with SCI is autonomic dysreflexia. This syndrome generally occurs when the level of the insult is above T6. Patients can experience crescendo hypertension, severe headache, and increased risk of stroke. These changes appear to be related to episodic massive sympathetic discharges within the spinal cord, culminating in vasospasm of the skin and visceral organs.

These episodes are typically precipitated by noxious stimuli below the level of the lesion which include constipation, fecal impaction, bladder contractions or can occur during bladder or bowel treatment procedures. Therapeutic considerations for those with autonomic hyperreflexia include elevation of the head of the bed and the use of antihypertensive agents, especially calcium channel blockers.

Anesthetic agents can also be used before manipulations that may trigger these reactions.

Bowel dysfunction in SCI. A study of spinal cord injured patients showed that bowel dysfunction is a major physical and psychological problem [21]. Nausea, diarrhea, constipation and fecal incontinence were all much more common after SCI, but the major problems arise as a result of loss of voluntary control of defecation. Ninety-five percent of SCI patients required at least one therapeutic method to initiate defecation and half of them became dependent on others for toileting. The procedure was prolonged and in almost half bowel evacuation took more than 30 minutes and the time taken correlated with measures of distress and depression. On a scale of 0 (no perceived problem) to 10 (maximum perceived problem), patients rated their loss of

mobility as a mean of 6.8 (SD 3.3), sexual satisfaction 5.5 (SD 4.2), urinary management 4.9 (SD 3.5) and bowel management 5.1 (SD 3.6).

Optimizing bowel function can help to restore dignity and control to a person following SCI. Failure to avoid the complications of constipation can result in significant morbidity (e.g. bed sores, anal fissure). Furthermore, some 10% of SCI fatalities may be ascribed to undiagnosed abdominal emergencies. Management of bowel problems requires effort on the part of both patient and carer, who must set aside time regularly for bowel care.

Management. Establishment of a bowel program should be individualized. Patients will have different bowel patterns in terms of the frequency of bowel movements. It is important to recognize when an individual patient is more likely to produce stool. For some patients this will be in the morning while in other it will be later in the day. The majority of SCI patients practice regular manual evacuation to prevent impaction and reduce the risk of autonomic dysreflexia. In those SCI patients with a preserved defecation reflex, reflex emptying can be stimulated every 1-3 days by gentle rotation of a gloved finger in the anus until the rectal wall is felt to relax, or flatus is passed and the stool comes down.

This is repeated every 10 minutes until the internal anal sphincter is felt to close off again, or no stool has been passed after the last two stimulations. Alternatively, they can infuse a mini enema to stimulate the reflex. A few SCI maintain a deep nonspecific pelvic sensation of rectal fullness and can be taught to identify this sensation and then stimulate reflex emptying. Many patients can sense when defecation is complete.

Adequate hydration should be ensured and dietary and supplemental fiber should also be adequate. Hyperosmotic agents such as lactulose and sorbitol can contribute to facilitating bowel motility and regularity.

Sexual dysfunction following SCI. The person who suffers spinal cord injury is typically a fit young man at a sexually intense time of life. Most men following SCI are able to obtain reflex erections, but these are not usually adequate for intercourse and few experience psychogenic erections. The possibility of resuming sexual activity is a major concern of those injured and it has been shown that

the successfulness of rehabilitation is correlated with sexual potency. Although intracavernosal injections and vacuum pump devices were used by men with SCI, the introduction of Viagra, which increases erectile response within the context of sexual stimulation by their partner, has been greatly welcomed (see Chapter 4). A placebo-controlled trial showed sildenafil was highly effective in men with SCI in improving ability to achieve and maintain an erection and increase satisfaction with intercourse. It was effective even in those who did not have residual erectile function [22].

Very few men following SCI are able to ejaculate during intercourse, but if fertility is an issue, either a vibrator applied to the penis or electrical stimulation of the pelvic plexus by a rectal probe will induce ejaculation in most cases.

CONCLUSION Patients with myelopathy frequently present with major problems with pelvic organ function. A comprehensive approach that integrates the assessment and treatment of bowel, bladder, and sexual dysfunction represents the strategy with the greatest likelihood of achieving satisfactory results. However, their caring physicians can institute effective diagnostic and treatment approaches that can enhance functional capability and ultimately promote a higher quality of life for patients with abnormalities of the genitourinary system. While the neurologist can successfully serve as the principal care provider for such patients, close collaboration with the urologist substantially adds value to the multidisciplinary management of those with spinal cord disease.

KEYPOINTS: à

Patients with myelopathy frequently present with major problems with pelvic organ function. A comprehensive approach that integrates the assessment and treatment of bowel, bladder, and sexual dysfunction represents the strategy with the greatest likelihood of achieving satisfactory results.

CASE-ORIENTED MULTIPLE CHOICE QUESTIONS þ

A woman of 45 with secondary progressive MS complains of worsening bladder control.

Despite taking 2.5 mg oxybutynin t.d.s. she had daily episodes of urge incontinence and wets the bed at night at least twice a week. The most appropriate next step in establishing more effective management is: A. B. C. D. E.

Spinal cord MRI. Cystometry.

Measurement of post micturition residual urine volume.

Cystoscopy.

Measurement of pudendal evoked potential.

The answer is C. Post micturition residual urine is a significant cause of symptoms of storage dysfunction. Oxybutynin will reduce the amplitude and frequency of unstable contractions and also increase bladder capacity; however, a persistent post micturition residual will decrease the time taken to fill the bladder to capacity. þ

A man of 35 with a diagnosis of relapsing and remitting MS was recovering from a relapse in which there had been spinal cord demyelination with spastic paraparesis and lower limb weakness such that his mobility was reduced to 10 yards (9.1 meters) and he needed a stick to walk. Following a course of steroids, his walking improved somewhat, but he then presented with erectile dysfunction. Although morning erections were preserved, the patient was unable to obtain an erection sufficient for intercourse. The most appropriate initial step in management for the above case is: A. Investigation by a glucose tolerance test.

B. Referral for psychosexual counseling.

C. Consultation during which it is explained to him his ED is an expected result of spinal cord demyelination.

D. MRI of the spinal cord.

E. Nocturnal penile tumescence studies.

59

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

The answer is C. When a patient with an established neurological diagnosis presents with ED there is no requirement to perform investigations, as the likely cause of the ED is neurological. þ

A 40-year-old man with secondary progressive MS describes difficulty with urinary urgency, urge-incontinence and nocturia. There has been no recent history of urinary tract infections.

Which of the following is the most important initial evaluation: A. B. C. D. E.

Urinalysis.

Renal ultrasound.

Cystoscopy.

Prostate specific antigen.

Post-void residual urine measurement.

The answer is E. Again, post micturition residual measurement is the most important test to perform as the neurological diagnosis is certain, a residual is expected in this condition and would account for the symptoms. þA

31-year-old woman presents with an 8-year history of multiple sclerosis. Her clinical course has been characterized by episodes of optic neuritis, transverse myelitis, and bilateral internuclear ophthalmoplegia. Over the last 6 months she has developed moderately severe lower extremity spasticity in association with involuntary jerks and spasms. Examination shows a spastic paraparesis, diffuse hyperreflexia, bilateral extensor plantar responses, bilateral ankle clonus, and a spastic gait. She complains of bowel urgency and also inability of evacuation. Which of the following accurately describes the underlying mechanism for her complaint: A. B. C. D. E.

Constipation from poor neuro-gastrointestinal signaling.

Immobility.

Weak abdominal muscles.

Reduced gastrocolic reflex.

Pelvic floor muscular spasticity (recto-sphincter dyssynergia).

The answer is E. Patients with MS present with a wide variety of bowel complaints from constipation to fecal incontinence, especially of loose stools. However, in this case, the combination of fecal urgency and difficulty in evacuation indicate that pelvic floor muscular spasticity is the underlying problem. þ

A 51-year-old woman with secondary progressive MS has recently ceased to have menstrual periods and now complains of hot flushes, depression, sexual dysfunction and fatigue. Her MS history includes two episodes of partial sensory transverse myelitis that left her with residual dysesthesias in the lower extremities and in the perineum. In terms of her sexual dysfunction, with a specific focus on treatment intervention, all of the following are important to explore initially except: A. B. C. D. E.

Vaginal lubrication.

Serum testosterone levels.

Ability to become aroused and achieve orgasm (sensory threshold).

Current use of antidepressants.

Pain during sexual activity.

The answer is B. A raised testosterone level would be the most unexpected cause of female sexual dysfunction in this case, given that there is an established neurological diagnosis that would account for her symptoms.

60

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

References continued Ăž

[13] Betts CD, Jones SJ, Fowler CJ. Erectile dysfunction in multiple sclerosis: associated neurological and neurophysiological deficits, and treatment of the condition. Brain 1994;117:1303-10.

Comprehensive analysis of sexual dysfunction in MS. [14] Muller H. Studies on disseminated multiple sclerosis. Acta Med Scand 1949;222:67-71.

Early study of sexual dysfunction in MS. [15] Fowler CJ, Miller J, Sharief M. Viagra (sildenafil citrate) for the treatment of erectile dysfunction in men with multiple sclerosis. Ann Neurol, 1999;46:497.

Initial observations on the role of Viagra in men with MS and erectile dysfunction.

[16] Hinds J, Eidelman B, Wald A. Prevalence of bowel dysfunction in multiple sclerosis: a population survey. Gastroenterology 1990;98:1538-42.

Population survey of bowel dysfunction in MS. [17] Chia YW, Fowler CJ, Kamm M et al. Prevalence of bowel dysfunction in patients with multiple sclerosis and bladder dysfunction. J Neurol 1995;242:105-8.

Majority of MS patients experience bowel dysfunction.

[18] Glick E, Meshkinpour H, Haldeman S et al. Colonic dysfunction in multiple sclerosis.

Gastroenterology 1982;83:1002-7.

Mechanisms of bowel dysfunction in MS. [19] Dasgupta P, Hussain IF. Tropical spastic paraparesis. In: Fowler CJ, editor. Neurology of bladder, bowel, and sexual dysfunction. Boston: Butterworth-Heinemann; 1999. p. 315-24.

Superb review.

[20] Arnold EP. Spinal cord injury. In: Fowler CJ, editor. Neurology of bladder, bowel, and sexual dysfunction. Boston: Butterworth-Heinemann; 1999. p. 275-88.

Excellent review on the neurourology of spinal cord injury.

[21] Glickman S, Kamm M. Bowel dysfunction in spinal cord injury patients. Lancet 1996;347:1651-3.

[22] Giuliano F, Hultling C, Masry E et al. Randomized trial of sildenafil for the treatment of erectile dysfunction in spinal cord injury. Ann Neurol 1999;46:15-21.

Large placebo controlled trial showing efficacy of Viagra in men with spinal cord injury.

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KEYPOINTS:

CHAPTER 6

à

Nerves from the cauda equina provide the motor and sensory innervation of the lower limbs and pelvic organs.

à

Disorders affecting the cauda equina are characterized by weakness and sensory loss in the lower limbs, buttocks and perineum, usually with important abnormalities of bladder, bowel and sexual function.

CAUDA EQUINA DISORDERS ANATOMY The spinal cord tapers to its end, the conus medullaris, usually at the lower edge of the first lumbar vertebra. The continuation of the spinal cord is a strand of connective tissue, the filum terminale. The ventral and dorsal lumbar and sacral nerve roots that arise from the conus medullaris form a bundle, the cauda equina (Figure 1). These lumbar and sacral spinal nerve roots separate in pairs to exit laterally through the nerve root foramina.

The main destinations for these roots are the lumbar and sacral plexuses. Nerves from these plexuses provide the motor and sensory innervation of the lower limbs and pelvic organs. The cauda equina, like the spinal cord, is invested by the meninges. The arachnoid membrane envelops it loosely as the thecal sac.

TABLE 2

Causes of chronic cauda equina compression

Extrinsic tumors Primary tumors arising from the cauda Spinal stenosis • Degenerative spondylosis • Achondroplasia • Fluorosis Chronic central disk herniation Abscess; tuberculoma

DISORDERS Disorders affecting the cauda equina are characterized by weakness and sensory loss in the lower limbs, buttocks and perineum, usually with important abnormalities of bladder, bowel and sexual function. The causes of cauda equina damage are listed in Tables 1 and 2.

Central disk herniations. Disk herniations usually occur in a dorsolateral direction, thereby leading to compression of individual spinal nerve roots after they have separated

TABLE 1

Causes of acute cauda equina damage

Central disk herniation Vertebral collapse due to metastatic infiltration Spinal subarachnoid hemorrhage

Dorsal view of the lower lumbar spine and sacrum.

The laminae of the vertebrae have been removed, showing the cauda equina and nerve roots in the spinal canal, then leaving through the nerve root foramina. For clarity, only the ventral rami of the sacral spinal nerves are shown.

FIGURE 1

Acute extradural hematoma Trauma

From Stewart JD. Focal peripheral neuropathies, 3rd ed. Lippincott, Williams and Wilkins; 1999. Reproduced with permission.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

anesthesia” (Figure 3). Smaller herniations produce a more limited syndrome of mainly saddle anesthesia and sphincter dysfunction (see Case 1). Some central disk herniations produce the opposite clinical picture: the roots that lie more laterally in the cauda equina — the lower lumbar and upper sacral roots — may be most affected, while the centrally lying S3-S5 roots are spared, and thus sphincter function is normal [1].

Other causes of acute cauda equina lesions are rare.

These include vertebral collapse due to metastatic infiltration, spinal subarachnoid FIGURE 2 Dorsal view of the lower lumbar spine and sacrum, showing the different types of hemorrhage from a vascular disk herniation. Note, particularly, the central L4-L5 central disk herniation. malformation or ependyFrom Stewart JD. Focal peripheral neuropathies, 3rd ed. Lippincott, Williams and Wilkins; 1999. moma, and an acute extraReproduced with permission. dural hematoma.

Chronic central disk herniations mimic tumors of the KEYPOINTS: from the cauda equina. Such individual conus medullaris or cauda equina. Back pain radiculopathies will not be discussed further and radicular sensory symptoms may be à Large acute central here. Central disk herniations comprise less absent, and the presenting complaints are disk herniations prothan 3% of all disk herniations (Figure 2). often perineal pain or paresthesias, urinary duce a dramatic and The disk usually involved is L4-L5, but dysfunction and erectile dysfunction (ED) in serious syndrome of herniations at other levels can occur; they all men. The physical signs are similar to those of bilateral sacral, buttock, perineal and posproduce a similar syndrome. The symptoms acute central disk herniation. terior leg pain and and signs vary depending on the rate and Primary tumors of the cauda equina. numbness, weakness in extent of the herniation, the size of the Ependymomas and neurofibromas are the the legs, and sphincter spinal canal, and the number of nerve roots most frequent primary tumors of the cauda dysfunction. involved. Because the sacral roots lie closest equina; rarer types include meningiomas, lipoà An important feature to the midline in the cauda equina, they bear mas, dermoid tumors, schwannomas, hemanof the pain is that the brunt of the damage. gioblastomas, and paragangliomas. An intrait is usually not Large acute central disk herniations produce medullary spinal tuberculoma can also mimic relapsing and a dramatic and serious syndrome of bilateral a conus tumor. remitting, and it may worsen with recumsacral, buttock, perineal and posterior leg pain The main symptoms are pain, which is bency and be particuand numbness, weakness in the legs, and variably located in the low back, sacral, butlarly severe during the sphincter dysfunction. Examination usually tock or perineal areas. This pain can be of night. shows weakness in the S1 and S2 innervated sudden or gradual onset. A herniated intermuscles (gastrocnemius, hamstrings, gluteal vertebral disk or spondylosis is, therefore, the muscles), variable sensory loss extending from usual initial diagnosis. An important feature the soles of the feet to the perianal region, a of the pain is that it is usually not relapsing patulous anal sphincter, and loss of the anal and remitting, and it may worsen with recumwink and bulbocavernosus reflexes. This pat- bency and be particularly severe during the tern of sensory loss restricted to the medial night (see Case 2). Symptoms of nerve root buttocks and perianal area is termed “saddle compression usually develop later, sometimes

64

is often abnormal, lumbar scoliosis or lordosis may be present, and deficits due to root compression vary from none to being widespread. The classical signs of saddle anesthesia and a patulous anus are valuable, but are infrequently present.

There are several other, less common, ways in which cauda equina tumors can present. Some paFIGURE 3 The dermatomes subserving the perineal and buttock areas. tients have progresInvolvement of the S3-S5 dermatomes bilaterally gives rise to sive painless weakthe clinical sign of saddle anesthesia, characteristic of many cauda equina ness of the legs that lesions. may be misdiagFrom Haymaker W, Woodhall B. Peripheral nerve injuries: principles and nosed as generalized diagnosis. Philadelphia: Saunders; 1953. Reproduced with permission. peripheral neuropathy or spinal muscular atrophy. Occaeven many years later. They include pares- sionally, sphincter disturbances are the first thesias, leg weakness, and often bladder dis- and only symptom and no neurological signs turbances; bowel and ED are less common. are present; a cauda equina tumor is discovThere are no particular characteristic features ered years later when back pain and radicuon physical examination. Straight leg raising lar symptoms appear. One rare, but distinc-

CASE 1 This 34-year-old woman had been healthy, apart from a 10-year history of chronic low back pain. She presented at the Emergency Room with worsening of the low back pain over the last 10 days, but because, in particular, on the previous day, she had developed a new, severe pain in the perineal and sacral area. A few hours later, she noted numbness in the perineum and increased urinary frequency. She felt that she was not emptying her bladder completely. She also had some increased frequency of bowel movements and defecation was painful. She denied any weakness in the legs.

On examination, she was in pain. The abnormalities were restricted to the lower limbs. Straight leg raising was markedly limited bilaterally. Power was normal in the legs. The right ankle reflex was absent. Sensory examination showed marked diminution of light touch and pin prick in the perineal and perianal areas. A rectal examination showed reduced rectal tone.

A diagnosis of a central lumbosacral disk herniation was made and a CT scan was performed. This showed a large posterior disk herniation at L4-L5 (Figures 1 and 4). She underwent surgical diskectomy within hours. The following day, her back pain was considerably better and sensation in the perineum and bowel function gradually returned to normal. Bladder function was normal from the first postoperative day.

Comment: This history is characteristic of an acute central disk herniation causing cauda equina compression. Urgent imaging for confirmation of the diagnosis and urgent surgery are required in order to optimize the patient’s chances of a good recovery of bladder and bowel function.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

CASE 2 This 73-year-old man had suffered from diabetes mellitus which had been controlled by oral hypoglycemic agents for the last 18 years. He was referred for evaluation with a history of pain in the anal, sacral, right gluteal area, and the posterior aspect of the upper right thigh over the last 3 years. The pain was consistently brought on by lying down and relieved by standing. He had to sleep in a reclining chair. He denied any motor or sensory symptoms in his legs.

However, for 3 years, he had had erectile dysfunction, would have to get up three times at night to urinate, and had developed constipation that required regular laxatives. A urological evaluation showed no prostatic hypertrophy, and a thorough gastroenterological evaluation revealed no explanation for the constipation.

Neurological examination was completely normal except in the lower limbs. Here the power was normal, but the ankle reflexes were absent, which could have been due to diabetic neuropathy or to bilateral S1 radicular involvement. A careful sensory examination with light touch and pin prick showed no abnormalities anywhere in the legs, and, in particular, this was normal in the sacral dermatomes. Rectal tone was normal.

A myelogram and CT-myelogram scans were performed and these showed an intradural lobulated mass opposite the lower border of the L5 vertebra causing complete obstruction of the sub-arachnoid space. Surgical exploration revealed that the tumor, although largely intradural, did have some extension through the dura and, indeed, through the posterior lamina of the sacrum and into the muscles overlying the sacrum. The tumor was resected almost entirely, which involved removing a few filaments of sacral spinal nerve roots. The pathology of this tumor was greatly debated, the consensus being an atypical schwannoma.

Postoperatively, the patient had urinary retention requiring catheterization. This improved, but from then on, he had to self-catheterize twice a day. The partial constipation and erectile dysfunction continued unchanged. Six years later, the patient had the recurrence of pain, less ability to micturate, requiring increased bladder self-catheterizations, and a marked worsening of the constipation requiring increased laxatives, suppositories, and enemas. Re-examination showed signs of a mild peripheral neuropathy in the feet, presumably due to his diabetes. However, there was a clear reduction in sensation in the perianal area and there was a reduction in anal tone. Further radiological studies showed a large soft-tissue mass producing destruction of the majority of the sacrum and spreading to the soft tissues both anteriorly and posteriorly to the sacrum. A biopsy was performed and again the pathology was debated, but the consensus was that this represented a malignant schwannoma. The patient had radiotherapy and there was some reduction in the bulk of the tumor as seen on CT scanning. The pain disappeared, but the bladder and bowel dysfunction remained unchanged. The patient died 8 years later of unrelated causes.

Comment: The pattern of pain in this patient, particularly pain that is worsened by lying and relieved by standing, is characteristic of cauda equina mass lesions. Although the patient’s erectile, bladder and bowel symptoms at the time of presentation could have been attributed to his long-standing diabetes mellitus, in the context of this type of pain, it was thought to be due to involvement of the cauda equina.

KEYPOINTS: Ă

Compression of the conus medullaris or the cauda equina can produce the classic picture of saddle anesthesia and loss of sphincter control, but more often it gives rise to patchy and asymmetrical motor and sensory loss, with variable sphincter involvement.

66

tive, feature of cauda equina tumors (particularly ependymomas) is their propensity to bleed, causing spinal subarachnoid hemorrhage. This usually occurs in young patients with a long history of low back pain, who then have an acute episode of severe headache and neck stiffness followed by increased back pain and sciatica. Finally, cauda equina tumors can present with the cauda equina claudication syndrome (see below).

Other types of malignant disease involving the cauda equina. Vertebral metastases (most commonly from breast and prostate cancer), primary bone tumors (e.g. chordoma), or multiple myeloma can cause one or more of the following: compression of a nerve root or roots in the foramen; gradual compression

of the conus medullaris or cauda equina; collapse of a vertebra, often acutely compressing the entire cauda equina; and invasion of the paravertebral area involving the spinal nerves outside the foramina or the lumbosacral plexus itself.

The initial symptom is usually low back pain, which precedes other symptoms from a few days to 2 years. Pain radiating into the legs is less frequent. Compression of the conus medullaris or the cauda equina can produce the classic picture of saddle anesthesia and loss of sphincter control, but more often it gives rise to patchy and asymmetrical motor and sensory loss, with variable sphincter involvement.

Other forms of metastatic dissemination include diffuse meningeal carcinomatosis,

nodular metastases in the meninges of the cauda equina and nerve roots, and intramedullary metastasis to the conus medullaris. In its full-blown form, meningeal carcinomatosis presents with the triad of headache, cranial neuropathies, and lumbosacral radiculopathies [2]. But early in its course, the predominant features are usually low back pain radiating into the legs, leg weakness and numbness, and bladder dysfunction. The neurological deficits in the lower limbs are very variable. This diagnosis should be suspected in a patient with a known malignancy (usually of the breast or lung), and it is confirmed by finding malignant cells in the cerebrospinal fluid. Nodular metastases to the meninges also cause radicular dysfunction that varies in degree and site. These usually occur in patients with lymphomas and leukemias, although carcinomas sometimes produce nodular deposits rather than diffuse meningeal infiltration.

Metastases to the conus medullaris are rare, but when they occur, they produce symmetric involvement of the lower sacral spinal nerve roots, simulating a cauda equina lesion.

Trauma to cauda equina. Severe injuries to the lower spine, as in high velocity impacts in motor vehicle accidents or falls from great heights, will often injure the cauda equina.

Stabbings, gunshot and shrapnel wounds are other causes of such an injury. These patients usually have many other associated injuries.

Congenital malformations. Congenital malformations of the distal spinal cord often involve the cauda equina. Such malformations constitute part of a larger group of congenital neurological disorders termed spinal dysraphism. Myelomeningocele is the most frequent and important of these. Discussion of myelomeningocele falls outside the scope of this chapter, but it is important to note that these patients should be under the long-term care of a urologist since they are at risk of developing upper urinary tract dilatation and serious impairment of renal function.

The tethered cord syndrome (TCS) can present in patients with known spinal dysraphism (usually myelomeningocele), usually already operated on, or in patients without known dysraphism; the latter group is discussed here.

This disorder consists of conus medullaris and cauda equina dysfunction caused by the tethering and longitudinal traction on the conus

by abnormal structures, such as a thick filum terminale or a lipoma [3]. TCS usually presents in childhood with sensorimotor symptoms and signs, often in both legs, bladder dysfunction, and skeletal abnormalities, such as scoliosis or foot deformity. There may be other features of a dysraphic state — myelomeningocele, subcutaneous lipomas, or a sacral hairy patch.

Less well recognized is TCS in adults.

Some of these patients have lifelong neurological and/or skeletal deformities, while others are normal until symptoms and signs developed in adulthood. These late presentations can occur even in the elderly, and are easily confused with spinal stenosis. Patients with TCS characteristically have pain localized to the anal, perineal and gluteal areas, sometimes radiating diffusely down the legs; radicular type pain is uncommon. Bladder dysfunction is a prominent symptom; this usually consists of urinary urgency due to a hyperreflexic bladder, sometimes in combination with sphincter weakness contributing to incontinence. Leg weakness is usually present with several myotomes often involved bilaterally. An important feature that may be present is upper motor neuron signs, such as extensor plantar responses; these are due to distal spinal cord involvement. Imaging studies show the presence of a thickened filum or lipoma. Surgical resection of these is very effective for relieving pain and some of the motor and sensory deficits, but bladder function seldom improves.

Lumbosacral spinal stenosis syndromes.

Chronic degenerative disk disease and osteoarthritis of the spine contribute to narrowing of the central canal and/or spinal nerve root foramina — lumbar spinal stenosis (LSS). The resulting symptoms can be classified as (a) radicular, (b) cauda equina claudication, and (c) weakness.

Chronic radicular symptoms are similar to those of acute radiculopathy, but often less severe. Pain is present in the lower back and radiates into one or both legs. Cauda equina claudication is the hallmark symptom of spinal stenosis. Synonyms include pseudoclaudication, neurogenic intermittent claudication, and intermittent ischemia of the cauda equina.

It consists of various combinations of low back, buttock and leg pain, and/or paresthe-

KEYPOINTS: à

Myelomeningocele falls outside the scope of this chapter, but it is important to note that these patients should be under the longterm care of a urologist since they are at risk of developing upper urinary tract dilatation and serious impairment of renal function.

à

Chronic degenerative disk disease and osteoarthritis of the spine contribute to narrowing of the central canal and/or spinal nerve root foramina — lumbar spinal stenosis (LSS).

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

sias brought on or exacerbated by walking Spinal dural arteriovenous fistulas. Spinal and often just by standing. A few patients dural arteriovenous fistulas are a distinct type also have leg weakness occurring at this time. of spinal vascular malformations. They are Symptoms are relieved by sitting and resting usually located in the lower thoracic or lumbar for many minutes, by contrast with the brief spine, usually occurring in middle-aged and rest of less than a minute required to relieve older men. The symptoms are remarkably true vascular claudication. Chronic leg weak- similar to those of spinal stenosis. The diagness is infrequent as the predominant symp- nosis is often best made by myelography and tom of spinal stenosis. Bladder dysfunction angiography, though CT and MR imaging also is an uncommon feature of LSS, but in indi- add useful information. vidual patients may be prominent. Because Spinal arachnoiditis. This can develop these patients are usually elderly, prostatism anywhere in the meninges, but the lumbois more likely to be the cause of such symp- sacral region is most commonly affected [5]. toms. When LSS is the result of ankylosing The arachnoid becomes thickened, scarred, spondylitis, marked bladder and bowel dys- and adherent to the pia and dura, obliterating meningeal blood vessels. Single or multiple function is the rule [4].

Physical examination is normal in about half roots within the cauda equina can be affected. of the patients. The others have varying degrees At higher levels, the spinal cord itself is conof motor and sensory abnormalities attribut- stricted. The causes of spinal arachnoiditis are able to involvement of one or more lumbar listed in Table 3. The commonest used to be and/or sacral roots. Patients often adopt a the oil-based contrast agents used for myelogslightly bent forward posture on walking, this raphy. However, considering the large numbeing the position in which the spinal canal bers of myelograms performed, this is a relspace is at its maximum. A unique, though atively rare event. The newer water-soluble uncommon, feature of the cauda equina claudi- contrast agents are safer. Another cause, also cation syndrome is that exercise may unmask rare, is lumbar spinal surgery. The combination of oil-based myelography, spinal stenosis, or worsen the neurological signs.

The main structural abnormality is narrow- and lumbar spinal surgery further increases ing of the spinal canal, although there are often the risk of arachnoiditis. Intrathecal corticosteassociated stenoses of individual nerve root roid injections have been implicated in causforamina. These changes are usually due to ing spinal arachnoiditis, but if they do, it is a a combination of developmental stenosis and superimposed spondylosis.

Other causes include severe spondyTABLE 3 Causes of spinal arachnoiditis losis without congenital narrowing, ankylosing spondylitis, Paget’s disIntrathecal drugs or chemical agents ease, and achondroplasia. Another rare • Radiological contrast agents cause is fluorosis, a condition occur• Local anesthetic drugs • Amphotericin B, methotrexate, corticosteroids(?) ring in areas where the water contains excessive amounts of natural fluoride.

Spinal and epidural anesthesia Although the bones appear excessively Infections dense on X-rays, they are softer than • Tuberculosis normal and develop excessive degen• Cryptococcosis • Syphilis erative changes that cause spinal ste• Viral infections nosis.

Trauma The diagnosis of LSS can some• Spinal surgery times be made on plain X-rays, but • Vertebral injuries is best confirmed by axial views of • Lumbar disk herniation the spine with computerized tomogSpinal subarachnoid hemorrhage raphy (CT) or magnetic resonance Idiopathic (MR) imaging studies (Figure 5). Electrophysiological testing is discussed below.

68

rare occurrence, relating to large doses and/or multiple injections. Spinal epidural anesthesia can also rarely cause arachnoiditis. The damage can be in the lower cervical, thoracic, or lumbar area, and the neurological deficits can be severe. The cause is thought to be chemical irritation, but infection is a possibility.

In some countries, infections (mainly tuberculosis) are an important cause of arachnoiditis. Tuberculous meningitis usually presents as a chronic cranial meningitic syndrome with headache and fever being cardinal features.

The spinal meningitis form is less frequent and may lead to spinal arachnoiditis. In the cauda equina, this produces thecal scarring, nodularity, thickening and clumping of the nerve roots.

The symptoms of arachnoiditis are constant low back pain usually radiating into both legs, and motor and sensory symptoms in the legs. Bladder dysfunction is infrequent except in advanced cases. The symptoms may begin within days of the damage to the arachnoid or there may be a delay of many years. Examination usually shows involvement of more than one lumbar or sacral nerve root, and the motor deficit ranges from being mild to a devastating paraplegia.

CT scanning, CT myelography and MR imaging will confirm the diagnosis. The last of these is preferred, not only because of highly diagnostic images, but because it avoids further intrathecal injections.

Cauda equina complications of epidural and spinal anesthesia. Serious neurological complications of these procedures are rare.

Delayed arachnoiditis has been described already. Other complications attributed to damage or irritation of the lumbar and spinal nerve roots become apparent after the effects of the spinal anesthesia have worn off. An increasingly recognized syndrome is that of transient radicular irritation (TRI) (also called transient neurological syndrome — TNS) [6], but bladder and bowel function are not affected, so this will not be discussed further here. Longer lasting sequelae are very rare and generally improve with time, but may be permanent. They include paresthesias in one or both legs in various areas, and focal or more generalized weakness. More serious is a cauda equina syndrome of bilateral leg weak-

ness, extensive sensory loss, and urinary and fecal incontinence [7]. This may occur when higher than usual doses of local anesthetic are used. Another risk factor is spinal stenosis. Such patients may be asymptomatic from this point of view preoperatively, so this risk factor is unsuspected. Recovery may be slow and incomplete.

Viral cauda equina syndromes. The cytomegalovirus cauda equina syndrome is a dramatic and serious infectious disorder occurring in patients with acquired immune deficiency syndrome (AIDS) [8]. Low back pain and urinary disturbances are early symptoms, followed by asymmetric leg weakness and sensory loss that extends into the saddle area.

This usually rapidly advances to a flaccid paraplegia with bladder and bowel incontinence. The cerebrospinal fluid shows abnormalities indicative of acute infection, and cultures grow cytomegalovirus (CMV); there is also usually evidence of CMV infection in other organs. Antiviral agents effective against CMV may arrest the course, or partially reverse it, so early diagnosis is important. Lymphomatous meningitis and syphilis are other disorders producing a similar syndrome in patients with AIDS. Genital herpes simplex infections may cause a neurological syndrome consisting of urinary retention, constipation, and sacral pain or numbness [9]. Examination usually shows a lax anal sphincter, absent bulbocavernosus reflexes, sensory loss in the lower sacral dermatomes, variable loss of deep tendon reflexes in the legs, and herpetic genital ulcers. Spontaneous recovery usually occurs, though treatment with antiviral agents may hasten the recovery. Although the sensory abnormalities in herpes infections are known to be due to virus invasion of the dorsal root ganglia, the exact site and mechanism of the motor neuron damage is unknown. The damage may be in the motor neuron cell bodies in the spinal cord, or in the nerve fibers within the lumbosacral spinal nerves, plexus, or peripheral nerves.

KEYPOINTS: Ă

The symptoms of arachnoiditis are constant low back pain usually radiating into both legs, and motor and sensory symptoms in the legs. Bladder dysfunction is infrequent except in advanced cases.

INVESTIGATIONS Electrophysiological testing. Standard nerve conduction and EMG studies of the nerves and muscles of the lower limbs are often useful to confirm or determine damage to nerve roots within the cauda equina. Motor nerve conduc-

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

FIGURE 4

Sagittal (a) and axial (b) T2 weighted MR images of the lumbar spine to show a large central L4,5 disk extrusion (asterisks). The patient had an acute cauda equina syndrome.

From Stewart JD. Focal peripheral neuropathies, 3rd ed. Lippincott, Williams and Wilkins; 1999. Reproduced with permission.

KEYPOINTS: Ă

Imaging studies with myelography or CT scanning or MR should be done urgently, and the disk removed surgically.

70

tion studies show reduced amplitudes of compound motor action potentials when axon loss in the spinal nerve roots (L5 and S1 mainly) innervating them has occurred. Electromyographic (EMG) studies often show chronic neurogenic changes in leg muscles in a pattern reflecting the nerve roots involved. Muscles innervated by L2-S2 roots can be evaluated in this way. Finding such abnormalities in proximal muscles, such as the glutei, helps to differentiate patients with severe chronic cauda equina syndromes from a chronic axonal polyneuropathy (the latter producing distal much greater than proximal abnormalities in muscles). Paraspinal muscle denervation localizes the abnormalities to the roots rather than plexus or more peripheral level. Sensory nerve action potentials in the legs are usually normal because the spinal nerve roots are compressed proximally to their dorsal root ganglia. This finding is also useful in differentiating cauda/root lesions from those of the lumbosacral plexus, or more distal nerves of the legs.

