Neurogenic Voiding Dysfunctions (NVD)

Transcription

1 Curriculum in Urology Neurogenic Voiding Dysfunctions (NVD)... U. Jonas a,*, D. Castro-Diaz b, B.L.H. Bemelmans c, H. Madersbacher d, A.A.B. Lycklama à Nijeholt e a Department of Urology, Medizinizche Hochschule Hannover, Carl Neubergstrasse 1, D Hannover, Germany b Department of Urology, University Hospital of the Canary Islands, Tenerife, Spain c Department of Urology, University Medical Centre, Nijmegen, The Netherlands d Department of Neurology, Neuro-Urology Unit, University Hospital, Innsbruck, Austria e Leiden University Medical Centre, Leiden, The Netherlands Abstract Neurogenic lower urinary tract dysfunction continues to represent a diagnostic and therapeutic challenge. Many different conditions affecting the vesicourethral system have their origins in the nervous system, and it is important to recognise that lower urinary tract symptoms (LUTS) may sometimes be one of the first signs of neurological disorders such as multiple sclerosis (MS). A sound urodynamic investigation forms the basis for both the diagnosis and the therapy of neurogenic voiding dysfunction, the treatment of which is usually symptomatic. Pathophysiology and Classification Any lesion between the central nervous system (CNS) and the bladder can produce symptoms of a neurogenic voiding * Corresponding author. address: jonas.udo@mh-hannover.de (U. Jonas). dysfunction (NVD), with the type and location of the lesion determining the nature of those symptoms. Vesicourethral dysfunction is a common feature of many local and systemic neurological conditions. Numerous classification systems have been devised to aid the understanding and management of NVD, and may be based upon: neurological cause (i.e. the type and location of the lesion), neuro-urological manifestations of the lesion, functional disorders of the micturition cycle (Fig. 1). Neuro-urologic classifications The classic neuro-urologic classification was developed by Bors and Comarr in 1971 [1]. It is based on the clinical effects of traumatic spinal cord injury with respect to the site and completeness of the lesion (sensory neuron, motor neuron, lower motor neuron or mixed lesion), and whether lower urinary tract (LUT) function is balanced or unbalanced as defined by the *I /$ see front matter # 2003 Published by Elsevier Science B.V. doi: /s (02)

2 Fig. 1. The neurological, neuro-urological and functional bases for classification of neurogenic voiding dysfunction. post-void residual urine volume expressed as a percentage of total bladder capacity (residual urine >20% of total bladder capacity is a sign of an unbalanced bladder). This system identifies two basic categories of NVD: upper motor neuron bladder is characterised by detrusor hyperreflexia with skeletal muscle spasticity, which may be accompanied by uncoordinated activity of the detrusor and sphincter, lower motor neuron bladder exhibits detrusor areflexia with skeletal muscle flaccidity. One of the limitations of the Bors and Comarr classification is the large number of categories it identifies, and the Hald and Bradley classification [2] was devised in an attempt to simplify the situation. This is essentially a neurotopographic classification, allowing lesions at five different levels to be linked to particular patterns of LUTS (Table 1). However, this system also relies upon residual urine volume to determine the severity of bladder dysfunction, which most authors agree is an unreliable urodynamic measure for bladder outlet obstruction and NVD. The Bradley neurologic classification [3] identifies four conceptual loops for control of the LUT by the CNS, with dysfunctions classified by the loop affected. Thus, Loop I, which connects the cerebral cortex and pontine micturition centres (Fig. 2), may be implicated in cerebro-vascular accidents, Parkinson s disease and brain tumours, the lesion resulting in detrusor hyperreflexia. Loop II is formed by detrusor afferents in the spinal cord innervating the micturition centre as well as efferents to the sacral spinal cord (Fig. 3). It is typically compromised in spinal cord trauma, myelitis and multiple sclerosis, resulting in low threshold detrusor reflex, poor emptying, areflexia, and urinary retention. Loop III represents the spinal pathway from the detrusor and striated sphincter sensory afferents to the pudendal nuclei in the sacral spinal cord (Fig. 4), and lesions Table 1. The Hald and Bradley classification for neurogenic voiding dysfunction [2] *II Lesion type Supraspinal lesion Suprasacral spinal lesion Intrasacral spinal lesion Peripheral autonomic lesion (typically diabetic neuropathy) Muscular lesion (of the detrusor or sphincter) Nature of symptoms Detrusor hyperreflexia with synergy between detrusor contraction and smooth and striated sphincter; defective inhibition of voiding reflex Detrusor hyperreflexia with or without sphincter dyssynergia Autonomic bladder Deficient bladder sensation, gradually increasing residual urine and decompensation, ultimately leading to loss of detrusor contractibility Jonas/Castro-Diaz/Bemelmans/Madersbacher/Lycklama à Nijeholt

3 Fig. 2. Loop I of the Bradley classification for neurogenic voiding dysfunction. Fig. 3. Loop II of the Bradley classification for neurogenic voiding dysfunction. Fig. 4. Loop III of the Bradley classification for neurogenic voiding dysfunction. *III Neurogenic Voiding Dysfunctions (NVD)

