Functional brain imaging studies have demonstrated that neurological control of the bladder in humans is essentially similar to that demonstrated in experimental animals. A number of positron emission tomography (PET) and, more recently, functional magnetic resonance imaging (fMRI) studies have investigated human control of urinary storage and voiding. The initial PET experiments of Blok and colleagues identified the brain centers activated during attempted micturition (Blok et al., 1997, 1998). In those able to void during the scanning, activity was shown in a region of the medioposterior pons called the M-region. In those subjects unable to void, a distinct region in the ventrolateral pontine tegmentum was activated, the L-region. Although it had been demonstrated in cats that separate pontine nuclei exist for the storage and voiding phases of bladder activity, subsequent experiments have failed to consistently demonstrate activity in this distinct L-region. In the cortex, the PET scans showed significant activity in the right inferior frontal gyrus and the right anterior cingulate gyrus during voiding that was not present during the withholding phase. Nour and associates then corroborated these findings with their own PET study of 12 healthy male volunteers, showing activity in a number of brain areas including the cerebellum (Nour et al., 2000). Other areas that show activation in fMRI during bladder filling include the anterior cingulate gyrus and right insula; fMRI has shown that the medial prefrontal cortex, responsible for complex cognitive and socially appropriate behavior, plays an important role in voiding. A recent article reviews the functional imaging studies evaluating bladder functions and their contributions to our understanding of bladder control (Fowler and Griffiths, 2010).

Bowel and Its Neurological Control

The processing of rectal sensation is relevant in bladder function because unlike other gut organs, it has an important sensory role, and the rectum is a visceral organ that contains both unmyelinated C fibers and thinly myelinated Aδ afferents. In contrast, the anal canal has somatic innervation from the pudendal nerve. The study by Hobday and associates has highlighted the differences in its cortical representation from that of the rectum. The various brain imaging studies of visceral stimulation, including the foregoing report, have been reviewed (Derbyshire, 2003). When different visceral stimuli—esophageal distension, esophageal pain, rectal distension, or the mechanisms operative in irritable bowel syndrome—were analyzed, esophageal stimulation was found to activate the insula most consistently, with other commonly involved areas including somatosensory and motor cortices. Considerable variation was observed in whether the periaqueductal gray was activated or not. Lower GI stimuli predominantly activated the prefrontal and orbitofrontal cortices as well as the insula, with variability in cingulate activation. Overall, esophageal stimulation involved a more central sensory and motor neural circuit, whereas lower GI stimulation activated areas with projections to autonomic and affective control centers such as the brainstem and amygdala.

Sexual Function and Its Neurological Control

Physiological sexual response in men and women has been divided classically into four phases: excitement, plateau, orgasm, and resolution. Excitation occurs in response to either physical or psychological stimulation and results in penile or clitoral tumescence and erection or vaginal lubrication. The plateau phase is accompanied by the various physical changes of high sexual arousal in anticipation of orgasm. Orgasm, an intensely sensory event, usually is associated with rhythmic contraction of the pelvic floor and culminates with ejaculation in men. During resolution, the increased genital blood flow resolves. A modification of this model of sexual response was the three-phase model proposed by Kaplan, consisting of desire, arousal, and orgasm.

Much remains to be discovered about cortical control of 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. Libido is hormone dependent with a major hypothalamic component, and loss of libido may be the earliest symptom of a pituitary tumor. In experimental animals, the deep anterior midline structures that form the limbic system have been shown to be important for sexual responses, and the medial preoptic–anterior hypothalamic area has an integrating function (Andersson, 2001). Functional brain imaging experiments including five PET studies and seven fMRI studies have highlighted the key areas of brain activity associated with sexual functioning—for example, the role of the hypothalamus in reproductive function, regulation of human sexuality, and regulation of erection through medial preoptic area, or the roles of the insula and claustrum in autonomic regulation and visceral sensory processing. The aspects of sexual function covered include penile sexual stimulation (Arnow et al., 2002; Georgiadis and Holstege, 2005), male ejaculation (Holstege et al., 2003), and visual sexual stimuli (Karama et al., 2002).

Male Sexual Response

Erection results from increased blood flow into the corpora cavernosa caused by relaxation of the smooth muscle in the cavernosal arteries and a reduction in venous return. The major peripheral innervation determining this is parasympathetic, which arises from the S2-S4 segments and travels to the genital region in the pelvic nerves. Sympathetic input is also important: sympathetic innervation of the genital region originates in the thoracolumbar chain (T11-L2) and travels through the hypogastric nerves to the confluence of nerves that lies on either side of the rectum and the lower urinary tract—the pelvic plexus.

The pelvic plexus also receives input from the pelvic nerves. It is from the pelvic plexus that the cavernous nerves arise and innervate the corpora cavernosa. Although erection is induced by parasympathetic activity, nitric oxide has been identified as important in causing relaxation of the corporeal blood vessels and the increase in penile blood flow that causes erection. Psychogenic erection requires cortical activation of spinal pathways, and the preservation of this type of responsiveness in men with low spinal cord lesions suggests that sympathetic pathways can mediate it. Reflex erections occur as the result of cutaneous genital stimulation. Preservation of reflex erections in men with lesions above T11 indicates that the response is the result of spinal reflexes, with afferent signals conveyed in the pudendal nerve and S2-S4 roots, and efferent signals through the same sacral roots. In health, reflex and psychogenic responses are thought to reinforce one another. In men, orgasm and ejaculation are not the same process; ejaculation is the release of semen, and orgasm consists of the sensory changes accompanied by pelvic floor contractions. Ejaculation involves emission of semen from the vas and seminal vesicles into the posterior urethra and closure of the bladder neck. The latter processes are under sympathetic control, whereas contraction of the pelvic floor muscles is under somatic nerve control, innervation being from the perineal branch of the pudendal nerve. After ejaculation, a period of resolution is necessary before sexual activity can be reinitiated.

Female Sexual Response

The neurological control of sexual function in women is less well understood than that in men, but similarities exist. The main parasympathetic innervation is from the pelvic nerves, sympathetic innervation from the hypogastric nerves, and bilateral somatic innervation from the pudendal nerves. The finding of acetylcholinesterase-positive nerves around blood vessels in the vagina points to parasympathetic control of vaginal vasodilation and secretomotor function. It seems likely that increased vaginal blood flow, erection of the cavernous tissue of the clitoris and around the outer part of the vagina, and lubrication are brought about through neural mechanisms similar to those that control erection in men. The lubrication that occurs as part of sexual arousal results from transudation through the vaginal walls and fluid from Bartholin glands.

During orgasm, a series of synchronous contractions of the sphincter and vaginal muscles may occur. As many as 20 consecutive contractions have been registered, lasting for 10 to 50 seconds. The accompanying sensory experiences generally are described as an intensely pleasurable pelvic event.

Neurogenic Bladder Dysfunction

Lesions of the nervous system, central or peripheral, can result in characteristic patterns of bladder dysfunction depending upon the level of the lesions in the neurological axis (Panicker et al., 2010). The storage function of the bladder is affected following suprapontine or infrapontine/suprasacral lesions. This results in involuntary spontaneous or induced contractions of the detrusor muscle (detrusor overactivity), which can be identified during the filling phase of urodynamics. The voiding function of the bladder can be affected by infrapontine lesions. Following spinal cord damage, there is simultaneous contraction of the external urethral sphincter and detrusor muscle, detrusor-sphincter dyssynergia, which results in incomplete bladder emptying and abnormally high bladder pressures. Following lesions of the conus medullaris or cauda equina, voiding dysfunction can be due to poorly sustained detrusor contractions and possibly non-relaxing urethral sphincters (Table 38.1).