Electrophysiological techniques may also be used to evaluate lesions of the lower sacral roots, spinal nerves and the sacral plexus, as described in Chapter 1.

Imaging studies. Plain radiographs may be very useful in revealing lesions causing cauda equina damage, such as bone tumors and severe degenerative spondylosis. Isotope bone scans are useful in demonstrating malignant lesions in the vertebrae. CT scanning, CT myelography, and particularly MR are the imaging techniques of choice for most disorders of the cauda equina (Figures 4 and 5).

MANAGEMENT Acute central disk herniation. Imaging studies with myelography or CT scanning or MR should be done urgently, and the disk removed surgically. Delays in treatment lessen the chance of good recovery of bladder, bowel and sexual function (see Case 1).

Spinal stenosis. Management decisions in spinal stenosis are complicated by several factors: (a) the natural history of the disorder

is poorly understood, as are FIGURE 5 CT myelogram: indicators of prognosis, but in axial view through the most patients, the course is relL4,5 disk space showing severe spinal atively benign; (b) the patients stenosis in a patient with a chronic are often elderly and have cauda equina syndrome. The thecal sac is extremely small and a tiny other medical problems; (c) amount of contrast is seen among the there is little consensus regardtightly clumped roots of the cauda ing the correlation between equina (white arrow). This narrowing the imaging abnormalities and is caused by: (a) diffuse bulging of symptoms, and with surgical the disk; (b) marked thickening of the ligamentum flavum (asterisks); outcomes; (d) there are no good and (c) facet joint hypertrophy. The studies comparing conservasmall dark triangle outlined by the tive measures and surgery; (e) diminutive thecal sac and the the best surgical procedures are ligamenta flava is epidural fat. debated; and (f) there is a wide From Stewart JD. Focal peripheral variability and a degree of neuropathies, 3rd ed. Lippincott, inadequacy in reports describWilliams and Wilkins; 1999. ing surgical results.

Reproduced with permission.

Conservative treatments are widely mentioned in the literature, but there is a paucity of critical evaluations regarding specific methods and their outcomes. carcinomatosis is treated in the same way and There is considerable divergence of opinion with intrathecal chemotherapy, but the results regarding the outcome of surgery. A useful are usually poor. generalization is that two-thirds of patients Treatment of bladder, bowel and sexual either stabilize or improve after surgery. dysfunction. Treatment of symptoms arising Other disorders. The treatment of arach- from cauda equina damage are those described noiditis is notoriously difficult. Intrathecal ste- in Chapters 2, 3 and 4, respectively. The type roids have been tried, but are usually ineffec- of bladder dysfunction often includes a protive, and can possibly worsen the situation. nounced element of incomplete bladder empActive infections, such as tuberculosis, have tying, but detrusor hyperreflexia can also to be treated. Attempts at surgically remov- occur (see Chapter 2). Weakness of the urethral ing the adhesions around the roots are usu- sphincter can lead to urinary stress incontially unsuccessful, although other reports con- nence. tradict this view [10,11]. Others have found Patients with cauda equina lesions have that only milder cases benefit from surgery a lax perineum, an altered sensation of [12]. For treating chronic severe pain, long- fecal urgency and perianal numbness. These term analgesics or dorsal column stimulators patients often need to manually evacuate the are often required. The neurological deficits rectum once a day or more to stay continent. usually gradually worsen, but eventually sta- Incontinence of flatus is an additional probbilize. lem that is extremely embarrassing for these Primary tumors of the cauda equina are patients who are very often ambulant and usually surgically removed (see Case 2). Met- show no outward stigmata of neurological astatic tumors are usually treated with a com- disease. bination of radiotherapy and chemotherapy; Treatment of ED may not be successful relief of pain is often excellent, though the because of concomitant penile sensory impairneurological deficits often remain. Meningeal ment.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

CASE-ORIENTED MULTIPLE CHOICE QUESTIONS þ

A 30-year-old otherwise healthy man has a 4-year history of lower back pain. Over a 24-hour period, this pain has markedly worsened and, in addition, he finds he needs to strain to urinate and to defecate, and notices that his anal area feels numb. Which of the following is the likely diagnosis?

A. B. C. D. E.

A metastasis to the L4 vertebra.

Acute cytomegalovirus infection of the cauda equina.

A central lumbar disk herniation.

A rapidly growing malignant lesion in the pelvis.

Acute transverse myelitis of the thoracic spinal cord.

The answer is C. This is the characteristic story of a central lumbosacral disk herniation — years or months of nonspecific lower back pain, then an acute worsening of the pain and the development of bladder and bowel symptoms and perineal sensory loss. þ

On examination of the patient described above, which clinical sign is important in supporting your diagnosis?

A. B. C. D. E.

A lax anal sphincter on rectal examination.

Hyperactive tendon reflexes in the legs.

Extensor plantar responses.

A sensory level to the mid-abdomen level.

An absence of pain on gentle squeezing of the testicles.

The answer is A. The easiest way to quickly detect serious involvement of the lower sacral nerve roots is to do a rectal examination for reduced anal sphincter tone. þ

In this clinical setting, which is the most appropriate diagnostic test?

A. B. C. D. E.

Nerve conduction and electromyography (EMG) studies.

Lumbosacral spine plain X-rays.

Lumbosacral spine isotope bone scan.

Lumbosacral spine CT scan.

Lumbar puncture.

The answer is D. A plain CT scan will reliably show a large central disk herniation most of the time. Plain X-ray films may show disk space narrowing which is very non-specific and so are essentially useless. An isotope bone scan is best used for metastases which may cause an acute cauda equina syndrome if there is bony collapse, but will not show an acute disk herniation. A CT scan will reliably show not just the herniation, but also other unusual causes of acute cauda compression, including bone metastases, hemorrhages, etc. þ

In this diagnosis, what is the appropriate treatment?

A. B. C. D. E.

72

Strict bedrest and anti-inflammatory medication.

A progressive physiotherapy program.

Radiotherapy to the lesion.

Managing the bladder dysfunction with an indwelling catheter, then performing elec tive surgery the following week.

Immediate surgical excision of the lesion.

The answer is E. Speed is required in order to avoid permanent bladder, bowel, sexual dysfunction. Ăž

A 70-year-old man with type II diabetes mellitus has a 2-year history of progressively worsening low back pain. The pain is relieved by standing and aggravated by lying, so he also has difficulty sleeping. In addition, he has become constipated and has recently required laxatives. His urinary stream has weakened to a dribble. Which of the following is the likely diagnosis?

A. B. C. D. E.

Diabetic neuropathy with involvement of the autonomic peripheral nerve fibers.

Degenerative arthritis of the spine, benign prostatic hypertrophy, and age-related non specific constipation.

Prostate cancer with bone metastases.

A cauda equina tumor.

Chronic arachnoiditis.

The answer is D. This is a difficult case scenario. Bladder dysfunction is most often due to prostatic disease in this age group. However, these symptoms, when coexisting with a new onset of constipation, should alert the physician to the possibility of nerve damage. In a diabetic, both of these symptoms, as well as erectile dysfunction, could be attributable to the diabetes (see Chapter 7). However, the symptom of increasing pain with the unusual features described above, is characteristic of a cauda equina tumor.

REFERENCES [1]

Lafuente DJ, Andrew J, Joy A. Sacral sparing with cauda equina compression from central lumbar intervertebral disc prolapse. J Neurol Neurosurg Psychiatry 1985;48:579-81.

This paper points out that some central disk herniations spare the centrally lying roots in the cauda equina. Thus bladder and bowel function is preserved.

[2]

Little JR, Dale AJD, Okazaki H. Meningeal carcinomatosis: clinical manifestations. Arch Neurol 1974;30:138-43.

An old but classic paper describing the manifestations of carcinomatous meningitis, including the involvement of the lumbosacral roots/cauda equina.

[3]

Hoffman HJ, Hendrick EB, Humphreys RP. The tethered spinal cord: its protean manifestations, diagnosis and surgical correction. Childs Brain 1976;2:145-55.

Another old but classic paper describing the various ways in which tethered cord presents at various ages.

[4]

Bartleson JD. Cauda equina syndrome secondary to long-standing ankylosing spondylitis. Ann Neurol 1983;14:662-9.

Points out the under-appreciated fact that ankylosing spondylitis can not only produce a lumbar spinal stenosis syndrome, but when it does so, bladder and bowel function are particularly compromised.

[5]

Esses SI, Morley TP. Spinal arachnoiditis. Can J Neurol Sci 1983;10:2-10.

An older but comprehensive review of this topic.

References continued Ăž

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

References continued Ăž

[6]

Schneider M, Ettlin T, Kaufmann M, Schumacher P, Urwyler A et al. Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5% lidocaine. Anesth Analg 1993;76:1154-7.

This paper outlines some of the complications of spinal anesthesia.

[7]

Yuen EC, Layzer RB, Weitz SR, Olney RK. Neurologic complications of lumbar epidural anesthesia and analgesia. Neurology 1995;45:1795-1801.

Excellent review of the topic, with case descriptions of some of the complications discussed.

[8]

Behar R, Wiley C, McCutchan JA. Cytomegalovirus polyradiculoneuropathy in acquired immune deficiency syndrome. Neurology 1987;37:557-61.

The definitive paper describing this acute and usually devastating condition. The lesson is that it has to be recognized and treated early.

[9]

Oates JK, Greenhouse PR. Retention of urine in anogenital herpetic infection. Lancet 1978;1:691-2.

An excellent description of this generally under-recognized syndrome.

[10] Shikata J, Yamamuro T, Iida H, Sugimoto M. Surgical treatment for symptomatic spinal adhesive arachnoiditis. Spine 1989;14:870-5.

See below.

[11] Dolan RA. Spinal adhesive arachnoiditis. Surg Neurol 1993;39:479-84.

See below.

[12] Roca J, Moreta D, Ubierna MT, Caceres E, Gomez JC. The results of surgical treatment of lumbar arachnoiditis. Int Orthopaed 1993;17:77-81.

These papers discuss the possibilities or otherwise of attempting to treat, particularly surgically, this disorder. The argument for surgical intervention remains unconvincing.

74

CHAPTER 8

KEYPOINTS:

PARKINSONIAN DISORDERS AND PURE AUTONOMIC FAILURE INTRODUCTION Disorders of bladder, bowel and sexual function are common problems in Parkinson’s disease (PD), multiple system atrophy (MSA) and pure autonomic failure (PAF). Although the pathology of PD and MSA is quite different and distinct, the differential diagnosis of the conditions in life, particularly in the early stages, may be difficult and the presence of autonomic failure, as indicated by postural hypotension, may assist in the differential diagnosis. Figure 1 shows the major clinical features of these various disorders and the relationship between them [1]. However, it should be noted that the pathophysiological cause of postural hypotension does not necessarily also cause bladder, bowel and sexual dysfunction in these diseases and pelvic organ disorders may occur without postural hypotension.

In patients with PD, pelvic organ dysfunction usually occurs late in the course of the disease and is not associated with postural hypotension. MSA is commonly misdiagnosed as PD, but pelvic organ dysfunction usually occurs early in the course of the disease, before the onset of symptoms of hypotension and it is often the prominent complaints of bladder and sexual dysfunction which raise the suspicion of the correct diagnosis.

Although the commonest presentation of MSA is as a parkinsonian syndrome (striatonigral degeneration: SND) (Case 1), cerebellar syndrome (olivopontocerebellar atrophy: OPCA) and autonomic disorder (Shy-Drager syndrome) (Case 2) may also occur. PAF is a sporadic disorder characterized by widespread autonomic failure without other neurological features. It usually occurs in older age and has a less rapidly progressive course than MSA. In all these disorders, complaints of bladder, bowel and sexual dysfunction may add considerably to the patients’ disabilities. The neurologist needs to be aware of the possible

à

Although the pathology of PD and MSA is quite different and distinct, the differential diagnosis of the conditions in life, particularly in the early stages, may be difficult and the presence of autonomic failure, as indicated by postural hypotension, may assist in the differential diagnosis.

à

Much of the attention to autonomic failure in MSA has focussed on postural hypotension which is considered to be a marker for autonomic involvement. Urinary dysfunction has attracted less attention.

diagnostic significance of such symptoms as well as the various treatments available for the conditions.

DISORDERS OF MICTURITION MSA. Much of the attention to autonomic failure in MSA has focussed on postural hypotension which is considered to be a marker for autonomic involvement [2]. Urinary dysfunction has attracted less attention, despite the fact that both of the two original patients with Shy-Drager type had urinary frequency, incontinence and urinary retention. A recent study has shown that over 90% of all three variants of MSA patients had urinary symptoms, whereas only 43% had symptoms of

FIGURE 1

The major clinical features of syndromes of primary chronic autonomic failure and Parkinson’s disease.

From Mathias C. Autonomic disorders and their recognition. New Engl J Med 1997;336:721-4.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

micturition are more common and occur earlier than orthostatic hypotension in MSA. The urodynamic features of these 128 patients with MSA were also analyzed [3]. Fiftytwo percent had a raised postmicturition residual volume of more than 100 ml. Detrusor hyperreflexia was demonstrated in 56%, reduced compliance in 31%, and detrusor atonia in 5%.

Sphincter EMG showed detrusor-sphincter dyssynergia in 45% and changes due to chronic reinnervation were found in 74% of the patients, in keeping with other reports [4,5]. A subcutaneous injection of Bethanechol (2.5 mg) showed abnormal increment of detrusor pressure > 15 mm H2O after 30 minutes in 19%, suggesting cholinergic denervation supersensitivity. The balance of pathophysiology may change during the course of the disease so that whereas early on symptoms due to detrusor hyperreflexia are prominent, as the disease progresses symptoms may change to those due to incomplete bladder emptying with low compliance and atonic bladder [3].

The sites of neurological involvement responsible for the urinary dysfunction in MSA FIGURE 2 (a) Urinary and orthostatic symptoms in patients with MSA. (b) Urinary and orthostatic symptoms in three variants: OPCA type, SND type and Shy-Drager are probably both central and type. peripheral and have been illustrated in Figure 3. These include From Sakakibara R et al. Urinary dysfunction and orthostatic hypotension in multiple neuronal degeneration and glial system atrophy: which is the more common and earlier manifestation. J Neurol Neurosurg cytoplasmic inclusions (GCIs) in Psychiatry 2000;68:65-9. the pontine micturition center (PMC), the putamen, the subKEYPOINTS: orthostatic hypotension [3] (Figure 2). In some stantia nigra, sacral intermediolateral (IML) patients, urinary symptoms were the sole pre- and Onuf’s nuclei, and possibly some involveà The sites of neurosenting complaints (Case 3) and these included ment of the frontal cortex and postganglionic logical involvement difficulty in voiding (79%), nocturnal urinary cholinergic fibers. responsible for the urifrequency of more than twice (74%), sensation Changes of chronic reinnervation on EMG nary dysfunction in MSA are probably both of urgency (63%), urge incontinence (63%), of the anal or urethral sphincter have been central and peripheral. daytime frequency of more than eight times used as a test to recognize MSA (Figure 4) [6].

(45%), nocturnal enuresis (19%) and urinary These changes reflect the selective degenerretention (8%) (see Figure 2). Disorders of ation of the Onuf’s nucleus, the group of

86

KEYPOINTS: à

Because PAF is a much less common disorder than MSA, the precise incidence of bladder dysfunction in PAF is uncertain.

Schematic presentation of the central neural structures as for urinary and cardiovascular dysfunction in MSA. Commonly affected sites critical for urinary function include the basal ganglia, the pontine micturition centre, the lumbosacral spinal cord (IML) and Onuf’s nucleus.

Commonly affected sites critical for cardiovascular function include catecholamine-containing medullary nuclei and the thoracic spinal cord (IML nuclei).

FIGURE 3

sacral anterior horn cells. Because in PD the anterior horn cells of Onuf’s nucleus are not affected, sphincter EMG has been proposed as a means of distinguishing between PD and MSA, although there is disagreement about this [7]. In some patients with MSA, the degeneration of Onuf’s nucleus may lead to sphincter weakness, thus causing stress incontinence with low urethral closure pressure.

PAF. Because PAF is a much less common disorder than MSA, the precise incidence of

bladder dysfunction in PAF is uncertain. A recent study investigated micturition function of six patients who met the criteria of clinical findings and autonomic function tests without abnormal brain magnetic resonance imaging (MRI) [8]. All patients had urinary symptoms (see Table 1). Only one patient had urinary symptoms at the onset of disease, whereas in the others, bladder symptoms appeared following the onset of erectile dysfunction (ED) or orthostatic faintness. Two of six patients

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

CASE 1 History: A 60-year-old man complained of a short-step, festinating gait with postural tremor and rigidity in both hands. Two years earlier, he had been diagnosed with Parkinson’s disease and was commenced on 300 mg of L-Dopa/carbidopa without benefit. He also had urinary urge incontinence and voiding difficulty with postmicturition residuals of 320 ml.

Examination: Neurological examination revealed evidence of a parkinsonian syndrome without evidence of laterality or resting tremor. The patient was unable to perform tandem gait and on turning, his footing was wide-based, suggestive of gait ataxia.

Cystometry with simultaneous sphincter EMG revealed a poorly compliant bladder on filling and detrusor areflexia with detrusor-sphincter dyssynergia (DSD) on voiding. Analysis of the external sphincter EMG showed neurogenic motor unit potentials (MUP) with mean duration over 10 ms.

Management: For his urinary dysfunction, the patient was taught to perform clean, intermittent self-catheterization (CISC).

Comment: This patient did not demonstrate either resting tremor or laterality and this was suggestive of atypical Parkinson’s disease. Detrusor areflexia, DSD and a neurogenic sphincter were all demonstrated on investigation.

Neuro-urological assessment can help to distinguish patients with MSA from those with Parkinson’s disease, the former being the diagnosis in this case.

ganglionic pelvic nerve lesions, respectively.

These findings are in keeping with pathologià Urinary dysfunction cal reports of neuronal cell loss in the IML colusually occurs together umns of the spinal cord, Lewy bodies in the with a higher HoehnIML cells and in the bladder wall in patients Yahr grade. dying of PAF [9].

Urinary dysfunction in PAF appears to be as common, but less severe, than that in MSA (Case 4).

PD. Patients with PD often have bladder symptoms: one survey reported the frequency of urinary dysfunction to be 57% of 97 patients [10] (Figure 5). Similar figures for prevalence, ranging from 40 to 70% have been found in other studies [5,11]. Urinary dysfunction usually occurs together with a higher Hoehn-Yahr grade [12] and is related to striatal presynaptic dopamine depletion shown by in vivo SPECT study, sugFIGURE 4 An example of a motor unit recorded from the anal sphincter of a patient with MSA, gesting urinary dysfuncusing a concentric needle electrode. Extreme changes of chronic reinnervation are tion in PD may reflect seen in this highly polyphasic unit of prolonged duration (36.7 ms). pathology of the disease.

KEYPOINTS:

88

who had had symptoms for more than 10 years had raised postmicturition residuals. Urodynamic findings showed low compliance bladder in two and denervation supersensitivity of the detrusor in two, indicating pre- and post-

TABLE 1

Urinary dysfunction in six patients with PAF Y.I.

F.A.

H.S.

I.M.

S.M.

S.T.

Age at onset (years), sex

59, male

64, female

66, male

64, male

56, male

46, male

Initial symptoms

Impotence syncope

Orthostatic faintness

Orthostatic Voiding difficulty and constipation

Impotence

Orthostatic faintness

Duration (years)

4

4

6

9

10

18

Appearance of minimum rigidity (years after onset)

-

3

6

-

10

16

Autonomic signs and symptoms Orthostatic syncope Horner’s syndrome Laryngeal stridor Perspiratory abnormality Erectile dysfunction Constipation

+ + + +

+ + +

+ + + ? +

+ + ? +

+ + +

+ + + +

Micturitional symptoms Nocturnal frequency Diurnal frequency Urgency Incontinence Hesitancy/prolongation

+ Stress +

+ + +

+ + Urge +

+ + +

+ + + -

+ + +

From Sakakibara R et al. Micturitional disturbance in pure autonomic failure. Neurology 2000;54:499-501.

The common urinary symptoms in PD are urgency, frequency and sometimes, urge incontinence. Urodynamic study shows detrusor hyperreflexia in 45-93% of the symptomatic patients as a cause of filling disorder

FIGURE 5

Urinary dysfunction in Parkinson’s disease.

From Hattori T et al. Voiding dysfunction in Parkinson’s disease. Jpn J Psychiatry Neurol 1992;46:181-6.

[5,9,10]. Sphincter EMG rarely shows denervation which, in contrast, is the common finding in MSA. Some authors have suggested that an impaired relaxation, or bradykinesia, of the external urethral sphincter can result in voiding dysfunction due to bladder outlet obstruction. However, this phenomenon is not common and large postmicturition residuals are rare in PD. Nevertheless, there are still some patients whose main abnormality is hypocontractile detrusor.

The responsible sites for the detrusor hyperreflexia seem to be the nigrostriatal lesions in PD. Experimental studies showed that electrical stimulation of the basal ganglia inhibits micturition reflex in the cat [13], probably by activating striatal GABAergic neurons which descend to the locus ceruleus (PMC). Bladder hyperreflexia occurs in MPTP (1-methyl-4-phenyl1,2,3,6-tetrahydropyridine)-induced parkinsonian animals. There is experimental evidence that D1 repecptors have an inhibitory and D2 a facilitatory effect on the micturition reflex [14].

Therefore, it seems likely that bladder hyperactivity in PD is associated with a reduction in the central dopamine D1 receptors.

KEYPOINTS: à

The responsible sites for the detrusor hyperreflexia seems to be the nigrostriatal lesions in PD.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

CASE 2 History: A 58-year-old man had a new onset of frequent fainting episodes that tended to occur after standing from a sitting position and on walking up stairs. In addition, he noticed dizziness that occurred after urination at night and about half an hour after a meal. He also described erectile dysfunction (ED), frequent urination (three voids per night) and urinary urgency for 2 years preceding the onset of faintness. He had recently begun to have slight slurring of speech.

Examination: Neurological examination showed a mild ataxic dysarthria, incoordination of the limbs and mild rigidity of the hands and the neck. He had a somewhat ataxic, short-stepping gait. Deep tendon reflexes were preserved. On standing, his blood pressure fell from 130/80 to 82/60 mm Hg without an increase in heart rate.

Management: His postural and postprandial hypotension were treated with an indirect sympathomimetic drug. His postvoid residual urine volume was insignificant and so he was commenced on an anticholinergic. Treatment with sildenafil citrate was contraindicated because of his postural hypotension.

Comment: This patient was considered to have the Shy-Drager type of MSA, because the autonomic failure (postural hypotension, urinary dysfunction and ED) preceded cerebellar and extrapyramidal involvement.

Other common autonomic abnormalities in MSA are respiratory (vocal cord paresis, sleep apnea syndrome), gastrointestinal (constipation) and perspiratory (hypohidrosis) involvement. Postprandial hypotension and exerciseinduced hypotension are also features in patients with MSA.

Treatment. The approach to treatment of urinary dysfunction is no different to that of other neurological causes of these symptoms and is discussed in Chapter 2.

Clinical studies examining the effect of dopaminergic agonists on bladder behavior in

CASE 3 History: A 62-year-old man was referred because of gait difficulty that had become apparent 6 months earlier. Five years previously, he had undergone a transurethral resection of the prostate for symptoms of voiding dysfunction and urinary urge incontinence.

However, the operation had failed to decrease his postmicturition residuals and he was taught to perform CISC. Examination: On admission, he had a parkinsonian syndrome with marked ataxia and exaggerated deep tendon reflexes. Extensor plantar reflexes were noted bilaterally. He was also found to have a postural systolic pressure fall of 46 mm Hg (126/86 lying to 80/55 mm Hg on standing), which was only associated with a mild headache in the nuchal area.

Management: He was prescribed 300 mg of L-Dopa/carbidopa with minimal improvement. His urinary urge incontinence was treated with 20 mg of propiverine hydrochloride, an anticholinergic drug.

He still required CISC for his high postmicturition residuals.

Comment: Male patients with MSA sometimes undergo prostate surgery prior to referral to neurologists because MSA can present with isolated genitourinary symptoms initially. In such cases, urinary urgency and frequency can be treated with anticholinergic medications and high postmicturition residuals can be treated with CISC.

90

patients with PD have produced conflicting results. Using L-Dopa, apomorphine, pergolide (D1/D2 agonists) or bromocriptine (D2 agonist) some reports showed lessening of detrusor hyperreflexia, whereas others showed improvement of voiding difficulty. Whereas peripherally acting drugs, such as anticholinergic agents, lessen detrusor contractility, dopaminergic agonists may modulate both filling and voiding functions by acting on the specific central pathways.

There is a particular problem with the use of α-blockers in an attempt to improve bladder emptying in patients with MSA, since these can exacerbate postural hypotension.

DISORDERS OF DEFECATION MSA. Duration of patients’ symptoms of anorectal dysfunction is shorter in those with MSA than in patients with PD, and constipation appears to be increasingly common with advancing disease [15]. Several mechanisms may cause constipation in MSA, including reduced small and large bowel motility and chronic rectal impaction leading to decreased colorectal sensation or paradoxical contraction of the puborectal muscle during attempts at defecation — a phenomenon similar to detrusor-urethral sphincter dyssynergia and suggestive of supranuclear pudendal dysfunction.

Although much less common than constipation, fecal incontinence may also occur in

MSA, which does not appear to be correlated with the occurrence of urinary incontinence.

Low resting anal pressure and reduced maximal contraction pressure may account for fecal incontinence for liquid stools sometimes induced by laxative treatment. Anorectal manometric variables did not differentiate patients with MSA from those with PD [15].

PD. In his classic monograph, James Parkinson described the bowel dysfunction of shaking palsy: “the bowels which all along had torpid, now in most cases, demand stimulating medicines of very considerable power: the expulsion of the feces from the rectum sometimes requiring mechanical aid.”

Constipation occurs in 29-77% of PD patients compared to 10-13% of age-matched controls. Difficulty in defecation occurs in 67-94% of PD compared to 28% of a control group [16].

Colonography has shown megacolon in selected PD patients with severe fecal impaction (intestinal pseudo-obstruction) and in PD, rectal transit times are prolonged, indicating reduction of rectal contractility. Immunostaining of biopsied colonic musculature and the submucosa showed a reduction of dopaminecontaining neurons and there has also been a report showing Lewy bodies in the myenteric plexus of the colon [17]. These findings suggest that not only central, but also peripheral dopamine dysfunction in the colon account for the prolonged transit time and constipation in PD. Rectoanal manometry has shown reduced resting and defecating pressures [15]. These probably reflect dysfunction of the internal

anal sphincter innervated by lumbosacral sympathetic nerve. Other possible causes include over extension injury of the myenteric plexus due to severe fecal impaction, and an adverse effect of anticholinergic agents in PD. Defecography and anal sphincter EMG showed paradoxical contraction of the puborectal muscle in PD as a cause of rectal constipation [18] (Figure 6).

Treatment. The treatment of constipation and fecal incontinence is discussed in Chapter 3.

The prokinetic agent cisapride improves both symptoms and accelerates colonic transit time in patients with PD and constipation.

Psyllium has been shown to increase stool frequency and weight, but did not increase colonic transit or anorectal function in PD patients with confirmed constipation. A diet rich in insoluble fiber produced a significant improvement in constipation, as indicated by an increase in stool frequency and an improvement in stool consistency [19].

Pelvic floor relaxation problems and paradoxical puborectalis contraction may respond to dopaminergic drugs; however, some patients may still experience evacuation difficulties. A study using rectal manometry and defecography showed that apomorphine (a D1/D2 agonist) improved defecatory dysfunction in PD [20]. The effect was not antagonized by domperidone, a peripheral type dopamine blocker that does not penetrate the blood-brain barrier, but two of five patients showed marked hypotension on defecation.

Although not described in detail, L-Dopa and other dopamine agonists are also reported to

KEYPOINTS: à

Several mechanisms may cause constipation in MSA, including reduced small and large bowel motility and chronic rectal impaction leading to decreased colorectal sensation or paradoxical contraction of the puborectal muscle during attempts at defecation.

à

In his classic monograph, James Parkinson described the bowel dysfunction of shaking palsy: “the bowels which all along had torpid, now in most cases, demand stimulating medicines of very considerable power: the expulsion of the feces from the rectum sometimes requiring mechanical aid.”

CASE 4 History: A 71-year-old man had a 10-year history of headache, dizziness and occasional syncope on standing, which was gradually worsening. He had also noticed decreased sweating and experienced considerable discomfort during the summer time. In addition, he had nocturia and symptoms of voiding dysfunction, but had a normal size prostate.

He had no gait difficulty or speech disturbance at all.

Examination: Neurological examination did not reveal cerebellar ataxia, parkinsonism or pyramidal signs and deep tendon reflexes were preserved. However, the head-up tilt test revealed marked postural hypotension, with a blood pressure fall (from 140/80 lying to 75/50 mm Hg standing) accompanied by dizziness.

Management: Cystometry revealed detrusor areflexia with a large postmicturition residual. The patient was commenced on CISC with good symptomatic benefit.

Comment: This elderly patient has long-standing, widespread autonomic failure with bladder involvement, but lacks any other neurological abnormality, so he was therefore diagnosed as having pure autonomic failure (PAF).

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

be effective on defecatory dysfunction in PD, particularly in the early stage. Dopamine may modulate defecatory function via central neural pathways.

Paradoxical anal sphincter muscle contraction. (a) Control patient.

EMG recordings from puborectalis (PR), external anal sphincter (EAS), gluteus maximus (GM) and external oblique (EO) muscles at rest, during voluntary sphincter contraction (squeeze) and during simulated defecation straining (push).

A normal pattern of sphincter muscle inhibition is seen during straining. (b) Parkinson’s disease with constipation. Paradoxical sphincter muscle contraction and gluteal recruitment during straining.

FIGURE 6

From Mathers S et al. Constipation and paradoxical puborectalis contractions in anismus and Parkinson’s disease: a dystonic phenomenon? J Neurol, Neurosurg Psychiatry 1988;51:1503-7.

92

SEXUAL DYSFUNCTION AND ED IN MEN MSA. A well-documented feature of MSA is that the first symptom in men is often ED. This usually predates the onset of any other neurological symptoms by several years [4] and is quite separate from the development of postural hypotension. Preserved erectile dysfunction is a clinical feature strongly against a diagnosis of MSA. It is not known why ED should be such an early and constant feature in MSA. PD. Estimates of the prevalence of erectile dysfunction in patients with PD show that it is a significant problem, affecting 60% of a group of men compared with an age-matched healthy group without PD in whom the prevalence was 37%.

In the same study, ED preceded the onset of PD in 17%, although the author concludes “the five cases … may actually represent cases of MSA”, whereas in another study, ED was found to affect men with PD only some years after the neurological disease had been established [21].

A survey of young patients with PD (mean age 49.6 years) and their partners revealed a high level of dysfunction, with most severely affected couples being those in which the patient was male. ED and premature ejaculation was a complaint in a significant proportion. In general terms, however, sexual dysfunction appeared to be multifactorial with no simple single cause identified [22].

Treatment. The treatment of ED is discussed in Chapter 4.

Special care must be taken to recognize autonomic failure causing postural hypotension in men with parkinsonism and MSA since it has been shown in a small number of patients with this combination that sildenafil exacerbated the hypotension.

Apomorphine has been used by men with PD to improve sexual function [23]. Bromocriptine (a D2 receptor agonist) decreases serum level of prolactin, which is shown to improve erectile dysfunction with hyperprolactinemia.

Dopamine agonists may also cause hypersexuality, although the frequency with which this occurs has not been well documented.

KEYPOINTS: à

A well-documented feature of MSA is that the first symptom in men is often ED.

CASE-ORIENTED MULTIPLE CHOICE QUESTIONS þ

A 52-year-old man with a resting tremor and rigidity of the right hand was diagnosed as having Parkinson’s disease. Ten years after the onset of symptoms, he gradually developed urinary urgency with frequency and nocturia.

What is the most likely cause of his bladder symptoms?

A. B. C. D. E.

Detrusor hyperreflexia.

A poorly compliant bladder.

An atonic bladder.

Stress urinary incontinence.

Detrusor instability secondary to prostatic obstruction.

The answer is A. Detrusor hyperreflexia is common in Parkinson’s disease because bladder function is affected by input from supra-nuclear areas, including the nigrostriatal dopaminergic system. The nigrostriatal neurons probably influence the pontine micturition center (PMC) via GABAergic inhibitory mechanism. þ

A 60-year-old man was referred with a short-step, festinating gait, rigidity of both hands and a postural tremor. He also had urge urinary incontinence and symptoms of voiding dysfunction with postmicturition residuals of 320 ml. He was thought to have a Parkinsonian syndrome by the referring clinician. Cystometry revealed a poorly compliant bladder, with detrusor areflexia and detrusor-sphincter dyssynergia (DSD). External sphincter EMG showed neurogenic motor unit potentials.

Which is the correct diagnosis?

A. B. C. D. E.

Parkinson’s disease.

Multiple system atrophy.

Multiple cerebral infarction.

Benign prostatic obstruction with detrusor instability and Parkinson’s disease.

Detrusor areflexia and Parkinson’s disease.

The answer is B. This constellation of symptoms is not typical of Parkinson’s disease, particularly because a resting tremor and evidence of laterality are absent. Urodynamic studies revealed detrusor areflexia with DSD, and the sphincter EMG showed neurogenic motor unit potentials. All of these are the features of MSA, not of Parkinson’s disease.

Multiple choice questions þ continued

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

Multiple choice questions continued

þ

þ

A 58-year-old man presented with frequent fainting episodes that tended to occur when standing from the sitting position and also when walking up stairs. He also complained of faintness after urination and after meals. Over the preceding 2 years he had worsening genitourinary problems with erectile dysfunction, urinary urgency and nocturia. A year after presentation, he developed an abnormal gait and a mild speech disturbance. Examination demonstrated a mild gait ataxia and rigidity of the hands with preserved deep tendon reflex. On standing, his blood pressure fell from 130/80 to 82/60 mm Hg without an increase in the heart rate.

Which is the patient’s diagnosis?

A. B. C. D. E.

Autonomic failure with multiple system atrophy.

Autonomic failure with Parkinson’s disease.

Pure autonomic failure.

Diabetic autonomic neuropathy.

Amyloidosis.

The answer is A. All the above disorders can present with widespread autonomic failure; however, this patient was diagnosed with MSA, because of the cerebellar and extrapyramidal involvement and preserved deep tendon reflexes. Other typical presenting features are vocal cord paresis, sleep apnea syndrome, constipation and hypohidrosis. þ

A 42-year-old nulliparous woman had a 2-year history of intractable urinary frequency and incontinence. The incontinence occurred when coughing, washing her hands and carrying a heavy load. She also had a shuffling gait and difficulty speaking. Examination demonstrated mild parkinsonism, limb ataxia, exaggerated deep tendon reflexes and postural hypotension. On ultrasonography of the bladder, there was no postmicturition residual urine. The urethral pressure profile showed low maximum urethral closure pressure (UPmax) and Valsalva straining with 150 ml in the bladder demonstrated leakage at a low abdominal leak point pressure.

