of storage and emptying problems 612 Bladder management techniques for the neuropathic patient 614 Catheters and sheaths and the neuropathic patient 622 Management of incontinence in the neu ropathic patient 624 Management of recurrent urinary tract infections (UTIs) in the neuropathic patient 628 Management of hydronephrosis in the neuropathic patient 630 Bladder dysfunction in multiple sclerosis, Parkinson \200\231s disease, spina bi \201 da, after stroke, and in other neurological disease 632 Neuromodulation in neuropathic and non-neuropathic lower urinary tract dysfunction 636 CHAPTER 14 Neuropathic bladder 604 Innervation of the lower urinary tract (LUT) Motor innervation of the bladder Parasympathet ic motor innervation of the bladder Preganglionic, parasympathetic nerve cell bodies are lo cated in the intermediolateral column of spinal segments S2 \200\2234. These preganglionic, parasympathetic \201 bres pass out of the spinal cord through the anterior primary rami of S2, S3, and S4 and contained within nerves called the nervi erigentes, they head towards the pelvic plexus. In the pelvic plexus (in front of the piriformis muscle), the pregangli onic, parasympathetic \201 bres synapse within ganglia with the cell bodies of the post-g anglionic parasym- pathetic nerves which then run to the bladder and urethra. Fifty percent of the ganglia of the pelvic plexus lie in the adventitia of the bladder and bladder base (the connective tissue surrounding the bladder) and 50% are within the bladder wall. The po st-ganglionic axons provide cholinergic excitatory input to the smooth muscle of the bladde r. Sympathetic motor innervation of the bladder In the male, preganglionic sympathetic nerve \201 bres arise from the interme- diolateral column of T10 \200\22312 and L1 \200\2232. Th ese preganglionic neurons syn- apse in the sympathetic chain and post-ganglionic sympatheti c nerve \201 bres travel as the hypogastric nerves to innervate the trigone, blood vessel s of the bladder, and the smooth muscle of the prostate and preprostatic sphincter (i.e. th e bladder neck). In the female, there is sparse sympathetic innervation of the bladder neck and urethra. In both sexes, some post-ganglionic sympathetic nerves also terminate in parasympathetic ga nglia (in the adventitia surrounding the bladder and within the bladder wall) and exert an inhibitory effect on bladder smooth muscle contraction. Afferent innervation of the bladder Afferent nerves from receptors throughout the bladder a scend with para- sympathetic neurons back to the cord and from there, up to the pontine sto rage and micturition centers or to the cerebral cortex. They sense bladder \201 lling. Other receptors are located in the trigone and afferent neurons from these neurons ascend w ith sympathetic neurons up to the thoracolumbar cord and thence to the pons and cerebral co rtex. Other receptors are located in the urethra. The afferent neurons pass through the pudendal nerve and again ascend to the pons and cerebral cortex. All these neurons have local relays in the cord. Somatic motor innervation of the urethral sphincter: the distal urethral sphincter mechanis m Anatomically, this is located slightly distal to the apex of the prostate in the male (be tween the verumontanum and proximal bulbar urethra) and in the mid-urethra in the female. I t has three components: - Extrinsic skeletal muscle: urethral sling (part of levator ani). Composed of striated muscl e and this is the outermost layer, the pubo- INNERVATION OF THE LOWER URINARY TRACT (LUT) 605 innervated by the pudendal nerve (spinal segments S2 \200\2234, somatic nerve \201 bres). It is activated under conditions of stress and augments urethral occlusion pressure. Smoot h muscle within the wall of the urethra: innervation. Tonically active. Relaxed by nitric o xide (NO). Intrinsic striated muscle urethra, hence known as the \200\230intrinsic rhabdos phincter \200\231): it forms a \200\230U \200\231 shape around the urethra and around the anterior and lateral aspects of the membranous urethra and is absent posteriorly (i.e. it d oes not completely encircle the membranous urethra). It may produce urethral occlusion by k inking the urethra rather than by circumferential compression. cholinergic (i.e. skeletal muscle within the wall of the Preganglionic somatic nerve \201 bres (i.e. neurons which innervate