4 Fig. 5. Loop IV of the Bradley classification for neurogenic voiding dysfunction. may produce detrusor sphincter dyssynergia (DSD) or involuntary sphincter relaxation. Finally, Loop IV consists of suprascral and segmental innervation of the periurethral striated muscles and provides volitional control of the striated sphincter (Fig. 5). Although this may be a useful way of conceptualising the neurophysiology underlying the different manifestations of NVD, the system is generally difficult to use in routine clinical practice. Urodynamic classifications Classifications based on urodynamic findings can increase the accuracy of neuro-urologic classifications. The Lapides classification [4] is familiar to urologists and non-urologists alike, and combines the clinical and cystometric findings (capacity, proprioception, contractility, heat and cold sensation and residual urine) associated with many types of NVD. It describes five different categories of dysfunction, based upon urodynamic evaluation and functional description of the associated neurologic lesion (Table 2). The Krane and Siroky classification [5] is based around detrusor hyperreflexia or areflexia, and within these two conditions it assesses the functional interaction of the distal and internal sphincters. Functional classifications The phases of the micturition cycle are a central concept in understanding voiding dysfunction, and functional classifications according to the storage and emptying functions of the LUT provide a practical Table 2. The Lapides classification for neurogenic voiding dysfunction [4] Category Nature of lesion Urodynamic findings Sensory neurogenic bladder Motor paralytic bladder Interruption of sensory afferents Impaired bladder sensation; decompensation with significant residual urine Destruction of parasympathetic motor innervation Early cystometric filling normal, but bladder contraction absent; large residual urine due to chronic overdistension and decompensation Autonomous neurogenic bladder Complete sensory and motor separation of bladder from sacral spinal cord No voluntary initiation of micturition; no reflex bladder activity; no specific sensation; diminished compliance is common Uninhibited neurogenic bladder Injury/disease in the corticoregulatory tract, leading to loss of inhibition of the sacral micturition reflex centre Voluntary bladder contraction possible; sensation intact; residual urine generally small *IV Reflex neurogenic bladder Complete interruption of pathways between brainstem and sacral micturition centre No bladder sensation; inability to initiate voluntary micturition; hyperreflexic involuntary bladder contractions and detrusor-sphincter dyssynergia present Jonas/Castro-Diaz/Bemelmans/Madersbacher/Lycklama à Nijeholt

5 approach to diagnosis and therapy. For example, the Wein classification [6] is based upon determining whether failures of storage and of emptying are attributable to dysfunction of either the bladder or the sphincter. The International Continence Society (ICS) has provided the best classification using this approach, taking into account detrusor activity, bladder sensation, capacity and compliance together with urethral function during the storage phase, and detrusor and urethral function in the voiding phase (Table 3) [7]. The functional classifications allow for four basic scenarios which may be used to guide treatment decisions. Good bladder (compliant), good sphincter the majority of patients can be managed with chronic intermittent catheterisation and anticholinergics for detrusor hyperreflexia. Good bladder (compliant), bad sphincter treatment will be aimed at increasing outlet resistance. Bad bladder (low compliance), good sphincter (innervated, but failing to relax properly) leads to a risk of upper urinary tract complications. The bladder Table 3. The International Continence Society classification system for vesicourethral activity [7] Storage phase Bladder function Detrusor activity Normal or stable Overactive Unstable Hyperreflexic Bladder sensation Normal Increased or hypersensitive Reduced or hyposensitive Absent Bladder capacity Normal High Low Compliance Normal High Low Urethral function Normal Incompetent Voiding phase Neurogenic Voiding Dysfunctions (NVD) Bladder function Detrusor activity Normal Underactive Acontractile Urethral function Normal Obstructive Overactive Mechanical should be treated alone unless total incontinence is contemplated through a sphincterotomy. Bad bladder (poor compliance), bad sphincter; treatment of both elements will be required to make the patient continent. An individual approach should be adopted for each patient, depending on the neurological evaluation and categorisation, and bearing in mind that no classification is perfect. The goals of treatment are to preserve renal function, to improve continence and thereby improve the patient s quality of life. Diagnosis Any dysfunction of the LUT that can be ascribed to a known neurological disease constitutes an NVD, and LUTS associated with traumatic spinal cord lesions, multiple sclerosis, meningomyelocele, Parkinson s disease and diabetes mellitus are commonly encountered. In the last 20 years, diagnosis and treatment has improved markedly, to the extent that NVD is no longer considered fatal. Consequently, accurate diagnosis is central to the success of therapeutic decisions, and also determines the level of follow-up, as these patients require ongoing care for the rest of their lives. The diagnosis can also help to determine the prognosis for the patient and identifying co-existing urological problems of a non-neurologic nature. Urodynamics are the cornerstone of the diagnostic work-up, but a good history and thorough physical examination are also essential. Although the patient s perception of bladder function will necessarily be unreliable, much background information will be gained from taking a detailed history. Initially it is important to reach an agreement with the patient that a problem actually exists, since many potentially severe conditions such as urinary retention and chronic LUT infection may be silent, especially in paraplegics. Without acceptance of the diagnosis, patients are poorly motivated for treatment, especially when this represents significant additional disruption to *V

