How to manage a patient with bladder dysfunction

3 rd Congress of the European Academy of Neurology Amsterdam, The Netherlands, June 24 27, 2017 Teaching Course 13 How to manage a patient with autonomic dysfunction - Level 2 How to manage a patient with bladder dysfunction David B. Vodušek Ljubljana, Slovenia Email: vodusek.david.b@gmail.com

Conflict of interest: The author has no conflict of interest in relation to this manuscript Summary Lower urinary tract (LUT) dysfunction is common in neurological patients; it may lead to serious health problems and it significantly affects quality of life. Such dysfunction is often related to the neurological disorder itself (i.e. it is neurogenic), but non-neurogenic causes particularly in patients who are elderly - need to be ruled out. Neurological causes of LUT dysfunction (LUTD) are often a combination of a lesion (lesions) affecting relevant LUT neural control (either autonomic, or somatic, or both), and constraints on normal functioning of the patient imposed by sensory, motor, or cognitive deficits. Patients with spinal cord injury (and those with dysraphism), who have as a rule severe neurogenic LUTD, are managed in specialized centers according to established guidelines by rehabilitation specialists and neurourologist. The majority of»primary«neurological patients (stroke, multiple sclerosis, neurodegenerative diseases, neuropathies ) also may suffer from LUTD (although usually not as incapacitating and dangerous). These patients often have poor access to urologists, who furthermore do not have much understanding of their often progressive neurological disease; thus, it is most practical if management of such neurological patients with noncomplicated neurogenic LUTD is guided by the treating neurologist (who should, of course, be adequately instructed). 1

Rational management of LUTD begins with an appropriate assessment. Urinary infections should first be ruled out. The bladder and the sphincter (urethra) need then to be diagnosed as normal, over- or underactive. Urodynamic testing is the gold standard for functional diagnosis; the whole range of tests is usually available in a tertiary urological unit, but need not be applied in every neurological patient with LUTD. Assessment of the residual urine and uroflow are, however, required before considering first line treatment, and should be easily obtainable for the neurological patient; if possible, available in the neurological department. Neurological patients with LUTD most often complain of frequency, urgency and nocturia, which are due to an overactive bladder; its management can be seen as modular and can be combined. The noninvasive approaches include: explanation, counselling, bladder training, peroral drug treatment, and non-invasive electrical stimulation (ES) (like tibial nerve ES). In the patient with a hypoactive bladder the residual urine is often clinically silent and is only revealed after frequent LUT infections lead to some further diagnostic exploration; clean intermittent catheterisation is the management of choice and should be taught to the patient or carer. Patients with complex problems or those failing primary management should be referred to a (neuro)urologist. Further studies are necessary to test the best approaches for diagnosing and managing particular types of neurogenic LUTD in the different neurological patient populations. 2

Introduction The field of neuro-urology arose in spinal cord injury centers, as the special needs of this patient population became recognized. In the middle of the 20th century appropriate management of the neurogenic bladder became widely established, thus contributing significantly to the survival and quality of life of para/tetraplegics. Measurements of function of the bladder and urethra (»urodynamics«) became a powerful tool to demonstrate lower urinary tract (LUT) dysfunction (LUTD) and to suggest (and guide) treatment strategies for the individual patient. (1) The conceptual and organizational achievements in spinal cord injury rehabilitation are only slowly spreading to the care of patients with diseases of the nervous system. There are only few high-quality studies related to the epidemiology, appropriate diagnostics and therapy of neurogenic LUTD apart from the spinal cord injury population, but there is growing consensus that neurogenic pelvic organ dysfunction demands (also) neurological expertise. Clare J. Fowler established the first neurological unit devoted to management of neurogenic LUTD (and SD) at»queen Square«in London, UK towards the end of the 20th century; she also coined the term uroneurology for this particular field of neurology. Queen Square set an example to tertiary/academic neurological institutions; a uroneurological service should be available in centers looking after large populations of neurological patients, particularly those with MS, neurodegenerative diseases or neuropathy. The full scope of management of all the manifold consequences of a nervous system disease (affecting many if not all body functions) is still difficult to establish in the typical neurological department. The 3