Table 38.1 Diagnostic Findings in Patients with Suspected Neurogenic Bladder Dysfunction

Cortical Lesions

The role of hormonal dysfunction has yet to be fully determined. On the basis of measurements of sex hormones and pituitary function, it has been suggested that the hyposexuality of TLE results from a subclinical hypogonadotropic hypogonadism, and that dysfunction of medial temporal lobe structures may dysmodulate hypothalamopituitary secretion (Murialdo et al., 1995). Erectile dysfunction (ED) with preservation of libido can occur in men with temporal lobe damage with or without epilepsy and may be characterized by loss of nocturnal penile tumescence. Surgery for epilepsy rarely restores erectile function, although a survey of operated patients showed a higher level of satisfaction with sexual function among those who were free of seizures. Sexual dysfunction is common after head injury, particularly in patients who demonstrate cognitive damage. Hypersexual behavior may occur after frontal lobe damage. Lesions of the frontal lobes, the basal-medial part in particular, may lead to loss of social control, which also may affect sexual behavior.

Basal Ganglia Lesions

Bladder Dysfunction

Bladder symptoms in Parkinson disease (PD) correlate with neurological disability (Araki and Kuno, 2000) and stage of disease; both findings appear to support a link between dopaminergic degeneration and symptoms of urinary dysfunction. In line with current thinking about staging of PD in terms of underlying neuropathology (Braak et al., 2004), it appears that bladder dysfunction does not occur until some years after the onset of motor symptoms, and the dysfunction is correlated with the extent of dopamine depletion (Sakakibara et al., 2001b). This means that the underlying pathological process is likely to have extended into the neocortex and explains why the clinical context in which bladder dysfunction is seen in PD is common in patients with cerebral symptoms, as well as with adverse effects of long-standing treatment with dopaminergic agents.

The most frequent complaints are of nighttime frequency, urgency, and difficulty voiding (Sakakibara et al., 2001a), and the most common abnormality in urodynamic studies is detrusor overactivity (Araki et al., 2000). Of the several possible explanations for this finding, the hypothesis most widely accepted is that in healthy persons, the basal ganglia has an inhibitory effect on the micturition reflex, and with neuronal loss in the substantia nigra, detrusor overactivity develops. Studies on anesthetized cats demonstrated that rhythmic bladder contractions were inhibited by intracerebroventricular administration of a dopamine D₁ receptor agonist but were not affected by a D₂ receptor agonist. From this evidence, it was concluded that the D₁ receptor provides the main inhibitory influence on the micturition reflex (Yoshimura et al., 2003). Clinical studies that have looked at the effect of l-dopa or apomorphine on bladder behavior in patients with PD have, however, produced conflicting results. In patients demonstrating the on/off phenomenon, cystometry done after taking l-dopa showed improvement of overactivity in some and worsening in others. The unpredictable effect of antiparkinsonian medications on urinary symptoms has not been definitively shown to correlate with age or stage of disease (Winge and Fowler, 2006). Many patients with PD have nocturnal polyuria as well, which contributes to bladder symptoms and would not be expected to improve with antimuscarinics. In addition to neurogenic bladder dysfunction, benign prostatic obstruction may occur concomitantly in some men with PD and contribute to bladder dysfunction. A recent study suggests that contrary to previous teaching, transurethral prostate resection may be successful in carefully selected PD men and is associated with minimal risk of incontinence (Roth et al., 2009).

In a patient with severe urinary symptoms but mild parkinsonism, a diagnosis of multiple system atrophy (MSA) should be considered. The onset of urogenital symptoms in MSA may precede overt neurological involvement; ED and bladder symptoms begin on average 4 to 5 years before diagnosis and 2 years before more specific neurological symptoms appear. The neuronal degeneration of MSA affects the central nervous system (CNS) at several locations that are important for bladder control, which probably explains why urinary complaints occur so early and are so severe in this condition. It is thought that detrusor overactivity is caused by neuronal loss in the pontine region, whereas incomplete bladder emptying is caused by loss of parasympathetic innervation of the detrusor after neuronal degeneration in the intermediolateral cell columns of the spinal cord. In addition, anterior horn cell loss in the Onuf nucleus results in denervation of the urethral sphincter so that the patient has a combination of detrusor overactivity, incomplete bladder emptying, and a weak sphincter. Bladder dysfunction may change during the progression of MSA, and serial studies have shown that the mean postmicturition residual volume increases as the condition progresses (Ito et al., 2006). Bladder symptoms in other parkinsonian syndromes are less prominent than in MSA, and although they may occur as part of the patient’s general disability, they rarely are as severe as in MSA and do not occur at a stage of the disease when a neurological cause is not evident.

Bowel Dysfunction

Constipation is now thought to be a preclinical manifestation of PD, and a symptom questionnaire showed that this was considered to be the most bothersome nonmotor symptom for PD patients (Sakakibara et al., 2001a). Several possible causes for constipation are recognized: a slow colonic transit time has been demonstrated in a number of studies; this finding may be secondary to a reduction in dopaminergic myenteric neurons. An abnormality of the defecation process has also been demonstrated in some patients with PD, with paradoxical contraction of the external anal sphincter and pubococcygeus causing outlet obstruction. This phenomenon can result in anismus and is thought to be a form of focal dystonia. Bowel dysfunction appears earlier and progresses faster in patients with MSA than in those with PD (Stocchi et al., 2000).

Sexual Dysfunction

Experimental evidence from animals and humans shows that dopaminergic mechanisms are involved in determining libido and inducing penile erection. In animal studies, the medial preoptic area of the hypothalamus has been shown to regulate sexual drive, and selective stimulation of dopamine D₂ receptors in this region increases sexual activity in rats (Andersson, 2001). An increase in libido in some patients with PD treated with dopamine agonists and l-dopa as part of the “hedonistic homeostatic dysregulation” syndrome (Giovannoni et al., 2000) is a well-recognized phenomenon, although its incidence is uncertain. The cause of ED in PD is unclear, but it is a significant problem and in one study was shown to affect 60% of a group of men with PD, compared with 37.5% of age-matched healthy men. ED usually affects men later in the course of PD, with onset years after the diagnosis of neurological disease has been established. A survey of relatively young patients with PD (mean age, 49.6 years) and their partners revealed a high level of sexual dysfunction, with the most severely affected couples being those in which the patient was male.

ED may be the first symptom in men with MSA, predating the onset of any other neurological symptoms by several years. The disorder appears to be chronologically distinct from the development of postural hypotension. The reason for the apparently early selective involvement of neural mechanisms for erection is not known. Preserved erectile function in a man with parkinsonism strongly contradicts the diagnosis of MSA. The available literature on female sexual problems in movement disorders is limited (Jacobs et al., 2000; Oertel et al., 2003).

Brainstem Lesions

Voiding difficulty is a rare but recognized symptom of a posterior fossa tumor and has been reported in series of patients with brainstem disorders (Fowler, 1999). In an analysis of urinary symptoms of 39 patients who had had brainstem strokes, lesions that resulted in micturition disturbance usually were dorsally situated (Sakakibara et al., 1996)—a finding consistent with the known location of the brainstem centers involved in bladder control. The proximity in the dorsal pons between the pontine micturition center and medial longitudinal fasciculus means that a disorder of eye movements, such as an internuclear ophthalmoplegia (INO), is highly likely in patients with a pontine disorder causing a voiding difficulty.

Spinal Cord Lesions

Bladder Dysfunction

Spinal cord disorders are the most common cause for neurogenic bladder dysfunction. Transspinal pathways connect the pontine micturition centers to the sacral cord. Intact connections are necessary to effect the reciprocal activity of the detrusor and sphincter needed to switch between storage and voiding. After disconnection from the pons, this synergistic activity is lost, resulting in detrusor-sphincter dyssynergia.