6 *VI their lifestyle. For example, the patients main concerns are often focussed on the practical aspects of treatment rather than the necessity of regular self-catheterisation. However, information provided by specialist nurses can help them make the necessary adjustments to their daily routine. Patient history The onset of disease and timescale of symptoms may give clues to the cause of urinary problems. In some cases, LUT symptoms occur early in the course of disease, whereas they may develop later in others, and could be confused with dysfunctions of a non-neurogenic origin, such as benign prostatic hyperplasia (BPH). The extent to which symptoms bother the patient is important, and should be determined both subjectively and objectively, through the use of a voiding diary. This enables the urologist to match therapy with patient motivation, and also to monitor the success of treatment. The exact neurological diagnosis, provided by the neurologist s notes, is a central aspect of the history. The extent of the lesion, and whether it is at the sensory, motor or autonomic level is important. However, this may not always be clearcut. For example, MS is not well defined, and the course of disease can vary between benign, progressive or relapsing-remitting. The physical status of the patient will have an important bearing on his capabilities for maintaining a therapeutic strategy and should be included in the neurology or rehabilitation records. Any history of abdominal surgery may have an influence on the diagnosis and also on future treatment decisions. For example, hysterectomy or colorectal surgery may be directly related to bladder dysfunction due to prolapse or peripheral neuropathies. Similarly, the obstetric history could also be relevant, and genuine stress-incontinence may be overlooked in a patient with complicated neurological disease. Penetrating injuries causing spinal cord lesions may also have resulted in the removal of sections of intestine, which may limit the options for reconstructive surgery. The social and economic situation of the patient is also important, as the burden of care generally falls to their partner or other relatives. Although the cost of medical care should be borne by health care systems and insurance, considerable expense is also incurred by patients with neurologic conditions in relation to all aspects of daily life. Such considerations will affect the decision on whether a patient is cared for at home or in a nursing home. Attention should be paid to any medications taken by the patient, as several drugs can have detrimental effects on the urinary tract. For example, diuretics prescribed for hypertension are associated with overstretching of the bladder. Furthermore, the use of any antihypertensive agent in younger patients should alert the urologist to the likelihood kidney dysfunction due to obstructive uropathy. Drugs that can alter the functioning of the urinary tract include opiate-containing painkillers which reduce bowel motility and antiparkinsonian agents which act as parasympatholytics and so impair detrusor contractility. Muscle relaxants used to treat spasticity may also cause bladder hypocontractility and urinary retention; alternatively, they can induce pelvic floor laxity leading to stress incontinence. Physical examination Assuming that a complete neurological diagnosis has already been made, the urologist can restrict the examination to those aspects that are relevant to the urological diagnosis and its management. Nevertheless, a thorough physical examination can provide a wealth of information about the patient s overall status. The examination should include assessment of gait and mobility, as well as habitus (obesity is common in wheelchair-bound patients and has profound implications for surgery) and hand function, as this is essential to the patient s ability to self-catheterise. Examination of the skin for lesions such as pressure sores and assessment of the patient s personal hygiene provides information about the potential for infection. Skeletal deformations are common in meningomyelocele and may seriously complicate Jonas/Castro-Diaz/Bemelmans/Madersbacher/Lycklama à Nijeholt

7 surgery. The abdomen should be examined for presence of scars from previous surgery, and the position of the umbilicus should be noted, as these factors will influence stoma placement. The anal reflex and the presence of sensation in the anogenital region should be confirmed when considering a Brindley procedure, and the external genitalia should be inspected for pressure ulcers caused by condom or in-dwelling catheters. Vaginal and rectal examinations should be performed and any signs such as oestrogen deficiency, anogenital prolapse, abnormalities of tone in the pelvic floor musculature or prostatic enlargement should be noted. Finally, blood pressure measurement is essential, as the presence of hypertension may be related to renal damage. Urodynamic investigation A comprehensive urodynamic investigation is essential in all patients with NVD (Table 4). Urodynamic profiling of the storage and voiding phases will permit a functional classification of the NVD. Bladder capacity, sensation and compliance, detrusor function and the closure mechanism should be assessed during the storage phase. During the voiding phase, the method of bladder emptying (e.g. detrusor contraction, abdominal straining, triggered voiding or expression), plus the adequacy and duration of bladder emptying should be noted, along with the nature of any outlet obstruction. The use of a voiding diary can assist both diagnosis and assessment of therapy, and should include details of fluid intake, time and volume of voiding, clean intermittent catheterisation (CIC) and residual volume, and the use of any appliances to assist bladder emptying. Any episodes of involuntary urine loss should also be recorded. This diary provides direct information about functional bladder capacity, as well as possible detrusor overactivity and/ or associated incontinence. In patients who can void spontaneously, a free flow investigation detailing functional capacity, Q max, pattern and residual urine should be included. If in the group with a normal flow pattern no gross abnormalities are found on cystometry and pressure-flow study a simple uroflowmetry will suffice for future follow-up of these patients. This is surely an important point, because neuropathic patients will be under life-long surveillance and economic use of follow-up urodynamics will benefit patients as well as health-care systems. Medium-fill cystometry on top of the residual urine identified by the bladder diary or uroflowmetry, will characterise bladder sensations (first sensation of filling, first desire to void, strong desire to void and maximum cystometric capacity), compliance, detrusor leak point pressure, detrusor instability and incontinence. Provocative cystometry using either rapid fill or ice water should be employed if there is any reason to suspect the presence of neurogenic detrusor overactivity, if this has not been detected during medium-fill cystometry. Bladder compliance is important, since a pressure rise >40 cmh 2 O is a risk factor for hydronephrosis. Direct visualisation of the cystogram is the best way to identify patients at risk, bearing in mind that the duration of high pressure episodes is more significant for renal pathology than the amplitude per se. The leak point pressure should be compared to high pressure resulting from detrusor instability. It is important to remember that a poor sphincter may be protective for kidney function by acting as a safety valve and allowing some loss of urine. Table 4. Urodynamic evaluations in patients with neurogenic voiding dysfunction Procedure Voiding diary Free uroflow Cystometry Pressure flow study Information obtained Functional bladder capacity; severity of incontinence Normal versus abnormal Bladder sensation; cystometric capacity; detrusor hyperreflexia (with or without incontinence); detrusor-sphincter dyssynergia; bladder compliance; motor-urge incontinence; stress incontinence Detrusor function; outflow obstruction (anatomical or functional); residual urine *VII Neurogenic Voiding Dysfunctions (NVD)