Which type of urinary incontinence is most likely in this patient?

A. B. C. D. E.

Urge incontinence (secondary to detrusor instability).

Genuine stress incontinence.

Overflow incontinence.

Neurogenic incontinence (secondary to detrusor hyperreflexia).

Mixed incontinence.

The answer is B. Despite the fact that she is nulliparous, the incontinence occurred during conditions where intra-abdominal pressure rises. A low abdominal leak point pressure (on cystometry) combined with a low maximum urethral closure pressure (on urethral pressure profilometry) indicate that there is an intrinsic weakness in the external sphincter. In relation to the co-existing neurological symptoms and signs, the patient was diagnosed with MSA. þ

A 71-year-old man had a 10-year history of headache, dizziness and occasional syncope on standing. He also had nocturnal urinary frequency and decreased sweating. On examination, the gait was normal and deep tendon reflexes and speech normal. There was no evidence of cerebellar ataxia, parkinsonism or pyramidal signs. However, the head-up tilt test revealed marked postural hypotension.

What is the diagnosis of this patient?

94

A. B. C. D.

Autonomic failure with multiple system atrophy.

Autonomic failure with Parkinson’s disease.

Pure autonomic failure.

Diabetic autonomic neuropathy.

The answer is C. This patient has widespread autonomic failure, but he has no other neurological abnormality.

REFERENCES [1]

Mathias C. Autonomic disorders and their recognition. New Engl J Med 1997;336:721-4.

A proposed clinical definition of pure autonomic failure (PAF), autonomic failure with Parkinson’s disease and multiple system atrophy (MSA) which is used worldwide.

[2]

Bannister RCJM. Clinical features and investigation of primary autonomic failure syndromes. In: Mathias C, editor. Autonomic failure, 4th ed. Oxford: Oxford Medical Publications; 1999.

An excellent review of clinical features and investigations of primary autonomic failure.

[3]

Sakakibara R, Hattori T, Uchiyama T, Asahina M, Suzuki A, Yamanishi T. Urinary dysfunction and orthostatic hypotension in multiple system atrophy: which is the more common and earlier manifestation. J Neurol Neurosurg Psychiatry 2000;68:65-9.

A study focussing on urinary dysfunction and orthostatic hypotension in MSA. The authors showed that urinary dysfunction is the more common and earlier manifestation.

[4]

Beck RO, Betts CD, Fowler CJ. Genito-urinary dysfunction in multiple system atrophy: clinical features and treatment in 62 cases. J Urol 1994;151:1336-41.

A study of genitourinary dysfunction in 62 MSA patients with special reference to neurogenic sphincter EMG abnormalities.

[5]

Stocchi F, Carbone A, Inghilleri M, Monge A, Ruggieri S, Berardelli A et al. Urodynamic and neurophysiological evaluation in Parkinson’s disease and multiple system atrophy. J Neurol Neurosurg Psychiatry 1997;62:507-11.

A study of urodynamic and neurophysiological evaluation which can differentiate these two disorders.

[6]

Palace J, Chandiramani VA, Fowler CJ. Value of sphincter EMG in the diagnosis of multiple system atrophy. Muscle Nerve 1997;20:1396-1403.

A study showing neurophysiological investigation of the pelvic floor is a key to diagnose MSA.

[7]

Giladi N, Simon E, Korczyn A, Groozman GB, Orlov Y, Shabtai H, Drory VE. Anal sphincter EMG does not distinguish between multiple system atrophy and Parkinson’s disease. Muscle Nerve 2000;23:731-4.

This study found no statistical difference between the sphincter motor units of patients with MSA and PD and in particular did not find the highly prolonged motor units other studies have reported.

[8]

Sakakibara R, Hattori T, Uchiyama T, Yamanishi T. Micturitional disturbance in pure autonomic failure. Neurology 2000;54:499-501.

The first report of urodynamic investigation in six patients with PAF.

[9]

Terao Y, Takeda K, Sakuta M, Nemoto T, Takemura T, Kawai M. Pure progressive autonomic failure; a clinicopathological study. Eur Neurol 1993;33:409-15.

References continued þ

A pathological study of a patient with PAF with a review of the literature.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

References continued þ

[10] Hattori T, Yasuda K, Kita K, Hirayama K. Voiding dysfunction in Parkinson’s disease. Jpn J Psychiatry Neurol 1992;46:181-6.

A study of urinary dysfunction in serial patients with Parkinson’s disease also showing the relationship between neurological signs with urinary dysfunction.

[11] Berger Y, Blaivas JG, DeLaRocha ER, Salinas JM. Urodynamic findings in Parkinson’s disease. J Urol 1987;138:836-8.

A report of urodynamic analysis in parkinsonian patients with urinary dysfunction.

[12]

Araki, I, Kuno, S. Assessment of voiding dysfunction in Parkinson’s disease by the international prostate symptom score. J Neurol Neurosurg Psychiatry 2000;68:429-33.

The international prostate symptom score showed abnormalities increasing in men and women with increasing severity rather than duration of PD or patients’ age.

[13] Lewin RJ, Dillard GV, Porter RW. Extrapyramidal inhibition of the urinary bladder. Brain Res 1967;4:301-7.

An early experimental study showing electrical stimulation of the basal ganglia inhibited bladder contraction.

[14] Yoshimura N, Mizuta E, Yoshida O, Kuno S. Therapeutic effects of dopamine D1/D2 receptor agonists on detrusor hyperreflexia in 1-methyl-4-phenyl-1,2,3,5-tetrhydropyridine lesioned parkinsonian cynomolgus monkeys. J Pharmacol Exp Ther 1998;286:228-33.

A thorough experimental study of the role of dopamine D1/D2 receptors on micturition in MPTPinduced parkinsonian monkeys.

[15] Stocchi F, Badiali D, Vacca L, D’Alba L, Bracci F, Ruggieri S, Torti M, Berardelli A, Corazziari E. Anorectal function in multiple system atrophy and Parkinson’s disease. Mov Disord 2000;15:71-6.

A study showing manometric abnormalities occur earlier and develop faster in MSA than in Parkinson’s disease.

[16] Edwards LL, Quigley EMM, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease; frequency and pathophysiology. Neurology 1992;42:726-32.

Gastrointestinal dysfunction in Parkinson’s disease.

[17] Singaram C, Ashraf W, Gaumnitz E et al. Dopaminergic defect of enteric nervous system in Parkinson’s disease patients with chronic constipation. Lancet 1005;346:861-4.

A study showing peripheral dopaminergic deficit plays a role in gastrointestinal dysfunction of Parkinson’s disease.

[18] Mathers S, Kempster P, Swash M, Lees A. Constipation and paradoxical puborectalis contractions in anismus and Parkinson’s disease: a dystonic phenomenon? J Neurol Neurosurg Psychiatry 1988;51:1503-7.

Anorectal function in Parkinson’s disease showing paradoxical pelvic floor muscle contraction on defecation which resembles DSD. [19] Edwards LL, Quigley EMM, Harned RK, Hoffman R, Pfeiffer RF. Defecatory function in Parkinson’s disease; response to apomorphine. Ann Neurol 1993;33:490-3.

A study showing dopaminergic drug could modify defecatory dysfunction in Parkinson’s disease.

[20] Josh WH. Gastrointestinal motility problems in patients with Parkinson's disease. Effect of antiparkinsonian treatment and guidelines for management. Drugs Ageing 1997;10(4):249-58.

Review of all the problems related to this issue, and guidelines for treatment.

[22] Brown RG, Jahanshahi M, Quinn N, Marsden CD. Sexual function in patients with Parkinson’s disease and their partners. J Neurol Neurosurg Psychiatry 1990;53(6):480-6.

A questionnaire analysis of sexual dysfunction in young patients with Parkinson’s disease and their partners.

96

[23] O’Sullivan J, Hughes A. Apomorphine-induced penile erections in Parkinson’s disease. Mov Disord 1998;13:536-9.

A report of a small group of men with Parkinson’s disease who use apomorphine to improve their sexual function. It is not known how general this application might be.

97

TEXT-BASED MULTIPLE CHOICE QUESTIONS þ

1.

Which is true regarding the normal control of urine storage?

A.

The intravesical pressure increases to a threshold pressure (approximately 25 cm H2O) as the bladder slowly fills.

Reflex activation of the parasympathetic innervation of the detrusor during filling prevents bladder contraction and facilitates storage.

Both the internal and external sphincters must remain closed during filling for continence.

Pelvic nerve afferents monitor the bladder volume.

Sensory urgency is associated with an acontractile bladder.

B. C. D. E. þ

2.

Which of the following statements regarding the innervation of the lower urinary tract is correct?

A. B.

E.

The motor neurons that innervate the bladder lie within Onuf’s nucleus.

The pelvic parasympathetic preganglionic fibers are contained in the second, third and fourth sacral spinal nerve roots within the cauda equina.

The sympathetic innervation of the lower urinary tract passes to the bladder via the pudendal nerves.

During voiding, bladder neck relaxation is brought about by activation of α-adrenoceptors in the smooth muscle of the bladder neck.

Voiding is brought about by activation the lateral part of the PMC.

3.

Which of the statements below regarding incontinence is correct?

A. B. C. D. E.

Genuine stress incontinence is typically associated with the sensation of urinary urgency.

Detrusor instability is the expected bladder disorder in neurological disease.

Detrusor hyperreflexia is a common cause of incontinence in a postpartum woman.

Mixed urinary incontinence refers to coexisting stress and urge incontinence.

Incontinence in MSA is due solely to denervation of the sphincters.

4.

Which statement below relating to neurogenic incontinence is correct?

A.

Spinal injury results in DH that is generally accompanied by appropriate sphincter relaxation.

Urinary frequency, urgency and urge incontinence are most commonly seen with detrusor hyperreflexia.

In detrusor sphincter dyssynergia (DSD), hyperreflexic bladder contractions are synchronized with external sphincteric relaxation, but internal sphincter contraction occurs.

In cauda equina injury, bladder control is impaired, but ano-rectal function is preserved.

Detrusor hyperreflexia may be associated with urge, but not stress, incontinence.

C. D.

þ

þ

B. C.

D. E.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

þ

þ

5.

In the investigation of patients with lower urinary tract symptoms and established neurological disease known to cause bladder dysfunction, which of the following tests is most important?

A. B. C. D. E.

Cystometry.

Urine cytology.

Post-void residual urine measurement.

Renal ultrasound.

Cystoscopy.

6.

Which of the following statements relating to the role of cystometry in the investigation of lower urinary tract symptoms in patients with MS is true?

A. B. C.

Videocystometry can identify ureteric reflux.

Cystometry is indicated in patients with MS and recurrent urinary tract infections.

Cystometry should only be performed following a cystoscopy to check for bladder cancer.

Cystometry may provide information regarding the level of the spinal cord lesion.

Cystometry can identify co-existing detrusor instability in patients with early MS.

D. E. þ

þ

7.

In patients with neurogenic bladder problems, urological investigations, such as cystoscopy and upper tract imaging, are performed in which of the following situations?

A. B. C. D. E.

Urinary symptoms are long-standing.

Recurrent urinary tract infections are a problem.

Urinary urgency is causing incontinence.

The neurological condition is deteriorating.

Prior to commencement of invasive management options (e.g. clean intermittent selfcatheterization).

8.

Which of the following statements regarding oral therapy in the treatment of neurogenic bladder dysfunction is true?

A.

Detrusor muscle contraction is mediated through sympathetic activation and results in calcium influx into the detrusor cell.

Oxybutynin acts primarily by blocking calcium channels.

M3 receptors are most important in mediating detrusor contraction.

Oxybutynin is a selective M3 receptor blocker.

Anticholinergic medications also assist in cases of incomplete emptying by increasing detrusor contractility.

B. C. D. E.

þ

9.

Which of the following statements regarding clean intermittent self-catheterization (CISC) in neuropathic patients is true?

A. B. C. D.

CISC is an effective treatment for detrusor hyperreflexia.

Sterile gloves are not required in CISC, but a sterile catheter is mandatory.

CISC is not advised when recurrent urinary tract infections are a problem.

Weakening of the external sphincter is a long-term complication of CISC and can result in incontinence.

When the postvoid residual is in excess of 100 ml, CISC should be considered.

E.

112

þ

10. In patients with neurogenic bladder dysfunction, which of the following statements regarding indwelling catheters is true?

A. B. C. D. E.

þ

11. Which statement relating to surgical options in the management of neurogenic bladder dysfunction is true?

A. B. C. D. E.

þ

B. C. D. E.

Patients with detrusor hyperreflexia and partial urinary retention usually respond to treatment with anticholinergic medication.

Indwelling catheterization is the treatment of choice when the postmicturition residual volume exceeds 250 ml.

Mechanical obstruction to flow (e.g. urethral stricture) is a cause of urinary retention.

Partial urinary retention in neurological patients warrants referral to a urologist for urethro-cystoscopy as the aetiology is likely to be urological.

Most cases of complete retention have a neurological cause.

13. Which of the following is true?

A. B. C. D. E.

þ

Surgery should be considered when neurological deterioration accounts for bladder symptoms that are difficult to manage conservatively.

Patients with low capacity bladders and non-progressive neurological disease may benefit from augmentation cystoplasty.

Augmentation cystoplasty avoids the commencement of CISC. Sphincterotomy has now replaced CISC in patients with spinal cord injury and DSD. Continence is preserved following urethral sphincterotomy as the internal sphincter is not incised.

12. Which of the following statements regarding urinary retention is true?

A.

þ

Indwelling catheters are more effective than CISC in the prevention of upper tract disease in neurogenic bladder dysfunction.

Indwelling catheterization carries a higher risk of urethral trauma than CISC. When a patient is unsuitable for CISC, urethral catheters should not be considered because of the long-term risk of squamous cell carcinoma.

Suprapubic catheters have a lower incidence of urinary tract infection when compared to urethral catheters.

Suprapubic catheters do not require changing as often as urethral catheters.

Complete urinary retention in young women is usually psychogenic in origin.

Acute urinary retention for urological reasons is never painful.

Regular clean intermittent self-catheterization has been shown to weaken detrusor contractility and exacerbate retention.

Patients with incomplete bladder emptying are usually able to report their disorder.

Incomplete bladder emptying together with detrusor hyperreflexia can occur in neurological patients.

14. Which statement regarding the pelvic floor and anal sphincters is correct?

A. B. C. D.

The puborectalis consists of smooth muscle.

Constipation is relatively rare in patients with multiple sclerosis when compared to the incidence of fecal incontinence in these patients.

Voluntary contraction of the puborectalis is necessary for bowel emptying.

The internal sphincter is comprised of an inner circular smooth muscle layer and an outer longitudinal striated muscle layer.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

E.

þ

15. Which statement regarding colonic and anorectal function is correct?

A.

B. C. D. E. þ

C. D. E.

B. C. D. E.

Constipating medication has a role in the treatment of fecal incontinence secondary to dementia.

In patients with fecal incontinence secondary to obstetric anal sphincter damage, bowel washout regimens are the first-line treatment.

In intractable fecal incontinence, disposable anal plugs are successful in the majority of patients.

Patients with severe fecal urgency are best managed with a stoma.

Incontinence of flatus is a common problem in patients who have sustained a cauda equina injury.

19. Which of the following statements regarding the innervation of the male genital region is true?

A. B. C.

114

Decreasing fiber intake will increase transit time by reducing stool bulk.

A high intake of bulking agents (fiber supplements) is recommended in immobile patients with slow colonic transit.

Stool softeners usually help in outlet obstruction.

Colonic stimulants generally aggravate slow transit constipation.

There is an established risk of fecal incontinence where manual evacuation is practiced as a long-term treatment strategy.

18. Which of the following statements regarding fecal incontinence is correct?

A.

þ

Most patients with a rectocele complain of constipation.

Intussusception is due to denervation of the rectum.

Intussusception may be a cause of intrarectal obstruction.

Fecal impaction is a rare cause of overflow incontinence.

In non-neurological patients, anal sphincteric incompetence is a rare cause of fecal incontinence.

17. In relation to the treatment of constipation, which of the following statements is correct?

A. B.

þ

Just prior to defecation, volitional Valsalva straining results in an increase in intraabdominal pressure which is followed by reflex contraction of the internal anal sphincter.

Colonic “mass movements” are modified peristaltic contractions that mix the fecal matter to facilitate water absorption.

Distension of the rectum to approximately 150 ml results in a drop in the internal anal sphincter closing pressure.

Pubococcygeal relaxation is associated with a decrease in the anorectal angle.

Anal sphincter squeeze pressure increases with age.

16. Which of the following statements is correct?

A. B. C. D. E.

þ

Pregnancy and childbirth are the commonest causes of anal sphincter incompetence in the community.

The sympathetic nerve fibers travel mainly in the pudendal nerves.

The parasympathetic fibers travel in the pelvic nerves.

The cavernous nerves are branches of the hypogastric nerves.

D. E. þ

20. Which of the following statements regarding the neurological pathways for erection is true?

A. B. C. D. E.

þ

D. E.

At full erection, intracavernosal pressure exceeds systolic blood pressure.

A single helicine artery supplies each corpus cavernosum.

Cavernosal smooth muscle relaxation is mediated by release of nitric oxide.

Endothelial nitric oxide release follows sympathetic activity.

The subtunical veins are closed during erection by intraluminal valves.

23. Which of the following statements regarding ejaculation is true?

A. B. C. D. E.

þ

Because the spinal cord reflexes are intact, ED is rare in Parkinson’s disease.

ED may be an early symptom of hypothalamic-pituitary disorders.

In multiple sclerosis, sexual responsiveness (i.e. erection) is impaired, but ejaculation is rarely affected.

Men with spinal cord injury experience psychogenic, but not reflex, erections.

In multiple system atrophy, symptoms and signs of postural hypotension usually predate the onset of ED.

22. In relation to penile erection, which of the following statements is true?

A. B. C. D. E.

þ

A sacral segmental pathway subserves psychogenic erections.

In men with cauda equina lesions and ED, genital somatic sensation is generally preserved.

Reflex erections are generally preserved in spinal cord injury.

Afferent impulses are conveyed from the genital regions exclusively in the pelvic nerves.

If a man experiences nocturnal penile erection, but cannot achieve erection for intercourse, he is likely to have psychogenic ED.

21. Which of the following statements regarding neurological diseases and erectile dysfunction is true?

A. B. C.

þ

The cavernous nerves are branches of the pudendal nerves.

The hypogastric nerves originate in Onuf’s nucleus.

Parasympathetic activity is responsible for bladder neck closure during ejaculation.

Sympathetic activity results in emission of the ejaculate into the urethra.

Sympathetic activity results in contraction of the pelvic floor muscles during ejaculation.

Nitric oxide release decreases penile blood flow after ejaculation.

Ejaculation and orgasm are rarely affected in spinal cord lesions.

24. In a patient with established neurological disease, which of the following, may be useful in the initial assessment of ED? A. B. C. D. E.

Nocturnal penile tumescence testing.

Glucose tolerance test.

Cavernosometry.

Cavernosography.

None of the above.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

þ

25. Which statement regarding the treatment of ED is true?

A. B. C. D. E.

þ

26. Of the following statements regarding intracavernosal pharmacotherapy in ED, which is true?

A. B. C. D. E.

þ

B. C. D. E.

B. C. D. E.

After 10 years of disease activity, >95% of MS patients will experience lower urinary tract symptoms.

The number of spinal cord lesions or extent of cord atrophy correlates well with specific urodynamic parameters.

Approximately 10% of patients with lower urinary tract symptoms and DSD demonstrate extensor plantar responses (Babinski’s sign) on clinical examination.

Detrusor sphincter dyssynergia is seen in >90% of patients with MS and lower urinary tract symptoms.

Urinary incontinence in MS is secondary to denervation of the urinary sphincter.

29. Which of the following statements regarding lower urinary tract function in MS is correct?

A. B. C. D. E.

116

Nitric oxide-mediated vasoconstriction results in venous engorgement and swelling of the vaginal tissues.

Secretions from the cervix are the primary source of vaginal lubrication during sexual activity.

The clitoris has a density of innervation almost equivalent to the glans penis.

The bulbocavernosus clitoral reflex results in a phasic contraction of the introital and pelvic floor musculature.

The clitoral nerve is a branch of the fine pelvic nerves.

28. Which of the following statements regarding lower urinary tract function in MS is correct?

A.

þ

Prostaglandins are potent vasoconstrictors, causing occlusion of the penile veins.

The intracavernosal injection of alprostadil is associated with penile pain in up to 40% of patients.

When priapism occurs, treatment options include watchful waiting, as 50% of cases will resolve spontaneously.

In those with ED who will not or are unable to self-inject alprostadil, the intraurethral route is an option with excellent results in most patients.

If a patient does not respond to sildenafil citrate, they are unlikely to respond to intracavernosal injection therapy.

27. In relation to female sexual function, which of the following statements is true?

A.

þ

Sildenafil citrate is a highly selective agonist of type 5 phosphodiesterase.

Sildenafil citrate acts by inducing erections in the absence of sexual stimulation.

Sildenafil citrate acts in part by increasing sexual desire.

Adverse effects associated with sildenafil citrate include facial flushing and nasal stuffiness.

There is an increase in cardiovascular risk whilst taking sildenafil citrate.

Most patients with a postvoid residual report a sensation of incomplete emptying.

It is contraindicated to prescribe anticholinergics in a patient with a postvoid residual.

Renal damage secondary to lower urinary tract dysfunction is common in patients with advanced MS. Detrusor sphincter dyssynergia (DSD) results in decreased bladder pressures.

DSD and impaired detrusor contraction can result in a high postvoid residual.

þ

30. Which of the following statements regarding tropical spastic paraparesis (TSP) is correct?

A. B. C. D. E.

þ

31. Which statement regarding urinary tract dysfunction in spinal cord injury (SCI) is correct?

A. B. C. D. E.

þ

C. D. E.

The incidence of bowel problems in patients with MS is similar to urinary symptoms.

The most frequent abnormalities of bowel dysfunction are incontinence of feces and flatus.

Insufficient contraction of the pubococcygeus muscle during defecation results in incomplete bowel emptying.

Patients with severe constipation secondary to colonic inertia will benefit from phosphate enemas.

The most common cause of fecal incontinence in MS is uninhibitable rectal contraction.

33. Which of the following statements regarding bowel dysfunction in spinal cord injury (SCI) is correct?

A. B. C. D. E.

þ

The period of intense detrusor overactivity, which immediately follows SCI, is best managed with an indwelling catheter.

Patients with SCI and MS are at an equal risk of renal failure.

In a patient with long-term SCI, cystoscopy reveals a thin-walled, atonic bladder.

Stone formation can serve as a nidus for recurrent urinary tract infections.

Brindley sacral root stimulators are used to suppress unstable contractions and incontinence secondary to detrusor hyperreflexia.

32. Which of the following statements relating to bowel dysfunction in MS is correct?

A. B.

þ

Bladder dysfunction occurs in up to 25% of infected individuals.

The commonest urodynamic abnormality is decreased detrusor activity.

Bladder capacity is decreased in most patients with TSP. A postvoid residual is unlikely, as detrusor sphincter dyssynergia (DSD) is rarely observed.

Upper tract disease is common.

In SCI, the predominant problem is constipation secondary to immobility.

The majority of patients with SCI do not need to do regular manual evacuation.

The best management option for patients with SCI is colostomy.

Autonomic dysreflexia can be precipitated by fecal impaction.

Autonomic dysreflexia generally occurs when the level of the SCI is below T6.

34. Which of the following statements regarding cauda equina anatomy is correct?

A. B. C.

D. E.

The conus medullaris usually ends at the lower border of the twelfth thoracic vertebra.

The thoracic and lumbar spinal nerve roots converge in the celiac and paravertebral plexi.

Disorders affecting the cauda equina are characterized by weakness and sensory loss in the lower limbs, buttocks and perineum, but usually with preserved uro-genital function.

Disk herniations usually occur in the central portion.

The sacral roots lie closest to the midline in the cauda equina.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

þ

35. Saddle anesthesia is characteristic of which of the following conditions below?

A. B. C. D. E.

þ

36. Lumbosacral spinal stenosis is associated with which of the following conditions?

A. B. C. D. E.

þ

B. C. D. E.

C. D. E.

B. C. D. E.

EMG studies of the lower limbs are able to confirm damage to the S3, S4 nerve roots within the cauda equina.

In transient radicular irritation (or transient neurological syndrome), both bladder and bowel function are affected.

In spinal stenosis, surgery has no impact on symptoms or disease progression in the majority of patients.

In patients with cauda equina lesions, incontinence is secondary to weakness of the urethral sphincter.

Most patients with cauda equina lesions have perianal hyperesthesia.

40. Which of the following statements regarding bladder and bowel dysfunction in diabetes mellitus is correct?

A.

118

Bladder dysfunction is common in spinal arachnoiditis.

Bladder dysfunction associated with transient radicular irritation resolves spontaneously.

Urinary disturbance occurs late in the cytomegalovirus cauda equina syndrome.

Genital herpes simplex infections may cause a neurological syndrome consisting of sacral pain or numbness and detrusor hyperreflexia.

Cytomegalovirus cauda equina syndrome may occur in patients with AIDS and urinary disturbance is often an early symptom.

39. Which of the following statements below is correct?

A.

þ

Neurosurgical intervention in patients with a tethered cord results in improved bladder symptoms.

Patients with myelomeningocele are at a low risk of developing renal impairment.

Most patients with tethered cord syndrome have a hypocontractile bladder.

In patients with tethered cord syndrome, radicular type pain is uncommon.

Tethered cord syndrome usually presents in middle to late adulthood with sensorimotor symptoms and signs, often in both legs, and bladder dysfunction.

38. Which of the following statements below is correct?

A. B.

þ

Paget’s disease.

Ankylosing spondylitis.

Achondroplasia.

Fluorosis.

All of the above.

37. Which of the following statements below is correct?

A.

þ

Spinal arachnoiditis.

Lesions of the centrally lying roots within the cauda equina.

Bilateral S1 radiculopathies.

Pelvic nerve injury.

Carcinomatous meningitis.

Diabetic cystopathy typically presents with urge incontinence.

B. C. D. E. þ

41. Which of the following statements regarding diabetes mellitus and autonomic dysfunction is correct?

A. B. C. D. E.

þ

B. C. D. E.

The somatic polyneuropathy in amyloid disease is initially of the small fibre type, causing painful paraesthesiae.

When pelvic organ dysfunction is present in amyloid neuropathy, it is unusual to see other features of dysautonomia.

Somatic and autonomic neuropathy is rare in immunoglobulin amyloidosis.

Porphyria is typified by the acute onset of mainly sensory distal neuropathy.

Neurological manifestations are seen only in the hereditary coproporphyria and variegate types of porphyria.

43. Which of the following statements regarding bladder, bowel and sexual dysfunction in demyelinating peripheral neuropathy is correct?

A. B. C. D. E.

þ

ED generally presents with other symptoms and signs of dysautonomia.

Failure of ejaculation is common in diabetics.

Spontaneous nocturnal erections are generally preserved in most diabetic patients with ED. ED in diabetes is solely due to atherosclerosis of the cavernosal arteries.

Esophageal motility studies are frequently abnormal in diabetics, but symptoms are uncommon.

42. Which of the following statements regarding amyloid neuropathy and porphyria is correct?

A.

þ

When post void residuals are large and recurrent urinary tract infection is a problem, clean intermittent self-catherisation is inappropriate for diabetics.

Diabetic cystopathy rarely presents concurrently with other manifestations of autonomic failure.

Diarrhoea in diabetic patients can be caused by faecal impaction.

In diabetic diarrhoea, anorectal incompetence is common.

Dysautonomia occurs in a minority of patients with Guillain-Barré syndrome (GBS).

The presence of dysautonomia in the acute period of paralysis carries a poor prognosis.

Bladder dysfunction occurs in 20% patients with GBS. Pelvic organ dysfunction is common in Charcot-Marie-Tooth neuropathy (hereditary sensorimotor neuropathy).

Erectile dysfunction is a common presenting feature in chronic inflammatory demyelinating neuropathy.

44. Which of the following statements regarding focal peripheral neuropathy and pelvic organ dysfunction is correct?

A. B. C. D. E.

Trauma (e.g. pelvic fractures involving the sacrum) is the commonest cause of injury to the pelvic nerves.

Postpartum faecal incontinence is primarily caused by damage to the autonomic supply of the internal anal sphincter.

Abdominoperineal resection rarely results in damage to the pelvic nerves.

Erectile dysfunction following radical prostatectomy is solely due to vascular damage.

30% of patients develop ED following radiotherapy for prostate cancer.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

þ

45. Which of the following statements regarding the diagnosis and management of pelvic organ dysfunction in patients with peripheral neuropathy is correct?

A. B. C. D. E.

þ

46. Which statement regarding pelvic dysfunction in parkinsonism is correct?

A. B. C. D. E.

þ

C. D. E.

D. E.

Apomorphine has no effect on erectile function.

Hypersexuality may occur in patients on L-Dopa therapy.

Erectile dysfunction (ED) is rarely encountered in patients with PD on treatment because dopamine receptor agonists are erectogenic.

The onset of ED in patients with MSA generally heralds a rapid neurological decline.

Erectile function is generally preserved in pure autonomic failure.

49. Which of the following statements regarding the role of higher centers in the control of lower urinary tract function is correct?

A. B. C. D. E.

120

The commonest urodynamic abnormality in PD is sphincter bradykinesia.

Autonomic responses to rectal distention at anorectal manometry can distinguish between MSA and PD. In MSA, constipation is more common than fecal incontinence.

In PD, difficulty in defecation is secondary to reduced resting and defecating pressures.

Dopamine agonists do not have an effect on defecatory dysfunction in PD.

48. Which statement regarding sexual dysfunction in parkinsonism is correct?

A. B. C.

þ

In patients with Parkinson’s disease, pelvic organ dysfunction usually occurs early in the course of the disease.

In MSA, urinary symptoms are less common than symptoms of orthostatic hypotension.

Detrusor hyperreflexia is common in MSA. Urinary incontinence in MSA is solely due to sphincter denervation.

Anal sphincter EMG may show myogenic abnormalities in patients with PD.

47. Which statement regarding pelvic dysfunction in parkinsonism is correct?

A. B.

þ

Patients with polyneuropathies that are associated with pelvic organ dysfunction rarely have motor and sensory symptoms in the hands and feet.

Clinical examination is not sufficiently sensitive to detect the changes in peripheral nerve function likely to result in pelvic organ dysfunction.

A resting tachycardia indicates parasympathetic cardiovagal dysfunction.

A decrease of > 20mm Hg systolic pressure when the patient is moved from the lying to standing position indicates a parasympathetic vasoconstrictor abnormality.

Clinical examination of the perineum will detect changes in peripheral nerve function following pelvic nerve damage.

Bladder control always resides in the hemisphere opposite to that in which speech is localized.

In a typical case of frontal lobe incontinence, the patient has severe urinary frequency, urgency and urge incontinence about which they are not concerned.

Urinary retention follows brainstem, but not cortical, lesions.

Following frontal or anterior cingulate damage, micturition proceeds automatically and involuntarily.

The onset of incontinence in patients with Alzheimer’s disease is not related to the duration and stage of the illness.

Ăž

50. Which of the following statements regarding lower urinary tract dysfunction after cerebrovascular accidents is correct?

A. B. C. D. E.

A correlation between urinary incontinence following a stroke and prognosis has not been shown.

The majority of patients with internal capsular CVA have uninhibited relaxation of the sphincter during involuntary bladder contractions.

In the acute phase of a CVA, the commonest urodynamic abnormality is detrusor hypocontractility.

A disturbance of bladder control is commoner following a posterior than an anterior cerebral infarct.

In patients with persisting urinary symptoms post-CVA, urodynamic studies correlate well with the site and size of the lesion.

121

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

ANSWERS TO TEXT-BASED QUESTIONS 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

D B D B C A B C E B

122

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

B C E E C C C E B C

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

B C B E D B D A E C

31.

32.

33.

34.

35.

36.

37.

38.

39.

40.

D D D E B E D E D D

41.

42.

43.

44.

45.

46.

47.

48.

49.

50.

E A C E C C C B D B

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

à

Although the number of men in an ED prevalence study who have neurological disease will be low, the incidence of ED and other types of sexual dysfunction in men with neurological disease is very high.

38

CHAPTER 4

NEUROGENIC SEXUAL DYSFUNCTION IN MEN AND WOMEN INTRODUCTION Physiological sexual function depends on both central and peripheral neurological pathways.

Neurological disease of many different types can, therefore, adversely affect function in both men and women.

In general terms, sexual libido and arousal depend upon psychological factors and on the integrity of higher brain centers, whereas function of the spinal cord and peripheral pathways is essential for effecting sexual responsiveness. Central centers which determine drive include the basal hypothalamus and limbic system, and the frontal and fronto-temporal regions where testosterone, dihydrotestosterone and estrogen may have important modulatory effects. Spinal pathways and the peripheral nervous system conveying efferent and afferent activity to pelvic parasympathetic, sympathetic and somatic innervated structures are critical for the voluntary and autonomically mediated aspects of genital responses.

Study of male sexual function and the many disorders, both neurological and nonneurological, which can affect it, is a relatively new medical subject, little being known, researched or discussed before the mid 1970s.

The change in public attitude towards sexuality which occurred in Europe and the US at that time, together with the appearance of some effective therapies, has altered the situation, and male sexual dysfunction is now an area of intense research and active treatment.

Female sexual dysfunction (FSD) is only just beginning to be scientifically studied, driven by the hope that some of the therapies which have proved to be so effective in men might be extended to women. Still much less is now known and possible therapies lag significantly behind.

The focus of treatment of sexual dysfunction so far has been the treatment of erectile dysfunction (ED). This chapter follows the

traditional approach and deals first with male sexual dysfunction, ED in particular, before covering the lesser studied topic of FSD. ERECTILE DYSFUNCTION A definition of ED is the persistent inability to develop and maintain an erection sufficient for satisfactory sexual activity [1]. The term ‘‘impotence” should now be avoided because of its broader, negative connotations.

General prevalence. In the late 1980s, a large study was carried out of men aged 40-70 years living around Boston, USA which showed that ED was a common problem and that its incidence increased with age [2]. More than 1000 men completed a self-administered questionnaire which asked, if they had impotence, to rate the problem. Their ED was then categorized as ‘‘minimal”, ‘‘moderate” or ‘‘complete”. The combined prevalence of all categories of ED was 52%. Figure 1 shows a break down of severity with aging. Other general associated factors were identified, which are summarized in Table 1.

80

Prevalence (%)

KEYPOINTS:

Complete ED Moderate ED Minimal ED

67% 57%

60 48%

40

39%

20 0

40

50

60

70

Age (yrs) FIGURE 1

Association between age and prevalence of erectile dysfunction.