Initially after acute SCI, there usually is a phase of neuronal shock of variable duration, characterized clinically by complete urinary retention and urodynamics demonstrating an acontractile detrusor. Gradually over the course of weeks, new reflexes emerge to drive bladder emptying and cause detrusor contractions in response to low filling volumes. The neurophysiology of this recovery has been studied in cats, and it has been proposed that after spinal injury, C fibers emerge as the major afferents, forming a spinal segmental reflex that results in automatic voiding. It is assumed that the same pathophysiology occurs in humans. In support of this assumption is the observed response to intravesical capsaicin (a C-fiber neurotoxin) in patients with acute traumatic spinal cord injury (SCI) or chronically progressive spinal cord disease from multiple sclerosis (MS). The abnormally overactive, small-capacity bladder that characterizes spinal cord disease causes patients to experience urgency and frequency. However, patients with complete transection of the cord may not complain of urinary urgency. If detrusor overactivity is severe, incontinence is highly likely. Poor neural drive on the detrusor muscle during attempts to void, together with an element of detrusor-sphincter dyssynergia, contributes to incomplete bladder emptying. This difficulty may exacerbate the symptoms of the overactive bladder. Although the neurological process of voiding may have been as severely disrupted as the process of storage, the symptoms of difficulty emptying can be minor compared with those of urge incontinence. Only on direct questioning may the patient admit to having difficulty initiating micturition, an interrupted stream, or possibly a sensation of incomplete emptying.

Because bladder innervation arises more caudally than innervation of the lower limbs, any form of spinal cord disease that causes bladder dysfunction is likely to produce clinical signs in the lower limbs as well, unless the lesion is limited to the conus. This rule is sufficiently reliable to be of great value in determining whether a patient has a neurogenic bladder caused by spinal cord disease.

Spinal Cord Injury

After SCI, bladder dysfunction can be of such severity as to cause ureteric reflux, hydronephrosis, and eventual upper urinary tract damage. Before the introduction of modern treatments, renal failure was a common cause of death after SCI. The bladder problems of persons with SCI, therefore, must be managed aggressively to lessen the possibility of upper tract disease and to provide the patient with adequate bladder control for a fully rehabilitated life. People with SCI often are young and otherwise fit, and it may be best for them to undergo surgery on the lower urinary tract with a view to fulfilling these two aims, rather than to be treated medically.

Multiple Sclerosis

The pathophysiological consequences of progressive MS affecting the spinal cord for the bladder are similar to those of SCI, but the medical context of increasing disability is such that management must be quite different. Estimates of the proportion of patients with MS who have lower urinary tract symptoms vary according to the severity of the neurological disability in the group under study, but a figure of about 75% is frequently cited (Marrie et al., 2007). Several studies have shown that urinary incontinence is considered to be one of the worst aspects of the disease; 70% of a self-selected group of patients with MS responding to a questionnaire classified the impact bladder symptoms had on their life as “high” or “moderate” (Hemmett et al., 2004). A strong association between bladder symptoms and the presence of clinical spinal cord involvement, including paraparesis and UMN signs, has been recognized on examination of the lower limbs in patients with MS. This observation has also been made in patients with a similar condition, acute disseminated encephalomyelitis (ADEM) (Panicker et al., 2009).

The most common urinary symptom is urgency; all series of urodynamic studies in patients with MS have shown that this is due to detrusor overactivity. Hesitancy of micturition may be a symptom patients volunteer or admit on direct questioning, but the more disabled may find themselves unable to initiate micturition voluntarily, emptying their bladders only with an involuntary hyperreflexic contraction and an interrupted urinary flow. Evidence of incomplete emptying may come not from a sensation of continued fullness after voiding but rather from the need to pass urine again within 5 to 10 minutes (double voiding).

As the neurological condition progresses, bladder dysfunction may become more difficult to treat. However, unlike with the bladder dysfunction that follows SCI, progressive neurological diseases such as MS rarely result in upper urinary tract involvement. This is the case even when long-standing MS has resulted in severe disability and spasticity. The reason for this sparing of the upper urinary tract is not known, but it means that in such patients, management should emphasize symptomatic relief (Fowler, 1999).

A particular problem in MS is that neurological symptoms may deteriorate acutely when the patient has an infection and pyrexia, including urinary tract infection (UTI). As MS progresses, recurrent infections are likely to result in deficits that accumulate and lead to progressive neurological deterioration (Buljevac et al., 2002).

Bowel Dysfunction

Half of all patients need help with bowel management. A questionnaire survey of patients with SCI found that bowel dysfunction was a major problem, rated as only slightly less serious than loss of mobility (Glickman and Kamm, 1996). Bowel management may be equally problematic for patients with progressive spinal cord disease such as MS, with prevalence rates for bowel dysfunction reported at 30% to 50% (DasGupta and Fowler, 2003). The loss of rectal sensation and the normal urge to defecate means that bowel emptying must be induced at a convenient time by digital anal stimulation, use of suppositories or enemas, or manual evacuation. The consequence of losing the ability to postpone bowel emptying because of impaired sensation of impending defecation and inability to voluntarily contract the anal sphincter is that fecal incontinence is common.

Sexual Dysfunction

Male Sexual Dysfunction

The level and completeness of a spinal cord lesion determine erectile and ejaculatory capability after SCI (Bors and Comarr, 1960). With a complete cervical lesion, psychogenic erections are lost, but the capacity for spontaneous or reflex erections may be intact. With low spinal cord lesions, particularly if the cauda equina is involved, little or no erectile capacity may be retained. Theoretically, a lesion below spinal level L2 leaves psychogenic erections intact, but in practice it is uncommon for men with such a lesion to have erections adequate for intercourse. Psychogenic erections are more likely to be preserved in incomplete lesions. Preservation of ejaculation function after a spinal cord lesion is unusual (Sipski, Alexander, and Gómez-Marín, 2006). Although earlier studies indicated a much lower figure, it is now known that 60% to 65% of men with MS have ED, often coexisting with urinary symptoms, with urodynamically demonstrable overactivity in a majority of those affected. Typically, in the early stages of MS, the chief complaint is difficulty sustaining an erection for intercourse. With advancing neurological disability, erectile function may cease, and difficulty with ejaculation may develop. A study of pudendal evoked potentials in men with MS found that those with severely delayed latencies (i.e., with more severe spinal cord disease) were more likely to be unable to ejaculate (Betts et al., 1994). Though it has been said that a diagnosis of MS should be considered in a young man presenting with impotence, this possibility seems unlikely in the absence of clinical spinal cord disease. In one series, only a single patient had erectile difficulties at the time of the first symptoms of MS, and neurological disease did not develop subsequently in any of the men who presented with ED.

Female Sexual Dysfunction

Studies of women with SCI at different levels, both complete and incomplete, have advanced current understanding of the neural pathways involved in female sexual response. It has been hypothesized that the sensory experience of orgasm may have an autonomic basis because orgasmic capacity is preserved in a proportion of affected women, particularly with higher cord lesions (Sipski et al., 2001); fMRI studies in SCI patients suggest preservation of vagal pathways. Sexual dysfunction in women with MS is common, affecting 50% to 60%, although probably underdiagnosed, with the incidence increasing with worsening disability. Neurogenic problems during intercourse include decreased lubrication and reduced orgasmic capacity. A double-blind, randomized, placebo-controlled crossover study of sildenafil citrate in treating females with sexual dysfunction due to MS showed no overall benefit with the drug, shown to be far more effective in men with MS (DasGupta et al., 2004). In women with advanced disease, additional problems may include lower limb spasticity, loss of pelvic sensation, genital dysesthesia, and fear of incontinence (Hulter and Lundberg, 1995).

Impaired Sympathetic Thoracolumbar Outflow

The fibers that travel from the thoracolumbar sympathetic chain emerge from the T10-L2 spinal levels and course through the retroperitoneal space to the bifurcation of the aorta, from which they enter the pelvic plexus. Loss of sympathetic innervation of the genitalia causes disorders of ejaculation, with either failure of emission or retrograde ejaculation; ability to experience the sensation of orgasm may be retained. Sympathetic thoracolumbar fibers are particularly likely to be injured by the procedure of retroperitoneal lymph node dissection or surgeries involving an anterior approach to the lumbar spine, and complaints of loss of ejaculation are common after these surgeries.