8 *VIII Pressure-flow studies should follow cystometry in patients who are able to void spontaneously. These will provide information about detrusor contractility and endurance, voiding pressure, abdominal straining and can also highlight anatomical or functional outflow obstructions (e.g. prostatic enlargement or DSD). The complete urodynamic investigation will allow the patient to be classified according to the four basic scenarios of detrusor and outlet function. The patient s perception of an acceptable situation is likely to be based on the management of incontinence, whereas the urologist s principal concern is to minimise the risks to kidney function. Additional investigations Urinalysis for the detection of infection or carcinoma should always be part of the neuro-urological work-up, and urinary cytology should be performed regularly in patients with in-dwelling catheters. Similarly, annual cystoscopy for the detection of stones, carcinoma or diverticuli is required for patients who have relied exclusively on catheters for bladder emptying for more than 5 years. Ultrasound of the kidneys and bladder is a valuable tool for assessing upper urinary tract dilatation and deterioration, while intravenous urography will provide detailed information about the anatomy of the upper urinary tract, and should be performed in all patients scheduled for major surgery. Disease-specific considerations Traumatic cord lesions. These are classified simply into upper and lower motor neurone lesions, and may be complete or incomplete. However, the actual cause of the trauma gives additional information about the extent of the neural damage. For example, diving accidents often result in high-level cord transections and clinical quadroplegia with unbalanced bladder dysfunction, whereas high velocity traumas, such as road traffic accidents, may have caused damage distally to the highest local transection, giving rise to an unpredictable clinical picture. High level cervical lesions (C 5 C 7 ) cause tetraplegia with poor hand function, posture and balance, diaphragm driven respiration and complete dependency with an unbalanced reflex bladder. Depending on the sphincter, the patient may be incontinent. There is a high risk of hydronephrosis and urinary tract infection due to hyperreflexia and DSD, so the patient requires a high level of urological care. Thoracic level lesions (T 1 T 10 ) result in wheelchair-bound paraplegics with good hand function, posture and balance who are able to care for themselves independently. Reflex erections may be functional, but the reflex bladder is unbalanced. Lowlevel lesions also result in independent, though wheelchair-bound, paraplegia with good hand function and posture. However, the bladder is atonic and stress incontinence is possible; erections are absent. Bladder capacity is large and pressure low, so the kidneys are not at risk although incomplete micturition may lead to infections. Multiple sclerosis. MS is an autoimmune disease found predominantly in young, Northern European people, especially women. Approximately 2% present with LUTS as the first symptoms of disease. MS has a relapsing-remitting course and the patchy, multifocal pathology results in unpredictable symptoms. Nevertheless, among patients with a duration of disease of more than 10 years, 96% will have LUTS and/or impotence. Infections and other stresses (e.g. sleep deprivation) will exacerbate the disease, so urological treatment should aim to prevent infection and maintain quality of life; nocturia is a particular problem. Urologic symptoms in the relapsing-remitting form of disease may be treated successfully, while the chronicprogressive form is devastating and aggressive therapies should be avoided. However, the choice of therapy may be complicated by the presence of co-morbid conditions, such as BPH. Regular urodynamic followup is unnecessary in patients whose condition is stable, but urodynamics should be repeated if there is progression of MS or a change in the pattern of urinary symptoms. Jonas/Castro-Diaz/Bemelmans/Madersbacher/Lycklama à Nijeholt