From the Massachusetts Male Aging Study (n=1290) [2].

posterior urethra, closure of KEYPOINTS: the bladder neck and rhythmic contractions of the ischio- Ă Smooth muscle relaxation of the traAging cavernosus and bulbocaverbecular smooth muscle (as shown in Figure 1 [2]) nosus. Bladder neck closure in this vascular system Chronic illness is mediated by the and emission are under symAtherosclerosis, diabetes, cardiovascular disease, release of nitric oxide pathetic control from the thorenal disease, hepatic failure, depression, endocrine from the vascular racolumbar sympathetic outdisorders and neurological disease endothelium in flow, whereas the contraction response to pelvic Surgery and trauma of the pelvic floor muscles is parasympathetic activSpinal cord injury, pelvic injury/surgery, prostatectomy ity. under somatic nerve control.

Drug and other modifiable factors Following orgasm and Alcohol, tobacco, medication (antihypertensives, antiejaculation, sympathetic tone à Visual, olfactory, audidepressants, hormones, tranquilizers, H2 antagonists, tory, tactile and imagireturns and causes the cavernonsteroidal anti-inflammatory drugs native stimuli are intenosal and helicine arteries to grated in the medial pre-optic area (MPOA), contract, restricting blood flow but there is no direct into the lacunar spaces. The fallconnection demonstraBecause the subject population of the ing intralacunar pressure then decompresses ble between this strucMassachusetts study was racially unmixed the subtunical venules and allows increased ture and the spinal and unusually well educated, further venous outflow so that detumescence occurs. cord. The paravenepidemiological studies are now being carried tricular nucleus (PVN) Neurological control of male sexual funcis the origin of out to reassess the prevalence of ED globally. tion and penile erection. Central control of descending, oxytocinEarly results are producing figures of the sexual response is currently an area of intense ergic autonomic pathsame order of magnitude as those of the research and animal experiments, often in ways to the sacral cord Massachusetts study, although there are some the rat, have now defined the importance of which mediate erectile regional differences. responses and this regions in the hypothalamus. Visual, olfacreceives input from the Prevalence of ED in neurological disease. tory, auditory, tactile and imaginative stimuli MPOA. Although the number of men in an ED prev- are integrated in the medial pre-optic area alence study who have neurological disease (MPOA), but there is no direct connection will be low, the incidence of ED and other demonstrable between this structure and types of sexual dysfunction in men with neu- the spinal cord. The paraventricular nucleus rological disease is very high. The data are (PVN) is the origin of descending, oxytocinsparse, but Table 2 gives some published inci- ergic autonomic pathways to the sacral cord dences from various small studies of specific which mediate erectile responses and this neurological illnesses. receives input from the MPOA. Dopaminergic Physiology of penile erection and receptors, probably D2 receptors in the PVN ejaculation. Erection results from filling of the paired corpora cavernosa with blood at TABLE 2 Incidence of sexual dysfunction, including ED, in systolic pressure. The lacunar spaces within neurological disease the corpora are fed by the numerous helicine arteries which branch off the cavernosal Hypothalamic-pituitary disorders 78% [3] arteries. Smooth muscle relaxation of the Parkinson’s disease 60% [4] trabecular smooth muscle in this vascular MSA 98% [5] system is mediated by the release of nitric 1 Spinal cord injury 25-95% [6] oxide from the vascular endothelium in MS 62-83% [7-9] response to pelvic parasympathetic activity.

Reduction of corporeal venous drainage is Diabetic neuropathy approx. 100% 2 critical in the erectile response and occurs 1 as a result of compression of the subtunical Depending on level and completeness of lesion. draining veins against the rigid tunica 2 The extent to which micro-vascular disease and metabolic factors albuginea (Figure 2). contribute to the common problem of ED in diabetics is uncertain, but a man with diabetic neuropathy is highly likely to have ED. Ejaculation involves emission of semen from the vas and seminal vesicles into the TABLE 1

General factors known to predispose to ED

39

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

FIGURE 2

Physiology of penile erection.

From [24].

induce erection in animals, which is the rationale for the therapeutic use of apomorphine (a mainly D2 agonist) as an erectogenic agent.

FIGURE 3

Diagram showing the peripheral innervation of the male and female sexual organs.

Reproduced by courtesy of Petter Hedlund and Axel Brattberg.

40

Many inhibitory, mainly serotoninergic, pathways have also been identified within the diencephalon.

tory spinal input. Very little is known about the neurophysiology of orgasm — the senCentral input sation is blocked by bilateral anterolateral (i.e. spinothalPsychogenic amic tracts) cordotomy. A erection SPECT study showed an increase in activity in the right Sympathetic (thoraco-lumbar) frontal lobe region during ejaculation in healthy male Peripheral subjects, but no focal activainnervation tion in the medial anterior parietal lobe corresponding Reflex erection Penis to somatosensory cortex of the genital projection area.

This was interpreted as FIGURE 4 Neurological pathways involved in erectile implying that the right preresponse. frontal cortex is important for the emotional responses of male sexuality.

The parasympathetic innervation travels to Neurological diseases causing ED. Figure the genital region in the pelvic nerves, the so 5 and Table 3 show the various different neucalled ‘‘nervi erigentes” and pudendal nerves. rological diseases that may adversely affect Sympathetic innervation of the genital region sexual function, penile erection, in particular. originates in the thoracolumbar chain (T11-L2) A detailed description of what is known about and travels in the hypogastric nerves to the sexual dysfunction in both sexes with each confluence of neural tissue which lies either disease is given under the appropriate headside of the rectum and the lower urinary ings of Chapters 5-9. tract — the pelvic plexus. This also receives History in men with neurogenic ED. In input from the pelvic nerves and it is from men with established neurological disease and the pelvic plexus that the very fine cavernous ED, laboratory investigations are rarely indinerves pass to innervate the corpora caver- cated. It is usually clear from the history how nosa (Figure 3). the onset of ED relates to the development of There are essentially two neurological their neurological disability. pathways for erection: a sacral segmental pathway which subserves reflex erections and a spinal pathway which is necessary for TABLE 3 Neurological causes of ED psychogenic erections (Figure 4). Reflex erections result from cutaneous genital stimulaTemporal lobe epilepsy tion with afferent impulses conveyed in the Hypothalamic pituitary disorders pudendal nerve to S2- S4 the efferent activParkinson’s disease ity travelling through the same-level sacral Multiple system atrophy roots. Psychogenic erection requires cortical Spinal cord injury activation of erectogenic pathways via the spinal cord and the sometimes preservation Multiple sclerosis of this type of responsiveness in men with Spina bifida low spinal cord lesions suggests that it may Cauda equina be mediated by sympathetic pathways. In Peripheral neuropathy (especially health, psychogenic and reflex erections reinsmall fiber) force one another.

Surgical damage to cavernosal Ejaculation depends on descending spinal innervation pathways which are predominantly excitatory, although there may also be an inhibi-

KEYPOINTS: à

There are essentially two neurological pathways for erection: a sacral segmental pathway which subserves reflex erections and a spinal pathway which is necessary for psychogenic erections.

à

In men with established neurological disease and ED, laboratory investigations are rarely indicated.

41

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

Temporal lobe Hypothalamic-pituitary Parkinson’s Disease MSA

Central input

Trauma MS Spina bifida

Sympathetic (thoraco-lumbar) Cauda equina Small fibre neuropathy Cavernosal n. damage

Peripheral innervation Penis

FIGURE 5

KEYPOINTS: à

The sexual function deficit resulting from spinal cord disease (either traumatic or MS) depends on the level and extent of the lesion: typically, a man with a cervical or high thoracic lesion will have preserved reflex erections, but not be able to sustain erection for penetrative intercourse.

à

Bladder dysfunction occurs considerably later and evidence of relevant neuropathy is best detected by testing small fiber function in the feet, since many of the small fiber neuropathies are lengthdependent.

à

In the general population, ED often has a significant vascular component.

42

Sites at which neurological disease can affect pathways necessary for erectile response.

Temporal lobe disease and hypothalamicpituitary disease often causes loss of desire as an early symptom, which the patient may not complain of, although ED can occur with preserved libido with pathology at those sites.

The sexual function deficit resulting from spinal cord disease (either traumatic or multiple sclerosis (MS)) depends on the level and extent of the lesion: typically, a man with a cervical or high thoracic lesion will have preserved reflex erections, but not be able to sustain erection for penetrative intercourse. The teaching that if a man had nocturnal penile erections or reflex erections, but could not sustain an erection for intercourse, his impotence was psychogenic, is no longer thought to be correct, particularly in the case of spinal cord disease.

Ejaculation and orgasm are likely to be affected by spinal cord lesions. ED is very rarely the only symptom and the complaint is usually part of a symptom complex accompanied by a spastic paraparesis and neurogenic bladder dysfunction.

If ED occurs as a result of a cauda equina lesion, somatic sensation in the S2-S4 dermatomes is also likely to be impaired. Small fiber peripheral neuropathies, i.e. diabetes and amyloid disease, are particularly likely to cause ED, and this may occur early in the condition without disturbances of ejaculation.

Bladder dysfunction occurs considerably later,

and evidence of relevant neuropathy is best detected by testing small fiber function in the feet, since many of the small fiber neuropathies are length-dependent.

Following pelvic trauma or surgery which injures the pelvic nerves or cavernosal nerves, ED occurs, but with preservation of somatic sensation, unless the pudendal nerve is also damaged.

Clinical examination. Following a careful history, clinical examination focussing on the points shown in Table 4 will identify concomitant spinal cord disease, root lesions or peripheral neuropathy. In general, if a clinical neurological examination fails to discover evidence of neurological disease, sophisticated neurophysiological investigations are unlikely to be contributory.

Investigations. Now that there are simple and effective symptomatic treatments for ED, the emphasis on investigations has shifted. In former times, these were carried out to establish whether the problem was psychogenic or organic and, if organic, whether surgical intervention was indicated.

In the general population, ED often has a significant vascular component. A history of coronary or peripheral vascular disease suggests a vascular cause. This may be is investigated by andrologists using a variety of techniques including color Doppler ultrasonography imaging with intracavernosal injections, cavernosometry and cavernosography if surgery is being considered. A brief description of these investigations of penile hemodynamics, usually only performed in non-neurogenic ED, is given in Pullout 1.

Useful insight as to the cause of ED in a patient comes from observing their response to intracavernosal injection of an erectogenic agent, such as prostaglandin E1.

A good response from a low-dose injection suggests the cause is likely to be neurogenic,

TABLE 4

Clinical neurological examination for ED

Lower limb reflexes Plantar responses Sensation (thermal testing) of feet

psychogenic or endocrine, whilst a poor response using a high dose suggests there may be a vascular cause and those investigations described in Pullout 1 may be indicated.

However, false-negatives with this test do occur as the psychological inhibition caused by the anxiety of a penile injection in an impersonal setting, such as at a hospital clinic, may inhibit the response to intracavernosal injection.

There is continuing discussion as to the minimum biochemical investigations necessary, and some authorities recommend measurement of serum total and free testoster-

PULLOUT 1

one, prolactin, glucose and cholesterol [10]. If there is reason to suspect a hypothalamic-pituitary lesion, measurement of hormone levels is mandatory.

The use of neurophysiological tests to investigate genital innervation has been advocated in the past, but none of them is now used routinely. The various tests are described in Chapter 1, (Pullout 1) since many of them were promoted as being appropriate for investigating pelvic organ dysfunctions other than ED. Evaluation of the test specific for ED, socalled ‘‘corpus cavernosum EMG” is still ongoing, and although it may prove to be of

KEYPOINTS: à

If there is reason to suspect a hypothalamic-pituitary lesion, measurement of hormone levels is mandatory.

Investigation of penile hemodynamics

These investigations are sometimes requested by urologists and andrologists when a vascular cause for ED is suspected and they may be particularly indicated in patients who have not responded to oral agents.

Methods of investigating arterial supply Color Doppler ultrasonography (CDU) is considered to be an ideal screening method for both functional and anatomic evaluation of penile arterial blood flow. Following intracavernosal injection, components of the penis, including the corpora cavernosa, corpus spongiosum, septum, urethra, cavernous artery, and dorsal vein, can be visualized. Cavernosal artery diameter and peak systolic arterial velocity can be measured, although there is no general agreement as to what is regarded as normal, partly due to lack of control data in healthy volunteers and partly because arterial inflow is dependent on the degree of smooth muscle relaxation which may be determined by factors such as patient’s anxiety.

Selective pudendal arteriography is technically difficult and invasive and is rarely used, except in men with erectile failure secondary to pelvic trauma in whom pudendal arterial reconstruction is being considered.

Methods of investigating venous leakage Failure of the veno-occlusive mechanism to trap arterial blood within the penis results in ED. The underlying etiology, diagnosis and treatment of venous leakage remains controversial, but many different pathological processes have been described. The majority of patients with “venous leak” have normal venous anatomy, but fail to compress the emissary veins as they exit from the cavernosal bodies.

CDU, cavernosometry and cavernosography are all used in the diagnosis of venous leak. Following an intracavernosal injection of a vasodilator, flow should stop in diastole or even reverse if the veno-occlusive mechanism is functioning adequately. Excessive forward flow in the cavernosal arteries during diastole with failure to obtain a firm erection is taken as evidence for a venous leak.

Cavernosometry is the technique whereby intracavernosal pressure is measured in response to corporeal perfusion and cavernosography is the technique whereby abnormal venous outflow is seen radiologically following perfusion of contrast.

Smooth muscle degeneration, as occurs in diabetes, may result in inadequate sinusoidal relaxation with inadequate inflow and failure of the intracavernosal pressure to rise sufficiently to occlude the emissary veins. A healthy tunica albuginea that stretches and kinks the emerging emissary veins as the penis engorges is also necessary for venoocclusion. In Peyronie’s disease, firm fibrous plaques form at random on the tunica preventing full elongation of the penis with consequent penile curvature and venous leak in some patients. The treatment of erectile dysfunction secondary to venous leak is not straightforward as the underlying pathogenesis is often unclear. Attempts to reduce leakage by dividing draining veins have some short-term success, but the longer term results are poor.

43

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

value in assessing penile autonomic innervation, it is unlikely to assume importance as anything other than a research investigation.

Treatment. With the introduction of the orally active agent sildenafil (Viagra®, Pfizer) in 1998, the treatment of ED was transformed.

Prior to then, intracavernosal injection pharmacotherapy was the most used treatment, usually administered by urologists or andrologists. Before that, what help that was available was the provenance of psychotherapists or those surgeons who implanted penile prostheses. An effective oral treatment has meant that treatment of ED can now be offered by primary care physicians as well as specialists not previously therapeutically empowered, such as neurologists.

Oral medication: Sildenafil citrate (Viagra®) is a potent and highly selective inhibitor of type 5 cGMP phosphodiesterase (PDE5). Its action is to augment nitric oxide-mediated relaxation pathways in penile tissues by increasing available cGMP in the corpus cavernosum (Figure 6). The effect of the medication is therefore not to cause erection, but to enhance the response to sexual arousal. Sildenafil is rapidly absorbed with a maximal plasma concentration occurring within 1 hour, so that it

KEYPOINTS: à

An effective oral treatment has meant that treatment of ED can now be offered by primary care physicians as well as specialists not previously therapeutically empowered, such as neurologists.

NANC neurons

Endothelial cells

Nitric Oxide

+ Guanylate cyclase

Smooth Muscle Relaxation

+ cGMP

GTP

Sildenafil Citrate

_ PDE 5

Penile erection

+

GMP

Nitric oxide-cGMP mechanism of corpus cavernosal smooth muscle relaxation and penile erection. Sexual stimulation results in the release of nitric oxide from corporal vascular endothelium and nonadrenergic-noncholinergic (NANC neurons). PDE 5 = cGMP-specific phosphodiesterase type 5.

FIGURE 6

44

is necessary for it to be taken about 1 hour before intended sexual activity.

More than 6000 men with many different causes of ED have now participated in placebo-controlled trials of sildenafil citrate, and the medication was demonstrated to be effective, with few side effects or adverse events.

The pivotal study was a large placebo-controlled, flexible dose-escalation study with an open label extension in men with organic, psychogenic or mixed etiology ED [11]. Efficacy was assessed using the self-administered International Index of Erectile Function (IIEF) questionnaire which showed significantly higher mean scores for frequency of penetration and maintenance of erection in the sildenafil-treated group compared with men receiving placebo. Sexual desire was not increased in the active agent-treated group, but the scores for orgasmic function, intercourse satisfaction and overall satisfaction were all better. Adverse effects were headache, flushing, dyspepsia, nasal stuffiness and visual disturbances, but these were usually mild and were dose-related. Only 2% withdrew from the open-label study because of adverse effects. Similar findings for efficacy have been demonstrated since in other studies, although the response rate is variable, being less good in vasculopaths and diabetics and better in patients with neurogenic ED. The side-effect profile has also been consistent, with few patients discontinuing medication because of adverse reactions.

However, initially, there was public concern about the medication’s safety prompted by reports of death following the use of Viagra®, as monitored by ‘‘spontaneous” reports to the US Food and Drug Administration. This anxiety has now lessened and studies have shown that although the cardiovascular risk profile for myocardial infarction is similar to that which predisposes to ED, there has not been a higher rate of serious cardiovascular events in the treated groups than in the placebo groups in controlled studies. Epidemiological studies have shown that the incidence of serious events has been consistent with the expected background frequency in the treated population [12], and there is no evidence that sildenafil adds to the overall risk in patients with or without cardiovascular disease [13]. Sildenafil is contraindicated with concurrent use of

nitrates as it interacts to cause severe acute hypotension. Sildenafil is contraindicated in severe hepatic impairment and in conditions that predispose to priapism and bleeding disorders.

The efficacy of sildenafil in several neurological conditions has now been demonstrated. Following spinal cord injury, reflex erections may be preserved, but these are often not suitable for satisfactory sexual activity. In a placebo-controlled, cross-over study, 76% of 168 patients who had had traumatic spinal cord injury, reported improved erections and a preference for sildenafil [14]. The majority of the subjects had some residual erectile function, although in 25 of those who did not, sildenafil also improved erections in 16.

Preliminary analysis of a placebo-controlled trial of sildenafil in 217 men with MS has likewise demonstrated excellent efficacy, with 90% of 104 patients on sildenafil and 24% of 113 patients on placebo, reporting improved erections [15] as well as a measurable improvement in quality of life. A placebo-controlled trial in eight men with spina bifida showed improved erectile function in 63% [16]. Thus, the present evidence points to this form of treatment being particularly effective in men with ED caused by spinal pathology. Any pre-existing neurological difficulty with ejaculation, however, persists.

Abstract reports of an open label study of men with Parkinson’s disease have also shown sildenafil to be effective [17], although this study showed that in men with parkinsonism due to multiple system atrophy (MSA) who had ED and either symptomatic or asymptomatic autonomic failure, hypotension was significantly exacerbated by sildenafil. It is therefore important to check for postural hypotension in men with parkinsonism before prescribing sildenafil.

The efficacy of sildenafil in treating ED in diabetics is less than in most other patient groups with ED. In a study of 131 diabetics, 56% reported improved erections on active treatment compared with 10% of 127 in the placebo group [18]. The peripheral vascular component as well as the effect of advanced glycosylated end products which decrease nitric oxide activity are thought to be contribute to the severity and relative intractability of ED in diabetics.

In men who have ED following radical prostatectomy, sildenafil is ineffective in those in whom it was not possible to carry out a nerve-sparing procedure on either side [19].

At the time of writing, sildenafil is the only available orally active erectogenic agent, but preliminary studies have demonstrated an erectogenic effect with oral apomorphine [20], although nausea is a frequent side effect, particularly in those using higher dosages. However, it is certain that in the near future, other orally active treatments for ED will become available, either other phosphodiesterase inhibitors or agents which act on some other stage of the process of the erectile response.

Intracavernosal pharmacotherapy: Prior to the availability of an orally active treatment, injection of medication into the corpus cavernosum was the preferred treatment. The first used agent was papaverine, but this was subsequently replaced by alprostadil [21], a prostaglandin PGE1. Various combinations of injectable agents have also been tried.

The main side effect of alprostadil is penile pain, which occurs in about half of the patients. Priapism is characterized by a persistent erection that generally lasts 4-6 hours and can be associated with severe pain. When this condition occurs, it should be considered a medical emergency as permanent damage can be sustained after 12 hours of persistent erection. Treatment involves immediate injection of phenylephrine hydrochloride at 500 µg into the corpora cavernosum. This administration can be repeated at 20-minute intervals. Alternately, blood can be aspirated from the corpora via a 23-gauge butterfly needle along with α-adrenergic irrigation (1 mg phenylephrine HCl to 1 liter of normal saline). The main late complication is the appearance of fibrotic nodules or scarring within the corpora, but in most cases, these disappear after temporary discontinuation of the treatment.

Intracavernosal injection therapy still has a continuing role in treatment of patients who do not respond to sildenafil, although the determining features for responsiveness are not yet known. Patients with neurogenic ED responded well to low doses of alprostadil therapy, while those with vascular disease required higher doses.

KEYPOINTS: à

It is therefore important to check for postural hypotension in men with parkinsonism before prescribing sildenafil.

à

Patients with neurogenic ED responded well to low doses of alprostadil therapy, while those with vascular disease required higher doses.

45

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: à

Similar erection mechanisms to those that occur in men also operate in women, including NO- and cGMP-mediated vascular events.

à

The clitoris is homologous to the glans penis and is the most densely innervated area of the skin with an innervation density, approximately twice that of the male dorsal penile nerve, so that clitoral sensory thresholds are lower than that of the glans penis.

A high attrition rate for using the treatment was found in several studies, thought to be due to dislike of injections, the artificiality of the therapy and the practical difficulties preparing and administering the solution.

In order to overcome some of these problems, several easy self-injection devices have been manufactured.

Intraurethral pharmacotherapy and topical creams: Although intraurethral administration of alprostadil as a medicated pellet (MUSE®), which obviated the need for injection, was theoretically an attractive option, the efficacy of the preparation is much less, despite higher doses. Its use in clinical practice has been somewhat disappointing.

Topically acting vasodilator creams have been developed, some with a mixture including nitric oxide donors [22].

Vacuum devices: A vacuum device consists of a vacuum chamber, a vacuum pump that creates negative pressure within the chamber, and a constrictor or tension band that is applied to the base of the penis after the erection is achieved. Vacuum-induced erections are due to venous turgidity and the penis is only rigid distal to the constricting band. These devices have been successfully used in older men and have the advantage of having limited side effects, although these may include pain, hematoma, petichiae, and numbness. The use of this device is contraindicated in patients with bleeding disorders, Peyronie’s disease, and in those with intracavernosal scarring.

Vacuum devices may also be useful to enhance the effects other treatment modalities (intracavernosal, intraurethral).

Penile prosthesis: Penile prostheses are generally much less used nowadays. The complication rate in men with spinal cord disease was higher than in other patients, and, in general, a prosthesis is not suitable for a man who has progressive neurological disease.

FEMALE SEXUAL DYSFUNCTION Similar erection mechanisms to those that occur in men also operate in women, including NO- and cGMP-mediated vascular events.

Arousal and hyperalgesia of the genital tissues can be provoked by imagery and fantasy, or by stimulation of vaginal or cervical tissues or of other erogenous zones. During this process, blood flow is increased to the

46

vagina which results in lubrication and erection of the female cavernous tissues and clitoris. Women experience a period of REM-sleepassociated augmentation of vaginal blood flow and increased lubrication, analogous to male nocturnal tumescence.

Lubrication is derived mainly from a transudate from the vaginal tissues, although secretion from Bartholin’s glands, the cervix, and uterus also contribute [23]. Diminished lubrication can impair sexual function and can be caused by estrogen deficiency states, pituitary insufficiency, antiestrogen therapy, and anticholinergic agents.

Neurological control of sexual function in women. The clitoris is homologous to the glans penis and is the most densely innervated area of the skin with an innervation density approximately twice that of the male dorsal penile nerve, so that clitoral sensory thresholds are lower than that of the glans penis.

The clitoris contains three different types of nerve endings, including free endings that mediate response to pain, submucosal fibers that respond to pressure and movement, and onion bulbs that are involved in sensing pressure and vigorous movements. These latter two types of nerve endings are localized in close proximity to cavernous tissue and are thereby stimulated during the phase of vascular engorgement. The clitoral nerves join the pudendal nerves, which ultimately transmit information to the sacral spinal cord.

Two clitoral reflexes characterize the neurophysiology of the clitoris. The bulbocavernosus reflex is a phasic response that can be triggered by pinching the clitoris and involves contraction of the bulbocavernosus muscle and the external anal sphincter. Vibratory stimulation evokes a tonic reflex involving sustained contraction of the pelvic floor musculature. The bulbocavernosus muscles surround the vaginal introitus and insert on the dorsal surface of the clitoris forming an anatomical sling. During the process of muscle contraction, the dorsal vein is compressed and the cavernous tissue becomes engorged with blood, leading to clitoral erection.

In addition to the clitoris, there are areas on the anterior vaginal wall which respond to sexual stimulation, and some have claimed the existence of a highly localized area, the socalled ‘‘Grafenberg spot” (G-spot).

TABLE 5

Types of female orgasm

Clitoral or vulval Uterine or vaginal Blended Anal Erogenous zones (breasts/neck/hands) Psychogenic

With appropriate stimulation and rising sexual excitement, orgasm may be reached.

The female orgasm is characterized by the experience of a spreading sensation of warmth followed by up to 20 synchronous contractions of the vaginal musculature and sphincters lasting for 10-50 seconds. There are several forms of female orgasm, which provides for a broad diversity of stimulation sites (Table 5). Some women can experience multiple orgasms in sequence in response to repeated or persistent sexual stimulation.

Neurological causes of FSD. Much less is known about neurogenic FSD than is known about male sexual dysfunction and, furthermore, most female patients are still very much more reticent about discussing sexual problems, although that may change. However, based on considerations of the homologous nature of neurological control of sexual responses, it is reasonable to assume that the diseases shown in Figure 5 and listed in Table 3 adversely affected women in much the same way as men. Each of these and what therapy is available is discussed in the appropriate chapters (Chapters 5-9).

SEXUAL HEALTH AND REHABILITATION The ready availability of simple, effective treatment for ED has made both patients and their doctors more willing to talk about sexual dysfunction. The high incidence of ED in neurological disease (Table 2) means that every neurologist is taking care of many patients who have sexual dysfunction amongst their complaints. Ignoring this aspect of the patient’s health should be regarded as being as neglectful as failure by the physician to attend to some other major neurological dysfunction.

In treating sexual dysfunction, irrespective of the cause, the physician may or may not become involved in the extent to which the problem has affected partner relationships. In progressive neurological disease, the disease itself may have a considerable impact on a relationship, and restoring erectile function may have complicated repercussions when a patient’s partner has become their carer.

Following traumatic spinal cord injury, the problems are quite different and may include sexual rehabilitation of an otherwise fit young man, so that he is able to enjoy a full dyadic relationship.

A sympathetic and encouraging approach of enquiry is necessary, with the level of detail of discussion determined by the extent to which patient and doctor feel comfortable with the topic. Often the subject can be easily introduced following discussion of neurogenic bladder dysfunction, pointing out to the patient that, as is often the case, the same parts of the nervous system are needed for control of the bladder and sexual function. The neurologist must be sensitive to the patients’ situation and be nonjudgmental. Provided this approach is taken, the successful treatment of

KEYPOINTS: à

The high incidence of ED in neurological disease means that every neurologist is taking care of many patients who have sexual dysfunction amongst their complaints.

REFERENCES [1]

Impotence. National Institutes of Health Consensus Statement. December 1992. p. 10.

Early meeting of officially convened group to discuss the medical consequences of ED.

[2]

Feldman H, Goldstein I, Hatzichristou D, Krane R, McKinlay J. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994;151:54-61.

First large scale study of a population to look at the prevalence of ED.

References continued ►

47

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

References continued ►

[3]

Lundberg P, Hulter B. Sexual dysfunction in patients with hypothalamo-pituitary disorders. Exp Clin Endocrinol 1991;98:81-8.

Effect of pituitary tumors on sexual function — a Swedish study from a sexology unit receiving referrals from a regional neurosurgical unit.

[4]

Singer C, Weiner WJ, Sanchez-Ramos JR, Ackerman M. Sexual dysfunction in men with Parkinson’s Disease. J Neurol Rehabil 1989;3:199-204.

An early study of sexual dysfunction in Parkinson’s disease.

[5]

Beck RO, Betts CD, Fowler CJ. Genito-urinary dysfunction in multiple system atrophy: clinical features and treatment in 62 cases. J Urol 1994;151:1336-41.

Retrospective study of urinary symptoms in MSA: ED was found to be the earliest symptoms of the disease.

[6]

Bors E, Comarr A. Neurological disturbances of sexual function with special references to 529 patients with spinal cord injury. Urol Surv 1960;10:191-222.

First study of sexual dysfunction following SCI in a large cohort being rehabilitated.

[7]

Lilius HG, Valtonen EJ, Eikstrom J. Sexual problems in patients suffering from multiple sclerosis.

Scand J Soc Med 1976;4:41-4.

[8]

Minderhoud JM, Leemhuis JG, Kremer J, Laban E, Smits PML. Sexual disturbances arising from multiple sclerosis. Acta Neurol Scand 1984;70:299-306.

[9]

Valleroy ML, Kraft GH. Sexual dysfunction in multiple sclerosis. Arch Phys Med Rehabil 1984;65:125-8.

References 7, 8 and 9, questionnaire surveys of sexual problems sent to patients with MS.

[10] Morgentaler A. Male impotence. Lancet 1999;354:1713-18.

Recent review looking at current, i.e. post Viagra, management of ED. [11] Goldstein I, Lue T, Padma-Nathan H, Rosen R, Steers W, Wicker P, et al. Oral sildenafil in the treatment of erectile dysfunction. New Engl J Med 1998;338:1397-1404.

First published results of sildenafil in a large unselected population of men.

[12] Zusman R, Morales A, Glasser D, Osterloh I. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol 1999;83:35C-44C. [13] Jackson G, Betteridge J, Dean J, Hall R, Holdright D, Holmes S, et al. A systemic approach to erectile dysfunction in the cardiovascular patient: a consensus statement. Int J Clin Pract 1999;53:445-51.

Reference 12 from US, this from UK concluding lack of cardiovascular risk in treatment with sildenafil.

[14] Giuliano F, Hultling C, Masry E. Randomized trial of sildenafil for the treatment of erectile dysfunction in spinal cord injury. Ann Neurol 1999;46:15-21.

Large study showing efficacy of sildenafil in men with SCI. [15] Fowler CJ, Miller J, Sharief M. Viagra (sildenafil citrate) for the treatment of erectile dysfunction in men with multiple sclerosis. Ann Neurol 1999;46:497.

Abstract — result of multicenter study showing efficacy of sildenafil in men with MS. [16] Palmer J, Kaplan W, Firlit C. Erectile dysfunction in spina bifida is treatable. Lancet 1999;354:125-6.

Small group of men with spina bifida successfully treated with sildenafil.

48

[17] Hussain IF, Brady C, Swinn MJ, Mathias CJ, Fowler CJ. Exacerbation of orthostatic hypotension with sildenafil citrate (Viagra) in patients with autonomic failure due to MSA , submitted.

Small group of men with parkinsonism treated with sildenafil — those with Parkinson’s disease responded well; 3 out of 6 with MSA developed severe hypotension.

[18] Rendell M, Rajfer J, Wicker P, Smith M, Group ftSDS. Sildenafil for treatment of erectile dysfunction in men with diabetes. J Am Med Assoc. 1999;281:421-6.

Large study of diabetics.

[19] Lowentritt B, Scardino P, Miles B, Orejela F, Schatte E, Slawin K et al. Sildenafil citrate after radical retropubic prostatectomy. J Urol 1999;162:1614-17.

Poor response of men who have had bilateral nerve involvement.

[20] Heaton J, Morales A, Adams M, Johnston B, El-Rashidy R. Recovery of erectile function by the oral administration of apomorphine. Urology 1995;45:200-6.

Early study looking at the effect of apomorphine on erectile function.

[21] Linet O, Ogring F, Group ftAS. Efficacy and safety of intracavernosal alprostadil in men with erectile dysfunction. New Engl J Med 1996;334:873-7.

Formal study of intracavernosal alprostadil — prior to then papaverine made up by local pharmacy departments was used for cavernosal injection.

[22] Gomaa A, Shalaby M, Osman M, Eissa M, Eizat A, Mahmoud M et al. Topical treatment of erectile dysfunction: randomised double blind placebo controlled trial of cream containing aminophylline isosorbide dinitrate, and co-dergocrine mesylate. Br Med J 1996;312:1512-15.

A mixture of nitric oxide releasing creams assists ED applied topically.

[23] Lundberg P. Physiology of female sexual function and how it is affected in neurological disease. In: Fowler CJ, editor. Neurology of bladder, bowel and sexual dysfunction. Newton, MA: Butterworth Heinemann; 1999, pp. 33-46.

Excellent review of neurology of female sexual function.

[24] Krane R, Goldstein I, Saenz de Tejada I. Impotence. New Engl J Med 1989;321:1648-59.

Early research review of pathophysiology of ED.

49

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: à

à

Although genito-urinary tract abnormalities represent some of the most demoralizing and disabling manifestations of MS, there continues to be a lamentable code of silence between physicians and patients concerning these important issues.

Abnormalities of the lower urinary tract (bladder and urethra) will be experienced by at least 96% of MS patients after 10 years of disease activity.

CHAPTER 5

MULTIPLE SCLEROSIS (MS), OTHER MYELOPATHIES AND SPINAL CORD INJURY (SCI) INTRODUCTION A comprehensive assessment and treatment strategy for bowel, bladder, and sexual dysfunction in a patient with multiple sclerosis (MS), other myelopathies, or spinal cord injury (SCI) requires a co-ordinated approach based on a knowledge of the patient’s disease course, iatrogenic factors, concomitant symptomatic complaints, as well as a knowledge of their social and psychological factors. A multidisciplinary team is often required involving neurologists, urologists, gynecologists, rehabilitation specialists, nurses, and primary care physicians. Through their efforts, the function and quality of the patient’s life can be significantly improved.

MULTIPLE SCLEROSIS (MS) Although genito-urinary tract abnormalities represent some of the most demoralizing and disabling manifestations of MS, there continues to be a lamentable code of silence between physicians and patients concerning these important issues. Without exception, patients should be asked about bladder, bowel, and sexual function. A comprehensive exploration into the problems can facilitate the diagnosis and treatment of such ailments. A greater understanding of the pathophysiology, diagnostic techniques, and treatment interventions for genitourinary dysfunction will equip the neurologist to manage patients with MS more effectively.

BLADDER DYSFUNCTION A set of questions should be used to elicit information from the patient (Table 1). Furthermore, an interdisciplinary strategy of assessment and intervention that emphasizes the collaboration between the neurologist and urologist optimizes the broadest range of treatment

50

options and enhances the chances for successful management of the MS patient with genitourinary tract dysfunction.

Abnormalities of the lower urinary tract (bladder and urethra) will be experienced by at least 96% of MS patients after 10 years of disease activity. Bladder dysfunction can produce a diversity of symptomatic complaints that are differentiated on the basis of whether they relate to storage or emptying deficits. The most common complaints relating to bladder dysfunction in patients with MS are urgency, frequency, and urge incontinence, all of which are related to detrusor hyperreflexia. Others include hesitancy, interrupted stream, incomplete emptying, double voiding, nocturia, and enuresis.