neurologists' prevailing focus is still on the sensorimotor dysfunction, or cognitive dysfunction. Fort he sake of his patients, basic knowledge of neurogenic LUTD should, nowadays, be acquired by every neurologist. The next step in upgrading the care for chronic neurological patients with LUTD is recognizing the need for specialized nurses, who can take up much of the load of diagnosing and follow up of patients (questionnaires, residual urine determination by ultrasound; measurment of urine flow rate; explanation, counselling the patient and the carer, teaching clean intermittent selfcatheterization). Lower Urinary Tract Function and Neural Control Both the storage and elimination of urine are neurally controlled by coordinated activity of the autonomic and somatic nervous systems. In addition to the basic neural control of smooth and striated muscles involved in the functioning of bladder and the urethral sphincter, LUT functions are set within complex behaviors dependent on brain control networks. (2). These are increasingly being revealed by functional imaging. (3). Models of LUT neural control based on animal studies and functional imaging in humans have been proposed (3). The two alternating functions of LUT (storage and elimination of urine), which are also appreciated through conscious sensation, are coordinated by a spinobulbospinal reflex. The periaqueductal gray is the sensory relay nucleus, and the pontine micturition center (PMC; in the dorsomedial pontine tegmentum) is the coordinator of efferent commands to the detrusor and the sphincters. 4

Voluntary control is exerted by a complex brain network dominated by the lateral and medial prefrontal cortex. LUTD in patients can in principle be explained by the following model: lesions above the PMC produce an overactive bladder with coordinated sphincter; lesions involving the PMC or the spinal pathways to the detrusor and sphincter nuclei in the sacral spinal cord cause an overactive bladder with uncoordinated (dyssynergic) sphincter, and lesions to the peripheral sacral reflex arc cause an underactive bladder with underactive (denervated) sphincter. In an individual patient, however, several factors define the particular state of the bladder and its outlet, and a neurological classification of (neurogenic) LUTD has not proven clinically useful. The European Association of Urology Guidelines on Neurogenic Lower Urinary Tract Dysfunction (4) recommends the simple and therapeutically oriented Madersbacher classification system (5) for clinical practice, which differentiates between the state of the detrusor (on one side) and that of the urethral sphincter (on the other side) as either under- or overactive (or normal). The most common dysfunction related to central nervous system lesions is an overactive detrusor with urgency, frequency, nocturia and urge incontinence; if associated with an overactive/dyssynergic urethral sphincter, the result is high intravesical pressure leading to upper urinary tract affection and ultimatively to kidney failure. 5

Lower urinary tract dysfunction (LUTD) in neurological disease Generally, LUTD is more common in neurological patients than in the general population; it may arise not only as a direct consequence of nervous system lesions but also as a result of pharmacotherapy, or motor, sensory and cognitive deficits. Apart from spinal cord injury patients, the data so far come from mostly small observational studies performed in often poorly defined patient populations. Therefore, data on epidemiology, symptomatology, urodynamic characteristics and the requirements for particular diagnostic procedures and appropriate therapy are only preliminary or based on expert opinion. In patients with spinal cord or cauda equina lesions, autonomic failure (including Multiple system atrophy (MSA) and normotensive hydrocephalus, LUTD is so common that it is indeed part of the clinical picture. In focal brain lesions, frontal locations are particularly related to LUTD. In multiple sclerosis (MS), Parkinson s disease and polyneuropathies, LUTD typically appears with progression of the disease. Details of LUT symptoms in different diseases are beyond the scope of this text. A thorough overview of this topic is provided by the recent edition of the Handbook of Clinical neurology. (6). In general, although a certain type of dysfunction may be typical for a particular disease, in whole populations of patients, all possible LUTD symptoms may appear (i.e. symptoms due to dysfunctional storage or dysfunctional elimination of urine). LUTD has adverse effects on patient outcomes. It is accompanied by recurrent urinary tract infections. In spinal cord lesions and dysraphism, 6

there is continuing danger of upper urinary tract involvement; however, this seems not to be common in neurological diseases such as MS and Parkinson s disease. LUT symptoms and urodynamic abnormalities worsen during the course of progressive neurological disease and even change from one symptom complex to another (from a storage problem into an elimination problem in MSA, for instance). (cf. 6). General remarks on management As a rule, management of patients with spinal cord injury is undertaken by dedicated neuro-urological/neurorehabilitation teams localized in specialized rehabilitation centers according to established guidelines. In the tertiary general hospital, and for specialized outpatient clinics, it is in many settings impractical and probably unnecessary to refer a patient (with a chronic neurological disease known to cause LUTD), who develops some urinary symptom fort he first time, immediately to urology for firstline management. A well organized neurology service for patients with MS, neurodegenerative diseases and neuropathies should include enough uroneurological expertise that management of neurological patients with noncomplicated neurogenic LUTD can be coordinated / performed (or at least started) in house by the neurologist. A dedicated nurse (»continence advisor«) in the team is very helpful. Referral to urology (urogynecology) is necessary for complex patients, or if first-line treatment fails. 7