9 Parkinson s disease. The age of disease onset and pattern of LUTS in men with Parkinson s disease is very similar to that of BPH, making differential diagnosis difficult. Both conditions are characterised by small, overactive bladders, highpressure/low flow voiding as well as detrusor weakness and residual urine. Even the presence of an enlarged prostate is not sufficient reason on its own to consider invasive and irreversible therapies. Conservative management of urological symptoms is therefore indicated in men with Parkinson s disease. Spinal dysraphism. Spina bifida produces symptoms that are similar to a low motor neuron lesion, although the extent of disability is widely variable. Typically, patients with spina bifida have large, hypocontractile bladders and sever incontinence due to sphincteric and pelvic floor dysfunction. It is important to start treatment within a few days of birth to protect the kidney from hydronephrosis. Surgery in these patients is likely to be complicated by skeletal deformities. Diabetes mellitus. Patients with diabetes are especially prone to urinary infection because of glucosuria and incomplete bladder emptying. As in Parkinson s disease, LUTS resemble those associated with outflow obstruction. However, diabetic neuropathy results in detrusor hypocontractility, which can be distinguished from outflow obstruction due to BPH by a pressure-flow study. Conservative treatment The two aims in the management of patients with NVD are to protect the upper urinary tract and so improve life expectancy, and to manage or eliminate incontinence to improve the quality of life. The most important objective is to achieve a safe situation urodynamically, which requires a bladder of sufficient capacity, filling at low pressure and emptying fully without hyperpressure or obstruction of the outlet. A number of conservative treatment options may be Neurogenic Voiding Dysfunctions (NVD) used to provide this situation, including triggered voiding, bladder expression, CIC, pharmacotherapy, electrical stimulation or neuromodulation, appliances and indwelling catheters. Approximately 80% of patients can be managed by conservative therapy, the choice of therapy depending upon the nature and aetiology of the neurogenic LUT dysfunction, the individual situation and sex of the patient, and the presence of other disabilities. The patient s overall functional status has a major influence on treatment decisions. Spinal level lesions Overactivity of both the detrusor and the sphincter (spinal reflex bladder), with attendant DSD and the risk of hydronephrosis, is frequently encountered in patients with lesions at the suprasacral spinal-cord level (upper motor neuron lesion). Although spontaneous reflex voiding is possible it is unphysiologic, with inadequate detrusor contractions and DSD producing unbalanced voiding. Triggered reflex voiding is now recommended for only about 20% of patients as it is potentially dangerous, the long-term complication rate is high and reflex incontinence persists. Regular urodynamic follow-up is essential in patients using this technique. Currently, IC (intermittent catheterisation (IC) or self-ic, SIC) is the first choice management strategy for spinal reflex bladder. Experience over the past 20 years has demonstrated its safety and effectiveness for long-term treatment of NVD, and it is also a prerequisite for strategies such as bladder augmentation and continent diversion. IC is also valuable for achieving continence, although many patients require concomitant pharmacological therapy to achieve the necessary low bladder pressure. The success of the technique is dependent on an adequate frequency of IC/SIC (up to 6 times daily) to limit bladder overdistension and minimise UTI. Follow-up of 75 patients for over 7 years found that the upper urinary was well preserved in all patients, 92% were continent and 42% had chronic recurrent UTI [8]. At present, however, there are no controlled studies to identify the best techniques or materials for IC. *IX

10 Fig. 6. Targets of pharmacotherapy for hyperreflexive bladder. *X The aim of pharmacotherapy is to convert the overactive bladder into an underactive or acontractile one. The sacral reflex arc can be influenced on both efferent and afferent sides in the periphery, and also within the CNS (Fig. 6). Anticholinergic agents such as oxybutynin, propiverine, trospium and tolterodine that act on peripheral efferents reduce detrusor contractility and increase bladder capacity by 30% [9], to produce continence in 70% of patients in conjunction with IC. Typical anticholinergic sideeffects, including dry mouth, blurred vision and constipation may limit efficacy, but they can be minimised by careful drug choice and the use of slow release and intravesical preparations. Afferent C-fibres can be blocked by capsaicin and resiniferatoxin (RTX) resulting in relaxation of the reflex bladder. Intravesical instillation of capsaicin is an effective treatment for refractory detrusor overactivity, especially in MS patients where its effect is maintained for 3 4 months[10]. Recent findings suggest that RTX is superior to capsaicin, with a more rapid onset of desensitisation that is maintained for up to 12 months without the irritative symptoms that are characteristic of capsaicin [11]. Direct injection of botulinum-a toxin into the detrusor muscle under general, spinal or local anaesthesia also relaxes the overactive bladder, leading to a significant increase in cystometric bladder capacity and a reduction in detrusor pressure, with benefits maintained for up to 14 months after a single treatment [12]. This technique may be a valuable management option in cases where anticholinergic therapy has proved ineffective. Several neuroprostheses are available for the management of LUT dysfunction. Electrical stimulation of sacral anterior nerve roots by implanted electrodes connected to a subcutaneous receiver, activated from outside (the Brindley procedure) activates small, non-myelinated, efferent parasympathetic-visceromotor neurons to induce detrusor contraction. The procedure is possible only where the spinal lesion is complete or almost complete and the sacral efferent nerves are spared, since the amplitude of stimulation is high and would cause pain via non-myelinated nerve fibres in patients with incomplete lesions. The technique also requires complete sacral deafferentation (dorsal rhizotomy) to induce an acontractile state and low pressure storage, thus protecting the upper urinary tract. Alternatively, electrical neuromodulation is an option for treatment of overactive detrusor where the spinal lesion is incomplete and sensory input is intact. Low frequency (4 10 Hz) stimulation of the pudendal nerve afferents results in hypogastric nerve stimulation, and in producing direct inhibition of pelvic nerve outflow, thus achieving bladder relaxation. Moreover, it is very likely that also supraspinal mechanisms involved contribute to its therapeutic effects. Stimulation may be provided either non-invasively, using a transvaginal, transanal or transcutaneous Jonas/Castro-Diaz/Bemelmans/Madersbacher/Lycklama à Nijeholt