While MRI imaging has substantially advanced our ability to diagnose patients with MS and follow disease activity, there has been no recognized correlation between the number of lesions or atrophy and any specific urodynamic parameter or bladder dysfunction [1].

TABLE 1

Question set for evaluating bladder dysfunction

1.

Frequency

2.

Urgency

3.

Urge incontinence

4.

Frank incontinence

5.

Stress incontinence

6.

History of obstetrical injury or genitourinary surgery

7.

Hesitancy

8.

Double voiding

9.

Nocturia and/or enuresis

10. Iatrogenic agents

However, a number of features of the clinical examination appear to correlate with lower urinary tract dysfunction and lower extremity motor dysfunction seems to be the best predictor of bladder dysfunction. In a study with 170 MS patients and bladder symptoms, only four did not have symptoms and signs of pyramidal abnormalities [2]. Extensor plantar responses (Babinski’s sign) are evident in 70-95% of patients with bladder dysfunction and in 70% with detrusor sphincter dyssynergia (DSD). This strong positive relationship between bladder abnormalities and pyramidal dysfunction in the lower extremities is not surprising considering the neuroanatomical juxtaposition of these distinctive pathways, with the ‘legs above the bladder’ (Figure 1).

Other features include hyperreflexia, clonus, spasticity, pyramidal distribution weakness, and a sensory level (all suggestive of a myelopathy). There is also a correlation between urinary symptoms and lesions with the midbrain and pons [3-5]. In particular, specific brainstem syndromes are associated with a higher risk of bladder dysfunction, especially DSD. The most notable of these syndromes is internuclear ophthalmoplegia, a neuro-ophthalmologic hallmark of MS. While detrusor hyperreflexia with synergic voiding is the most common pattern of bladder dysfunction in MS, the incidence of DSD has been estimated to range from 18 to 66%. The uncoordinated dyssynergia is believed to result from an interruption in the descending regulatory pathways from the pontine micturition center such that there is simultaneous contraction of the detrusor

KEYPOINTS: à

Strong positive relationship between bladder abnormalities and pyramidal dysfunction in the lower extremities is not surprising considering the neuroanatomical juxtaposition of these distinctive pathways, with the ‘legs above the bladder’.

The relative levels of segmental innervation of the lower limbs and urogenital tract make it highly likely that a patient with a paraparesis will also have bladder and sexual dysfunction.

FIGURE 1

muscles and the urethral sphincters. The consequences of DSD can include a high post voiding residual (PVR), increased bladder pressures, a higher risk of urinary infections and urinary tract calculi, and upper tract disease — principally hydronephrosis, in occasional patients.

CASE 1: BLADDER DYSFUNCTION ML is a 41-year-old female patient with a 5-year history of relapsing-remitting MS. She has evidence of diffuse hyperreflexia, mild lower extremity pasticity, bilateral extensor plantar responses and subtle but definite bilateral internuclear ophthalmoplegia. She complains of frequency, hesitancy, urgency, and urge incontinence with two-time nocturia.

Treatment considerations 1.

2.

3.

4.

Measure a PVR, urinalysis, urine culture and sensitivity, BUN, creatinine, blood glucose, renal ultrasound.

If the PVR is less than 100 ml, treat with anticholinergic agent and repeat the PVR in 1-2 weeks.

If the PVR is greater than 100 ml and not reduced with double voiding or the application of a hand-held vibrator applied to the lower abdomen, begin intermittent catheterization and add anticholinergic agents for urgent bladder symptoms. Consider referral to a urologist for urodynamics.

If nocturia is not improved with the above measures, consider adding nighttime DDAVP.

51

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: à

à

à

à

It is important not to rely on the history in order to ascertain whether voiding dysfunction is present. For instance, in one study, only 47% of patients with an elevated PVR had a sensation of incomplete emptying [2]. However, of those who claimed to empty their bladders completely, 53% were incorrect.

For the majority of patients with MS that a general neurologist will evaluate, a PVR is often the only assessment that is necessary.

The emergence of effective treatment strategies for sexual dysfunction provides compelling justification to overcome the reluctance to explore these issues in a sensitive and objective manner.

Estimates suggest that the incidence of sexual dysfunction in MS ranges from 62 to 83%.

In a smaller percentage of patients, detrusor hypocontractility and areflexia can occur in association with large PVRs. This pattern may result from loss of cortical facilitation, from cerebellar lesions, or from lesions below the sacral cord.

It is important not to rely on the history in order to ascertain whether voiding dysfunction is present. For instance, in one study, only 47% of patients with an elevated PVR had a sensation of incomplete emptying [2]. However, of those who claimed to empty their bladders completely, 53% were incorrect [2].

Because of the effect of a raised post void residual volume on bladder function it is essential to measure the PVR before prescribing anticholinergic medication, as emphasized in Chapter 2.

Upper tract disease is exceptional in MS and is linked to predictable risk factors including DSD and the presence of an indwelling catheter. This is in marked contrast to those with spinal cord injury who are very much at risk of developing upper urinary tract complications. The reason for this difference is not known since MS can be associated with just as severe lower limb spasticity as may occur following SCI. For the majority of patients with MS that a general neurologist will evaluate, a PVR is often the only assessment that is necessary. However, in selected patients, urodynamic evaluation, as discussed in Chapter 2, can facilitate the proper identification of bladder and sphincteric abnormalities. This assessment can also provide compelling evidence to suggest upper motor neuron dysfunction in patients with a suspected CNS process such as MS. When no formal urinary investigation is completed, 73% of MS patients are treated inappropriately [6]. At a minimum, a PVR should be completed in all patients with MS on a periodic basis in order to capture evidence of voiding dysfunction.

SEXUAL DYSFUNCTION While sexual abnormalities represent some of the most distressing features of MS, they are often not discussed by patients with their physicians during the process of medical care. In a study involving 47 women with MS and sexual dysfunction, the majority had never

52

TABLE 2

Question set for evaluation of sexual dysfunction

1. Sexually active either with partner or by self stimulation 2. Communication with sexual partner 3. Interest in sex (libido) 4. Arousal 5. Sensation 6. Ability to achieve orgasm 7. Erection 8. Lubrication 9. Pain 10. Fatigue 11. Sexual practices and positions 12. Spasticity and its impact 13. Bladder dysfunction during sex

been asked to discuss their sexuality in relation to their disease [7].

The emergence of effective treatment strategies for sexual dysfunction provides compelling justification to overcome the reluctance to explore these issues in a sensitive and objective manner. A comprehensive assessment of the patient’s various symptomatic complaints is imperative in order to maximize sexual functioning (Table 2).

Chapter 4 discusses in general the various options for treating neurogenic sexual dysfunction. Specifically in MS, the therapy for fatigue, spasticity, pain, bowel and bladder dysfunction, and mood disorders should be optimized, as these various factors can directly impair sexual functioning. Even if therapeutic strategies are not effective in individual patients, the process of open and honest exploration of these issues can be an important and meaningful experience for both the patient and physician. A number of myths and misconceptions often serve as a powerful obstacle to pursuing education and treatment of sexual disorders (Table 3).

Estimates suggest that the incidence of sexual dysfunction in MS ranges from 62 to 83% [8-10].

Concomitant conditions such as diabetes and atherosclerosis can more strongly predispose patients to develop a sexual disturbance.

patients with MS and urinary dysfunction, there is a strong correspondence between ED and pyramidal dysfunction in the 1. I have MS and sexual dysfunction is the least of my lower extremities. Although concerns there has been an interest in the 2. Disabled patients have no sexual needs relationship between sexual dys3. My physician is not interested in hearing about sexual function in MS and neuroendodysfunction crine changes such as testoster4. It is not appropriate to discuss sexual dysfunction one deficiency, a correlation has with my doctor not been confirmed.

5. Sex must culminate in orgasm Men with MS may still expe6. Sex must involve intercourse rience spontaneous erections, 7. Physical contact must involve sexual activity particularly at night i.e. noc8. People should instinctively be sexually competent turnal penile tumescence, but 9. Patients should not masturbate or use fantasy the presence of nocturnal erections does not indicate that their problem is psychiatric, as was perhaps formerly thought. The Sexual dysfunction in men with MS. ability to sustain an erection adequately for Patients with MS will commonly experience intercourse depends largely on psychogenic sexual dysfunction, often in combination with erectile drive which is impaired by spinal cord urinary abnormalities. The initial assessment disease. should include a search for factors that potenA variety of neurophysiological tests have tially contribute to sexual abnormalities (Table been used to assess ED in MS, including the 4). Erectile dysfunction (ED) will occur in about pudendal evoked potential (see Chapters 1 70% of men with MS [11-13]. The mean time and 4). However, the current view is that these between the onset of neurological symptoms do not contribute to understanding the comand the emergence of ED in MS patients is plaint of ED in a man with MS who on clinical about 9 years: sexual dysfunction is rarely a examination has evidence of spinal cord dispresenting manifestation of MS [13,14]. As with ease.

TABLE 3

Myths and misconceptions of sexual dysfunction in MS

KEYPOINTS: Ă

As with patients with MS and urinary dysfunction, there is a strong correspondence between ED and pyramidal dysfunction in the lower extremities.

Ă

Men with MS may still experience spontaneous erections, particularly at night i.e. nocturnal penile tumescence but the presence of nocturnal erections does not indicate that their problem is psychiatric, as was perhaps formerly thought.

CASE 2: MALE SEXUAL DYSFUNCTION IN MS SL is a 35-year-old man with clinically definite secondary progressive MS with ongoing relapses. His clinical course has been stabilized with interferon therapy. He has mild spastic paraparesis and complains of sexual dysfunction characterized by decreased ability to achieve and maintain erection, difficulty achieving orgasm, chronic fatigue, and frequent extensor and adductor spasms during sexual intercourse. His wife is concerned that her husband no longer finds her attractive. Their primary sexual activity has consisted of intercourse.

Treatment considerations 1.

2.

3.

4.

5.

6.

7.

8.

9.

Begin a broad discussion about sexual dysfunction in MS with the patient and his wife.

Encourage more communication between the husband and wife.

Assess for any iatrogenic causes.

Optimize treatment for spasticity, especially before sexual activity.

Evaluate sleep hygiene and treat nocturnal spasms and nocturia if present.

If there are no contraindications, consider treating erectile dysfunction with sildenafil.

If sildenafil is ineffective, consider alternative treatment, such as intracorporeal alprostadil.

If orgasm is still difficult to achieve, suggest that vibrator stimulation be applied to the ventral surface of the glans penis (at the frenulum).

Emphasize the value of energy-conserving sexual positions and encourage alternative sexual practices other than intercourse.

53

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

TABLE 4

Factors that influence sexual dysfunction in MS and SCI

1. Dysfunction can fluctuate with disease activity 2. Reduced sensory responsiveness 3. Psychological factors and depression 4. Pain and paresthesias 5. Bowel and bladder dysfunction 6. Spasticity 7. Fatigue 8. Iatrogenic causes (e.g. SSRIs, tricyclic antidepressants) 9. Relationship discord 10. Physician neglect (‘code of silence’) 11. Preoccupied with misconceptions 12. Alteration of body image

Oral therapy for MED in MS. While a variety of therapeutic options are currently available for men with ED, oral agents have clearly eclipsed all other therapies in terms of popularity and effectiveness. Along this line, the most significant advance has been the development of oral sildenafil citrate (Viagra®) (see Chapter 4). The response of men with MS to treatment with this agent has been excellent [15]: comparisons across

studies showing a particular efficacy in this patient group. Ejaculatory difficulties may, however, persist.

Sexual dysfunction in women with MS. Women with MS will frequently experience sexual dysfunction, either related to the disease process or secondary to other factors that similarly affect males (Table 4). Diminished lubrication can be improved by the liberal use of lubricating agents that are now widely available. Some women will experience sensory disturbances during sexual activity that can often be treated effectively with membrane stabilizing medication such as gabapentin, carbamazepine, and similar agents.

In those who experience vaginal hypesthesia, most often secondary to sensory myelitis, vibratory stimulation of the clitoris and vaginal tissues can lead to pleasurable sensations and even orgasm.

Given the similarities between male and female sexual responses, there is rationale to study the potential role of agents such as sildenafil in the treatment of female sexual dysfunction. We are currently completing a randomized, double-blind, placebo-controlled cross-over study of sildenafil in women with MS and sexual dysfunction.

CASE 3: SEXUAL DYSFUNCTION IN A WOMAN WITH MS GN is a 58-year-old post-menopausal woman with secondary progressive MS. She complains of lower extremity spasticity, chronic fatigue, depression, and bladder urgency. There has been difficulty with diminished sexual arousal, numbness in the vaginal region, poor lubrication, painful sensations on attempted intercourse, and difficulty achieving orgasm. During sexual activity she experiences involuntary leg spasms with associated bladder urgency and urge incontinence. Her depression is well treated with fluoxetine.

Treatment considerations 1.

2.

3.

4.

5.

6.

7.

8.

9.

54

Strongly consider discontinuation of fluoxetine and treating her depression with an alternative agent that is less associated with sexual dysfunction (e.g. trazodone, venlafaxine).

Assess sleep hygiene and treat nocturnal motor spasms and bladder dysfunction if present.

Optimally treat spasticity.

Treat bladder urgency and urge incontinence, especially before sexual activity (void before sex and use anticholinergic agents for bladder relaxation).

Encourage the use of lubricating agents.

Treat painful sensations (consider a tricyclic antidepressant, which may be helpful for pain, depression, and bladder urgency).

Refer to gynecologist for possible hormone replacement therapy.

Encourage energy-conserving positions.

Emphasize the benefits of good communication with partner concerning problems and potential solutions.

BOWEL DYSFUNCTION Bowel dysfunction occurs in many patients with MS at some point during the course of the illness and can persist as a chronic manifestation of the disease [16,17]. Although there is a predilection for bowel dysfunction to occur in those patients with bladder complaints, in a study of patients with MS attending a clinic for treatment of urinary symptoms, one third did not have bowel problems [17].

A number of factors contribute to the onset of bowel dysfunction that must be recognized by the treating physician so that a strategic therapeutic plan can be formulated. The assessment of bowel abnormalities must begin with an inquiry about bowel symptoms and complaints (Table 5).

The most frequent abnormalities of bowel dysfunction are constipation, impaction, and incontinence, but by far the most common problem is constipation. Unlike the high frequency of bladder incontinence that occurs in MS patients, regular bowel incontinence is less common.

Constipation. The contributing factors that result in constipation are manifold (Table 6).

A reduction in neuro-gastrointestinal signaling through the autonomic nervous system has been advanced as a hypothesis on how MS can lead to a slowing in intestinal transit time [18].

MS patients can experience difficulty with voluntary transitions from the storage to defecation process in response to a full rectum.

Inadequate relaxation of the pubococcygeus and sphincter muscles can prohibit defecation despite the patient’s perception of bowel urgency and the performance of the Valsalva

TABLE 6

Constipation: contributing factors

1. Reduced neurogastrointestinal signaling 2. Reduced gastrocolic reflex 3. Pelvic floor muscular spasticity 4. Inadequate hydration 5. Drugs (e.g. anticholinergic agents) 6. Immobility 7. Lack of physical conditioning 8. Weak abdominal muscles

maneuver. AbdomiTABLE 5 Question set for evaluating nal muscle contracbowel dysfunction tions facilitate the process of fecal evac1. Problems with constipation uation. These mus2. Problems with diarrhea cles are innervated 3. Alternating bouts of constipation and

by T6-T12 spinal cord diarrhea segments and disease 4. Problems with incontinence activity within the 5. Bowel urgency spinal cord at these 6. Urgency with difficulty evacuating levels can lead to an rectum increase in abdomi7. Hard painful stools nal compliance.

8. Adequate hydration and fiber Following the 9. Iatrogenic agents ingestion of a meal, especially in the morning, many individuals experience the perceived need to defecate. This process is KEYPOINTS: recognized as the gastrocolic reflex, but it may be blunted in patients with MS. Nevertheless, à A number of factors contribute to the onset patients should be encouraged to identify the of bowel dysfunction time of day where the post-meal urge to defthat must be recognized by the treatecate is strongest. ing physician so that Inadequate fluid hydration is a major cona strategic therapeutic tributor to bowel constipation in MS patients. plan can be formuMany patients recognize that fluid intake can lated. provoke bladder urgency and urge incontinence and will therefore restrict their fluid à The most frequent abnormalities of bowel intake. It is crucial that an integrated treatdysfunction are constiment plan be formulated for each patient pation, impaction, and that takes into consideration the interaction incontinence, but by between bowel and bladder pathophysiologifar the most common problem is constipacal mechanisms. tion.

Other factors that contribute to constipation include iatrogenic causes, primarily from medications, inadequate dietary or supplemental fiber, immobility, and inadequate exercise. The most common agents that can cause or exacerbate constipation in MS patients include antihypertensive agents, anticholinergics (commonly used for bladder urgency), sedative-hypnotic agents, calcium supplements and aluminum containing antacids, tricyclic antidepressants, narcotic analgesics, diuretics, and iron supplements.

When constipation is prolonged, bowel incontinence or impaction can ensue. Treatment of impaction involves the use of hyperosmotic agents, enemas, and typically disimpaction. During this time, bulking agents should be discontinued until the colon is evacuated.

55

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: Ă

Fecal incontinence in MS is relatively uncommon and generally is associated with poorly treated constipation.

Isolated bowel incontinence should be investigated separately.

More severe consequences can occur and include intestinal obstruction, intussusception, and rectocele. Chronic straining can cause intussusception and intrarectal obstruction leading to severe difficulty with rectal emptying or a constant sensation of incomplete rectal emptying and the need to defecate. Patients with such complaints should be referred to a colo-rectal specialist.

Fecal incontinence. When fecal incontinence occurs, a number of factors may be responsible and include reduced sensation of rectal filling, poor voluntary contraction of the anal sphincter and pelvic floor musculature (poor voluntary squeeze pressure), and reduced rectal compliance.

Fecal incontinence in MS is relatively uncommon and generally is associated with poorly treated constipation. Isolated bowel incontinence should be investigated separately. The institution of a formal bowel program for treatment of constipation (see Chapter 3) will generally reduce the risk of incontinence. Furthermore, it is important to identify provocative factors (e.g. irritants, such as caffeine and alcohol) that can be altered to reduce the incidence of incontinence episodes.

In some patients with severe spinal cord dysfunction and loss of voluntary control, frequent episodes of fecal incontinence will mandate the use of protective pants and timed

elimination periods by the use of scheduled suppository treatment to establish a program of reliable bowel movements. The predictability of this regimen is of great benefit to both those demoralized by the experience of bowel accidents and their carers.

The general treatment of constipation and fecal incontinence is described in Chapter 3.

OTHER MYELOPATHIES INCLUDING HUMAN T-LYMPHOTROPIC VIRUS-1 ASSOCIATED MYELOPATHY (HAM) Various causes of myelopathy are given in Table 7. The approach to pelvic organ dysfunction in myelopathic disorders that cause upper motor neuron bladder dysfunction is the same as that detailed above.

One example of a condition that produces similar genitourinary dysfunction to that of MS is HAM, also known as tropical spastic paraparesis (TSP) [19]. This condition is caused by a retrovirus which has an expanding worldwide distribution. The risk factors for transmission include i.v. drug abuse, blood transfusion, and sexual intercourse. The virus can also be transmitted vertically from mother to infant during breast-feeding. The diagnosis of TSP can be made by a number of molecular techniques including immunofluorescence, ELISA, Western blot, with CSF antibodies, and

by PCR.

CASE 4: BOWEL DYSFUNCTION IN MS JH is a 30-year-old nurse with a history of clinically definite relapsing-remitting MS. She presents for a follow-up clinic visit complaining of severe constipation. She previosly would have daily bowel movements in the morning after breakfast. She now works the morning shift and often skips her morning meal. She has stopped her previous vigorous exercise routine and has gained 10 kg. It is clear that she has had some degree of abdominal distention secondary to her weight gain and poor abdominal muscle tone. The patient is well known to restrict fluids secondary to severe bladder urgency and a history of urge incontinence while at work. In addition, she is being treated with amitriptyline for depression and migraine headache prophylaxis. She has used laxatives and digital stimulation to promote bowel movements.

Treatment considerations 1.

2.

3.

4.

5.

6.

7.

56

Resume a regular exercise program to include abdominal muscle exercises.

Begin a weight loss program.

Perform a PVR and if less than 100 ml implement anticholinergic therapy in order to reduce bladder urgency and urge incontinence. Subsequently repeat the PVR to exclude anticholinergic induced urinary retention.

Strongly emphasize the importance of adequate fluid hydration of at least 2000 ml/day.

Increase dietary fiber and begin a bulking agent.

Suggest the use of glycerin or other suppositories if pelvic floor and spincteric muscular spasticity is suspected.

Alternative agents for depression and migraine could be considered.

TSP is characterized pathologically by a chronic inflammatory process primarily affecting the spinal cord white matter. Evidence of demyelination with axonal sparing in association with macrophage activation and oligodendrocyte apoptosis reminiscent of the pathology in MS. However, in TSP there is an additional component of pathology within the bladder lamina propria in conjunction with thickened neurons which assume the appearance of ‘sausage rolls’ [19]. These histopathological features are distinctive to TSP and have not been observed in other myelopathies that produce bladder dysfunction.

Assessment and management of genitourinary dysfunction in patients with TSP is similar to that of other myelopathies, as outlined in Chapter 2.

Bladder dysfunction occurs in 75-100% of infected individuals with the most common patterns being detrusor hyperreflexia and DSD. Approximately 60% of TSP patients will require the use of CIC at some point during the illness [19]. Occasional patients will exhibit evidence of decreased detrusor activity, which would appear to result from disease involvement of the posterior and anterior nerve roots in addition to Onuf’s nucleus. Similar to MS, upper tract disease is distinctly uncommon.

SPINAL CORD INJURY (SCI) Bladder dysfunction. In those patients who experience spinal cord injury (SCI), there is an initial period of cessation of spinal reflexes including bladder areflexia. This typically lasts for days to weeks during which the bladder requires continuous drainage, either by a urethral or suprapubic catheter.

Many of the same assessment and treatment strategies outlined for myelopathies as described in Chapter 2 can be applied to those with SCI. However, there are major urological differences between those with progressive spinal cord disease and the spinal cord injured. The former are usually not suitable to undergo urological surgery, whereas those with SCI are otherwise fit and need a definitive solution to their bladder dysfunction, and furthermore, because they are at risk of renal failure, they should remain under urological supervision.

The risk of renal failure is due to three principal disorders: obstruction; vesicoure-

TABLE 7

Causes of myelopathy

þ

Spinal cord injury

þ

Compressive-disc disease/spondylosis/chiari malformation

þ

Metastatic lesions

þ

Spinal cord tumors (glioma, lymphoma, etc.)

þ

Multiple sclerosis (MS)

þ

Post infectious or post vaccinal myelitis

þ

Idiopathic transverse myelitis

þ

Neuromyelitis optica (Devic’s syndrome)

þ

Neurosarcoidosis

þ

Amyotrophic lateral sclerosis (ALS)

þ

Primary lateral sclerosis (PLS) (bladder dysfunction exceptional)

þ

HIV (vacuolar myelopathy)

þ

HTLV-1 associated myelopathy (tropical spastic paraparesis)

þ

Leukodystrophy (e.g. adrenomyeloneuropathy)

þ

Nutritional causes (e.g. Vitamin B-12 deficiency)

þ

Hereditary myelopathies

teric reflux; and the formation of calculi. Urinary obstruction leads to an increase in bladder pressures and a thickened trabeculated bladder wall. Vesicoureteric reflux occurs secondary to elevated detrusor pressures and requires intervention with bladder drainage and the use of anticholinergic agents. Urinary tract calculi occur more commonly in those who are immobilized for prolonged periods.

Stone formation can serve as a nidus for recurrent urinary tract infections. In those with chronic indwelling catheters, the balloon can be the site for the formation of eggshell calcification ultimately leading to sloughing and the formation of bladder stones. Treatments for calculi include lithotripsy, percutaneous nephrolithotomy, and ureterorenoscopy. Chronic catheterization can be associated with a small risk of squamous cell carcinoma that is substantially higher than that seen in the general population and because of this, periodic cystoscopy is recommended. While renal failure was previously responsible for significant amount of mortality in those with SCI, new management strategies have substantially reduced morbidity and mortality. An important review on this subject has recently been published [20].

In some individuals, implantation of a Brindley sacral root stimulator may be appro-

KEYPOINTS: à

There are major urological differences between those with progressive spinal cord disease and the spinal cord injured. The former are usually not suitable to undergo urological surgery, whereas those with SCI are otherwise fit and need a definitive solution to their bladder dysfunction, and furthermore, because they are at risk of renal failure, they should remain under urological supervision.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: Ă

Ninety-five percent of SCI patients required at least one therapeutic method to initiate defecation and half of them became dependent on others for toileting.

Ă

Most men following SCI are able to obtain reflex erections, but these are not usually adequate for intercourse and few experience psychogenic erections.

58

priate. The procedure requires sacral deafferentation causing loss of reflex detrusor and erectile function and is therefore only indicated in those with a complete cord lesion.

Stimulating electrodes are placed on the anterior roots of S2-S4 and a radioreceiver is placed in the lower anterior chest. Micturition can be initiated by the application of a mirror-image radio transmitter over the receiver. Following a defined period of stimulation the current is terminated. During this phase, the sphincter will relax rapidly, while the detrusor contraction does so more slowly. It is during this phase of dyssynergic muscle relaxation that effective voiding occurs.

A distinctive abnormality that occurs in those with SCI is autonomic dysreflexia. This syndrome generally occurs when the level of the insult is above T6. Patients can experience crescendo hypertension, severe headache, and increased risk of stroke. These changes appear to be related to episodic massive sympathetic discharges within the spinal cord, culminating in vasospasm of the skin and visceral organs.

These episodes are typically precipitated by noxious stimuli below the level of the lesion which include constipation, fecal impaction, bladder contractions or can occur during bladder or bowel treatment procedures. Therapeutic considerations for those with autonomic hyperreflexia include elevation of the head of the bed and the use of antihypertensive agents, especially calcium channel blockers.

Anesthetic agents can also be used before manipulations that may trigger these reactions.

Bowel dysfunction in SCI. A study of spinal cord injured patients showed that bowel dysfunction is a major physical and psychological problem [21]. Nausea, diarrhea, constipation and fecal incontinence were all much more common after SCI, but the major problems arise as a result of loss of voluntary control of defecation. Ninety-five percent of SCI patients required at least one therapeutic method to initiate defecation and half of them became dependent on others for toileting. The procedure was prolonged and in almost half bowel evacuation took more than 30 minutes and the time taken correlated with measures of distress and depression. On a scale of 0 (no perceived problem) to 10 (maximum perceived problem), patients rated their loss of

mobility as a mean of 6.8 (SD 3.3), sexual satisfaction 5.5 (SD 4.2), urinary management 4.9 (SD 3.5) and bowel management 5.1 (SD 3.6).

Optimizing bowel function can help to restore dignity and control to a person following SCI. Failure to avoid the complications of constipation can result in significant morbidity (e.g. bed sores, anal fissure). Furthermore, some 10% of SCI fatalities may be ascribed to undiagnosed abdominal emergencies. Management of bowel problems requires effort on the part of both patient and carer, who must set aside time regularly for bowel care.

Management. Establishment of a bowel program should be individualized. Patients will have different bowel patterns in terms of the frequency of bowel movements. It is important to recognize when an individual patient is more likely to produce stool. For some patients this will be in the morning while in other it will be later in the day. The majority of SCI patients practice regular manual evacuation to prevent impaction and reduce the risk of autonomic dysreflexia. In those SCI patients with a preserved defecation reflex, reflex emptying can be stimulated every 1-3 days by gentle rotation of a gloved finger in the anus until the rectal wall is felt to relax, or flatus is passed and the stool comes down.

This is repeated every 10 minutes until the internal anal sphincter is felt to close off again, or no stool has been passed after the last two stimulations. Alternatively, they can infuse a mini enema to stimulate the reflex. A few SCI maintain a deep nonspecific pelvic sensation of rectal fullness and can be taught to identify this sensation and then stimulate reflex emptying. Many patients can sense when defecation is complete.

Adequate hydration should be ensured and dietary and supplemental fiber should also be adequate. Hyperosmotic agents such as lactulose and sorbitol can contribute to facilitating bowel motility and regularity.

Sexual dysfunction following SCI. The person who suffers spinal cord injury is typically a fit young man at a sexually intense time of life. Most men following SCI are able to obtain reflex erections, but these are not usually adequate for intercourse and few experience psychogenic erections. The possibility of resuming sexual activity is a major concern of those injured and it has been shown that

the successfulness of rehabilitation is correlated with sexual potency. Although intracavernosal injections and vacuum pump devices were used by men with SCI, the introduction of Viagra, which increases erectile response within the context of sexual stimulation by their partner, has been greatly welcomed (see Chapter 4). A placebo-controlled trial showed sildenafil was highly effective in men with SCI in improving ability to achieve and maintain an erection and increase satisfaction with intercourse. It was effective even in those who did not have residual erectile function [22].

Very few men following SCI are able to ejaculate during intercourse, but if fertility is an issue, either a vibrator applied to the penis or electrical stimulation of the pelvic plexus by a rectal probe will induce ejaculation in most cases.

CONCLUSION Patients with myelopathy frequently present with major problems with pelvic organ function. A comprehensive approach that integrates the assessment and treatment of bowel, bladder, and sexual dysfunction represents the strategy with the greatest likelihood of achieving satisfactory results. However, their caring physicians can institute effective diagnostic and treatment approaches that can enhance functional capability and ultimately promote a higher quality of life for patients with abnormalities of the genitourinary system. While the neurologist can successfully serve as the principal care provider for such patients, close collaboration with the urologist substantially adds value to the multidisciplinary management of those with spinal cord disease.

KEYPOINTS: à

Patients with myelopathy frequently present with major problems with pelvic organ function. A comprehensive approach that integrates the assessment and treatment of bowel, bladder, and sexual dysfunction represents the strategy with the greatest likelihood of achieving satisfactory results.

CASE-ORIENTED MULTIPLE CHOICE QUESTIONS þ

A woman of 45 with secondary progressive MS complains of worsening bladder control.

Despite taking 2.5 mg oxybutynin t.d.s. she had daily episodes of urge incontinence and wets the bed at night at least twice a week. The most appropriate next step in establishing more effective management is: A. B. C. D. E.

Spinal cord MRI. Cystometry.

Measurement of post micturition residual urine volume.

Cystoscopy.

Measurement of pudendal evoked potential.

The answer is C. Post micturition residual urine is a significant cause of symptoms of storage dysfunction. Oxybutynin will reduce the amplitude and frequency of unstable contractions and also increase bladder capacity; however, a persistent post micturition residual will decrease the time taken to fill the bladder to capacity. þ

A man of 35 with a diagnosis of relapsing and remitting MS was recovering from a relapse in which there had been spinal cord demyelination with spastic paraparesis and lower limb weakness such that his mobility was reduced to 10 yards (9.1 meters) and he needed a stick to walk. Following a course of steroids, his walking improved somewhat, but he then presented with erectile dysfunction. Although morning erections were preserved, the patient was unable to obtain an erection sufficient for intercourse. The most appropriate initial step in management for the above case is: A. Investigation by a glucose tolerance test.

B. Referral for psychosexual counseling.

C. Consultation during which it is explained to him his ED is an expected result of spinal cord demyelination.

D. MRI of the spinal cord.

E. Nocturnal penile tumescence studies.

59

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

The answer is C. When a patient with an established neurological diagnosis presents with ED there is no requirement to perform investigations, as the likely cause of the ED is neurological. þ

A 40-year-old man with secondary progressive MS describes difficulty with urinary urgency, urge-incontinence and nocturia. There has been no recent history of urinary tract infections.

Which of the following is the most important initial evaluation: A. B. C. D. E.

Urinalysis.

Renal ultrasound.

Cystoscopy.

Prostate specific antigen.

Post-void residual urine measurement.

The answer is E. Again, post micturition residual measurement is the most important test to perform as the neurological diagnosis is certain, a residual is expected in this condition and would account for the symptoms. þA

31-year-old woman presents with an 8-year history of multiple sclerosis. Her clinical course has been characterized by episodes of optic neuritis, transverse myelitis, and bilateral internuclear ophthalmoplegia. Over the last 6 months she has developed moderately severe lower extremity spasticity in association with involuntary jerks and spasms. Examination shows a spastic paraparesis, diffuse hyperreflexia, bilateral extensor plantar responses, bilateral ankle clonus, and a spastic gait. She complains of bowel urgency and also inability of evacuation. Which of the following accurately describes the underlying mechanism for her complaint: A. B. C. D. E.

Constipation from poor neuro-gastrointestinal signaling.

Immobility.

Weak abdominal muscles.

Reduced gastrocolic reflex.

Pelvic floor muscular spasticity (recto-sphincter dyssynergia).

The answer is E. Patients with MS present with a wide variety of bowel complaints from constipation to fecal incontinence, especially of loose stools. However, in this case, the combination of fecal urgency and difficulty in evacuation indicate that pelvic floor muscular spasticity is the underlying problem. þ

A 51-year-old woman with secondary progressive MS has recently ceased to have menstrual periods and now complains of hot flushes, depression, sexual dysfunction and fatigue. Her MS history includes two episodes of partial sensory transverse myelitis that left her with residual dysesthesias in the lower extremities and in the perineum. In terms of her sexual dysfunction, with a specific focus on treatment intervention, all of the following are important to explore initially except: A. B. C. D. E.

Vaginal lubrication.

Serum testosterone levels.

Ability to become aroused and achieve orgasm (sensory threshold).

Current use of antidepressants.

Pain during sexual activity.

The answer is B. A raised testosterone level would be the most unexpected cause of female sexual dysfunction in this case, given that there is an established neurological diagnosis that would account for her symptoms.

60

REFERENCES [1]

Kim YH, Goodman C, Omessi E, Rivera V, Kattan MW, Boone TB. The correlation of urodynamic findings with cranial magnetic resonance imaging findings in multiple sclerosis. J Urol 1998;159:972.

A study showing no correlation between MRI abnormalities and urodynamics.

[2]

Betts CD, D’Mellow MT, Fowler CJ. Urinary symptoms and neurological features of bladder dysfunction in multiple sclerosis. J Neurol Neurosurg Psychiatry 1993;56:245-50.

A large study linking bladder symptoms and neurological exam findings.

[3]

Filippi M, Miller DH. Magnetic resonance imaging in the differential diagnosis and monitoring of the treatment of multiple sclerosis. Curr Opin Neurol 1996;9:178.

A review on the utility of MRI in the diagnosis of MS.

[4]

Pozzilli C, Grasso MG, Bastianello S, Anzini A, Bozzao L, Von Heland M, Fieschi, C. Structural correlates of neurourologic abnormalities in multiple sclerosis. Eur Neurol 1992;32:228.

A study of the relationship between MRI lesions and urinary symptoms.

[5]

Stevens JC, Kinkel WR, Polanchini I. Clinical correlation in 64 patients with multiple sclerosis. J Neurol 1986;43:1145.