striated muscle) are, along with parasympathetic nerve \201 bres (which innervate the bladder), derived from s pinal segments S2 \200\2234, speci \201 cally from Onuf \200\231s nucleus (also known as s pinal nucleus X) which lies in the medial part of the anterior horn of the spinal cord. (On uf \200\231s nucleus is the location of the cell bodies of somatic motoneurons that provide motor input to the striated muscle of the pelvic \202 oor \200\224the external urethral and anal sphinc- ters.) These somatomotor nerves travel to the rhabdosphincter via the peri neal branch of the pudendal nerve (documented by direct stimulation studies and horseradish peroxidase (HRP) tracing \200\224accumulates in Onuf \200\231s nucleus following injection into either the pudendal or pelvic nerves). There also seems to be some innervation to the rhabdosphincter from branches of the pelvic plexus (speci \201 cally the inferior hypogas tric plexus) via pelvic nerves. In dogs, complete silence of the rhabdosphincter is seen on ly if both the pudendal and pelvic efferents are sectioned. Thus, puden- dal nerve block or pudendal neurectomy does not cause incontinence. The nerve \201 bres that pass distally to the distal sphincter mechanism are located in a dorsolateral position (5 and 7 o \200\231clock). More distally, they adopt a more lateral position. Sensory innervation of the urethra Afferent neurons from the urethra travel in the pudendal nerve. Their cell bodies lie in the dorsal root ganglia and they terminate in the dorsal h orn of the spinal cord at S2 \200\2234, connecting with neurons that relay sensory informat ion to the brainstem and cerebral cortex. The pudendal nerve (a somatic nerve derived from spinal segments S2 \200\2234) innervates s triated muscle of the pelvic \202 oor (levator ani, i.e. the pubo-urethral sling). Bilate ral pudendal nerve block1 does not lead to incontinence because of maintenance of internal (sympathetic innervation) and external sphincter function (somatic innervation, S2 \200\223 4, nerve \201 bres traveling to the external sphincter alongside parasympathetic neurons in the nervi erigentes). CHAPTER 14 Neuropathic bladder 606 Clinical consequences of damage to the nerves innervating the LUT Bladder neck function in the female About 75% of continent young women and 50% of perimenopausal conti- nent women h ave a closed bladder neck during the bladder \201 lling phase. Twenty- \201 ve percent o f continent young women and 50% of perimeno- pausal continent women have an open bladder ne ck and yet they remain continent (because of their functioning distal sphincter mechanism, the external sphincter).2,3 Presacral neurectomy (to destroy afferent pain pathways) does n ot lead to incontinence because of maintenance of the somatic innervation of the external s phincter. Sympathetic motor innervation of the bladder Division of the hypogastric plexus of nerves d uring a retroperitoneal lymph node dissection for metastatic testis tumors results in paral ysis of the blad- der neck. This is of signi \201 cance during ejaculation where normally sympathetic activity results in closure of the bladder neck so that the ejaculate is direct ed distally into the posterior and then anterior urethra. If the bladder neck is incompeten t, the patient develops retrograde ejaculation; they remain con- tinent of urine because th e distal urethral sphincter remains functional, being innervated by somatic neurons from S2 \200\2234. During pelvic fracture, the external sphincter and/or its somatic motor innervation may be damaged such that it is incompetent and unable to maintain continence of urine. Preservatio n of bladder neck function (the sympathetic innervation of the bladder neck usually remains intact) can preserve continence. However, if in later life, the patient undergoes a TURP o r bladder neck incision for symptomatic prostatic obstruction, they may well be rendered in continent because their one remaining sphincter mechanism (the bladder neck) will be divide d during these operations. 1 Brindley GS (1974) The pressure exerted by the external sphincter of the urethra when its motor nerve \201 bres are stimulated electrically. Br J Urol 46:453 \200\22362. 2 Chapple CR, Helm CW, Blease S, Milroy EJ, Rickards D, Osborne JL (1989) Asymptomatic blad der neck incompetence in nulliparous females. Br J Urol 64:357 \200\2239. 