11 approach via the dorsal penile or clitoral nerves, or invasively by direct stimulation of the sacral nerve. The efficacy of treatment depends on the proximity of electrodes to the nerves, as well as the number and specificity of nerves being stimulated, thus the penile or clitoral nerve is ideal for non-invasive neuromodulation, because it contains pure sensory branches and the distances between electrodes and nerves are small. This approach may be as effective as pharmacotherapy but without its side-effects, and can be continued at home. Although neuromodulation is cost-effective in the long term its availability may be limited under some social security systems. When continence cannot be achieved, appliances such as condom catheters and pads have a role. However, complications such as urinary obstruction, skin lesions and UTI may be encountered with condom catheters. Latex allergy is a particular problem in meningomyelocele children, and requires the use of latex-free appliances. Care should be taken to use the most appropriate size and fastening for condom catheters, and they must be regularly changed. The use of indwelling catheters should be avoided whenever possible. If their use is unavoidable, they should be removed as soon as possible due to the increased risk for complications with subsequent CIC, and should be small (12 14 Fr.), ideally of silicon and meticulously cared for. The penis should be fixed against the abdomen to reduce the risk of urethral ulceration in the penile-scrotal angle, which can lead to abscesses, fistulae and diverticulae, especially in patients with spinal cord injuries. If indwelling catheterisation is considered, a suprapubic catheter is preferred. Although the spinal reflex bladder is the most common scenario in patients with spinal lesions, three other urodynamic patterns may be encountered, each of which requires a different approach to management. Detrusor acontractility with underactive (acontractile) sphincter. This is associated with conus or cauda equina lesions (lower motor neuron lesions), and results in neurogenic stress incontinence, which Neurogenic Voiding Dysfunctions (NVD) may be combined with overflow incontinence if emptying is inadequate. Whilst the sphincter incompetence poses little risk to the upper urinary tract, bladder expression does. The use of CIC is preferred for emptying, and its combination with controlled fluid intake can reduce neurogenic stress incontinence, although full continence is usually only achieved with surgical interventions. Detrusor acontractility with sphincter overactivity (spasticity). No spontaneous voiding is possible in these patients, who are at risk for chronic urinary retention with upper urinary tract damage and overflow incontinence. The preferred management strategy is CIC, and patients are generally continent without adjunctive pharmacotherapy due to the spastic sphincter. However, an indwelling suprapubic catheter may be required in some cases. For patients with incomplete lesions, intravesical electrostimulation (IVES) of the bladder afferents can improve the functioning of the hyposensitive and hypocontractile detrusor. This procedure comprises artificial activation of the normal micturition mechanisms, with repeated activation of the reflex pathway improving the overall performance of the micturition reflex [13]. Good results may be obtained by experienced staff provided that the mechanoreceptors in the bladder wall are intact, the detrusor is still contractile and the cortex can perceive afferent stimuli. It is the only therapy which can improve detrusor dysfunction by direct activation of A-d bladder mechanoreceptor afferents [14]. Detrusor overactivity with underactive (acontracile) sphincter. Urinary incontinence is the main problem in this situation, resulting from a combination of reflex incontinence and neurogenic stress incontinence. A combination of pharmacotherapy for detrusor hyperreflexia to reduce reflex incontinence and electrical stimulation of the pelvic floor musculature in incomplete lesions to improve sphincter performance and reduce stress incontinence may help to minimise the involuntary loss of urine. However, surgery is usually *XI