Large clinical correlation series.

[6]

Blaivas JG, Holland N, Geisser B et al. Multiple sclerosis bladder studies and care. Ann New York Acad Sci 1984;436:328-46.

Emphasizes risk of inappropriate treatment in MS patients without any formal urinary investigations.

[7]

Hulter B, Lundberg PO. Sexual function in women with advanced multiple sclerosis. J Neurol Neurosurg Psychiatry 1995;59:83-6.

MS study in women demonstrating that discussion of sexual dysfunction is neglected.

[8]

Lilius HG, Valtonen EJ, Eikstrom J. Sexual problems in patients suffering from multiple sclerosis.

Scand J Soc Med 1976;4:41-4.

Incidence of sexual dysfunction in MS.

[9]

Minderhoud JM, Leemhuis JG, Kremer J, Laban E, Smits PML. Sexual disturbances arising from multiple sclerosis. Acta Neurol Scand 1984;70:299-306.

Incidence of sexual dysfunction in MS.

[10] Valleroy ML, Kraft GH. Sexual dysfunction in multiple sclerosis. Arch Phys Med Rehab 1984;65:125-8.

Incidence of sexual dysfunction in MS. [11] Ghezzi A, Malvestiti G, Baldini S et al. Erectile impotence in multiple sclerosis: a neuropysiological study. J Neurol 1995;242:123-6.

Frequency of sexual dysfunction and neurophysiological characterization.

[12] Kirkeby HJ, Poulsen EU, Petersen T et al. Erectile dysfunction in multiple sclerosis. Neurology 1988;38:1366-71.

Incidence of erectile dysfunction in MS. References continued Ăž

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

References continued Ăž

[13] Betts CD, Jones SJ, Fowler CJ. Erectile dysfunction in multiple sclerosis: associated neurological and neurophysiological deficits, and treatment of the condition. Brain 1994;117:1303-10.

Comprehensive analysis of sexual dysfunction in MS. [14] Muller H. Studies on disseminated multiple sclerosis. Acta Med Scand 1949;222:67-71.

Early study of sexual dysfunction in MS. [15] Fowler CJ, Miller J, Sharief M. Viagra (sildenafil citrate) for the treatment of erectile dysfunction in men with multiple sclerosis. Ann Neurol, 1999;46:497.

Initial observations on the role of Viagra in men with MS and erectile dysfunction.

[16] Hinds J, Eidelman B, Wald A. Prevalence of bowel dysfunction in multiple sclerosis: a population survey. Gastroenterology 1990;98:1538-42.

Population survey of bowel dysfunction in MS. [17] Chia YW, Fowler CJ, Kamm M et al. Prevalence of bowel dysfunction in patients with multiple sclerosis and bladder dysfunction. J Neurol 1995;242:105-8.

Majority of MS patients experience bowel dysfunction.

[18] Glick E, Meshkinpour H, Haldeman S et al. Colonic dysfunction in multiple sclerosis.

Gastroenterology 1982;83:1002-7.

Mechanisms of bowel dysfunction in MS. [19] Dasgupta P, Hussain IF. Tropical spastic paraparesis. In: Fowler CJ, editor. Neurology of bladder, bowel, and sexual dysfunction. Boston: Butterworth-Heinemann; 1999. p. 315-24.

Superb review.

[20] Arnold EP. Spinal cord injury. In: Fowler CJ, editor. Neurology of bladder, bowel, and sexual dysfunction. Boston: Butterworth-Heinemann; 1999. p. 275-88.

Excellent review on the neurourology of spinal cord injury.

[21] Glickman S, Kamm M. Bowel dysfunction in spinal cord injury patients. Lancet 1996;347:1651-3.

[22] Giuliano F, Hultling C, Masry E et al. Randomized trial of sildenafil for the treatment of erectile dysfunction in spinal cord injury. Ann Neurol 1999;46:15-21.

Large placebo controlled trial showing efficacy of Viagra in men with spinal cord injury.

62

KEYPOINTS:

CHAPTER 6

à

Nerves from the cauda equina provide the motor and sensory innervation of the lower limbs and pelvic organs.

à

Disorders affecting the cauda equina are characterized by weakness and sensory loss in the lower limbs, buttocks and perineum, usually with important abnormalities of bladder, bowel and sexual function.

CAUDA EQUINA DISORDERS ANATOMY The spinal cord tapers to its end, the conus medullaris, usually at the lower edge of the first lumbar vertebra. The continuation of the spinal cord is a strand of connective tissue, the filum terminale. The ventral and dorsal lumbar and sacral nerve roots that arise from the conus medullaris form a bundle, the cauda equina (Figure 1). These lumbar and sacral spinal nerve roots separate in pairs to exit laterally through the nerve root foramina.

The main destinations for these roots are the lumbar and sacral plexuses. Nerves from these plexuses provide the motor and sensory innervation of the lower limbs and pelvic organs. The cauda equina, like the spinal cord, is invested by the meninges. The arachnoid membrane envelops it loosely as the thecal sac.

TABLE 2

Causes of chronic cauda equina compression

Extrinsic tumors Primary tumors arising from the cauda Spinal stenosis • Degenerative spondylosis • Achondroplasia • Fluorosis Chronic central disk herniation Abscess; tuberculoma

DISORDERS Disorders affecting the cauda equina are characterized by weakness and sensory loss in the lower limbs, buttocks and perineum, usually with important abnormalities of bladder, bowel and sexual function. The causes of cauda equina damage are listed in Tables 1 and 2.

Central disk herniations. Disk herniations usually occur in a dorsolateral direction, thereby leading to compression of individual spinal nerve roots after they have separated

TABLE 1

Causes of acute cauda equina damage

Central disk herniation Vertebral collapse due to metastatic infiltration Spinal subarachnoid hemorrhage

Dorsal view of the lower lumbar spine and sacrum.

The laminae of the vertebrae have been removed, showing the cauda equina and nerve roots in the spinal canal, then leaving through the nerve root foramina. For clarity, only the ventral rami of the sacral spinal nerves are shown.

FIGURE 1

Acute extradural hematoma Trauma

From Stewart JD. Focal peripheral neuropathies, 3rd ed. Lippincott, Williams and Wilkins; 1999. Reproduced with permission.

63

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

anesthesia” (Figure 3). Smaller herniations produce a more limited syndrome of mainly saddle anesthesia and sphincter dysfunction (see Case 1). Some central disk herniations produce the opposite clinical picture: the roots that lie more laterally in the cauda equina — the lower lumbar and upper sacral roots — may be most affected, while the centrally lying S3-S5 roots are spared, and thus sphincter function is normal [1].

Other causes of acute cauda equina lesions are rare.

These include vertebral collapse due to metastatic infiltration, spinal subarachnoid FIGURE 2 Dorsal view of the lower lumbar spine and sacrum, showing the different types of hemorrhage from a vascular disk herniation. Note, particularly, the central L4-L5 central disk herniation. malformation or ependyFrom Stewart JD. Focal peripheral neuropathies, 3rd ed. Lippincott, Williams and Wilkins; 1999. moma, and an acute extraReproduced with permission. dural hematoma.

Chronic central disk herniations mimic tumors of the KEYPOINTS: from the cauda equina. Such individual conus medullaris or cauda equina. Back pain radiculopathies will not be discussed further and radicular sensory symptoms may be à Large acute central here. Central disk herniations comprise less absent, and the presenting complaints are disk herniations prothan 3% of all disk herniations (Figure 2). often perineal pain or paresthesias, urinary duce a dramatic and The disk usually involved is L4-L5, but dysfunction and erectile dysfunction (ED) in serious syndrome of herniations at other levels can occur; they all men. The physical signs are similar to those of bilateral sacral, buttock, perineal and posproduce a similar syndrome. The symptoms acute central disk herniation. terior leg pain and and signs vary depending on the rate and Primary tumors of the cauda equina. numbness, weakness in extent of the herniation, the size of the Ependymomas and neurofibromas are the the legs, and sphincter spinal canal, and the number of nerve roots most frequent primary tumors of the cauda dysfunction. involved. Because the sacral roots lie closest equina; rarer types include meningiomas, lipoà An important feature to the midline in the cauda equina, they bear mas, dermoid tumors, schwannomas, hemanof the pain is that the brunt of the damage. gioblastomas, and paragangliomas. An intrait is usually not Large acute central disk herniations produce medullary spinal tuberculoma can also mimic relapsing and a dramatic and serious syndrome of bilateral a conus tumor. remitting, and it may worsen with recumsacral, buttock, perineal and posterior leg pain The main symptoms are pain, which is bency and be particuand numbness, weakness in the legs, and variably located in the low back, sacral, butlarly severe during the sphincter dysfunction. Examination usually tock or perineal areas. This pain can be of night. shows weakness in the S1 and S2 innervated sudden or gradual onset. A herniated intermuscles (gastrocnemius, hamstrings, gluteal vertebral disk or spondylosis is, therefore, the muscles), variable sensory loss extending from usual initial diagnosis. An important feature the soles of the feet to the perianal region, a of the pain is that it is usually not relapsing patulous anal sphincter, and loss of the anal and remitting, and it may worsen with recumwink and bulbocavernosus reflexes. This pat- bency and be particularly severe during the tern of sensory loss restricted to the medial night (see Case 2). Symptoms of nerve root buttocks and perianal area is termed “saddle compression usually develop later, sometimes

64

is often abnormal, lumbar scoliosis or lordosis may be present, and deficits due to root compression vary from none to being widespread. The classical signs of saddle anesthesia and a patulous anus are valuable, but are infrequently present.

There are several other, less common, ways in which cauda equina tumors can present. Some paFIGURE 3 The dermatomes subserving the perineal and buttock areas. tients have progresInvolvement of the S3-S5 dermatomes bilaterally gives rise to sive painless weakthe clinical sign of saddle anesthesia, characteristic of many cauda equina ness of the legs that lesions. may be misdiagFrom Haymaker W, Woodhall B. Peripheral nerve injuries: principles and nosed as generalized diagnosis. Philadelphia: Saunders; 1953. Reproduced with permission. peripheral neuropathy or spinal muscular atrophy. Occaeven many years later. They include pares- sionally, sphincter disturbances are the first thesias, leg weakness, and often bladder dis- and only symptom and no neurological signs turbances; bowel and ED are less common. are present; a cauda equina tumor is discovThere are no particular characteristic features ered years later when back pain and radicuon physical examination. Straight leg raising lar symptoms appear. One rare, but distinc-

CASE 1 This 34-year-old woman had been healthy, apart from a 10-year history of chronic low back pain. She presented at the Emergency Room with worsening of the low back pain over the last 10 days, but because, in particular, on the previous day, she had developed a new, severe pain in the perineal and sacral area. A few hours later, she noted numbness in the perineum and increased urinary frequency. She felt that she was not emptying her bladder completely. She also had some increased frequency of bowel movements and defecation was painful. She denied any weakness in the legs.

On examination, she was in pain. The abnormalities were restricted to the lower limbs. Straight leg raising was markedly limited bilaterally. Power was normal in the legs. The right ankle reflex was absent. Sensory examination showed marked diminution of light touch and pin prick in the perineal and perianal areas. A rectal examination showed reduced rectal tone.

A diagnosis of a central lumbosacral disk herniation was made and a CT scan was performed. This showed a large posterior disk herniation at L4-L5 (Figures 1 and 4). She underwent surgical diskectomy within hours. The following day, her back pain was considerably better and sensation in the perineum and bowel function gradually returned to normal. Bladder function was normal from the first postoperative day.

Comment: This history is characteristic of an acute central disk herniation causing cauda equina compression. Urgent imaging for confirmation of the diagnosis and urgent surgery are required in order to optimize the patient’s chances of a good recovery of bladder and bowel function.

65

NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

CASE 2 This 73-year-old man had suffered from diabetes mellitus which had been controlled by oral hypoglycemic agents for the last 18 years. He was referred for evaluation with a history of pain in the anal, sacral, right gluteal area, and the posterior aspect of the upper right thigh over the last 3 years. The pain was consistently brought on by lying down and relieved by standing. He had to sleep in a reclining chair. He denied any motor or sensory symptoms in his legs.

However, for 3 years, he had had erectile dysfunction, would have to get up three times at night to urinate, and had developed constipation that required regular laxatives. A urological evaluation showed no prostatic hypertrophy, and a thorough gastroenterological evaluation revealed no explanation for the constipation.

Neurological examination was completely normal except in the lower limbs. Here the power was normal, but the ankle reflexes were absent, which could have been due to diabetic neuropathy or to bilateral S1 radicular involvement. A careful sensory examination with light touch and pin prick showed no abnormalities anywhere in the legs, and, in particular, this was normal in the sacral dermatomes. Rectal tone was normal.

A myelogram and CT-myelogram scans were performed and these showed an intradural lobulated mass opposite the lower border of the L5 vertebra causing complete obstruction of the sub-arachnoid space. Surgical exploration revealed that the tumor, although largely intradural, did have some extension through the dura and, indeed, through the posterior lamina of the sacrum and into the muscles overlying the sacrum. The tumor was resected almost entirely, which involved removing a few filaments of sacral spinal nerve roots. The pathology of this tumor was greatly debated, the consensus being an atypical schwannoma.

Postoperatively, the patient had urinary retention requiring catheterization. This improved, but from then on, he had to self-catheterize twice a day. The partial constipation and erectile dysfunction continued unchanged. Six years later, the patient had the recurrence of pain, less ability to micturate, requiring increased bladder self-catheterizations, and a marked worsening of the constipation requiring increased laxatives, suppositories, and enemas. Re-examination showed signs of a mild peripheral neuropathy in the feet, presumably due to his diabetes. However, there was a clear reduction in sensation in the perianal area and there was a reduction in anal tone. Further radiological studies showed a large soft-tissue mass producing destruction of the majority of the sacrum and spreading to the soft tissues both anteriorly and posteriorly to the sacrum. A biopsy was performed and again the pathology was debated, but the consensus was that this represented a malignant schwannoma. The patient had radiotherapy and there was some reduction in the bulk of the tumor as seen on CT scanning. The pain disappeared, but the bladder and bowel dysfunction remained unchanged. The patient died 8 years later of unrelated causes.

Comment: The pattern of pain in this patient, particularly pain that is worsened by lying and relieved by standing, is characteristic of cauda equina mass lesions. Although the patient’s erectile, bladder and bowel symptoms at the time of presentation could have been attributed to his long-standing diabetes mellitus, in the context of this type of pain, it was thought to be due to involvement of the cauda equina.

KEYPOINTS: Ă

Compression of the conus medullaris or the cauda equina can produce the classic picture of saddle anesthesia and loss of sphincter control, but more often it gives rise to patchy and asymmetrical motor and sensory loss, with variable sphincter involvement.

66

tive, feature of cauda equina tumors (particularly ependymomas) is their propensity to bleed, causing spinal subarachnoid hemorrhage. This usually occurs in young patients with a long history of low back pain, who then have an acute episode of severe headache and neck stiffness followed by increased back pain and sciatica. Finally, cauda equina tumors can present with the cauda equina claudication syndrome (see below).

Other types of malignant disease involving the cauda equina. Vertebral metastases (most commonly from breast and prostate cancer), primary bone tumors (e.g. chordoma), or multiple myeloma can cause one or more of the following: compression of a nerve root or roots in the foramen; gradual compression

of the conus medullaris or cauda equina; collapse of a vertebra, often acutely compressing the entire cauda equina; and invasion of the paravertebral area involving the spinal nerves outside the foramina or the lumbosacral plexus itself.

The initial symptom is usually low back pain, which precedes other symptoms from a few days to 2 years. Pain radiating into the legs is less frequent. Compression of the conus medullaris or the cauda equina can produce the classic picture of saddle anesthesia and loss of sphincter control, but more often it gives rise to patchy and asymmetrical motor and sensory loss, with variable sphincter involvement.

Other forms of metastatic dissemination include diffuse meningeal carcinomatosis,

nodular metastases in the meninges of the cauda equina and nerve roots, and intramedullary metastasis to the conus medullaris. In its full-blown form, meningeal carcinomatosis presents with the triad of headache, cranial neuropathies, and lumbosacral radiculopathies [2]. But early in its course, the predominant features are usually low back pain radiating into the legs, leg weakness and numbness, and bladder dysfunction. The neurological deficits in the lower limbs are very variable. This diagnosis should be suspected in a patient with a known malignancy (usually of the breast or lung), and it is confirmed by finding malignant cells in the cerebrospinal fluid. Nodular metastases to the meninges also cause radicular dysfunction that varies in degree and site. These usually occur in patients with lymphomas and leukemias, although carcinomas sometimes produce nodular deposits rather than diffuse meningeal infiltration.

Metastases to the conus medullaris are rare, but when they occur, they produce symmetric involvement of the lower sacral spinal nerve roots, simulating a cauda equina lesion.

Trauma to cauda equina. Severe injuries to the lower spine, as in high velocity impacts in motor vehicle accidents or falls from great heights, will often injure the cauda equina.

Stabbings, gunshot and shrapnel wounds are other causes of such an injury. These patients usually have many other associated injuries.

Congenital malformations. Congenital malformations of the distal spinal cord often involve the cauda equina. Such malformations constitute part of a larger group of congenital neurological disorders termed spinal dysraphism. Myelomeningocele is the most frequent and important of these. Discussion of myelomeningocele falls outside the scope of this chapter, but it is important to note that these patients should be under the long-term care of a urologist since they are at risk of developing upper urinary tract dilatation and serious impairment of renal function.

The tethered cord syndrome (TCS) can present in patients with known spinal dysraphism (usually myelomeningocele), usually already operated on, or in patients without known dysraphism; the latter group is discussed here.

This disorder consists of conus medullaris and cauda equina dysfunction caused by the tethering and longitudinal traction on the conus

by abnormal structures, such as a thick filum terminale or a lipoma [3]. TCS usually presents in childhood with sensorimotor symptoms and signs, often in both legs, bladder dysfunction, and skeletal abnormalities, such as scoliosis or foot deformity. There may be other features of a dysraphic state — myelomeningocele, subcutaneous lipomas, or a sacral hairy patch.

Less well recognized is TCS in adults.

Some of these patients have lifelong neurological and/or skeletal deformities, while others are normal until symptoms and signs developed in adulthood. These late presentations can occur even in the elderly, and are easily confused with spinal stenosis. Patients with TCS characteristically have pain localized to the anal, perineal and gluteal areas, sometimes radiating diffusely down the legs; radicular type pain is uncommon. Bladder dysfunction is a prominent symptom; this usually consists of urinary urgency due to a hyperreflexic bladder, sometimes in combination with sphincter weakness contributing to incontinence. Leg weakness is usually present with several myotomes often involved bilaterally. An important feature that may be present is upper motor neuron signs, such as extensor plantar responses; these are due to distal spinal cord involvement. Imaging studies show the presence of a thickened filum or lipoma. Surgical resection of these is very effective for relieving pain and some of the motor and sensory deficits, but bladder function seldom improves.

Lumbosacral spinal stenosis syndromes.

Chronic degenerative disk disease and osteoarthritis of the spine contribute to narrowing of the central canal and/or spinal nerve root foramina — lumbar spinal stenosis (LSS). The resulting symptoms can be classified as (a) radicular, (b) cauda equina claudication, and (c) weakness.

Chronic radicular symptoms are similar to those of acute radiculopathy, but often less severe. Pain is present in the lower back and radiates into one or both legs. Cauda equina claudication is the hallmark symptom of spinal stenosis. Synonyms include pseudoclaudication, neurogenic intermittent claudication, and intermittent ischemia of the cauda equina.

It consists of various combinations of low back, buttock and leg pain, and/or paresthe-

KEYPOINTS: à

Myelomeningocele falls outside the scope of this chapter, but it is important to note that these patients should be under the longterm care of a urologist since they are at risk of developing upper urinary tract dilatation and serious impairment of renal function.

à

Chronic degenerative disk disease and osteoarthritis of the spine contribute to narrowing of the central canal and/or spinal nerve root foramina — lumbar spinal stenosis (LSS).

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

sias brought on or exacerbated by walking Spinal dural arteriovenous fistulas. Spinal and often just by standing. A few patients dural arteriovenous fistulas are a distinct type also have leg weakness occurring at this time. of spinal vascular malformations. They are Symptoms are relieved by sitting and resting usually located in the lower thoracic or lumbar for many minutes, by contrast with the brief spine, usually occurring in middle-aged and rest of less than a minute required to relieve older men. The symptoms are remarkably true vascular claudication. Chronic leg weak- similar to those of spinal stenosis. The diagness is infrequent as the predominant symp- nosis is often best made by myelography and tom of spinal stenosis. Bladder dysfunction angiography, though CT and MR imaging also is an uncommon feature of LSS, but in indi- add useful information. vidual patients may be prominent. Because Spinal arachnoiditis. This can develop these patients are usually elderly, prostatism anywhere in the meninges, but the lumbois more likely to be the cause of such symp- sacral region is most commonly affected [5]. toms. When LSS is the result of ankylosing The arachnoid becomes thickened, scarred, spondylitis, marked bladder and bowel dys- and adherent to the pia and dura, obliterating meningeal blood vessels. Single or multiple function is the rule [4].

Physical examination is normal in about half roots within the cauda equina can be affected. of the patients. The others have varying degrees At higher levels, the spinal cord itself is conof motor and sensory abnormalities attribut- stricted. The causes of spinal arachnoiditis are able to involvement of one or more lumbar listed in Table 3. The commonest used to be and/or sacral roots. Patients often adopt a the oil-based contrast agents used for myelogslightly bent forward posture on walking, this raphy. However, considering the large numbeing the position in which the spinal canal bers of myelograms performed, this is a relspace is at its maximum. A unique, though atively rare event. The newer water-soluble uncommon, feature of the cauda equina claudi- contrast agents are safer. Another cause, also cation syndrome is that exercise may unmask rare, is lumbar spinal surgery. The combination of oil-based myelography, spinal stenosis, or worsen the neurological signs.

The main structural abnormality is narrow- and lumbar spinal surgery further increases ing of the spinal canal, although there are often the risk of arachnoiditis. Intrathecal corticosteassociated stenoses of individual nerve root roid injections have been implicated in causforamina. These changes are usually due to ing spinal arachnoiditis, but if they do, it is a a combination of developmental stenosis and superimposed spondylosis.

Other causes include severe spondyTABLE 3 Causes of spinal arachnoiditis losis without congenital narrowing, ankylosing spondylitis, Paget’s disIntrathecal drugs or chemical agents ease, and achondroplasia. Another rare • Radiological contrast agents cause is fluorosis, a condition occur• Local anesthetic drugs • Amphotericin B, methotrexate, corticosteroids(?) ring in areas where the water contains excessive amounts of natural fluoride.

Spinal and epidural anesthesia Although the bones appear excessively Infections dense on X-rays, they are softer than • Tuberculosis normal and develop excessive degen• Cryptococcosis • Syphilis erative changes that cause spinal ste• Viral infections nosis.

Trauma The diagnosis of LSS can some• Spinal surgery times be made on plain X-rays, but • Vertebral injuries is best confirmed by axial views of • Lumbar disk herniation the spine with computerized tomogSpinal subarachnoid hemorrhage raphy (CT) or magnetic resonance Idiopathic (MR) imaging studies (Figure 5). Electrophysiological testing is discussed below.

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rare occurrence, relating to large doses and/or multiple injections. Spinal epidural anesthesia can also rarely cause arachnoiditis. The damage can be in the lower cervical, thoracic, or lumbar area, and the neurological deficits can be severe. The cause is thought to be chemical irritation, but infection is a possibility.

In some countries, infections (mainly tuberculosis) are an important cause of arachnoiditis. Tuberculous meningitis usually presents as a chronic cranial meningitic syndrome with headache and fever being cardinal features.

The spinal meningitis form is less frequent and may lead to spinal arachnoiditis. In the cauda equina, this produces thecal scarring, nodularity, thickening and clumping of the nerve roots.

The symptoms of arachnoiditis are constant low back pain usually radiating into both legs, and motor and sensory symptoms in the legs. Bladder dysfunction is infrequent except in advanced cases. The symptoms may begin within days of the damage to the arachnoid or there may be a delay of many years. Examination usually shows involvement of more than one lumbar or sacral nerve root, and the motor deficit ranges from being mild to a devastating paraplegia.

CT scanning, CT myelography and MR imaging will confirm the diagnosis. The last of these is preferred, not only because of highly diagnostic images, but because it avoids further intrathecal injections.

Cauda equina complications of epidural and spinal anesthesia. Serious neurological complications of these procedures are rare.

Delayed arachnoiditis has been described already. Other complications attributed to damage or irritation of the lumbar and spinal nerve roots become apparent after the effects of the spinal anesthesia have worn off. An increasingly recognized syndrome is that of transient radicular irritation (TRI) (also called transient neurological syndrome — TNS) [6], but bladder and bowel function are not affected, so this will not be discussed further here. Longer lasting sequelae are very rare and generally improve with time, but may be permanent. They include paresthesias in one or both legs in various areas, and focal or more generalized weakness. More serious is a cauda equina syndrome of bilateral leg weak-

ness, extensive sensory loss, and urinary and fecal incontinence [7]. This may occur when higher than usual doses of local anesthetic are used. Another risk factor is spinal stenosis. Such patients may be asymptomatic from this point of view preoperatively, so this risk factor is unsuspected. Recovery may be slow and incomplete.

Viral cauda equina syndromes. The cytomegalovirus cauda equina syndrome is a dramatic and serious infectious disorder occurring in patients with acquired immune deficiency syndrome (AIDS) [8]. Low back pain and urinary disturbances are early symptoms, followed by asymmetric leg weakness and sensory loss that extends into the saddle area.

This usually rapidly advances to a flaccid paraplegia with bladder and bowel incontinence. The cerebrospinal fluid shows abnormalities indicative of acute infection, and cultures grow cytomegalovirus (CMV); there is also usually evidence of CMV infection in other organs. Antiviral agents effective against CMV may arrest the course, or partially reverse it, so early diagnosis is important. Lymphomatous meningitis and syphilis are other disorders producing a similar syndrome in patients with AIDS. Genital herpes simplex infections may cause a neurological syndrome consisting of urinary retention, constipation, and sacral pain or numbness [9]. Examination usually shows a lax anal sphincter, absent bulbocavernosus reflexes, sensory loss in the lower sacral dermatomes, variable loss of deep tendon reflexes in the legs, and herpetic genital ulcers. Spontaneous recovery usually occurs, though treatment with antiviral agents may hasten the recovery. Although the sensory abnormalities in herpes infections are known to be due to virus invasion of the dorsal root ganglia, the exact site and mechanism of the motor neuron damage is unknown. The damage may be in the motor neuron cell bodies in the spinal cord, or in the nerve fibers within the lumbosacral spinal nerves, plexus, or peripheral nerves.

KEYPOINTS: Ă

The symptoms of arachnoiditis are constant low back pain usually radiating into both legs, and motor and sensory symptoms in the legs. Bladder dysfunction is infrequent except in advanced cases.

INVESTIGATIONS Electrophysiological testing. Standard nerve conduction and EMG studies of the nerves and muscles of the lower limbs are often useful to confirm or determine damage to nerve roots within the cauda equina. Motor nerve conduc-

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

FIGURE 4

Sagittal (a) and axial (b) T2 weighted MR images of the lumbar spine to show a large central L4,5 disk extrusion (asterisks). The patient had an acute cauda equina syndrome.

From Stewart JD. Focal peripheral neuropathies, 3rd ed. Lippincott, Williams and Wilkins; 1999. Reproduced with permission.

KEYPOINTS: Ă

Imaging studies with myelography or CT scanning or MR should be done urgently, and the disk removed surgically.

70

tion studies show reduced amplitudes of compound motor action potentials when axon loss in the spinal nerve roots (L5 and S1 mainly) innervating them has occurred. Electromyographic (EMG) studies often show chronic neurogenic changes in leg muscles in a pattern reflecting the nerve roots involved. Muscles innervated by L2-S2 roots can be evaluated in this way. Finding such abnormalities in proximal muscles, such as the glutei, helps to differentiate patients with severe chronic cauda equina syndromes from a chronic axonal polyneuropathy (the latter producing distal much greater than proximal abnormalities in muscles). Paraspinal muscle denervation localizes the abnormalities to the roots rather than plexus or more peripheral level. Sensory nerve action potentials in the legs are usually normal because the spinal nerve roots are compressed proximally to their dorsal root ganglia. This finding is also useful in differentiating cauda/root lesions from those of the lumbosacral plexus, or more distal nerves of the legs.

Electrophysiological techniques may also be used to evaluate lesions of the lower sacral roots, spinal nerves and the sacral plexus, as described in Chapter 1.

Imaging studies. Plain radiographs may be very useful in revealing lesions causing cauda equina damage, such as bone tumors and severe degenerative spondylosis. Isotope bone scans are useful in demonstrating malignant lesions in the vertebrae. CT scanning, CT myelography, and particularly MR are the imaging techniques of choice for most disorders of the cauda equina (Figures 4 and 5).

MANAGEMENT Acute central disk herniation. Imaging studies with myelography or CT scanning or MR should be done urgently, and the disk removed surgically. Delays in treatment lessen the chance of good recovery of bladder, bowel and sexual function (see Case 1).

Spinal stenosis. Management decisions in spinal stenosis are complicated by several factors: (a) the natural history of the disorder

is poorly understood, as are FIGURE 5 CT myelogram: indicators of prognosis, but in axial view through the most patients, the course is relL4,5 disk space showing severe spinal atively benign; (b) the patients stenosis in a patient with a chronic are often elderly and have cauda equina syndrome. The thecal sac is extremely small and a tiny other medical problems; (c) amount of contrast is seen among the there is little consensus regardtightly clumped roots of the cauda ing the correlation between equina (white arrow). This narrowing the imaging abnormalities and is caused by: (a) diffuse bulging of symptoms, and with surgical the disk; (b) marked thickening of the ligamentum flavum (asterisks); outcomes; (d) there are no good and (c) facet joint hypertrophy. The studies comparing conservasmall dark triangle outlined by the tive measures and surgery; (e) diminutive thecal sac and the the best surgical procedures are ligamenta flava is epidural fat. debated; and (f) there is a wide From Stewart JD. Focal peripheral variability and a degree of neuropathies, 3rd ed. Lippincott, inadequacy in reports describWilliams and Wilkins; 1999. ing surgical results.

Reproduced with permission.

Conservative treatments are widely mentioned in the literature, but there is a paucity of critical evaluations regarding specific methods and their outcomes. carcinomatosis is treated in the same way and There is considerable divergence of opinion with intrathecal chemotherapy, but the results regarding the outcome of surgery. A useful are usually poor. generalization is that two-thirds of patients Treatment of bladder, bowel and sexual either stabilize or improve after surgery. dysfunction. Treatment of symptoms arising Other disorders. The treatment of arach- from cauda equina damage are those described noiditis is notoriously difficult. Intrathecal ste- in Chapters 2, 3 and 4, respectively. The type roids have been tried, but are usually ineffec- of bladder dysfunction often includes a protive, and can possibly worsen the situation. nounced element of incomplete bladder empActive infections, such as tuberculosis, have tying, but detrusor hyperreflexia can also to be treated. Attempts at surgically remov- occur (see Chapter 2). Weakness of the urethral ing the adhesions around the roots are usu- sphincter can lead to urinary stress incontially unsuccessful, although other reports con- nence. tradict this view [10,11]. Others have found Patients with cauda equina lesions have that only milder cases benefit from surgery a lax perineum, an altered sensation of [12]. For treating chronic severe pain, long- fecal urgency and perianal numbness. These term analgesics or dorsal column stimulators patients often need to manually evacuate the are often required. The neurological deficits rectum once a day or more to stay continent. usually gradually worsen, but eventually sta- Incontinence of flatus is an additional probbilize. lem that is extremely embarrassing for these Primary tumors of the cauda equina are patients who are very often ambulant and usually surgically removed (see Case 2). Met- show no outward stigmata of neurological astatic tumors are usually treated with a com- disease. bination of radiotherapy and chemotherapy; Treatment of ED may not be successful relief of pain is often excellent, though the because of concomitant penile sensory impairneurological deficits often remain. Meningeal ment.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

CASE-ORIENTED MULTIPLE CHOICE QUESTIONS þ

A 30-year-old otherwise healthy man has a 4-year history of lower back pain. Over a 24-hour period, this pain has markedly worsened and, in addition, he finds he needs to strain to urinate and to defecate, and notices that his anal area feels numb. Which of the following is the likely diagnosis?

A. B. C. D. E.

A metastasis to the L4 vertebra.

Acute cytomegalovirus infection of the cauda equina.

A central lumbar disk herniation.

A rapidly growing malignant lesion in the pelvis.

Acute transverse myelitis of the thoracic spinal cord.

The answer is C. This is the characteristic story of a central lumbosacral disk herniation — years or months of nonspecific lower back pain, then an acute worsening of the pain and the development of bladder and bowel symptoms and perineal sensory loss. þ

On examination of the patient described above, which clinical sign is important in supporting your diagnosis?

A. B. C. D. E.

A lax anal sphincter on rectal examination.

Hyperactive tendon reflexes in the legs.

Extensor plantar responses.

A sensory level to the mid-abdomen level.

An absence of pain on gentle squeezing of the testicles.

The answer is A. The easiest way to quickly detect serious involvement of the lower sacral nerve roots is to do a rectal examination for reduced anal sphincter tone. þ

In this clinical setting, which is the most appropriate diagnostic test?

A. B. C. D. E.

Nerve conduction and electromyography (EMG) studies.

Lumbosacral spine plain X-rays.

Lumbosacral spine isotope bone scan.

Lumbosacral spine CT scan.

Lumbar puncture.

The answer is D. A plain CT scan will reliably show a large central disk herniation most of the time. Plain X-ray films may show disk space narrowing which is very non-specific and so are essentially useless. An isotope bone scan is best used for metastases which may cause an acute cauda equina syndrome if there is bony collapse, but will not show an acute disk herniation. A CT scan will reliably show not just the herniation, but also other unusual causes of acute cauda compression, including bone metastases, hemorrhages, etc. þ

In this diagnosis, what is the appropriate treatment?

A. B. C. D. E.

72

Strict bedrest and anti-inflammatory medication.

A progressive physiotherapy program.

Radiotherapy to the lesion.

Managing the bladder dysfunction with an indwelling catheter, then performing elec tive surgery the following week.

Immediate surgical excision of the lesion.

The answer is E. Speed is required in order to avoid permanent bladder, bowel, sexual dysfunction. Ăž

A 70-year-old man with type II diabetes mellitus has a 2-year history of progressively worsening low back pain. The pain is relieved by standing and aggravated by lying, so he also has difficulty sleeping. In addition, he has become constipated and has recently required laxatives. His urinary stream has weakened to a dribble. Which of the following is the likely diagnosis?

A. B. C. D. E.

Diabetic neuropathy with involvement of the autonomic peripheral nerve fibers.

Degenerative arthritis of the spine, benign prostatic hypertrophy, and age-related non specific constipation.

Prostate cancer with bone metastases.

A cauda equina tumor.

Chronic arachnoiditis.