Conus and Cauda Equina Lesions

The cauda equina contains the sacral parasympathetic outflow together with the somatic efferent and afferent fibers. Damage to the cauda equina leaves the detrusor decentralized rather than denervated because the postganglionic parasympathetic innervation is unaffected. This distinction may explain why bladder dysfunction after a cauda equina lesion is unpredictable and why even detrusor overactivity has been described (Podnar and Fowler, 2010).

Inability to evacuate the bowel may be a severe problem, and manual evacuation may be necessary for the long term. Additional denervation of the anal sphincter can result in incontinence of flatus and feces. Damage to the cauda equina results in sensory loss, and both men and women complain of perineal sensory loss and loss of erotic genital sensation, for which no effective treatment is available. In men, ED is also a complaint (Podnar et al., 2006).

Impairment of bladder, bowel, and sexual function is particularly difficult for patients to bear psychologically when they are otherwise ambulant and mobile. Although a number of series have reported the urodynamic changes that can occur after a cauda equina lesion, no analysis has been performed to assess the effect of a cauda equina lesion on quality of life. The levels of compensation awarded in medicolegal cases reflect the fact that loss of control of the pelvic organs is a catastrophe.

For most patients, contact with other persons similarly affected may prove supportive.

Disturbances of Peripheral Innervation

Diabetic Neuropathy

Bladder involvement once was considered an uncommon complication of diabetes, but the increase in use of techniques for studying bladder function has shown that such involvement is common, although often asymptomatic. Bladder dysfunction does not occur in isolation, and other symptoms and signs of generalized neuropathy are necessarily present in affected patients. The onset of the bladder dysfunction is insidious, with progressive loss of bladder sensation and impairment of bladder emptying over years, eventually culminating in chronic low-pressure urinary retention (Hill et al., 2008). Urodynamic studies demonstrate impaired detrusor contractility, reduced urine flow, increased postmicturition residual volume, and reduced bladder sensation. It seems likely that vesical afferent and efferent fibers are involved, causing reduced awareness of bladder filling and decreased bladder contractility.

Diabetes is the most common cause of ED. Surveys of andrology clinics have found that 20% to 31% of men attending are diabetic. The prevalence of ED increases with age and duration of diabetes, and the problem is known to be associated with severe retinopathy, a history of peripheral neuropathy, amputation, cardiovascular disease, raised glycosylated hemoglobin, and the use of antihypertensives such as beta-blockers. A large population study of men with early-onset diabetes found that 20% had ED. Whether its pathogenesis in diabetic patients results mainly from neuropathy or involves a significant microvascular contribution, or whether the two processes are codependent, is not yet resolved. Age-matched studies of women with and without diabetes suggest that diabetic women also may be affected by specific disorders of sexual function including decreased vaginal lubrication and capacity for orgasm.

Amyloid Neuropathy

Autonomic manifestations are common in amyloid neuropathy and include ED, orthostatic hypotension, bladder dysfunction, distal anhidrosis and abnormal pupils. Lower urinary tract symptoms generally appear early on and are present in 50% of patients within the first 3 years of the disease. Patients most often complain of difficulty in bladder emptying and incontinence (Andrade, 2009). Often, however, bladder dysfunction may be asymptomatic and uncovered only during investigations. Urodynamic studies have demonstrated reduced bladder sensations, underactive detrusor, poor urinary flow, and opening of the bladder neck. Bladder wall thickening may be seen on ultrasound scan. Some 10% of patients with familial amyloidotic polyneuropathy (FAP) type I may proceed to end-stage renal disease (Lobato, 2003) and may complain of polyuria. Urinary incontinence has been shown to be associated with higher post–liver transplant mortality (Adams et al., 2000).

Bowel dysfunction results in alternating constipation and diarrhea. This occurs concomitantly with other manifestations such as episodic nausea, vomiting, and malnutrition. Anorectal physiology studies have demonstrated prolonged colonic transit time, low anal pressure at rest, and loss of spontaneous phasic rectal contractions during squeeze, suggesting an enteric neuropathy. Reduced libido and ED are common, and phosphodiesterase inhibitors may have the adverse effect of accentuating orthostatic hypotension and should therefore be used with caution.

Immune-Mediated Neuropathies

Approximately one-fourth of patients with Guillain-Barré syndrome have bladder symptoms. These symptoms usually occur in those patients with more severe neuropathy and appear after limb weakness is established. Both detrusor areflexia and bladder overactivity have been described.

Autoimmune Autonomic Ganglionopathy

Patients with autoimmune autonomic ganglionopathy present with rapid onset of severe autonomic failure, with orthostatic hypotension, GI dysmotility, anhidrosis, bladder dysfunction, ED, and sicca symptoms and may have ganglionic acetylcholine receptor (AChR) antibodies. Bladder dysfunction generally manifests with voiding difficulty and incomplete emptying. Severity and distribution of autonomic dysfunction appear to depend upon the level of antibody titers (Gibbons and Freeman, 2009).

Pure Autonomic Failure

Pure autonomic failure (PAF) is a degenerative postganglionic autonomic disorder. There is now evidence to suggest that the underlying basis is a synucleinopathy, with Lewy bodies confined primarily to the autonomic ganglia neurons. Nocturia and voiding dysfunction are common, and bladder emptying is often affected. Bladder dysfunction in PAF appears to be as common but less severe than in MSA, and this could possibly reflect slower progression of the disease (Sakakibara et al., 2000). ED and constipation are common.

Myotonic Dystrophy

Although myotonic activity has not been found in the sphincter or pelvic floor of patients with myotonic dystrophy, bladder symptoms may be prominent and difficult to treat, presumably because bladder smooth muscle is involved. With advancing disease, megacolon and fecal incontinence also may become intractable problems.

Urinary Retention in Young Women

Urinary retention or symptoms of obstructed voiding in young women in the absence of overt neurological disease have long puzzled urologists and neurologists alike, and in the absence of any convincing organic cause, the condition was once said to be “hysterical.” The typical clinical picture is that of a young woman in the age range of 20 to 30 years who presents with retention and a bladder capacity greater than 1 L. Although patients retaining such quantities may be uncomfortable, they do not have the sensation of extreme urgency that might be expected. Many affected women have previously experienced interruption of the urinary stream but are unaware that this is abnormal, so a voiding history can be misleading unless taken carefully. Other clinical neurological features or findings on laboratory investigations that would support a diagnosis of MS are lacking, and MRI of the brain, spinal cord, and cauda equina are normal. The lack of sacral anesthesia makes a cauda equina lesion improbable. An association between this syndrome and polycystic ovaries was described in the original description of the syndrome.

In some young women with urinary retention, concentric needle electrode examination of the striated muscle of the urethral sphincter reveals complex repetitive discharges and myotonia-like activity, decelerating bursts. Known as Fowler syndrome, it could until recently only be managed symptomatically. However, it is now known that these patients respond particularly favorably to sacral neuromodulation.

Diagnostic Evaluation

History

History forms the cornerstone for evaluation and should address both storage and voiding dysfunction. Patients with storage dysfunction complain of frequency for micturition, nocturia, urgency, and urgency incontinence. Urgency, frequency, and nocturia, with or without incontinence, is called overactive bladder syndrome, urge syndrome, or urgency-frequency syndrome (Abrams et al., 2002). Patients experiencing voiding dysfunction report hesitancy for micturition, a slow and interrupted urinary stream, the need to strain to pass urine, and double voiding. Patients may be in complete urinary retention. The history of voiding dysfunction is often unreliable, and patients may be unaware of incomplete bladder emptying. Therefore, the history should be supplemented by a bladder scan (see later discussion).