3 Versi E, et al. (1990) Distal urethral compensatory mechanisms in women with an incompete nt bladder neck who remain continent and the effect of the menopause. Neurourol Urodyn 9:57 9 \200\22390. This page intentionally left blank CHAPTER 14 Neuropathic bladder 608 The physiology of urine storage and micturition Urine storage During bladder \201 lling, bladder pressure remains low despite a substantial increase in volume. The bladder is thus highly compliant. Its high compli- ance is partly due to the elastic properties (viscoelast icity) of the connec- tive tissues of the bladder and partly due to the ability of detrusor smooth muscle cells to increase their length without any change in tension. The detrusor i s able to do this as a consequence of prevention of transmission of activity from pregangli onic parasympathetic neurons to post-ganglionic efferent neurons \200\224a so-called \200 \230gating \200\231 mechanism within the parasympa- thetic ganglia. In addition, inhibitory interneuron activity in the spinal cord prevents transmission of afferent activity from se nsors of bladder \201 lling. Micturition A spino-bulbar-spinal re \202 ex, coordinated in the pontine micturition cente r in the brainstem (also known as Barrington \200\231s nucleus or the M region), results in simultanous detrusor contraction, urethral relaxation, and subsequent micturition. Recepto rs located in the bladder wall sense increasing tension as the bladder \201 lls (rather t han stretch). This informa- tion is relayed, by afferent neurons to the dorsal horn of the sacral cord. Neurons project from here to the periaqueductal gray (PAG) matter in the pons. The PAG is thus informed about the state of bladder \201 lling. The PAG and other areas of the brain (limbic system orbitofrontal cortex) input into the pontine micturition center (PMC) and determine whether it is appropriate to start micturition. At times when it is appropriate to void, micturition is initiated by relaxa- tion of the ex ternal urethral sphincter and pelvic \202 oor. Urine enters the posterior urethra and thi s, combined with pelvic \202 oor relaxation, activates afferent neurons, which results in stimulation of the PMC (located in the brainstem). Activation of the PMC switches on a det rusor contraction via a direct communication between neurons of the PMC and the cell bodies of parasympathetic, preganglionic motoneurons located in the sacral intermediolateral cell column of S2 \200\2234. At the same time that the detrusor contracts, the urethra (the ext ernal sphincter) relaxes. The PMC inhibits the somatic motoneurons located in Onuf \200\231 s nucleus (the activation of which causes external sphincter contraction) by exciting GABA and glycine-containing inhibitory neurons in the intermediolateral cell column of the sacra l cord, which in turn project to the motoneurons in Onuf \200\231s nucleus. In this way, th e PMC relaxes the external sphincter. Micturition is an example of a positive feedback loop, the aim being to maintain bladder co ntraction until the bladder is empty. As the detru- sor contracts, tension in the bladder w all rises. The bladder wall tension receptors are stimulated and the detrusor contraction i s driven harder. One of the problems of positive feedback loops is their instability. Sever al inhibitory pathways exist to stabilize the storage \200\223micturition \200\230loop \200\231. THE PHYSIOLOGY OF URINE STORAGE AND MICTURITION 609 Tension receptors activate bladder afferents, which via the pudendal and hypogastric nerves , inhibit S2 \200\2234 parasympathetic motor nerve output. An ongoing detrusor contraction cannot be overridden. Afferents in the anal and genital regions and in the distribution of the posterior tibial nerve stimulate inhibitory neurons in the sacral cord and these neuron s inhibit S2 \200\2234 parasympathetic motor nerve output. This pathway can override an ong oing detrusor contraction. It is hypothesized that this system prevents involuntary detruso r contraction during sexual activity, defaecation, and while walking, running, and jumping. Excitatory neurotransmission in the normal detrusor is exclusively cho- linergic and recipr ocal relaxation of the urethral sphincter and bladder neck is mediated by NO released from post-ganglionic parasympathetic neurons. Further reading De Groat WC (1993) Anatomy and