The answer is D. This is a difficult case scenario. Bladder dysfunction is most often due to prostatic disease in this age group. However, these symptoms, when coexisting with a new onset of constipation, should alert the physician to the possibility of nerve damage. In a diabetic, both of these symptoms, as well as erectile dysfunction, could be attributable to the diabetes (see Chapter 7). However, the symptom of increasing pain with the unusual features described above, is characteristic of a cauda equina tumor.

REFERENCES [1]

Lafuente DJ, Andrew J, Joy A. Sacral sparing with cauda equina compression from central lumbar intervertebral disc prolapse. J Neurol Neurosurg Psychiatry 1985;48:579-81.

This paper points out that some central disk herniations spare the centrally lying roots in the cauda equina. Thus bladder and bowel function is preserved.

[2]

Little JR, Dale AJD, Okazaki H. Meningeal carcinomatosis: clinical manifestations. Arch Neurol 1974;30:138-43.

An old but classic paper describing the manifestations of carcinomatous meningitis, including the involvement of the lumbosacral roots/cauda equina.

[3]

Hoffman HJ, Hendrick EB, Humphreys RP. The tethered spinal cord: its protean manifestations, diagnosis and surgical correction. Childs Brain 1976;2:145-55.

Another old but classic paper describing the various ways in which tethered cord presents at various ages.

[4]

Bartleson JD. Cauda equina syndrome secondary to long-standing ankylosing spondylitis. Ann Neurol 1983;14:662-9.

Points out the under-appreciated fact that ankylosing spondylitis can not only produce a lumbar spinal stenosis syndrome, but when it does so, bladder and bowel function are particularly compromised.

[5]

Esses SI, Morley TP. Spinal arachnoiditis. Can J Neurol Sci 1983;10:2-10.

An older but comprehensive review of this topic.

References continued Ăž

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

References continued Ăž

[6]

Schneider M, Ettlin T, Kaufmann M, Schumacher P, Urwyler A et al. Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5% lidocaine. Anesth Analg 1993;76:1154-7.

This paper outlines some of the complications of spinal anesthesia.

[7]

Yuen EC, Layzer RB, Weitz SR, Olney RK. Neurologic complications of lumbar epidural anesthesia and analgesia. Neurology 1995;45:1795-1801.

Excellent review of the topic, with case descriptions of some of the complications discussed.

[8]

Behar R, Wiley C, McCutchan JA. Cytomegalovirus polyradiculoneuropathy in acquired immune deficiency syndrome. Neurology 1987;37:557-61.

The definitive paper describing this acute and usually devastating condition. The lesson is that it has to be recognized and treated early.

[9]

Oates JK, Greenhouse PR. Retention of urine in anogenital herpetic infection. Lancet 1978;1:691-2.

An excellent description of this generally under-recognized syndrome.

[10] Shikata J, Yamamuro T, Iida H, Sugimoto M. Surgical treatment for symptomatic spinal adhesive arachnoiditis. Spine 1989;14:870-5.

See below.

[11] Dolan RA. Spinal adhesive arachnoiditis. Surg Neurol 1993;39:479-84.

See below.

[12] Roca J, Moreta D, Ubierna MT, Caceres E, Gomez JC. The results of surgical treatment of lumbar arachnoiditis. Int Orthopaed 1993;17:77-81.

These papers discuss the possibilities or otherwise of attempting to treat, particularly surgically, this disorder. The argument for surgical intervention remains unconvincing.

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CHAPTER 8

KEYPOINTS:

PARKINSONIAN DISORDERS AND PURE AUTONOMIC FAILURE INTRODUCTION Disorders of bladder, bowel and sexual function are common problems in Parkinson’s disease (PD), multiple system atrophy (MSA) and pure autonomic failure (PAF). Although the pathology of PD and MSA is quite different and distinct, the differential diagnosis of the conditions in life, particularly in the early stages, may be difficult and the presence of autonomic failure, as indicated by postural hypotension, may assist in the differential diagnosis. Figure 1 shows the major clinical features of these various disorders and the relationship between them [1]. However, it should be noted that the pathophysiological cause of postural hypotension does not necessarily also cause bladder, bowel and sexual dysfunction in these diseases and pelvic organ disorders may occur without postural hypotension.

In patients with PD, pelvic organ dysfunction usually occurs late in the course of the disease and is not associated with postural hypotension. MSA is commonly misdiagnosed as PD, but pelvic organ dysfunction usually occurs early in the course of the disease, before the onset of symptoms of hypotension and it is often the prominent complaints of bladder and sexual dysfunction which raise the suspicion of the correct diagnosis.

Although the commonest presentation of MSA is as a parkinsonian syndrome (striatonigral degeneration: SND) (Case 1), cerebellar syndrome (olivopontocerebellar atrophy: OPCA) and autonomic disorder (Shy-Drager syndrome) (Case 2) may also occur. PAF is a sporadic disorder characterized by widespread autonomic failure without other neurological features. It usually occurs in older age and has a less rapidly progressive course than MSA. In all these disorders, complaints of bladder, bowel and sexual dysfunction may add considerably to the patients’ disabilities. The neurologist needs to be aware of the possible

à

Although the pathology of PD and MSA is quite different and distinct, the differential diagnosis of the conditions in life, particularly in the early stages, may be difficult and the presence of autonomic failure, as indicated by postural hypotension, may assist in the differential diagnosis.

à

Much of the attention to autonomic failure in MSA has focussed on postural hypotension which is considered to be a marker for autonomic involvement. Urinary dysfunction has attracted less attention.

diagnostic significance of such symptoms as well as the various treatments available for the conditions.

DISORDERS OF MICTURITION MSA. Much of the attention to autonomic failure in MSA has focussed on postural hypotension which is considered to be a marker for autonomic involvement [2]. Urinary dysfunction has attracted less attention, despite the fact that both of the two original patients with Shy-Drager type had urinary frequency, incontinence and urinary retention. A recent study has shown that over 90% of all three variants of MSA patients had urinary symptoms, whereas only 43% had symptoms of

FIGURE 1

The major clinical features of syndromes of primary chronic autonomic failure and Parkinson’s disease.

From Mathias C. Autonomic disorders and their recognition. New Engl J Med 1997;336:721-4.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

micturition are more common and occur earlier than orthostatic hypotension in MSA. The urodynamic features of these 128 patients with MSA were also analyzed [3]. Fiftytwo percent had a raised postmicturition residual volume of more than 100 ml. Detrusor hyperreflexia was demonstrated in 56%, reduced compliance in 31%, and detrusor atonia in 5%.

Sphincter EMG showed detrusor-sphincter dyssynergia in 45% and changes due to chronic reinnervation were found in 74% of the patients, in keeping with other reports [4,5]. A subcutaneous injection of Bethanechol (2.5 mg) showed abnormal increment of detrusor pressure > 15 mm H2O after 30 minutes in 19%, suggesting cholinergic denervation supersensitivity. The balance of pathophysiology may change during the course of the disease so that whereas early on symptoms due to detrusor hyperreflexia are prominent, as the disease progresses symptoms may change to those due to incomplete bladder emptying with low compliance and atonic bladder [3].

The sites of neurological involvement responsible for the urinary dysfunction in MSA FIGURE 2 (a) Urinary and orthostatic symptoms in patients with MSA. (b) Urinary and orthostatic symptoms in three variants: OPCA type, SND type and Shy-Drager are probably both central and type. peripheral and have been illustrated in Figure 3. These include From Sakakibara R et al. Urinary dysfunction and orthostatic hypotension in multiple neuronal degeneration and glial system atrophy: which is the more common and earlier manifestation. J Neurol Neurosurg cytoplasmic inclusions (GCIs) in Psychiatry 2000;68:65-9. the pontine micturition center (PMC), the putamen, the subKEYPOINTS: orthostatic hypotension [3] (Figure 2). In some stantia nigra, sacral intermediolateral (IML) patients, urinary symptoms were the sole pre- and Onuf’s nuclei, and possibly some involveà The sites of neurosenting complaints (Case 3) and these included ment of the frontal cortex and postganglionic logical involvement difficulty in voiding (79%), nocturnal urinary cholinergic fibers. responsible for the urifrequency of more than twice (74%), sensation Changes of chronic reinnervation on EMG nary dysfunction in MSA are probably both of urgency (63%), urge incontinence (63%), of the anal or urethral sphincter have been central and peripheral. daytime frequency of more than eight times used as a test to recognize MSA (Figure 4) [6].

(45%), nocturnal enuresis (19%) and urinary These changes reflect the selective degenerretention (8%) (see Figure 2). Disorders of ation of the Onuf’s nucleus, the group of

86

KEYPOINTS: à

Because PAF is a much less common disorder than MSA, the precise incidence of bladder dysfunction in PAF is uncertain.

Schematic presentation of the central neural structures as for urinary and cardiovascular dysfunction in MSA. Commonly affected sites critical for urinary function include the basal ganglia, the pontine micturition centre, the lumbosacral spinal cord (IML) and Onuf’s nucleus.

Commonly affected sites critical for cardiovascular function include catecholamine-containing medullary nuclei and the thoracic spinal cord (IML nuclei).

FIGURE 3

sacral anterior horn cells. Because in PD the anterior horn cells of Onuf’s nucleus are not affected, sphincter EMG has been proposed as a means of distinguishing between PD and MSA, although there is disagreement about this [7]. In some patients with MSA, the degeneration of Onuf’s nucleus may lead to sphincter weakness, thus causing stress incontinence with low urethral closure pressure.

PAF. Because PAF is a much less common disorder than MSA, the precise incidence of

bladder dysfunction in PAF is uncertain. A recent study investigated micturition function of six patients who met the criteria of clinical findings and autonomic function tests without abnormal brain magnetic resonance imaging (MRI) [8]. All patients had urinary symptoms (see Table 1). Only one patient had urinary symptoms at the onset of disease, whereas in the others, bladder symptoms appeared following the onset of erectile dysfunction (ED) or orthostatic faintness. Two of six patients

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

CASE 1 History: A 60-year-old man complained of a short-step, festinating gait with postural tremor and rigidity in both hands. Two years earlier, he had been diagnosed with Parkinson’s disease and was commenced on 300 mg of L-Dopa/carbidopa without benefit. He also had urinary urge incontinence and voiding difficulty with postmicturition residuals of 320 ml.

Examination: Neurological examination revealed evidence of a parkinsonian syndrome without evidence of laterality or resting tremor. The patient was unable to perform tandem gait and on turning, his footing was wide-based, suggestive of gait ataxia.

Cystometry with simultaneous sphincter EMG revealed a poorly compliant bladder on filling and detrusor areflexia with detrusor-sphincter dyssynergia (DSD) on voiding. Analysis of the external sphincter EMG showed neurogenic motor unit potentials (MUP) with mean duration over 10 ms.

Management: For his urinary dysfunction, the patient was taught to perform clean, intermittent self-catheterization (CISC).

Comment: This patient did not demonstrate either resting tremor or laterality and this was suggestive of atypical Parkinson’s disease. Detrusor areflexia, DSD and a neurogenic sphincter were all demonstrated on investigation.

Neuro-urological assessment can help to distinguish patients with MSA from those with Parkinson’s disease, the former being the diagnosis in this case.

ganglionic pelvic nerve lesions, respectively.

These findings are in keeping with pathologià Urinary dysfunction cal reports of neuronal cell loss in the IML colusually occurs together umns of the spinal cord, Lewy bodies in the with a higher HoehnIML cells and in the bladder wall in patients Yahr grade. dying of PAF [9].

Urinary dysfunction in PAF appears to be as common, but less severe, than that in MSA (Case 4).

PD. Patients with PD often have bladder symptoms: one survey reported the frequency of urinary dysfunction to be 57% of 97 patients [10] (Figure 5). Similar figures for prevalence, ranging from 40 to 70% have been found in other studies [5,11]. Urinary dysfunction usually occurs together with a higher Hoehn-Yahr grade [12] and is related to striatal presynaptic dopamine depletion shown by in vivo SPECT study, sugFIGURE 4 An example of a motor unit recorded from the anal sphincter of a patient with MSA, gesting urinary dysfuncusing a concentric needle electrode. Extreme changes of chronic reinnervation are tion in PD may reflect seen in this highly polyphasic unit of prolonged duration (36.7 ms). pathology of the disease.

KEYPOINTS:

88

who had had symptoms for more than 10 years had raised postmicturition residuals. Urodynamic findings showed low compliance bladder in two and denervation supersensitivity of the detrusor in two, indicating pre- and post-

TABLE 1

Urinary dysfunction in six patients with PAF Y.I.

F.A.

H.S.

I.M.

S.M.

S.T.

Age at onset (years), sex

59, male

64, female

66, male

64, male

56, male

46, male

Initial symptoms

Impotence syncope

Orthostatic faintness

Orthostatic Voiding difficulty and constipation

Impotence

Orthostatic faintness

Duration (years)

4

4

6

9

10

18

Appearance of minimum rigidity (years after onset)

-

3

6

-

10

16

Autonomic signs and symptoms Orthostatic syncope Horner’s syndrome Laryngeal stridor Perspiratory abnormality Erectile dysfunction Constipation

+ + + +

+ + +

+ + + ? +

+ + ? +

+ + +

+ + + +

Micturitional symptoms Nocturnal frequency Diurnal frequency Urgency Incontinence Hesitancy/prolongation

+ Stress +

+ + +

+ + Urge +

+ + +

+ + + -

+ + +

From Sakakibara R et al. Micturitional disturbance in pure autonomic failure. Neurology 2000;54:499-501.

The common urinary symptoms in PD are urgency, frequency and sometimes, urge incontinence. Urodynamic study shows detrusor hyperreflexia in 45-93% of the symptomatic patients as a cause of filling disorder

FIGURE 5

Urinary dysfunction in Parkinson’s disease.

From Hattori T et al. Voiding dysfunction in Parkinson’s disease. Jpn J Psychiatry Neurol 1992;46:181-6.

[5,9,10]. Sphincter EMG rarely shows denervation which, in contrast, is the common finding in MSA. Some authors have suggested that an impaired relaxation, or bradykinesia, of the external urethral sphincter can result in voiding dysfunction due to bladder outlet obstruction. However, this phenomenon is not common and large postmicturition residuals are rare in PD. Nevertheless, there are still some patients whose main abnormality is hypocontractile detrusor.

The responsible sites for the detrusor hyperreflexia seem to be the nigrostriatal lesions in PD. Experimental studies showed that electrical stimulation of the basal ganglia inhibits micturition reflex in the cat [13], probably by activating striatal GABAergic neurons which descend to the locus ceruleus (PMC). Bladder hyperreflexia occurs in MPTP (1-methyl-4-phenyl1,2,3,6-tetrahydropyridine)-induced parkinsonian animals. There is experimental evidence that D1 repecptors have an inhibitory and D2 a facilitatory effect on the micturition reflex [14].

Therefore, it seems likely that bladder hyperactivity in PD is associated with a reduction in the central dopamine D1 receptors.

KEYPOINTS: à

The responsible sites for the detrusor hyperreflexia seems to be the nigrostriatal lesions in PD.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

CASE 2 History: A 58-year-old man had a new onset of frequent fainting episodes that tended to occur after standing from a sitting position and on walking up stairs. In addition, he noticed dizziness that occurred after urination at night and about half an hour after a meal. He also described erectile dysfunction (ED), frequent urination (three voids per night) and urinary urgency for 2 years preceding the onset of faintness. He had recently begun to have slight slurring of speech.

Examination: Neurological examination showed a mild ataxic dysarthria, incoordination of the limbs and mild rigidity of the hands and the neck. He had a somewhat ataxic, short-stepping gait. Deep tendon reflexes were preserved. On standing, his blood pressure fell from 130/80 to 82/60 mm Hg without an increase in heart rate.

Management: His postural and postprandial hypotension were treated with an indirect sympathomimetic drug. His postvoid residual urine volume was insignificant and so he was commenced on an anticholinergic. Treatment with sildenafil citrate was contraindicated because of his postural hypotension.

Comment: This patient was considered to have the Shy-Drager type of MSA, because the autonomic failure (postural hypotension, urinary dysfunction and ED) preceded cerebellar and extrapyramidal involvement.

Other common autonomic abnormalities in MSA are respiratory (vocal cord paresis, sleep apnea syndrome), gastrointestinal (constipation) and perspiratory (hypohidrosis) involvement. Postprandial hypotension and exerciseinduced hypotension are also features in patients with MSA.

Treatment. The approach to treatment of urinary dysfunction is no different to that of other neurological causes of these symptoms and is discussed in Chapter 2.

Clinical studies examining the effect of dopaminergic agonists on bladder behavior in

CASE 3 History: A 62-year-old man was referred because of gait difficulty that had become apparent 6 months earlier. Five years previously, he had undergone a transurethral resection of the prostate for symptoms of voiding dysfunction and urinary urge incontinence.

However, the operation had failed to decrease his postmicturition residuals and he was taught to perform CISC. Examination: On admission, he had a parkinsonian syndrome with marked ataxia and exaggerated deep tendon reflexes. Extensor plantar reflexes were noted bilaterally. He was also found to have a postural systolic pressure fall of 46 mm Hg (126/86 lying to 80/55 mm Hg on standing), which was only associated with a mild headache in the nuchal area.

Management: He was prescribed 300 mg of L-Dopa/carbidopa with minimal improvement. His urinary urge incontinence was treated with 20 mg of propiverine hydrochloride, an anticholinergic drug.

He still required CISC for his high postmicturition residuals.

Comment: Male patients with MSA sometimes undergo prostate surgery prior to referral to neurologists because MSA can present with isolated genitourinary symptoms initially. In such cases, urinary urgency and frequency can be treated with anticholinergic medications and high postmicturition residuals can be treated with CISC.

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patients with PD have produced conflicting results. Using L-Dopa, apomorphine, pergolide (D1/D2 agonists) or bromocriptine (D2 agonist) some reports showed lessening of detrusor hyperreflexia, whereas others showed improvement of voiding difficulty. Whereas peripherally acting drugs, such as anticholinergic agents, lessen detrusor contractility, dopaminergic agonists may modulate both filling and voiding functions by acting on the specific central pathways.

There is a particular problem with the use of α-blockers in an attempt to improve bladder emptying in patients with MSA, since these can exacerbate postural hypotension.

DISORDERS OF DEFECATION MSA. Duration of patients’ symptoms of anorectal dysfunction is shorter in those with MSA than in patients with PD, and constipation appears to be increasingly common with advancing disease [15]. Several mechanisms may cause constipation in MSA, including reduced small and large bowel motility and chronic rectal impaction leading to decreased colorectal sensation or paradoxical contraction of the puborectal muscle during attempts at defecation — a phenomenon similar to detrusor-urethral sphincter dyssynergia and suggestive of supranuclear pudendal dysfunction.

Although much less common than constipation, fecal incontinence may also occur in

MSA, which does not appear to be correlated with the occurrence of urinary incontinence.

Low resting anal pressure and reduced maximal contraction pressure may account for fecal incontinence for liquid stools sometimes induced by laxative treatment. Anorectal manometric variables did not differentiate patients with MSA from those with PD [15].

PD. In his classic monograph, James Parkinson described the bowel dysfunction of shaking palsy: “the bowels which all along had torpid, now in most cases, demand stimulating medicines of very considerable power: the expulsion of the feces from the rectum sometimes requiring mechanical aid.”

Constipation occurs in 29-77% of PD patients compared to 10-13% of age-matched controls. Difficulty in defecation occurs in 67-94% of PD compared to 28% of a control group [16].

Colonography has shown megacolon in selected PD patients with severe fecal impaction (intestinal pseudo-obstruction) and in PD, rectal transit times are prolonged, indicating reduction of rectal contractility. Immunostaining of biopsied colonic musculature and the submucosa showed a reduction of dopaminecontaining neurons and there has also been a report showing Lewy bodies in the myenteric plexus of the colon [17]. These findings suggest that not only central, but also peripheral dopamine dysfunction in the colon account for the prolonged transit time and constipation in PD. Rectoanal manometry has shown reduced resting and defecating pressures [15]. These probably reflect dysfunction of the internal

anal sphincter innervated by lumbosacral sympathetic nerve. Other possible causes include over extension injury of the myenteric plexus due to severe fecal impaction, and an adverse effect of anticholinergic agents in PD. Defecography and anal sphincter EMG showed paradoxical contraction of the puborectal muscle in PD as a cause of rectal constipation [18] (Figure 6).

Treatment. The treatment of constipation and fecal incontinence is discussed in Chapter 3.

The prokinetic agent cisapride improves both symptoms and accelerates colonic transit time in patients with PD and constipation.

Psyllium has been shown to increase stool frequency and weight, but did not increase colonic transit or anorectal function in PD patients with confirmed constipation. A diet rich in insoluble fiber produced a significant improvement in constipation, as indicated by an increase in stool frequency and an improvement in stool consistency [19].

Pelvic floor relaxation problems and paradoxical puborectalis contraction may respond to dopaminergic drugs; however, some patients may still experience evacuation difficulties. A study using rectal manometry and defecography showed that apomorphine (a D1/D2 agonist) improved defecatory dysfunction in PD [20]. The effect was not antagonized by domperidone, a peripheral type dopamine blocker that does not penetrate the blood-brain barrier, but two of five patients showed marked hypotension on defecation.

Although not described in detail, L-Dopa and other dopamine agonists are also reported to

KEYPOINTS: à

Several mechanisms may cause constipation in MSA, including reduced small and large bowel motility and chronic rectal impaction leading to decreased colorectal sensation or paradoxical contraction of the puborectal muscle during attempts at defecation.

à

In his classic monograph, James Parkinson described the bowel dysfunction of shaking palsy: “the bowels which all along had torpid, now in most cases, demand stimulating medicines of very considerable power: the expulsion of the feces from the rectum sometimes requiring mechanical aid.”

CASE 4 History: A 71-year-old man had a 10-year history of headache, dizziness and occasional syncope on standing, which was gradually worsening. He had also noticed decreased sweating and experienced considerable discomfort during the summer time. In addition, he had nocturia and symptoms of voiding dysfunction, but had a normal size prostate.

He had no gait difficulty or speech disturbance at all.

Examination: Neurological examination did not reveal cerebellar ataxia, parkinsonism or pyramidal signs and deep tendon reflexes were preserved. However, the head-up tilt test revealed marked postural hypotension, with a blood pressure fall (from 140/80 lying to 75/50 mm Hg standing) accompanied by dizziness.

Management: Cystometry revealed detrusor areflexia with a large postmicturition residual. The patient was commenced on CISC with good symptomatic benefit.

Comment: This elderly patient has long-standing, widespread autonomic failure with bladder involvement, but lacks any other neurological abnormality, so he was therefore diagnosed as having pure autonomic failure (PAF).

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

be effective on defecatory dysfunction in PD, particularly in the early stage. Dopamine may modulate defecatory function via central neural pathways.

Paradoxical anal sphincter muscle contraction. (a) Control patient.

EMG recordings from puborectalis (PR), external anal sphincter (EAS), gluteus maximus (GM) and external oblique (EO) muscles at rest, during voluntary sphincter contraction (squeeze) and during simulated defecation straining (push).

A normal pattern of sphincter muscle inhibition is seen during straining. (b) Parkinson’s disease with constipation. Paradoxical sphincter muscle contraction and gluteal recruitment during straining.

FIGURE 6

From Mathers S et al. Constipation and paradoxical puborectalis contractions in anismus and Parkinson’s disease: a dystonic phenomenon? J Neurol, Neurosurg Psychiatry 1988;51:1503-7.

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SEXUAL DYSFUNCTION AND ED IN MEN MSA. A well-documented feature of MSA is that the first symptom in men is often ED. This usually predates the onset of any other neurological symptoms by several years [4] and is quite separate from the development of postural hypotension. Preserved erectile dysfunction is a clinical feature strongly against a diagnosis of MSA. It is not known why ED should be such an early and constant feature in MSA. PD. Estimates of the prevalence of erectile dysfunction in patients with PD show that it is a significant problem, affecting 60% of a group of men compared with an age-matched healthy group without PD in whom the prevalence was 37%.

In the same study, ED preceded the onset of PD in 17%, although the author concludes “the five cases … may actually represent cases of MSA”, whereas in another study, ED was found to affect men with PD only some years after the neurological disease had been established [21].

A survey of young patients with PD (mean age 49.6 years) and their partners revealed a high level of dysfunction, with most severely affected couples being those in which the patient was male. ED and premature ejaculation was a complaint in a significant proportion. In general terms, however, sexual dysfunction appeared to be multifactorial with no simple single cause identified [22].

Treatment. The treatment of ED is discussed in Chapter 4.

Special care must be taken to recognize autonomic failure causing postural hypotension in men with parkinsonism and MSA since it has been shown in a small number of patients with this combination that sildenafil exacerbated the hypotension.

Apomorphine has been used by men with PD to improve sexual function [23]. Bromocriptine (a D2 receptor agonist) decreases serum level of prolactin, which is shown to improve erectile dysfunction with hyperprolactinemia.

Dopamine agonists may also cause hypersexuality, although the frequency with which this occurs has not been well documented.

KEYPOINTS: à

A well-documented feature of MSA is that the first symptom in men is often ED.

CASE-ORIENTED MULTIPLE CHOICE QUESTIONS þ

A 52-year-old man with a resting tremor and rigidity of the right hand was diagnosed as having Parkinson’s disease. Ten years after the onset of symptoms, he gradually developed urinary urgency with frequency and nocturia.

What is the most likely cause of his bladder symptoms?

A. B. C. D. E.

Detrusor hyperreflexia.

A poorly compliant bladder.

An atonic bladder.

Stress urinary incontinence.

Detrusor instability secondary to prostatic obstruction.

The answer is A. Detrusor hyperreflexia is common in Parkinson’s disease because bladder function is affected by input from supra-nuclear areas, including the nigrostriatal dopaminergic system. The nigrostriatal neurons probably influence the pontine micturition center (PMC) via GABAergic inhibitory mechanism. þ

A 60-year-old man was referred with a short-step, festinating gait, rigidity of both hands and a postural tremor. He also had urge urinary incontinence and symptoms of voiding dysfunction with postmicturition residuals of 320 ml. He was thought to have a Parkinsonian syndrome by the referring clinician. Cystometry revealed a poorly compliant bladder, with detrusor areflexia and detrusor-sphincter dyssynergia (DSD). External sphincter EMG showed neurogenic motor unit potentials.

Which is the correct diagnosis?

A. B. C. D. E.

Parkinson’s disease.

Multiple system atrophy.

Multiple cerebral infarction.

Benign prostatic obstruction with detrusor instability and Parkinson’s disease.

Detrusor areflexia and Parkinson’s disease.

The answer is B. This constellation of symptoms is not typical of Parkinson’s disease, particularly because a resting tremor and evidence of laterality are absent. Urodynamic studies revealed detrusor areflexia with DSD, and the sphincter EMG showed neurogenic motor unit potentials. All of these are the features of MSA, not of Parkinson’s disease.

Multiple choice questions þ continued

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

Multiple choice questions continued

þ

þ

A 58-year-old man presented with frequent fainting episodes that tended to occur when standing from the sitting position and also when walking up stairs. He also complained of faintness after urination and after meals. Over the preceding 2 years he had worsening genitourinary problems with erectile dysfunction, urinary urgency and nocturia. A year after presentation, he developed an abnormal gait and a mild speech disturbance. Examination demonstrated a mild gait ataxia and rigidity of the hands with preserved deep tendon reflex. On standing, his blood pressure fell from 130/80 to 82/60 mm Hg without an increase in the heart rate.

Which is the patient’s diagnosis?

A. B. C. D. E.

Autonomic failure with multiple system atrophy.

Autonomic failure with Parkinson’s disease.

Pure autonomic failure.

Diabetic autonomic neuropathy.

Amyloidosis.

The answer is A. All the above disorders can present with widespread autonomic failure; however, this patient was diagnosed with MSA, because of the cerebellar and extrapyramidal involvement and preserved deep tendon reflexes. Other typical presenting features are vocal cord paresis, sleep apnea syndrome, constipation and hypohidrosis. þ

A 42-year-old nulliparous woman had a 2-year history of intractable urinary frequency and incontinence. The incontinence occurred when coughing, washing her hands and carrying a heavy load. She also had a shuffling gait and difficulty speaking. Examination demonstrated mild parkinsonism, limb ataxia, exaggerated deep tendon reflexes and postural hypotension. On ultrasonography of the bladder, there was no postmicturition residual urine. The urethral pressure profile showed low maximum urethral closure pressure (UPmax) and Valsalva straining with 150 ml in the bladder demonstrated leakage at a low abdominal leak point pressure.

Which type of urinary incontinence is most likely in this patient?

A. B. C. D. E.

Urge incontinence (secondary to detrusor instability).

Genuine stress incontinence.

Overflow incontinence.

Neurogenic incontinence (secondary to detrusor hyperreflexia).

Mixed incontinence.

The answer is B. Despite the fact that she is nulliparous, the incontinence occurred during conditions where intra-abdominal pressure rises. A low abdominal leak point pressure (on cystometry) combined with a low maximum urethral closure pressure (on urethral pressure profilometry) indicate that there is an intrinsic weakness in the external sphincter. In relation to the co-existing neurological symptoms and signs, the patient was diagnosed with MSA. þ

A 71-year-old man had a 10-year history of headache, dizziness and occasional syncope on standing. He also had nocturnal urinary frequency and decreased sweating. On examination, the gait was normal and deep tendon reflexes and speech normal. There was no evidence of cerebellar ataxia, parkinsonism or pyramidal signs. However, the head-up tilt test revealed marked postural hypotension.

What is the diagnosis of this patient?

94

A. B. C. D.

Autonomic failure with multiple system atrophy.

Autonomic failure with Parkinson’s disease.

Pure autonomic failure.

Diabetic autonomic neuropathy.

The answer is C. This patient has widespread autonomic failure, but he has no other neurological abnormality.

REFERENCES [1]

Mathias C. Autonomic disorders and their recognition. New Engl J Med 1997;336:721-4.

A proposed clinical definition of pure autonomic failure (PAF), autonomic failure with Parkinson’s disease and multiple system atrophy (MSA) which is used worldwide.

[2]

Bannister RCJM. Clinical features and investigation of primary autonomic failure syndromes. In: Mathias C, editor. Autonomic failure, 4th ed. Oxford: Oxford Medical Publications; 1999.

An excellent review of clinical features and investigations of primary autonomic failure.

[3]

Sakakibara R, Hattori T, Uchiyama T, Asahina M, Suzuki A, Yamanishi T. Urinary dysfunction and orthostatic hypotension in multiple system atrophy: which is the more common and earlier manifestation. J Neurol Neurosurg Psychiatry 2000;68:65-9.

A study focussing on urinary dysfunction and orthostatic hypotension in MSA. The authors showed that urinary dysfunction is the more common and earlier manifestation.

[4]

Beck RO, Betts CD, Fowler CJ. Genito-urinary dysfunction in multiple system atrophy: clinical features and treatment in 62 cases. J Urol 1994;151:1336-41.

A study of genitourinary dysfunction in 62 MSA patients with special reference to neurogenic sphincter EMG abnormalities.

[5]

Stocchi F, Carbone A, Inghilleri M, Monge A, Ruggieri S, Berardelli A et al. Urodynamic and neurophysiological evaluation in Parkinson’s disease and multiple system atrophy. J Neurol Neurosurg Psychiatry 1997;62:507-11.

A study of urodynamic and neurophysiological evaluation which can differentiate these two disorders.

[6]

Palace J, Chandiramani VA, Fowler CJ. Value of sphincter EMG in the diagnosis of multiple system atrophy. Muscle Nerve 1997;20:1396-1403.

A study showing neurophysiological investigation of the pelvic floor is a key to diagnose MSA.

[7]

Giladi N, Simon E, Korczyn A, Groozman GB, Orlov Y, Shabtai H, Drory VE. Anal sphincter EMG does not distinguish between multiple system atrophy and Parkinson’s disease. Muscle Nerve 2000;23:731-4.

This study found no statistical difference between the sphincter motor units of patients with MSA and PD and in particular did not find the highly prolonged motor units other studies have reported.

[8]

Sakakibara R, Hattori T, Uchiyama T, Yamanishi T. Micturitional disturbance in pure autonomic failure. Neurology 2000;54:499-501.

The first report of urodynamic investigation in six patients with PAF.

[9]

Terao Y, Takeda K, Sakuta M, Nemoto T, Takemura T, Kawai M. Pure progressive autonomic failure; a clinicopathological study. Eur Neurol 1993;33:409-15.

References continued þ

A pathological study of a patient with PAF with a review of the literature.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

References continued þ

[10] Hattori T, Yasuda K, Kita K, Hirayama K. Voiding dysfunction in Parkinson’s disease. Jpn J Psychiatry Neurol 1992;46:181-6.

A study of urinary dysfunction in serial patients with Parkinson’s disease also showing the relationship between neurological signs with urinary dysfunction.

[11] Berger Y, Blaivas JG, DeLaRocha ER, Salinas JM. Urodynamic findings in Parkinson’s disease. J Urol 1987;138:836-8.

A report of urodynamic analysis in parkinsonian patients with urinary dysfunction.

[12]

Araki, I, Kuno, S. Assessment of voiding dysfunction in Parkinson’s disease by the international prostate symptom score. J Neurol Neurosurg Psychiatry 2000;68:429-33.

The international prostate symptom score showed abnormalities increasing in men and women with increasing severity rather than duration of PD or patients’ age.

[13] Lewin RJ, Dillard GV, Porter RW. Extrapyramidal inhibition of the urinary bladder. Brain Res 1967;4:301-7.

An early experimental study showing electrical stimulation of the basal ganglia inhibited bladder contraction.

[14] Yoshimura N, Mizuta E, Yoshida O, Kuno S. Therapeutic effects of dopamine D1/D2 receptor agonists on detrusor hyperreflexia in 1-methyl-4-phenyl-1,2,3,5-tetrhydropyridine lesioned parkinsonian cynomolgus monkeys. J Pharmacol Exp Ther 1998;286:228-33.

A thorough experimental study of the role of dopamine D1/D2 receptors on micturition in MPTPinduced parkinsonian monkeys.

[15] Stocchi F, Badiali D, Vacca L, D’Alba L, Bracci F, Ruggieri S, Torti M, Berardelli A, Corazziari E. Anorectal function in multiple system atrophy and Parkinson’s disease. Mov Disord 2000;15:71-6.

A study showing manometric abnormalities occur earlier and develop faster in MSA than in Parkinson’s disease.

[16] Edwards LL, Quigley EMM, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease; frequency and pathophysiology. Neurology 1992;42:726-32.

Gastrointestinal dysfunction in Parkinson’s disease.

[17] Singaram C, Ashraf W, Gaumnitz E et al. Dopaminergic defect of enteric nervous system in Parkinson’s disease patients with chronic constipation. Lancet 1005;346:861-4.

A study showing peripheral dopaminergic deficit plays a role in gastrointestinal dysfunction of Parkinson’s disease.

[18] Mathers S, Kempster P, Swash M, Lees A. Constipation and paradoxical puborectalis contractions in anismus and Parkinson’s disease: a dystonic phenomenon? J Neurol Neurosurg Psychiatry 1988;51:1503-7.