Diagnostics Medical history, assessing LUT symptoms and keeping a bladder diary are the mainstay of a working diagnosis of LUTD. (7). The use of a validated questionnaire is encouraged (8). As a rule, clinical examination of the patient who might suffer from neurogenic LUTD should include the anogenital region (assessment of anal sphincter tone and activation, eliciting the bulbocavernosus and anal reflex, sensation of touch and pinprick; the latter contributes the most towards the formulation of a neuroanatomical diagnosis). As for investigations, urodynamic testing is standard practice in patients with spinal cord injury and dysraphism. (7). For patients with chronic neurological disease and LUT symptoms, the practice of urological (urogynecological) consultation varies in different centers, but in all cases, structural lesions should be ruled out. In many hospitals or even countries it is difficult to obtain (neuro)urological counsel for a large number of heterogenous groups of neurological patients. It is suggested that basic clinical assessment (which should start by ruling out infection) should be performed by the neurological team, which is responsible for the long-term follow up of the patient. Because upper urinary tract involvement is rare in MS patients, it has been argued that urodynamic testing is not necessary for first-line symptomatic management of LUTD, though determination of postvoid residual urine should be performed. (In addition, uroflow is recommended to rule out infravesical obstruction). The same has be argued for patients with brain lesions (i.e. stroke, Parkinson s disease). 8

If patients are responding to simple management and followed up, eventually screening of upper urinary tract has to be performed yearly intervals. More invasive procedures are reserved for the patient with refractory problems. Neurourologists, however, recommend that patients with suspected neurogenic LUTD should receive urodynamic tests (including filling and voiding cystometry). Videourodynamics is recommended if relevant anatomical abnormalities are expected. (7). But single testing cannot provide guidance for long-term follow-up (in MS or movement disorder patients); urodynamic follow-up has been recommended. It should be pointed out that no prospective study has investigated the cost benefit of invasive urodynamics versus simpler diagnostic techniques (assessment of postvoid residual urine, uroflow, upper urinary tract ultrasound). An assessment of residual urine using ultrasound by a specialized nurse on follow-up visits is practical, cheap and noninvasive, and should be practised if specialized urological care is difficult to access. Thus far, LUTD diagnostics has been discussed with respect to patients with a known neurological disease. A different issue is isolated LUTD presented to a urologists or a gynecologist who not finding any urological cause suspects a neurogenic bladder. An isolated neurogenic SD case is most commonly due to polyneuropathy. LUTD may also be early manifestations of some rare conditions (MSA, tethered cord syndrome, conus/cauda equina tumor). MS only rarely starts with LUTD alone. As a rule, a thorough history and clinical examination in such patients suffices, but occasionally appropriate imaging or if a peripheral 9

lesion is suspected a concentric needle EMG of the anal sphincter and bulbocavernosus reflex testing may be performed (8). Therapy Urinary tract infections are common symptoms of chronic neurogenic LUTD, usually caused by incomplete emptying. Optimal treatment of urine retention is of primary importance. In the acute setting, use of a shortterm indwelling catheter in a patient with urinary retention is safe. In the chronic situation, clean intermittent (self)catheterisation is the management of choice. If urinary tract infections persist, a urologic evaluation is warranted in order to check for foreign bodies or bladder deformities (kidney and bladder stones are particularly common since certain types of bacteria may cause them). Chronic antibiotic use should be discouraged; this practice will almost certainly lead to infections with resistant bacteria. If antibiotics are warranted, use of intermittent or alternating courses of antibiotics (nitrofurantoin or trimethoprim) is recommended. In patients with indwelling catheters, asymptomatic bacteriuria should be expected and tolerated. (9). Scheduled voiding (bladder training) may be an adequate treatment for patients with mild symptoms of frequency and urgency or with hyposensitive bladders. Complete and regular emptying of the bladder may be all that is necessary to alleviate frequency, urgency, incontinence and bladder discomfort. In MS patients with difficulty in initiating voiding and poor bladder emptying, suprapubic vibration treatment has been reported to be effective (9) Intermittent (self) catheterization should be introduced if the amount of the postvoid residual is above 100 ml. (This can be performed by the patient or caregiver. Motivation, cognition and adequate 10