physiology of the lower urinary tract. Urol Clin NA 20: 383 \200\223401. CHAPTER 14 Neuropathic bladder 610 Bladder and sphincter behavior in the patient with neurological disease A variety of neurol ogical conditions are associated with abnormal blad- der and sphincter function (e.g. SCI, spina bi \201 da (myelomeningocele), MS). The bladder and sphincters of such patients are described as \200\230neuropathic \200\231. They may have abnormal bladder function or abnormal sphincter func- tion or, more usually, both. The bladder may be over- or underactive, as may the sphincter and any combination of bladder and sphincter over- or underactivity may coexist. \200\230Activity \200\231 here m eans bladder and sphincter pressure. In the normal LUT during bladder \201 lling, the detrusor muscle is inactive and the sphi ncter pressure is high. Bladder pressure is, therefore, low and the high sphincter pressure maintains continence. During voiding, the sphincter relaxes and the detrusor contracts. Th is leads to a short-lived increase in bladder pressure, sustained until the bladder is comp letely empty. The detrusor and sphincter thus function in synergy \200\224when the sphincte r is active, the detrusor is relaxed (storage phase) and when the detrusor contracts, the s phincter relaxes (voiding phase). An overactive bladder is one that intermittently contracts during blad- der \201 lling so developing high pressures when normally bladder pressure should be low. In between these w aves of contraction, bladder pressure returns to normal or near normal levels. In a patient with an underlying neurological problem, bladder overactivity is called detrusor hyperre \202 exia (DH). In other patients, the bladder wall is stiffer than normal, a condition kno wn as poor compliance. Bladder pressure rises progressively during \201 lling, such bladd ers being unable to store urine at low pressures. Some patients have a combination of DH an d poor compliance. The other end of the spectrum of bladder behavior is the underactive bla dder which is low pressure during \201 lling and voiding. This is called detrusor are \202 exia. An overactive sphincter generates high pressure during bladder \201 lling, but it also do es so during voiding when normally it should relax. This is known as detrusor \200\223exter nal sphincter dyssynergia (DESD or DSD; Fig. 14.1). During EMG recording, activity in the e xternal sphincter increases during attempted voiding (the external sphincter should normall y be \200\230quiet \200\231 during voiding; see Fig. 3.16). An underactive sphincter is un able to maintain enough pressure in the face of normal bladder pressures to prevent leakage of urine. BLADDER AND SPHINCTER behavior 611 Fig. 14.1 Detrusor \200\223external sphincter dyssynergia (DESD) seen during video cystoure thrography. CHAPTER 14 Neuropathic bladder 612 The neuropathic lower urinary tract: clinical consequences of storage and emptying problems Neuropathic patients experience two broad categories of problems \200\224 bladder \201 l ling and emptying \200\224depending on the balance between bladder and sphincter pressures during \201 lling and emptying. The effects of these bladder \201 lling and emptying pr oblems include incontinence, retention, recurrent UTIs, and renal failure. High-pressure sphincter High-pressure bladder If the bladder is overactive (detrusor hyperr e \202 exia) or poorly compliant, bladder pressures during \201 lling are high. The kidn eys have to function against these chronically high pressures. Hydronephrosis develops and ultimately, the kidneys fail (renal failure). At times, the bladder pressure overcomes the sphincter pressure and the patient leaks urine (inconti- nence). If the sphincter pressure is higher than the bladder pressure dur- ing voiding (DSD), bladder emptying is inef \201 cient (retention, recurrent UTIs). Low-pressure bladder If the bladder is underactive (detrusor are \202 exia), pressure duri ng \201 lling is low. The bladder simply \201 lls up \200\224it is unable to generate e nough pressure to empty (retention, recurrent UTIs). Urine leaks at times if the bladder pr essure becomes higher than the sphincter pressure (incontinence), but this may occur only a t very high bladder volumes or not at all. Low-pressure sphincter High-pressure bladder If the detrusor is hyperre \202 exic or poorl y compliant, the