Anorectal function in Parkinson’s disease showing paradoxical pelvic floor muscle contraction on defecation which resembles DSD. [19] Edwards LL, Quigley EMM, Harned RK, Hoffman R, Pfeiffer RF. Defecatory function in Parkinson’s disease; response to apomorphine. Ann Neurol 1993;33:490-3.

A study showing dopaminergic drug could modify defecatory dysfunction in Parkinson’s disease.

[20] Josh WH. Gastrointestinal motility problems in patients with Parkinson's disease. Effect of antiparkinsonian treatment and guidelines for management. Drugs Ageing 1997;10(4):249-58.

Review of all the problems related to this issue, and guidelines for treatment.

[22] Brown RG, Jahanshahi M, Quinn N, Marsden CD. Sexual function in patients with Parkinson’s disease and their partners. J Neurol Neurosurg Psychiatry 1990;53(6):480-6.

A questionnaire analysis of sexual dysfunction in young patients with Parkinson’s disease and their partners.

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[23] O’Sullivan J, Hughes A. Apomorphine-induced penile erections in Parkinson’s disease. Mov Disord 1998;13:536-9.

A report of a small group of men with Parkinson’s disease who use apomorphine to improve their sexual function. It is not known how general this application might be.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: à

à

à

Although the pelvic organs are innervated peripherally by the autonomic nervous system, an essential feature of their physiological behavior is that they are under voluntary control. Cortical input is therefore critical.

Lesions in the plane of the genu of the corpus callosum involving some of the white matter anterior to the anterior horns of the lateral ventricle cause a permanent disorder of control of micturition. The mechanism was thought to be that disconnection of the frontal or anterior cingulate regions from the septal and hypothalamic areas allowed micturition to proceed automatically and involuntarily.

Studies of patients’ bladder function following CVAs have examined the relationship in two different ways: there have been studies of urodynamic changes following CVAs in small groups of patients with correlation of the site of the lesion with the urodynamic findings; and other studies which have examined incontinence following stroke.

98

CHAPTER 9

BRAIN DISEASES INTRODUCTION Although the pelvic organs are innervated peripherally by the autonomic nervous system, an essential feature of their physiological behavior is that they are under voluntary control. Cortical input is therefore critical.

Whereas some clinical information currently exists in relation to the cortical control of the bladder, much less is known about cerebral determinants of bowel and sexual function.

This chapter focuses on how brain disease can cause disorders of bladder, bowel and sexual function.

CEREBRAL CONTROL OF MICTURITION Cortex. The most authoritative work in this area was the study by Andrew and Nathan in 1964, which described 38 patients with disturbances of micturition as a result of lesions in the anterior frontal lobe [1]. The infrequency with which such patients are encountered is highlighted by the fact that these authors had been collecting cases separately over a period of 24 years and only later learnt of each other’s interest and prepared a joint paper. There were 10 patients with intracranial tumors, two with anterior frontal lobe damage following rupture of an aneurysm, and four who had penetrating brain wounds. There were also 22 patients who had undergone leukotomy and these patients’ lesions proved to be the most valuable in terms of localization of important brain structures.

The conclusion was that lesions in the plane of the genu of the corpus callosum involving some of the white matter anterior to the anterior horns of the lateral ventricle cause a permanent disorder of control of micturition. The mechanism was thought to be that disconnection of the frontal or anterior cingulate regions from the septal and hypothalamic areas allowed micturition to proceed automatically and involuntarily. A typical case of incontinence due to frontal lobe impairment described in this paper was of a patient with severe urgency and frequency

of micturition and urge incontinence without dementia, socially aware and embarrassed by their incontinence. Micturition was normally coordinated, indicating that the disturbance was in the higher control of this process.

This paper was followed by the report of a series of 50 consecutive cases of frontal lobe tumors, seven of which were found to exhibit the syndrome previously described [2]. It was not found in 100 consecutive nonfrontal intracranial tumors, indicating the localizing value of the syndrome.

Although the paper of Andrew and Nathan has been the most influential in the study of frontal lobe control of the bladder, it was not the first. There had been a much earlier study from Germany, and in 1960, Ueki, a Japanese neurosurgeon, analyzed the urinary symptoms of 462 patients with brain tumors who had undergone surgery, 34 cases of frontal lobectomy and 16 cases of bilateral anterior cingulectomy [3]. His conclusions were illustrated with a diagram of the brain showing a strong positive influence on micturition of an area in the pons and an inhibitory input from the frontal lobe.

With the advent of computerized tomography (CT) scanning and magnetic resonance imaging (MRI), several other studies have examined the role of focal brain lesions causing urinary dysfunction [4].

Urinary retention may also occur as a result of a cortical lesion. In the series by Andrew and Nathan, two patients were in urinary retention at some stage. More recently, there have been single-case studies of patients with reversible right frontal lesions who presented with urinary retention [4]. Their voiding disorder resolved with successful treatment of the underlying neurological pathology.

Changes in bladder control following cerebrovascular accidents (CVAs). Studies of patients’ bladder function following CVAs have examined the relationship in two different ways: there have been studies of urodynamic changes following CVAs in small groups

of patients with correlation of the site of the lesion with the urodynamic findings; and other studies which have examined incontinence following stroke.

Urodynamics studies following CVAs. A study by Khan et al. [5] examined 20 patients who had presented at a urology department with urinary incontinence 3 or 4 more months after a CVA. CT scanning was performed to localize the area of brain injury. In four, the basal ganglia had been affected; in eight, the frontoparietal region; in one, the frontal region; in one, the parietal region; in four, there was diffuse bilateral ischemic damage; and in two, CT scans were normal. The most common cystometric finding in this disparate group was of detrusor hyperreflexia which was found in all but one patient who had a stable bladder, but was unable to communicate due to aphasia and had poor mobility.

These authors followed up their first report with a further study of a similar design in which there were 33 patients with voiding problems following a CVA [6]. Again, the predominant finding was of involuntary contractions of the bladder which was present in 26, all of whom had normal co-ordinated voiding.

The majority of patients with cerebral cortex and/or internal capsular lesions had uninhibited relaxation of the sphincter during involuntary bladder contractions, while all of the patients with lesions only in the basal ganglia or thalamus had normal sphincter function.

Similar findings were reported by Tsuchida et al. [7] who looked at 39 hemiplegic patients using urodynamic studies and CT scanning.

Again the most common finding was of urinary urge incontinence, although 13 patients complained of difficulty with micturition. Ten of the 11 patients who had frontal and internal capsular lesions showed bladder hyperreflexia, as did nine of the 10 patients who had lesions of the putamen. Normal sphincter relaxation was coordinated in all these patients. In the remaining patients, no correlation was found between urodynamic dysfunction and type of brain injury.

Most recently, Sakakibara et al. [8] reported on the bladder symptoms of 72 patients who had been admitted with an acute hemispheric stroke. When assessed at 3 months, 53% were found to have significant urinary complaints.

The commonest problem was of nocturnal

FIGURE 1

Urinary symptoms after cortical or brainstem stroke.

From Sakakibara R et al. Micturitional disturbance after acute hemispheric stroke: analysis of the lesion site by CT and MRI. J Neurol Sci 1996;137:47-56; and Sakakibara R et al. Micturitional disturbance and the pontine tegmental lesion: urodynamic and MRI analyses of vascular cases.

J Neurol Sci 1996;141:105-10.

urinary frequency which affected 36%, while urge incontinence affected 29% and a difficulty in voiding affected 25% (Figure 1).

Urodynamic studies of 22 symptomatic patients showed detrusor hyperreflexia in 68%, detrusor-sphincter dyssynergia in 14% and uninhibited sphincter relaxation in 36% (Figure 2). The phenomenon of uninhibited sphincter relaxation appears to be quite specific for frontal lesions and is not seen with basal ganglia lesions causing hyperreflexia and never seen following spinal cord injury.

The patients complain of first sensation and maximum desire to void simultaneously and a strong detrusor hyperreflexia occurs accompanied by sphincter relaxation (Figure 3). If the patient lacks a sensation of urgency, this is called “reflex incontinence”.

There was some indication that lesion size was related to the occurrence of urinary symptoms: large fronto-temporo-parietal lesions caused a higher incidence of urinary problems than frontal lesions alone, and whereas large lesions of the putamen or thalamus caused voiding difficulty, small lesions did not. Lacunar infarcts (smaller than 10 mm in diameter) of the internal capsule, however, also caused

KEYPOINTS: à

The phenomenon of uninhibited sphincter relaxation appears to be quite specific for frontal lesions and is not seen with basal ganglia lesions causing hyperreflexia and never seen following spinal cord injury. The patients complain of first sensation and maximum desire to void simultaneously and a strong detrusor hyperreflexia occurs accompanied by sphincter relaxation.

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Epidemiological studies of incontinence following CVA. Epidemiological studies of urinary incontinence following CVA indicate that urinary incontinence following a stroke is a specific indicator of poor prognosis. In acute brain disease, the occurrence of a voiding disorder may depend on the timing in relation to the stroke, and such symptoms tend to improve together with neurological signs.

Wade and Langton Hewer [9] analyzed the symptoms of 532 patients seen within 7 days of their stroke and found that the presence of urinary incontinence appeared to be a more powerful prognostic indicator for poor FIGURE 2

Urodynamic study results after cortical or brainstem stroke.

From Sakakibara R et al. Micturitional disturbance after acute hemispheric stroke: analysis of the lesion site by CT and MRI. J Neurol Sci 1996;137:47-56; and Sakakibara R et al. Micturitional disturbance and the pontine tegmental lesion: urodynamic and MRI analyses of vascular cases.

J Neurol Sci 1996;141:105-10.

KEYPOINTS: à

Epidemiological studies of urinary incontinence following CVA indicate that urinary incontinence following a stroke is a specific indicator of poor prognosis.

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urinary incontinence. From this, it seems lesion size is only a partial determinant of urinary dysfunction. In this study, no preponderance of laterality was demonstrated, whereas other studies have suggested urinary symptoms are more common in patients with right-sided lesions.

No statistically significant correlation could be demonstrated between any particular lesion site and urodynamic findings, but a significant correlation was found between the occurrence of a urinary disturbance and hemiparesis (P<0.05) and a negative correlation with hemianopia (P<0.05). Brain imaging techniques confirmed a more anterior location of brain lesions in the former group (Figure 4).

These findings further supported the idea that lesions of the anteromedial frontal lobe and its descending pathway and the basal ganglia are mainly responsible for micturitional dysfunction in stroke patients.

Urinary retention was seen in the acute phase of illness in 6% and these patients initially had detrusor areflexia and a nonrelaxing sphincter, but subsequently developed detrusor hyperreflexia. Detrusor areflexia soon after stroke can be regarded as similar to the “shock phase” (Cases 1 and 2) which occurs after acute spinal injury.

(a) Simultaneous sphincter EMG with cystometry demonstrating detrusor sphincter dyssynergia. The EMG and CMG traces are labeled. Volume infused (in ml) is recorded on the x-axis and subtracted detrusor pressure (in cm of water) is on the y-axis. (b) Simultaneous sphincter EMG with cystometry in a patient with involuntary detrusor contractions secondary to detrusor hyperreflexia demonstrating uninhibited sphincter relaxation.

FIGURE 3

KEYPOINTS: Ă

The role of diffuse brain disease in causing incontinence is not clear, although this is a problem of immense socio-economic importance because of the cost of caring for demented incontinent patients.

(a) Lesions on brain CT or MRI in patients with micturitional disturbance. Most of the patients had lesions on the anterior and medial surface of the frontal lobe, anterior edge of the paraventricular white matter, genu of the internal capsule, large lesion of the putamen and large lesion of the thalamus adjacent to or including the genu of the internal capsule. (b) Lesions on brain CT or MRI in patients without micturitional disturbance. Most of the patients had lesions of the occipital, temporal or parietal lobe, posterior lateral surface of the frontal lobe, crus posterius of the internal capsule and small lesion of the putamen or the thalamus.

FIGURE 4

From Sakakibara R et al. Micturitional disturbance after acute hemispheric stroke: analysis of the lesion site by CT and MRI. J Neurol Sci 1996;137:47-56.

survival and eventual functional dependence than was a depressed level of consciousness.

These authors stress that they did not attempt to investigate the cause of incontinence and pointed out that many patients were immobile or aphasic. They suggested either incontinence was the result of a severe, general deficit rather than specific loss of function or that those who were incontinent may have been less motivated to remain continent and to recover loss of function. Other large studies have confirmed this observation. It seems likely that incontinence is a strong predicting factor for poor prognosis for a number of reasons: the same lesion might cause neurogenic bladder dysfunction and motor or cognitive

impairment; urinary incontinence may cause psychological problems or urinary continence may be an important factor in rehabilitation, gaining independence and quality of life.

Diffuse brain disease. The role of diffuse brain disease in causing incontinence is not clear, although this is a problem of immense socio-economic importance because of the cost of caring for demented incontinent patients.

The onset of incontinence has been shown to bear a close relationship to the duration and stage of illness in patients with Alzheimerâ&#x20AC;&#x2122;s disease. Urinary incontinence usually appears 3-8 years after onset of dementia, indicating no direct relation between these two abnormalities [10]. Nevertheless, in established

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CASE 1 History: A 68-year-old, previously healthy woman was admitted to our hospital because of headache and acute-onset weakness of her left body.

Examination: Her blood pressure was high (180/105 mm Hg). Neurological examination showed that she was obtunded. She had left hemiplegia with decreased sensation for pin prick on the left side. She was also incontinent of urine. An indwelling catheter was inserted to facilitate bed-rest and to monitor urinary volume.

Emergency CT and MRI scan revealed hemorrhage in the right putamen.

Management: She was administered an anti-hypertensive drug to reduce her blood pressure, and 600 ml of glycerol to reduce brain swelling. After 2 weeks, she regained consciousness and her left hemiplegia gradually recovered. The catheter. was then removed.

However, she was still in a state of urinary retention. Urodynamic studies revealed detrusor areflexia and nonrelaxing sphincter on voiding. Nursing staff performed intermittent catheterization to avoid bladder retention, and after 3 weeks, she gradually regained voluntary voiding without large residual amounts.

Comment: One to 4 weeks after acute stroke, either infarction or hemorrhage, detrusor areflexia with nonrelaxing sphincter can occur. This is regarded as the “shock phase” and is similar to that which occurs after acute spinal cord injury.

KEYPOINTS: à

The incidence of urinary dysfunction depends on the nature and extent of the brain disease, but has probably been underestimated.

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Alzheimer’s disease, both detrusor hyperreflexia and functional incontinence due to cognitive decline are not uncommon [11]. On the other hand, urinary urgency and urge incontinence may be the earliest and even sole initial symptom in vascular dementia [12]. Detrusor hyperreflexia and uninhibited sphincter relaxation are the main features in these patients.

In diffuse Lewy body disease, urinary incontinence tends to appear with an intermediate period (2-4 years after onset of dementia) in between multiple cerebral infarction and Alzheimer’s disease [10].

Efforts should be made to treat urinary incontinence in patients with diffuse brain disease, particularly in the early stages.

Conclusion. The incidence of urinary dysfunction depends on the nature and extent of the brain disease, but has probably been underestimated. There are a number of possible reasons for this: brain disease is likely to cause conditions of critical illness, such as disturbance of consciousness and other major neurological deficits. In addition, a bladder disorder may not be so apparent when it is of

gradual onset due to the slow progression of a causative lesion. Careful observation of urinary symptoms should therefore be made in these situations and a cortical cause of bladder dysfunction should be considered in a patient with urinary dysfunction of unknown etiology [13].

Brainstem. The brainstem tegmentum contains areas critical for micturition, the so-called “pontine micturition center” (PMC). This was first demonstrated by the experimental studies of Barrington in the cat which showed that the mechanisms for co-ordinating bladder and sphincter activity reside in the brainstem. Subsequent experimental studies have defined the brainstem activity involved in bladder storage and voiding in animals in great detail and shown that separate centers control voiding and storage. The recent positron emission tomography (PET) imaging studies [14] have confirmed that the neurophysiology of bladder control is essentially similar in humans.

Studies of patients with brainstem lesions. That a posterior fossa tumor can cause voiding dysfunction has long been known. However, little attention has been paid to this because acute brainstem lesions commonly cause a serious neurological state characterized by disturbed consciousness or respiratory arrest.

Ueki found that in 152 patients with posterior fossa tumors, voiding difficulty occurred in 46 (30%) and urinary incontinence in three (1.9%) [3]. Looked at in greater detail, voiding difficulty occurred in 77.3% with lesions of pons, 66.7% with fourth ventricle, 40.9% with the midline of cerebellum, 24.2% with cerebellar hemisphere and 9.1% with cerebellopontine angle in posterior fossa tumors. Urinary retention may be an early feature in children with pontine gliomas.

An analysis of urinary symptoms of 39 patients who had had brainstem strokes showed dorsally situated lesions resulted in disturbance of micturition (Figure 5) [15].

Forty-nine percent of all the patients had urinary symptoms. Nocturnal urinary frequency and voiding difficulty occurred in 28%, urinary retention in 21% and urinary incontinence in 8% (Figure 1). The problems were more common in patients following hemorrhage, possibly because the damage was usually bilateral. MR scanning showed that the responsible lesions were in the pontine reticu-

lar nucleus and the reticular formation, adjacent to the medial parabrachial nucleus and the locus ceruleus. A correlation was found with urinary symptoms and sensory disturbance, abnormal eye movement and with inco-ordination. Urodynamics in 11 symptomatic patients showed detrusor hyperreflexia in eight (73%), low compliance bladder in one (9%), detrusor areflexia in three (27%) (3 months, 6 months and 3 years after the occurrence), nonrelaxing sphincter on voiding in five (45%) and uninhibited sphincter relaxation in three (27%). Three asymptomatic patients had normal findings.

Further single-case histories have reported patients with various pontine lesions and urinary retention due to detrusor areflexia [4]. The proximity of the medial longitudinal fasciculus in the dorsal pons to the presumed pontine micturition center means that a disorder of eye movements, such as an internuclear ophthalmoplegia, is highly likely in patients with pontine pathology causing a voiding disorder (Case 3).

CEREBRAL CONTROL OF DEFECATION Very much less has been written about cerebral control of the bowel than of the bladder.

Andrew and Nathan stated that, in general, defecation was affected much less often than micturition [1]. Three out of the 10 patients with brain tumors studied by them had fecal frequency, incontinence and constipation. One of two patients after aneurysm surgery had fecal incontinence on occasion with diarrhea. Two of four brain-injured cases had fecal incontinence without warning and one reported not to feel feces passing, while the other patient had fecal incontinence only when asleep. Rectal examination showed that these patients had full voluntary control of their levator ani muscles and of the external anal sphincter. Some

patients following leukotomy were incontinent of feces and, in such cases, this was always accompanied by urinary dysfunction.

Other papers which describe disorders of bladder function in frontal lobe disease mostly do not mention the patientsâ&#x20AC;&#x2122; bowel symptoms.

Weber et al. described the results of similar recordings in seven patients with frontal lobe injury [16]. Anorectal manometric recordings and urodynamic investigations were carried out in seven patients who had either right or left or bilateral frontal lobe injury. Two patients lacked sensation of bladder filling and

KEYPOINTS: Ă

The proximity of the medial longitudinal fasciculus in the dorsal pons to the presumed pontine micturition center means that a disorder of eye movements, such as an internuclear ophthalmoplegia, is highly likely in patients with pontine pathology causing a voiding disorder.

(a) Lesions on brain MRI in patients with micturitional disturbance. Most of the patients had lesions of the pontine tegmentum and the dorsal medulla. (b) Lesions on brain MRI in patients without micturitional disturbance. Most of the patients had lesions of the pontine basis and the lateral medulla. (c) Responsible sites of lesions for micturitional disturbance. The regions seemed to be located in the dorsolateral pons, including the pontine reticular nucleus and the reticular formation, adjacent to the medial parabrachial nucleus and the locus ceruleus.

FIGURE 5

From Sakakibara R et al. Micturitional disturbance and the pontine tegmental lesion: urodynamic and MRI analyses of vascular cases. J Neurol Sci 1996;141:105-10.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

KEYPOINTS: à

The authors concluded that the results favor the pons as the possible level of supraspinal control of colonic and anorectal motility.

two other patients had increased perception threshold of rectal distension, five cases had uninhibited detrusor hyperreflexia or spontaneous rectal contractions and one patient had lost reflex micturition and the rectoanal inhibitory reflex. The authors concluded that the medial prefrontal area and the anterior cingulate gyrus were involved in neurological control of anorectal motility as for bladder function, but the lack of correlation between urinary and anorectal abnormality in individual cases suggests that these functions depend on distinct areas of the frontal lobes.

A study using PET examined the areas of brain activation after rectal distension in both healthy control subjects and patients with irritable bowel syndrome [17]. A balloon catheter was inserted into the rectum, and different degrees of distension were produced at timed intervals. Differences in response were found between the control subjects and patients both on maximal filling and in anticipation of filling, but in healthy subjects, activation of the anterior cingulate cortex could be demonstrated on filling only to pressures that were perceived as painful.

Weber et al. [18] described the results of measuring transit times of radio-opaque markers, anorectal manometric recordings and urodynamic investigations in three patients with pontine vascular lesions. All three patients had severe constipation and distended abdomens.

One patient had right colonic inertia and lost the rectoanal inhibitory reflex. The other two had prolonged transit times of the left colon.

The authors concluded that the results favor the pons as the possible level of supraspinal control of colonic and anorectal motility. Uro-

dynamic studies showed large postmicturition residuals of 100-400 ml in two patients, detrusor hyperreflexia in two patients and detrusor-sphincter dyssynergia in two patients.

Experimental studies have suggested that Barrington’s nucleus (PMC) also plays an important role in colonic motility and defecation (the pontine defecation center) [19]. Other sites related to defecation include the hypothalamo-thalamic area, the limbic structures, including the medial frontal lobe. Chemical stimulation of Barrington’s nucleus in experimental animals results in colonic motility.

These areas may also account for the clinical fecal dysfunction in some cases.

CEREBRAL CONTROL OF SEXUAL FUNCTION In experimental animals, the deep anterior midline structures which form the limbic system have been shown to be important in determining sexual responses and the medial preoptic-anterior hypothalamic area has been shown to be an integrating area (see Chapter 4). Electrical stimulation of the hypothalamic and limbic pathways in experimental animals results in erection, although a review of reports of brain stimulation in awake man during stereotaxic neurosurgery concluded there had been no reliable instances of erection. However, damage to the dorsolateral hypothalamic nuclei during stereotaxic surgery for the relief of myoclonus, may cause loss of libido and erectile dysfunction, whereas hypersexuality occurs as a consequence of septal injury.

Little is known about the contribution of the cortex to sexual function, although it is thought that cerebral processing determines

CASE 2 History: A 62-year-old woman presented with vomiting and vertigo and was admitted to hospital. She had a 7-year history of hypertension, but her blood pressure was well controlled by medication.

Examination: Neurological examination revealed she was alert and cooperative. She had counter-clockwise rotatory nystagmus, mild right deafness and arm deviation to the right side. In addition, she also had mild ataxia of her right arm, very mild right facial paresis, mild right abducent nerve palsy and voiding difficulty. MRI scan revealed a lacunar infarction in the right dorsolateral pons.

Management: After a week her neurological signs started to improve. Urodynamic studies revealed detrusor areflexia on attempts to void, which also gradually ameliorated.

Comment: This patient had a vascular lesion in the right dorsolateral pons, which probably included locus, the pontine micturition center (PMC).

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libido and desire: the ability to effect a sexual response is determined by spinal, autonomic reflexes. Libido is hormone-dependent with a major hypothalamic component probably mediated by D1 receptors in the medial preoptic area. Prolactin acts centrally on the dopaminergic pathway and loss of libido may be the earliest symptom of a prolactin-producing pituitary tumor [20].

A study using SPET scanning, showed an increase in activity in the right prefrontal cortex during ejaculation in healthy male subjects [21]. The frontotemporal regions, particularly the right hemisphere, are important in sexual activity and these regions of the brain can be involved by pathology which causes epilepsy, by trauma, tumors, cerebrovascular disease, or encephalitis.

Temporal lobe epilepsy may cause sexual apathy of which patients rarely complain [22], although various sexual perversions and occasionally hypersexuality have also been described. Studies comparing sexual dysfunction between groups of patients with generalized epilepsy and those with focal temporal lobe epilepsy, provide evidence that the deficit is a function of the specific area of brain involvement rather than a consequence of epilepsy, psychosocial factors or anti-epileptic medication. Some investigators have suggested that the hyposexuality of temporal lobe epilepsy is due to a subclinical hypothalamicpituitary dysfunction.

Erectile dysfunction with preserved libido of which a patient therefore complains, can also occur in men with temporal lobe damage and epilepsy and may be characterized by loss of nocturnal penile tumescence. Surgery for epilepsy rarely restores function, although a survey of operated patients showed a higher level of satisfaction with sexual function amongst those who were seizure-free.

Sexual “problems” are not uncommon following head injury, particularly if there has been cognitive damage or a personality change and appear to contribute significantly to the long-term failure of relationships which predated the injury. A study of people who had been admitted to hospital for a minimum of 24 hours after a closed head injury found significant sexual dysfunction in 50% over a 15-year period. The most common complaint was of infrequency [23] and there is some evidence that hypogonadotrophic hypogonadism may be a significant factor. Sexually demanding behavior combined with a loss of empathic sensitivity can also occur after head injury.

KEYPOINTS: à

Little is known about the contribution of the cortex to sexual function although it is thought that cerebral processing determines libido and desire: the ability to effect a sexual response is determined by spinal, autonomic reflexes.

à

Temporal lobe epilepsy may cause sexual apathy of which patients rarely complain.

TREATMENT The approach to treatment is no different to that of other neurological causes of these symptoms. Such treatments are discussed in Chapter 2 (urinary incontinence and retention); Chapter 3 (constipation and fecal incontinence) and Chapter 4 (male and female sexual dysfunction).

CASE-ORIENTED MULTIPLE CHOICE QUESTIONS þ

A 68-year-old woman presented with an acute onset of left hemiplegia and an ipsilateral decrease in sharp sensation. She had an indwelling catheter inserted. A CT scan identified a hemorrhage in the right putamen. After 2 weeks the catheter was removed, but the patient remained in urinary retention.

What was the likely cause of this patient’s urinary retention?

A. B. C. D. E.

Detrusor areflexia and detrusor-sphincter dyssynergia.

Uninhibited sphincter relaxation.

Urethral stricture.

Severe constipation.

Urinary tract infection.

Multiple choice questions continued

þ

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

Multiple choice questions continued

The answer is A. Up to 1 month following an acute stroke, detrusor areflexia with nonrelaxing sphincter can occur. This time period is similar to the “shock phase” which follows acute spinal injury.

þ

þ

A 50-year-old man had a right thalamic hemorrhage. He was initially in urinary retention with detrusor areflexia and DSD on EMG cystometry. He was taught clean intermittent selfcatheterization (CISC). 2 months later, he developed urge urinary incontinence.

What is the likely cause of his new bladder symptoms?

A. B. C. D. E.

Detrusor areflexia.

Detrusor hyperreflexia.

Low compliance.

Genuine stress incontinence.

Detrusor instability.

The answer is B. After the acute illness (shock phase) in brain lesions, the patient’s bladder symptoms could either resolve or develop into detrusor hyperreflexia. þ

A 71-year-old, previously healthy woman had a new onset of nocturia and urge urinary incontinence. On examination, she had a mild short-stepping, festinating gait. She also complained of mild difficulty on drinking water and had an absent soft palate reflex. Brain MRI identified moderate leukoaraiosis.

What would be the expected cystometric finding?

A. B. C. D. E.

Detrusor areflexia.

Detrusor hyperreflexia.

Low compliance.

Genuine stress incontinence.

Absent sensation of filling.

The answer is B. Leukoaraiosis is a cause of detrusor hyperreflexia. þ

A 38-year-old woman presented with an acute onset of headache, vertigo, diplopia, difficulty using her right arm and voiding dysfunction. She was diagnosed with right MLF (medial longitudinal fasciculus) syndrome and right-sided cerebellar ataxia. An MRI scan identified a hemorrhage from a cavernous angioma of the pontine tegmentum.

What was the basis of her voiding dysfunction?

A. B. C. D. E.

Detrusor areflexia.

Low compliance.

Detrusor hyperreflexia.

Detrusor instability.

Detrusor-sphincter dyssynergia.

The answer is A. þ

What is the likely location of the lesion in the patient described above?

A. B.

106

Pyramidal tract.

Spinothalamic tract.

C. D. E.

Middle cerebellar peduncle.

Medial pontine micturition center.

Paraventricular nucleus.

The answer is D. The medial pontine micturition center is crucial for micturition particularly of voiding phase. Ăž

A 45-year-old man presented with an acute onset of confusion and left hemiparesis predominantly affecting the leg. Following recovery, he had forced use of his right hand (align hand sign) that his left hand tended to restrain. In addition, he had urge urinary and fecal incontinence.

Which site of lesion is expected on brain MRI scan?

A. B. C. D. E.

Medial frontal cortex.

Lateral frontal cortex.

Parietal cortex.

Occipital cortex.

Lateral pontine micturition center.

The answer is A. Lesions in the medial frontal cortex result in various neurological and neuropsychiatric signs, including the align hand sign. The medial frontal cortex also contains the frontal micturition center, and lesions in this area can present with detrusor hyperreflexia and/or detrusor areflexia.

REFERENCES [1]

Andrew J, Nathan PW. Lesions of the anterior frontal lobes and disturbances of micturition and defaecation. Brain 1964;87:233-62.

An authoritative clinico-pathologic study of 38 patients with frontal lobe lesions affecting micturition.

Cystometric findings are also available.

[2]

Maurice-Williams RS. Micturition symptoms in frontal tumours. J Neurol Neurosurg Psychiatry 1974;37:431-6.

A study of frontal tumors affecting micturition.

[3]

Ueki K. Disturbances of micturition observed in some patients with brain tumour. Neurol Med Chir 1960;2:25-33.

An extensive study of brain tumor affecting micturition by surgical and postmortem findings. Location of the tumor in the cortical lobes causing urinary dysfunction is described in detail.

[4]

Sakakibara R, Fowler CJ. Cerebral control of bladder, bowel and sexual function and effects of brain disease. In: Fowler CJ, editor. Neurology of bladder, bowel, and sexual dysfunction; Vol. 23, Blue Books of Practical Neurology. Boston: Butterworth Heinemann; 1999, pp 229-243.

A review of cerebral control of genitourinary function, in a recent textbook.

[5]

Khan Z, Hertanu J, Yang W, Melman A, Leiter E. Predictive correlation of urodynamic dysfunction and brain injury after cerebrovascular accident. J Urol 1981;126:86-8.

References continued Ăž

The first extensive study of urodynamic findings and CT lesion in 33 post-stroke patients with urinary symptoms.

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NEUROLOGIC BLADDER, BOWEL AND SEXUAL DYSFUNCTION

References continued þ

[6]

Khan Z, Starer P, Yang W, Bhola A. Analysis of voiding disorders in patients with cerebrovascular accidents. Urology 1990;35:263-70.

A similar study to these authors’ first (see reference 5).

[7]

Tsuchida S, Noto H, Yamaguchi O, Itoh M. Urodynamic studies on hemiplegic patients after cerebrovascular accident. Urology 1983;21:315-18.

Analysis of urodynamic findings and CT lesion in patients with urinary dysfunction.

[8]

Sakakibara R, Hattori T, Yasuda K, Yamanishi T. Micturitional disturbance after acute hemispheric stroke: analysis of the lesion site by CT and MRI. J Neurol Sci 1996;137:47-56.

A study of CT and MRI findings in relation to micturitional disturbance in 72 vascular cases.

[9]

Wade D, Langton Hewer R. Outlook after an acute stroke: urinary incontinence and loss of consciousness compared in 532 patients. Q J Med 1985;56:601-8.

An epidemiological study of incontinence following acute stroke.

[10] Del-Ser T, Munoz DG, Hachinski V. Temporal pattern of cognitive decline and incontinence is different in Alzheimer’s disease and diffuse Lewy body disease. Neurology 1996;46:682-6.

A study showing that in diffuse Lewy body disease, urinary incontinence appears earlier than in Alzheimer’s disease, probably reflecting each disease process.

[11] Resnick NM, Yalla SV, Laurino E. The pathophysiology of urinary incontinence among institutionalized elderly persons. New Engl J Med 1989;320:1-7.

An extensive study showing detrusor hyperreflexia with impaired contractility as a feature of frail elderly patients.

[12] Sakakibara R, Hattori T, Uchiyama T, Yamanishi T. Urinary function in the elderly with and without leukoaraiosis; in relation to cognitive and gait function. J Neurol Neurosurg Psychiatry 1999;67:658-60.

[13] Sakakibara R, Fowler CJ, Hattori T. Voiding and MRI analysis of the brain. Int Urogynecol 1999;10:192-9.

A review article of micturition and MRI analysis of the brain in particular for anteromedial frontal lobe and pontine tegmentum.

[14] Blok B, Sturms L, Holstege G. Brain activation during micturition in women. Brain 1998;121:2033-42.

The second report of the Netherlands group showing human brain activation detected by functional PET during micturition in female volunteers - the first report was about men.

[15] Sakakibara R, Hattori T, Yasuda K, Yamanishi T. Micturitional disturbance and the pontine tegmental lesion: urodynamic and MRI analyses of vascular cases. J Neurol Sci 1996;141:105-10.

The first report of 37 patients with vascular brainstem lesion indicating that pontine micturition center (PMC) is located around the locus ceruleus in human.

[16] Weber J, Delanger T, Hannequin D, Beuret-Blanquart F, Denis P. Anorectal manometric anomalies in seven patients with frontal lobe brain damage. Dig Dis Sci 1990;35:225-30.

A study from a French group showing frontal lobe lesions affect anorectal manometric findings.

[17] Silverman D, Munakata J, Ennes H, Mandelkern M, Hoh C, Mayer E. Regional cerebral activity in normal and pathological perception of visceral pain. Gastroenterology 1997;112:64-72.

A functional PET study showing activation in the anterior cingulate cortex by colon distension, which could be modified by irritable bowel syndrome.

[18] 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.

A small, but interesting study of three patients with severe disorders of defecation.

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[19] Valentino R, Miselis R, Pavcovich L. Pontine regulation of pelvic viscera; pharmacological target for pelvic visceral dysfunctions. Trends Pharmacol Sci 1999;20:253-60.

A recent review of experimental works about pontine regulation of pelvic viscera. Diverse role of the locus ceruleus for autonomic nervous system is discussed.

[20] Hutling A-L, Muhr C, Lundberg P, Werner S. Prolactinomas in men: clinical characteristics and the effect of bromocriptine treatment. Acta Med Scand 1985;217:101-9.

A report showing bromocriptine is an effective treatment for erectile dysfunction in patients with prolactinoma.

[21] Tiihonen J, Kikka J, Kuplia J, Partanen K, Vainio P, Airaksinen J. Increase in cerebral blood flow of right prefrontal cortex in man during orgasm. Neurosci Lett 1994;170:241-3.

A functional SPECT study of eight normal volunteers who showed brain activity in the right prefrontal cortex during sexual stimulation.

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