12 *XII required to restore full continence in these patients. Peripheral nerve lesions Pelvic surgery is the most common cause of peripheral nerve lesions. Typically, the innervation of the pelvic floor, and consequently striated sphincter function, is unaffected. The characteristic features are a hyposensitive and hypocontractile detrusor, resulting in bladder overdistension and the risk of chronic urinary retention. In addition, overflow incontinence may be a problem. Management involves regular bladder emptying, assisted by CIC if necessary. Pharmacotherapy may include cholinergic agents to increase detrusor tone and a 1 -blockers to decrease outflow incontinence. Intravesical Electrical Stimulation (IVES) is another potential therapeutic option for this group of patients, although its utility for bladder rehabilitation is currently underestimated. Supraspinal (suprapontine) lesions Suprapontine lesions affecting bladder control may occur as a result of stroke or in Parkinson s disease. Supraspinal detrusor overactivity (the supraspinal reflex bladder) is characterised by impaired perception of bladder fullness and loss of voluntary inhibition of micturition. Incontinence is therefore the main problem in such patients. However, management is complicated by the frequent presence of other aged-related conditions that may also promote incontinence. The first steps should be to eradicate any chronic UTI, address mobility problems and reduce medications which may promote incontinence. Specific measures to improve continence may include behavioural therapy (habit training, e.g. timed voiding to match bladder capacity), pelvic floor exercises to control urge incontinence. Pharmacotherapy with anticholinergic agents may be indicated if there is a co-existent decrease in functional bladder capacity. Surgical treatment Surgery is required in cases of NVD that are refractory to conservative therapy. Surgical intervention may be indicated to treat problems of incontinence or small capacity in the storage phase, as well as voiding dysfunctions such as DSD and detrusor areflexia. Recurrent urinary tract infection due to residual urine or bladder stones may also prompt surgery. However, the most important absolute indication for surgery is the preservation of renal function. For example, upper urinary tract deterioration will occur in 8 15% of young patients with NVD. The principal objective of surgery is therefore to increase functional bladder capacity and decrease maximal detrusor pressure, thereby ensuring free drainage of the kidneys and bladder emptying with low pressure and low residual volume. The ideal outcome from surgery would be unobstructed renal excretion, with a compliant bladder of normal capacity capable of spontaneous voiding and providing full continence. There should also be low rates of infection and of early and late complications, including acidosis and malignancy, and the procedure should be reversible. Small surgical procedures A number of minor surgical procedures are available for the management of relatively simple defects of either storage or voiding. Transurethral sphincterotomy. This procedure is only indicated in male patients with DSD where the resulting incontinence can be managed using condom catheters, although selected patients may benefit from a sphincter prosthesis or fascial sling procedure to control incontinence. However, failure rates are quite high, and repeat surgery may be required in up to 25% of cases. Subtrigonal bladder denervation. The modified Ingelman Sundberg procedure, in which the vaginal epithelium and perivesical fascia under the trigone are dissected off bladder to decrease sensory input, is an option for women with refractory urge incontinence. Transvaginal subtrigonal injection of local anaesthetic can be used before surgery to identify patients who are most likely to benefit Jonas/Castro-Diaz/Bemelmans/Madersbacher/Lycklama à Nijeholt

13 from the procedure, which carries fewer risks than bladder denervation using phenol. Continence rates of 64% have been reported following subtrigonal bladder denervation [15]. Hydrostatic bladder distension. This procedure, which results in denervation of the bladder wall, leads to some improvement in 30% of patients with detrusor instability or interstitial cystitis. Procedures preserving the urethral sphincter Bladder augmentation or replacement procedures in which the urethral sphincter is preserved are used for the management of refractory urge incontinence and problems associated with small bladder capacity. Enterocystoplasty. Bladder augmentation by procedures such as the clam ileocystoplasty, in which a section of opened ileum is patched into the bisected bladder, has been performed for many years. Although continence rates are good (63 87%), many patients will require CIC to ensure complete bladder emptying. In patients with NVD, enterocystoplasty is usually combined with a sling procedure or artificial sphincter to improve continence rates. Enterocystoplasty is, however, associated with a significant risk of complications resulting from the involvement of the bowel anastomosis. In patients with NVD, the incidence of permanent bowel dysfunction may be up to 30%, while stool frequency is increased in 39% of patients with 23% reporting increased faecal incontinence. These issues should be discussed with the patient before surgery. Detrusor myectomy. Auto-augmentation of bladder capacity by the creation of a mucosal diverticulum has been shown to produce excellent short-term results, with an increase in capacity of 15 70% and success rates of 60 90%. In addition, the rate of complications (3%) is lower than after enterocystoplasty. In the longer term, however, fibrotic contractions often occur, although these may respond to omental Neurogenic Voiding Dysfunctions (NVD) interposition. Nevertheless, there is a failure rate of almost 50% in patients with NVD; such patients may require a subsequent enterocystoplasty [16]. Orthotopic bladder replacement. Although ileal neobladders give good results in cancer patients, its use in young patients with NVD needs to be balanced against the potential for long-term complications. Nocturnal incontinence may be a particular problem, as both urethral tone and consciousness are reduced, and this adds to the effect of the neuropathy on outlet resistance. At the same time, the reservoir is challenged by the effect of bowel movements and the production of hyperosmotic urine, which attracts further fluid into the neobladder. An artificial sphincter or sling in combination with CIC may be necessary in these cases. The success of the procedure is related to the type of bowel used, the capacity of the reservoir and the age of the patient, with continence rates of % during the day and 33 94% at night being reported. Non-preservation of the urethral sphincter In patients with severely impaired urethral function, an alternative outlet must be supplied. Where sufficient bladder capacity exists a new outlet can be created. An incontinent vesicostomy using a short segment of bowel and a U-shaped bladder flap is a relatively simple procedure which results in a reservoir with a low leak point pressure and is a good option for those unable to perform CIC. Alternatively, the appendix (Mitrofanoff procedure) or a transversely tubularised ileal segment (Monti procedure) may be used to form a submucosal tunnel and create a continent reservoir. It should be noted that wheelchair-bound or obese patients find it easier to use an umbilical or abdominal stoma rather than transurethral CIC. The Mitrofanoff and Monti procedures may be combined with closure of the bladder neck and/or ileoplasty depending on the capacity of the reservoir. Continence rates of over 90% can be achieved with the Mitrofanoff technique, although stomal stenosis *XIII