Bladder Diary

The bladder diary supplements history taking and records the frequency for micturition, volumes voided, episodes of incontinence, and fluid intake over the course of a few days (Fig. 38.2).

Fig. 38.2 Bladder diary recorded over 24 hours, demonstrating increased daytime and nighttime urinary frequency, low voided volumes, and incontinence. These findings are seen in patients with detrusor overactivity.

(From Panicker, J.N., Kalsi, V., de Seze M., 2010. Approach and evaluation of neurogenic bladder dysfunction, in: Fowler, C.J., Panicker, J.N., Emmanuel, A, (Eds.), Pelvic Organ Dysfunction in Neurological Disease: Clinical Management and Rehabilitation. Cambridge University Press, New York.)

Physical Examination

Findings on clinical examination are critical in deciding whether a patient’s urogenital complaints are neurological in origin. Because the spinal segments that innervate the bladder and genitalia are distal to those that innervate the lower limbs, bladder disturbances generally have been shown to correlate with lower-limb deficits. The possible exceptions are lesions of the conus medullaris and cauda equina, where findings may be confined to saddle anesthesia and absence of sacral cord-mediated reflexes such as the anal reflex or bulbocavernosus reflex. Akinetic rigidity, cerebellar ataxia, and postural hypotension should raise the suspicion of MSA in conditions characterized by early and severe urinary incontinence and ED.

Examination for evidence of peripheral neuropathy is important. Peripheral neuropathy, notably diabetic, is the most common cause for male ED, and as neuropathy progresses, abnormalities and innervation of the detrusor muscle also develop. Clear evidence for peripheral neuropathy is likely before innervation of the bladder is involved.

The neurological examination is complete only after an inspection of the lumbosacral spine. Congenital malformations of the spine can sometimes present with pelvic organ symptoms in adulthood; dimpling, a tuft of hair, or a nevus or sinus in the sacral region may prove to be relevant.

If the neurological examination reveals normal findings in a patient with bladder complaints, detailed investigation with imaging and neurophysiology is unlikely to reveal relevant underlying neurological pathology.

Investigations

Screening for Urinary Tract Infections

It is advisable for patients presenting with bladder symptoms to be screened for UTIs. Combined rapid tests of urine using reagent strips (“dipstick” test) have a negative productive value of 98% for excluding UTI. However, the positive predictive value for confirming infection is only 50% (Fowlis et al., 1994), and hence if abnormal, a urine sample should be sent off to the lab for culture.

Bladder Scan

Because the extent of incomplete bladder emptying cannot be predicted from history or clinical examination, it is pertinent to estimate the postvoid residual urine by ultrasonography. This is most commonly carried out using a portable bladder scanner (Fig. 38.3), or by “in-out” catheterization, especially in patients who perform intermittent self-catheterization. It is recognized that a single measurement of a postvoid residual is often not representative; if possible, a series of measurements should be made over the course of 1 or 2 weeks.

Fig. 38.3 A small portable ultrasound machine can be used to measure postvoid residual urine.

Ultrasound Scan

In patients known to be at risk for upper tract disease, surveillance ultrasonography should be performed periodically to evaluate for evidence of damage such as upper urinary tract dilatation or renal scarring. Ultrasound may also detect complications of neurogenic bladder dysfunction such as bladder stones.

Urodynamic Studies

Urodynamic studies examine the function of the lower urinary tract. Included in this aspect of evaluation are measurements of urine flow rate and residual volume, cystometry during both filling and voiding, videocystometry, and urethral pressure profilometry. The term urodynamics is often used incorrectly as a synonym for cystometry. From the patient’s point of view, urodynamic studies can be divided into noninvasive investigations and those requiring urethral catheterization.

Noninvasive Bladder Investigations

Uroflowmetry is a valuable noninvasive investigation, particularly when combined with an ultrasound measurement of the postvoid residual volume. A commonly used design for a flow meter consists of a commode or urinal into which the patient passes urine as naturally as possible. In the base of the collecting system is a spinning disc, and flow of urine onto this disc tends to slow its speed of rotation, which a servomotor holds constant. The urinary flow is calculated based upon the power necessary to maintain the rotation speed. A graphic printout of the urinary flow is obtained, and time taken to reach maximum flow, maximum and average flow rates, and voided volume are analyzed (Fig. 38.4). It is important that the patient performs the test with a comfortably full bladder containing, if possible, a volume of at least 150 mL; privacy is essential insofar as a spurious result may be obtained if the individual is not fully relaxed.

Fig. 38.4 A, Urinary flow meter. Side of uroflow transducer has been cut away to show disk at base of funnel, which rotates as urine passes into collecting vessel. B, Normal printout from uroflowmeter. A total of 290 mL was voided (upper trace), with a maximum flow rate of 30 mL per second (lower trace).

(Reprinted with permission from Dantec Medical A/S, Copenhagen.)

A significant neurogenic bladder disorder is unlikely if a patient has good bladder capacity, normal urine flow rate, and empties to completion, all of which may be noninvasively demonstrated.

Investigations Requiring Catheterization

Cystometry evaluates the pressure/volume relationship during nonphysiological filling of the bladder and during voiding. The detrusor pressure is derived by subtraction of the abdominal pressure (measured using a catheter in the rectum) from the intravesical pressure (measured using a catheter in the bladder). The rate of filling is recorded by the machine, which pumps sterile water or saline through the catheter in the bladder. For speed and convenience, most laboratories use filling rates of between 50 and 100 mL/min. This nonphysiological rapid filling does mean that the full bladder capacity can be reached usually within 7 or 8 minutes. The first sensation of bladder filling may be reported at around 100 mL, and full capacity is reached between 400 and 600 mL. In healthy persons, the bladder expands to contain this amount of fluid without an increase of pressure more than 15 cm H₂O. A bladder that behaves in this way is said to be “stable.” The main abnormality sought during filling cystometry in patients with a neurological disease is the presence of detrusor overactivity (Fig. 38.5). This is a urodynamic observation characterized by involuntary detrusor contractions that may be spontaneous or provoked. It should be emphasized that on urodynamics, detrusor overactivity of neurogenic origin is indistinguishable from other causes for detrusor overactivity. When bladder filling has been completed, the patient voids into the flow meter, with the bladder and rectal lines still in place. Valuable information can be obtained by measuring detrusor pressure and urine flow simultaneously.

Fig. 38.5 Filling cystometry demonstrating detrusor overactivity. Red trace (Pabd) is the intraabdominal pressure recorded by the rectal catheter, dark blue trace (Pves) is the intravesical pressure recorded by the bladder catheter. Pink trace (Pdet) is the subtracted detrusor pressure (Pves-Pabd). Green traces represent volume infused (Vinf) during the test and volume voided (Vura); orange trace represents urinary flow (Qura). Black arrow demonstrates detrusor overactivity, and black arrowhead indicates associated incontinence.

(From Panicker, J.N., Fowler, C.J., 2010. The bare essentials: uro-neurology. Pract. Neurol. 10, 178-185.)

When cystometry is carried out using a contrast filling medium and the procedure visualized radiographically, the technique is known as videocystometry. This gives additional information about morphological changes that may occur consequent to neurogenic bladder dysfunction and the presence of vesicoureteric reflux. Urologists and urogynecologists have found videocystometry useful for detecting sphincter or bladder neck incompetence in genuine stress incontinence, and the opportunity to inspect the outflow tract during voiding is of great value in patients with suspected obstruction.

A general criticism of cystometric studies is that valuable as they may be in demonstrating the underlying pathophysiology of a patient’s urinary tract, the findings contribute little to elucidating the underlying cause of the disorder. A “urodynamic diagnosis” is therefore a meaningless term. The study provides information about the safety and efficiency of bladder filling and emptying. It is valuable for assessing risk factors for upper urinary tract damage and planning management. In addition, it is helpful in identifying concomitant urological conditions such as bladder outflow obstruction or stress incontinence.