manual dexterity are necessary conditions). If symptoms of overactive bladder persist, an anticholinergic drug should be added. Anticholinergic therapy is generally considered first line treatment for NDO and storage symptoms. (In metaanalysis, anticholinergics reduce intravesical pressure and incontinence episodes and increase bladder volume. Main side effects of anticholinergic therapy are dry mouth and constipation). The drug should be titrated individually; if one drug is not tolerated, another should be tried. Intermittent catheterizations may become necessary after introduction of the antimuscarinic agent because residual urine may be a side effect. Beta3-receptor agonists are also now available as a replacement for anticholinergic drugs. (10) Intermittent electrical stimulation therapy (stimuli administered to nerves of the lumbosacral segments) show promise in inhibiting the overactive bladder and reducing its symptoms; the tibial nerve stimulation technique has been FDA approved for this indication. Electrical stimulation has no systemic side effects and is usually well tolerated. Electrical stimulation with an implanted device ( Sacral neuromodulation ) is in the urological domaine, and is FDA approved. (Paradoxically, ES may also be effective in treating retention). Overall, more studies are needed to define the role of ES in treating neurogenic LUTD. In patients with bothersome day- or nighttime frequency, the synthetic analogue of vasopressin has been shown to confer symptomatic benefit, providing patients with up to 6 h of freedom from frequency. Desmopressin at a dose of 10 20 µg should only be used once in any 24- hour period; it should not be used regularly because of the danger of hyponatremia; it should not be used in patients over 65 years of age. 11

Patients with resistant neurogenic bladder overactivity generally respond to botulinum toxin injections into the detrusor muscle. The beneficial effects of this therapy have a median duration of 9 11 months, but many patients need to start intermittent self-catheterization because of poor bladder emptying. Botulinum toxin injection is recommended grade A in the EAU guidelines to be the most effective minimally invasive treatment to reduce NDO. (10) The injections are administered through a cystoscope by a urologist in local, regional or general anesthesia. Intrasphincteric injections of botulinum toxin may improve urinary retention and sphincter dyssynergia and ease catheterization. No drug treatment is available for neurogenic sphincter deficiency and detrusor underactivity. (9) In the highly disabled neurological patient with limited mobility, cognitive impairment, loss of manual dexterity and increased spasticity/rigidity, an indwelling catheter becomes a necessity. Traditionally, the suprapubic catheter is the preferred solution, but every use of indwelling catheters on a long-term basis causes complications, and controlled studies are limited. An indwelling catheter per se does not protect the upper urinary tract. (9) Surgical solutions for some complicated neurogenic LUTD exist but should be practiced in expert neurourological centers. Further details on the management of LUTD according to consensus recommendations can be found in (9). 12

Conclusion The neurologist should strive to become knowledgeable in basic uroneurology and coordinate both the diagnosis and management of LUTD in his/her patient; a specialized nurse can provide much help both with assessment and counselling. Neurological departments, particularly those specialized in treating MS, movement disorder patients and patients with neuropathies, should establish uroneurological expertise and should cooperate with an interested neurourologist, to whom complex cases should be referred. 13

References 1. Wyndaele JJ, Vodušek DB. Approach to the male patient with lower urinary tract dysfunction. In: DB Vodušek und Boller F. NEUROLOGY OF SEXUAL AND BLADDER DISORDERS, Elsevier, Amsterdam 2015; 143-163. 2. W.C. de Groat and N. Yoshimura. Anatomy and physiology of the lower urinary tract. In: DB Vodušek und Boller F. NEUROLOGY OF SEXUAL AND BLADDER DISORDERS, Elsevier, Amsterdam 2015; 61 118. 3. D. Griffiths Functional imaging of structures involved in neural control of the lower urinary tract. In: DB Vodušek und Boller F. NEUROLOGY OF SEXUAL AND BLADDER DISORDERS, Elsevier, Amsterdam 2015; 121-136. 4. Stoehrer M, Blok B, Castro-Diaz D, Chartier-Kastler E, Del Popolo G, Kramer G, Pannek J, Radziszewski P, Wyndaele JJ: EAU Guidelines on Neurogenic Lower Urinary Tract Dysfunction. Eur Urol 2009; 56: 81 88. 5. Madersbacher H: The various types of neurogenic bladder dysfunction: an update of current therapeutic concepts. Paraplegia 1990; 28: 217 229. 6. DB Vodušek und Boller F. NEUROLOGY OF SEXUAL AND BLADDER DISORDERS, Elsevier, Amsterdam 2015. 7. Rotar M, Tršinar B, Kisner K, Barbič M, Sedlar S, Gruden J, Vodušek DB: Correlations between the ICIQ-UI short form and urodynamic diagnosis. Neurourol Urodyn 2009; 28: 501 505. 8. Tubaro A, Vodušek, D B, Amarenco G, Doumouchtsis S K, DeLancey J O L,Fernando R et al. Imaging, Neurophysiological Testing and Other Tests. In: Abrams P, Cardozo L, Wein A (Eds). Incontinence, 5 th Ed. ICUD EAU 2013; 507-622. 9. Drake M.J. Management and rehabilitation of neurologic patients with lower urinary tract dysfunction. In: DB Vodušek und Boller F. NEUROLOGY OF SEXUAL AND BLADDER DISORDERS, Elsevier, Amsterdam 2015; 451-468 10. http://uroweb.org/wpcontent/uploads/21-neuro-urology_lr2.pdf 14