14 and difficulties with catheterisation may be encountered. The outcomes following urinary diversion using either the Mainz pouch or colonic conduit have been recently reviewed [17]. Both the Mainz I continent diversion and Mainz orthotopic bladder substitution achieve excellent continence (80 100%) over 6 10 years, with good preservation of the upper urinary tract. However, reoperation rates were higher for the Mainz I continent diversion (48%) than for the orthotopic bladder substitution (25%). The incontinent conduit (Bricker or colonic conduit) also provided excellent protection of the upper urinary tract. The latter procedure may be attractive for patients with mental retardation or those who are unable to perform CIC due to obesity or immobility, while orthotopic bladder substitution may be more appropriate in more mobile patients. Conclusion Neurogenic bladder dysfunction presents a number of challenges for the urologist, with respect to both diagnosis and management. As a first step, proper diagnosis is crucial for good treatment and follow-up, and urodynamics are the cornerstone of the diagnostic work-up. The information on detrusor and sphincter function provided by these investigations can then be used in the development of the therapeutic plan and during follow-up to assess the success of any interventions. The main objective of treatment is the protection of renal function, with the management of incontinence and its beneficial effects on quality of life as a secondary objective. Although the diagnosis and urodynamic findings have an important influence on treatment decisions, the patient s physical status, and particularly the ability to manage procedures such as CIC, must also be considered. A number of conservative approaches, including CIC, pharmacotherapy, electrical stimulation of the sacral nerve roots or the pudendal nerves, IVES may be used to improve bladder and sphincter function in a wide range of conditions, and many patients achieve continence through their use. In some cases, however, the use of condom or indwelling catheters may be necessary, although the use of the latter should be minimised to reduce the risk of complications with subsequent CIC. Despite the success of conservative therapies, between 8 30% of patients, depending on the aetiology of the neuropathic LUT dysfunction will require a surgical intervention, particularly procedures such as bladder augmentation with or without sphincter preservation. The success of these various different interventions is evidenced by the excellent preservation of renal function that they provide, with its consequent beneficial influence on the life expectancy of the patient. References *XIV [1] Bors E, Comarr AE. Neurological Urology. Baltimore (MD): University Park Press; [2] Hald T, Bradley WE. The Urinary Bladder: Neurology and Dynamics. Baltimore (MD): Williams and Wilkins; [3] Bradley W. Physiology of the urinary bladder. In: Walsh PC, Gitter, Pelmutter Stamey TA, editors. Campbell s Urology, 5th ed. Philadelphia (PA): WB Saunders; p [4] Lapides J. Neuromuscular vesical and urethral dysfunction. In: Campbell MF, Harrison JH, editors. Urology. Philadelphia (PA): WB Saunders; p [5] Krane RJ, Siroky MB. Classification of neuro-urologic disorders. In: Krane RJ, Siroky MB, editors. Clinical Neuro-urology. Boston (MA): Little, Brown; p [6] Wein AJ. Pathophysiology and categorization of voiding dysfunction. In: Walsh PC, Retik AB, Vaughan ED Jr, Wein AJ, editors. Campbell s Urology, 7th ed. Philadelphia (PA): WB Saunders; p [7] Abrams P, Blaivas JG, Stanton SL, Andersen JT. The standardization of terminology of lower urinary tract function. Neurourol Urodyn 1988;7: [8] Wyndaele JJ, Maes D. Clean intermittent selfcatheterization: a 12-year followup. J Urol 1990;143: [9] Madersbacher H, Stohrer M, Richter R, Burgdorfer H, Hachen HJ, Murtz G. Trospium chloride versus oxybutynin: a randomized, double-blind, multicentre trial in the treatment of detrusor hyper-reflexia. Br J Urol 1995;75: Jonas/Castro-Diaz/Bemelmans/Madersbacher/Lycklama à Nijeholt

15 [10] 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 center study with long-term followup. J Urol 1997;158: [11] Silva C, Rio ME, Cruz F. Desensitization of bladder sensory fibers by intravesical resiniferatoxin, a capsaicin analog: long-term results for the treatment of detrusor hyperreflexia. Eur Urol 2000;38: [12] Schürch B, Stöhrer M, Kramer G, Schmid DM, Gaul G, Hauri D. Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol 2000;164: [13] Ebner A, Jiang CH, Lindström S. Intravesical electrical stimulation an experimental analysis of the mechanism of action. J Urol 1992;148: [14] Madersbacher H. Intravesical electrical stimulation for the rehabilitation of the neuropathic bladder. Paraplegia 1990;28: [15] Duane Cespides R, Cross CA, McGuire EJ. Modified Ingelman-Sundberg bladder denervation procedure for intractable urge incontinence. J Urol 1996;156: [16] Leng WW, Blalock HJ, Freriksson WH, English SF, McGuire EJ. Enterocystoplasty or detrusor myectomy? Comparison of indications and outcomes for bladder augmentation. J Urol 1999;161: [17] Stein R, Fish M, Ermert A, Schwarz M, Black P, Filipas D, et al. Urinary diversion and orthotopic bladder substitution in children and young adults with neurogenic bladder: a safe option for treatment? J Urol 2000;163: *XV Neurogenic Voiding Dysfunctions (NVD)