Whether it is necessary to perform a complete urodynamic study in all patients with a suspected neurogenic bladder is a subject of debate. Patients with spinal cord injury, spina bifida, and possibly advanced MS should undergo urodynamic studies because of the higher risk for upper tract involvement and renal impairment, although ultrasound is a less invasive method for monitoring. Guidelines underlying the key role of urodynamics for baseline evaluation, management, and follow-up of a neurogenic bladder in these patient groups have been published. However, in other conditions such as early MS, stroke, and PD, some authors have recommended restricting the initial evaluation to noninvasive tests, on the basis that the risk for upper urinary tract damage is less (Fowler et al., 2009). In the absence of evidence-based medical data comparing these two models of management, the decision for performing complete baseline urodynamics would depend upon local resources and recommendations.

Urethral pressure profile is measured using a catheter-mounted transducer that is run slowly through the urethra by a motorized armature. The test can be performed in men or women and is called static if no additional maneuvers such as coughing or straining are performed. It has been found to be helpful in the assessment of women with obstructed voiding or urinary retention, some of whom have abnormally high urethral pressures.

Uroneurophysiology

Various neurophysiological investigations of the pelvic floor have been developed for assessing the innervation of muscles that are difficult to test clinically. These tests have been used by neurologists, urologists, andrologists, urogynecologists, and colorectal surgeons.

Electromyography

Pelvic floor electromyography (EMG) was first introduced as part of urodynamic studies to assess the extent of relaxation of the urethral sphincter during voiding, with the aim of recognizing detrusor-sphincter dyssynergia. However, it is now rarely recorded for several reasons. First, it is often technically difficult to obtain a good-quality EMG signal from a site as inaccessible as the urethral sphincter, particularly in the hostile recording environment in which urodynamic studies are performed. The best signal is obtained using a needle electrode, but the discomfort from the needle itself is likely to impair normal relaxation of the pelvic floor. Surface recording electrodes have been used, but they may record a considerable amount of noise, which makes interpretation of the results difficult. In addition to the difficulties of making a meaningful recording, the value of the information the procedure provides is limited. Video screening allows the outlet tract to be seen, and hence the indications for kinesiological sphincter EMG recording is now limited. One situation in which it is helpful is evaluating men with suspected dysfunctional voiding. These are usually young men who present with voiding difficulties and have otherwise normal neurological findings on examination and investigation. Recording electrical silence from the urethral sphincter during voiding would exonerate the external sphincter as the cause for voiding dysfunction.

Concentric needle EMG studies of the pelvic floor performed separately from urodynamics have been useful to assess innervation in certain scenarios. EMG has been used to demonstrate changes of reinnervation in the urethral or anal sphincter in a few neurogenic disorders. The motor units of the pelvic floor and sphincters fire tonically, so they may be conveniently captured using a trigger and delay line and subjected to individual motor unit analysis. Well-established values exist for the normal duration and amplitude of motor units recorded from the sphincter muscles.

Sphincter Electromyography in the Evaluation of Suspected Cauda Equina Lesions

Lesions of the cauda equina are an important cause for pelvic floor dysfunction. Most often, EMG of the external anal sphincter demonstrating changes of chronic reinnervation with a reduced interference pattern and enlarged polyphasic motor units (>1 mV amplitude) can be found in patients with long-standing cauda equina syndrome (Podnar et al., 2006). Though EMG may demonstrate pathological spontaneous activity 3 weeks or more after injury, these changes of moderate to severe partial denervation or complete denervation often become lost in the tonically firing motor units of the sphincter.

Sphincter Electromyography in the Diagnosis of Multiple System Atrophy

Neuropathological studies have shown that anterior horn cells in the Onuf nucleus are selectively lost in MSA, and this results in changes in the sphincter muscles that can be identified by EMG. The anal sphincter is once again most often studied, and compared to the changes of chronic reinnervation in patients with cauda equina syndrome described earlier, the changes of reinnervation in MSA tend to result in prolonged-duration motor units, presumably because the progressive nature of that disease precludes motor unit “compaction.” These changes can be detected easily, but it is important to include measurement of the late components of the potentials (Fig. 38.6).

Fig. 38.6 Concentric needle electromyography (EMG) of external anal sphincter from a 64-year-old male presenting with parkinsonism and urinary retention. Duration of the motor unit is 17.9 msec (normal < 10 msec); prolonged motor units suggest chronic reinnervation. Mean duration of motor unit potentials (MUPs) during study was 22.9 msec; EMG is compatible with a diagnosis of multiple system atrophy.

Although the value of sphincter EMG in the differential diagnosis of parkinsonism has been widely debated, a body of opinion exists that maintains that a highly abnormal result in a patient with mild parkinsonism is of value in establishing a diagnosis of probable MSA (Vodusek, 2001). This correlation is important not only for the neurologist but also for the urologist because inappropriate surgery for a suspected prostate enlargement as the cause for bladder troubles can then be avoided.

Sphincter Electromyography in the Investigation of Urinary Retention in Young Women

Isolated urinary retention in young woman has long been an enigma; the neurological examination is typically normal, and investigations such as MRI exclude a neurological cause for voiding dysfunction. A characteristic abnormality, however, can be found on urethral sphincter EMG: complex repetitive discharges akin to the “sound of helicopters” and decelerating bursts, a signal somewhat like myotonia and akin to the “sound of underwater recording of whales.” It has been proposed that this abnormal spontaneous activity results in impairment of relaxation of the urethral sphincter, which may cause urinary retention in some women and obstructed voiding in others. This condition, nowadays known as Fowler syndrome, is also characterized by elevated urethral pressures.

Penilocavernosus Reflex

The nomenclature of the various reflex responses that can be recorded from pelvic structures in response to electrical stimulation was recently revised so that the term used gives an indication of the site of stimulation and recording. The penilocavernosus reflex, formally known as the bulbocavernosus reflex, assesses the sacral root afferent and efferent pathways. The dorsal nerve of the penis (or clitoris) is electrically stimulated, and recordings are made from the bulbocavernosus muscle, usually with a concentric needle. It may be of value in patients with bladder dysfunction suspected to be secondary to cauda equina damage or damage to the lower motor neuron pathway. However, a normal value does not exclude the possibility of an axonal lesion.

Pudendal Nerve Terminal Motor Latency

The only test of motor conduction for the pelvic floor is the pudendal nerve terminal motor latency (PNTML). The pudendal nerve is stimulated either rectally or vaginally adjacent to the ischial spine using the St. Mark electrode, a finger-mounted device with a stimulating electrode at the fingertip and a surface EMG receiving electrode 7 cm proximal, around the base of the finger. This records from the external anal sphincter. Prolongation was initially considered evidence for pudendal nerve damage, although a prolonged latency is a poor marker of denervation. This test has not proved contributory in the investigation of patients with suspected pudendal neuralgia.

Pudendal Somatosensory Evoked Potentials

Pudendal somatosensory evoked potentials can be recorded from the scalp following electrical stimulation of the dorsal nerve of penis or clitoral nerve. Although this may be abnormal when a spinal cord lesion is the cause of sacral sensory loss or neurogenic detrusor overactivity, such pathology is usually apparent from the clinical examination. Results are compared to latencies of the tibial evoked potentials.

Complications Arising from Neurogenic Bladder Dysfunction

Detrusor overactivity and reduced bladder-wall compliance may result in raised intravesical pressure, which can in turn lead to structural changes in the bladder wall such as trabeculations and diverticuli. The upper urinary tract (kidney and ureter) can also show changes such as vesicoureteric reflux and hydronephrosis, renal impairment, and even end-stage renal disease. For reasons that are unclear, upper urinary tract damage and renal failure are surprisingly unusual in MS. On the other hand, patients with SCI and spina bifida have an increased risk for upper urinary tract damage and renal disease. The risk for upper urinary tract damage is highest in patients who have raised intravesical pressure due to detrusor overactivity, low bladder compliance, and a competent bladder neck. Patients with a neurogenic bladder are also prone to a variety of genitourinary tract infections such as cystitis, pyelonephritis, and epididymo-orchitis, and also to bladder stones.

Management of Neurogenic Bladder Dysfunction

The pattern of lower urinary tract symptoms and findings from relevant bedside investigations such as uroflowmetry and bladder scan are useful in the localization of neurological lesions (see Table 38.1). Variations from these expected patterns of symptoms and findings should warrant a search for additional urological conditions that may be occurring concomitantly and alter the pattern of lower tract dysfunction.

The goals one would wish to achieve when managing neurogenic bladder dysfunction are urinary continence, preventing UTIs, and preserving upper urinary tract function (Stohrer et al., 2009). Attaining these goals would help improve quality of life of patients with neurological disease. The management of neurogenic bladder dysfunction must address both voiding and storage dysfunction.

General Measures

Nonpharmacological measures are generally effective in the early stages when symptoms are mild. A fluid intake of around 1 to 2 L a day is suggested, although this should be individualized; it is often helpful to assess fluid balance by means of a bladder diary (Hashim and Abrams, 2008). Caffeine reduction may reduce urgency and frequency, especially for patients who drink coffee or tea in excess. Bladder retraining, whereby patients void by the clock and voluntarily “hold on” for increasingly longer periods, aims to restore the normal pattern of micturition. If voiding dysfunction has been excluded, pelvic floor exercises and neuromuscular stimulation may play a role in ameliorating overactive bladder symptoms.

Voiding Dysfunction

Knowledge of a patient’s postvoid residual volume is critical in planning treatment of bladder symptoms. There is no consensus regarding the figure of residual volume at which intermittent self-catheterization should be initiated. However, in general, because patients with a neurogenic bladder have reduced bladder capacity, a volume of more than 100 mL or more than one-third of bladder capacity is taken as the amount of residual urine that contributes to bladder dysfunction (Fowler et al., 2009). The widespread use of intermittent self-catheterization has greatly improved management of neurogenic bladder dysfunction. Incomplete emptying can exacerbate detrusor overactivity, and an overactive bladder constantly stimulated by a residual volume responds by contracting and producing symptoms of urgency and frequency, thus making antimuscarinic medications less effective. Sterile intermittent catheterization was first introduced in the 1960s, but subsequently a clean rather than sterile technique was found to be adequate. Intermittent catheterization is best performed by patients themselves, who should be taught by someone experienced with this method, such as nurse continence advisors. Neurological lesions affecting manual dexterity, weakness, tremor, rigidity, spasticity, impaired visual acuity, and cognitive impairment may make it impossible for the patient to self-catheterize, in which case it may be performed by the partner or care assistant. The incidence of symptomatic UTIs is low when performed regularly.

Reflex voiding using trigger techniques and the Credé maneuver (nonforceful, smooth, even pressure applied from the umbilicus toward the pubis) are usually not recommended, as they may result in high detrusor pressure and incomplete bladder emptying during voiding (Fowler et al., 2009). Suprapubic vibration using a mechanical “buzzer” has been demonstrated to be effective in patients with MS with incomplete bladder emptying and detrusor overactivity, but its effect is limited (Prasad et al., 2003). Alpha-blockers relax the internal urethral sphincter in men, and there is evidence that they improve bladder emptying and reduce postvoid residual volumes (O’Riordan et al., 1995). However, this is not consistently seen in clinical practice unless there is concomitant bladder outlet obstruction. Botulinum toxin injections into the external urethral sphincter may improve bladder emptying in patients with SCI who have significant voiding dysfunction (Naumann et al., 2008).

Storage Dysfunction

Antimuscarinic Medications

Detrusor overactivity is a major cause for incontinence in patients with neurogenic bladder disorders. The sensation of urgency is experienced as the detrusor muscle begins to contract, and if the pressure continues to rise, the patient senses impending micturition. Antimuscarinic medications are the mainstay of treatment for detrusor overactivity. Table 38.2 lists the medications available in the United Kingdom. Oxybutynin was one of the earlier drugs introduced, and subsequently several newer agents have been marketed. Meta-analyses suggest that efficacy is similar between these medications. Adverse events arise owing to their nonspecific anticholinergic action and include dry mouth, blurred vision for near objects, tachycardia, and constipation. These drugs can also block central muscarinic M1 receptors and cause impairment of cognition and consciousness in susceptible individuals. This may be mitigated by medications that have low selectivity for the M1 receptor, such as darifenacin, or restricted permeability across the blood-brain barrier (BBB), such as trospium. The postvoid residual urine may increase following treatment, and it should be monitored by repeat bladder scans, especially if initial beneficial effects are short lasting. In many patients, there may also be underlying voiding dysfunction, and the judicious use of antimuscarinic medication coupled with clean intermittent self-catheterization (CISC) often proves most effective for managing neurogenic bladder dysfunction (Fowler et al., 2009) (Fig. 38.7).

Table 38.2 Antimuscarinic Medications Available in the United Kingdom

Fig. 38.7 Algorithm for the management of neurogenic lower urinary tract dysfunction.

(From Fowler, C.J., Panicker, J.N., Drake, M., et al., 2009. A UK consensus on the management of the bladder in multiple sclerosis. J Neurol Neurosurg Psychiatry 80, 470-477.)

Desmopressin

Desmopressin, a synthetic analog of arginine vasopressin, temporarily reduces urine production and volume-determined detrusor overactivity by promoting water reabsorption at the distal and collecting tubules of the kidney. It is useful for treating urinary frequency or nocturia in patients with MS, providing symptom relief for up to 6 hours (Bosma et al., 2005). It is also helpful in managing nocturnal polyuria, characterized by increased production of urine in the night. This may be seen in patients with PD and also various neurological conditions associated with dysautonomia and orthostatic hypotension. However, it should be prescribed with caution in patients over the age of 65 or with dependent leg edema, and it should not be used more than once in 24 hours for fear of hyponatremia or congestive heart failure.

Cannabinoids

Positive anecdotal reports on the effect of cannabis in controlling bladder symptoms in MS patients and identification of the cannabinoid receptor in animal and human studies led to studies of cannabis-based medicinal extracts in this group. An open-label study in patients with advanced MS produced promising results, with diminished frequency, nocturia, and incontinence (Freeman et al., 2006). A license was recently granted in the United Kingdom for the use of a cannabis-based medicine to treat spasticity in MS, but this does not cover bladder dysfunction.

Botulinum Toxin

Botulinum toxin type A injected into the detrusor muscle under cystoscopic guidance appears to be a highly promising, although at the time of writing an unlicensed treatment, for intractable detrusor overactivity. The effect lasts 9 to 13 months and significantly improves storage symptoms and quality of life (Kalsi et al., 2007), though patients often have to perform CISC afterwards. Studies also suggest that patients receiving botulinum toxin injections have fewer UTIs and reduced catheter bypassing (urethral leakage when using an indwelling catheter). Botulinum toxin was introduced on the theoretical basis that it blocks synaptic release of acetylcholine from the parasympathetic nerve endings and produces a paralysis of detrusor muscle (and indeed a demonstrable increase in bladder capacity has been reported in the various studies). However, accumulating evidence indicates that the mechanism of action is more complex and may actually involve the afferent innervation as well.

Vanilloids

Despite initial enthusiasm for their use, intravesical vanilloid therapy, capsaicin, and resiniferatoxin generally have been superseded by botulinum toxin therapy. Because only a few centers worldwide offer resiniferatoxin treatment, this treatment is not discussed further here.

Sacral Neuromodulation

An extradural sacral nerve stimulator can be highly effective in lessening detrusor overactivity that is resistant to antimuscarinic medication. It seems highly likely that the mechanism of action of this device is associated with stimulation in the presacral region of the pelvic afferents, which are known to have an inhibitory effect on the detrusor. Implanting the stimulator is a two-stage procedure, the first being a test phase with a stimulating lead inserted through the S3 foramen and connected to an external stimulator. During this test phase, it is noted whether the patient’s symptoms diminish significantly, as judged by bladder diaries and measurement of residual volumes; if so, the patient is eligible for a permanent stimulator. This is implanted in a subcutaneous pocket and connected to the stimulating lead. The stimulator is continuously active, although its efficacy can be maintained at a subsensory level so that patients are not aware of its chronic action. The permanent stimulators are expensive, and patient selection is crucial in order to minimize the need for revision procedures. Evidence suggests that there is only a limited role for sacral neuromodulation in patients with progressive neurological conditions such as MS.

Nerve Root Stimulators

In patients who have suffered a complete spinal cord transection but in whom the caudal section of the cord and its roots are intact, implantation of a nerve root stimulator should be considered. This device was pioneered by Professor Giles Brindley and his collaborators, and several thousand have now been implanted worldwide. Stimulating electrodes are placed around the lower sacral roots (S2 to S4) and activated by an external switching device. The stimulating electrodes are usually applied intrathecally to the anterior roots, and the posterior roots are cut at the same time. After the implant, adjustments are made to the stimulation parameters so that the patient obtains maximum benefit in terms of making the bladder contract for voiding, assisting defecation, or even producing a penile erection. Although such devices are highly effective in selected cases, the additional neurological deficit caused by the need for sectioning of the dorsal roots and consequent loss of reflex erections has reduced its acceptance. The stimulators are suitable only for patients with complete spinal cord lesions, rather than partial cord lesions or progressive neurological disease.

Surgery

Various urological surgeries can be carried out to treat incontinence and are summarized in Table 38.3. A surgical procedure to rectify a disorder causing incontinence in an otherwise fit and healthy person often is highly successful. Even after SCI, a surgical option might be the best solution for long-term bladder management. This, however, does not apply to patients with progressive neurological disease causing incontinence. For example, at a time when the bladder is becoming unmanageable by intermittent catheterization and an antimuscarinic medication, the patient with MS may only just be managing to remain independent. This is not the moment to suggest major urological surgery, and in practice few patients with progressive neurological disease affecting bladder control opt for surgery. With the advent of botulinum toxin for the bladder, some of these debilitating symptoms can now be better controlled.

Table 38.3 Urological Procedures That May Be Performed to Treat Various Causes for Incontinence

Stress incontinence: pelvic floor weakness

Bladder neck suspension

TVT

TOT

Stress incontinence: sphincter incompetence

Artificial sphincter

Urgency incontinence (detrusor overactivity)

Botulinum toxin

Sacral neuromodulation

Augmentation cystoplasty

?Myomectomy

Intractable incontinence

Urinary diversion with stoma

TOT, Transobturator tape; TVT, tension-free vaginal tape.

Permanent Indwelling Catheters

There comes a point when the patient is no longer able to perform self-catheterization, or when incontinence is refractory to management. It is at this stage that an indwelling catheter becomes necessary. The most immediate solution is an indwelling Foley catheter held in place by an inflatable balloon in the bladder, proximal to the catheter opening. The long-term ill effects of these devices are well known. One of the major problems may be catheter bypassing, which occurs when strong detrusor contractions produce a rapid urine flow that cannot drain sufficiently quickly. A common response to this would be to use a wider-caliber catheter, with the adverse effect that the bladder closure mechanism becomes progressively stretched and destroyed. The detrusor contraction may be of sufficient intensity to extrude the 10- or 20-mL balloon from the bladder, causing further damage to the bladder neck and resulting in a totally incompetent outlet. Bladder stones and recurrent infections are also more likely in patients with an indwelling catheter.

A preferred alternative to an indwelling urethral catheter is a suprapubic catheter. This can be inserted by a urologist, but extreme care is required because these patients often have small, contracted bladders, contributing to the risk of bowel perforation during catheter placement. Although by no means a perfect system, a suprapubic catheter is a better long-term alternative to a urethral catheter, since it preserves urethral integrity and helps promote perineal hygiene and sexual functions.

The option of intermittent bladder drainage using a catheter valve, as opposed to continuous drainage into a leg bag, depends upon whether the bladder has a reasonable capacity to store urine.

External Devices

If incontinence is the major problem and the bladder empties completely, some men are able to wear an external device such as a penile sheath.

Stepwise Approach to Neurogenic Bladder Dysfunction

The treatment options offered to a patient should reflect the severity of bladder dysfunction, which generally parallels the extent of neurological disease (Fig. 38.8). However, beyond a certain point, incontinence may become refractory to all treatment options, and it is at this stage that a long-term indwelling catheter should be offered. Although most patients can be managed along these lines, there are specific situations where specialist urology services should be involved earlier on in the disease course (Box 38.1).

Fig. 38.8 Stepwise approach to neurogenic bladder dysfunction and its relation with progression of disabilities (see text for details). BoNT/A, Botulinum toxin A; CISC, clean intermittent self-catheterization; DDAVP, desmopressin; IDC, indwelling catheter.

Box 38.1 Red Flags That Would Suggest Early Referral to a Specialist Urology Service

Hematuria

Renal impairment

Frequent UTIs

Suspicion of concomitant urological pathologies such as bladder outlet obstruction due to prostate enlargement in men or stress incontinence in women

Symptoms refractory to treatment

Consideration of suprapubic catheterization

Consideration of urological procedures such as intradetrusor injections of botulinum toxin A or surgeries such as augmentation cystoplasty or urinary diversion

UTI, Urinary tract infection.

Urinary Tract Infections

The presence of asymptomatic bacteria alone in a patient performing intermittent self-catheterization should not be an indication for antibiotics (Fowler et al., 2009). The usual indication would be presence of associated symptoms (local or systemic) and certainly if involvement of the upper urinary tract (pyelonephritis) occurs. In an individual with recurrent UTIs (more than 2 in 6 months or more than 3 in a year), the catheterization technique should be reviewed and if optimal, it is worthwhile to exclude a urological cause such as a bladder stone. In individuals with proven recurrent UTIs and when no urological structural abnormality has been identified, it is reasonable to start prophylactic low-dose antibiotics for a finite duration. Rotation of antibiotics is one approach to minimize antibiotic resistance developing. It is also important to distinguish relapsing from remitting infections and ensure that undertreatment of a causative organism is not the underlying cause of the symptoms. There is debate about the pros/cons of introducing CISC as a preventive measure against UTIs, as well as the threshold above which CISC should be recommended (e.g., a residual of 150 mL). The input of a specialist nurse in lower urinary tract dysfunction who teaches CISC is particularly helpful here.

The value of cranberry juice in preventing UTIs in neurogenic patients is debatable.

Management of Neurogenic Sexual Dysfunction

The first step in approaching sexual dysfunction of neurogenic origin is providing an opportunity for patients and their partners to openly discuss their sexual dysfunction. The topic can often be broached during the consultation while discussing concomitant bladder or bowel troubles. An explanation of the neurological basis for sexual dysfunction often relieves anxiety about the problem and removes assumptions that the problem is essentially psychological in origin.

Sexual dysfunction in neurological disease can be due to several different causes (Foley and Werner, 2000) (Box 38.2). Primary sexual dysfunction results from the actual neurological lesions directly affecting the neural pathways for sexual functions. For example, lesions in the spinal cord may cause loss of tactile sensations from the genitalia. Physical disabilities such as spasticity or pain resulting from the neurological disease can interfere with sexual functions as well. This is known as secondary sexual dysfunction. Sexual dysfunction arising from the psychological, emotional, or cultural impact of living with a neurological disease is known as tertiary sexual dysfunction. A holistic approach to managing sexual dysfunction involves identifying all these contributory factors.