bladder will only be able to hold low volumes of urine before leaking (inc ontinence). Low-pressure bladder If the detrusor is are \202 exic such that it cannot develop high pre ssures, the patient may be dry for much of the time. They may, however, leak urine (inconti nence) when abdominal pressure rises (e.g. when coughing, rising from a seated position, or when transferring to or from a wheelchair). Their low bladder pressure may compromise blad der emptying (recur- rent UTIs). This page intentionally left blank CHAPTER 14 Neuropathic bladder 614 Bladder management techniques for the neuropathic patient A variety of techniques and proce dures are used to treat retention, incon- tinence, recurrent UTIs, and hydronephrosis in th e patient with a neuro- pathic bladder. Each of the techniques described here can be used f or a variety of clinical problems. Thus, a patient with a high-pressure, hyper- re \202 ex ic bladder that is causing incontinence can be managed with an ISC (with intravesical botox injections, if necessary) or an SPC or by sphinc- terotomy with condom sheath drainage or by deafferentation combined with a sacral anterior root stimulator (SARS). Precisely which option to choose will depend on the individual patient \200\231s clinical problem, their ha nd function, their lifestyle, and other \200\230personal \200\231 factors such as body ima ge, sexual function, etc. Some patients will opt for an SPC as a simple, gener- ally safe, generally very convenient, and effective form of bladder drainage. Others wish to be free o f external appliances and devices because of an understandable desire to look and \200\230 feel \200\231 normal. They might opt for deaf- ferentation with a SARS. Intermittent self-catheterization (ISC) See b p. 622. Indwelling catheters See b p. 622. External sphincterotomy Deliberate division of the external sphincter to convert the high-p ressure, poorly emptying bladder due to DSD to a low-pressure, ef \201 ciently empty- ing bladder. Indications: retention, recurrent UTIs, hydronephrosis. Techniques - Surgical (with an electrically heated \200\230knife \200\231 or laser). irreversible, post -operative bleeding, septicaemia, and stricture formation.1 Intra-sphincteric botox (botuli num toxin). A minimally invasive and reversible alternative to surgical sphincterotomy. Dis advantage: repeat injection required every 6 \200\22312 months; in the authors opinion (bas ed on years of experience of botox and surgical sphincterotomies), probably not as effectiv e at lowering bladder pressure and improving bladder emptying as surgical sphincterotomy (b ut no trials have compared the two techniques). A third potential option is an oral or subl ingual nifedipine, GTN). NO is a neurotransmitter which relaxes the external sphincter. Hyp othesized as a treatment for DSD and preliminary studies support this hypothesis.2,3 Disadvantages: NO donor (e.g. Augmentation Technique of increasing bladder volume to lower pressure by implanting detubul arized small bowel into the bivalved bladder ( \200\230clam \200\231 ileocystoplasty) (Fig. 14.2) or by removing a disc of muscle from the dome of the bladder BLADDER MANAGEMENT TECHNIQUES 615 (a) Midline incision (b) The isolated small bowel segment is detubularized. (c) The ileal patch has been configured into a \200\230U \200\231 shape ready for anastomosis onto the bladder. (d) The patch of ileum is anastomosed to the bladder. Fig. 14.2 A \200\230clam \200\231 ileocystoplasty. (Reproduced from Reynard, J, Mark, S. e t al., Urological Surgery. Oxford University Press, with permission from OUP.) CHAPTER 14 Neuropathic bladder 616 (auto-augmentation or detrusor myectomy). In the botox era, augmenta- tion is becoming less and less frequently used because repeat (every 6 \200\22312 months) botox injections are o ften all that is required to achieve an accept- able level of continence, but also because of the short- and long-term mor- bidity of augmentation (bladder stones in 15%, bladder per foration, high grade invasive bladder cancers).4 Indications: incontinence unacceptable to the patient or hydronephrosis despite full conservative therapy (regular ISC combined with anticholinergics and a trial of bladder botox injections). Intravesical botlinum toxin injections Recently, intravesical botulinum toxin type A inject ions at multiple sites in the bladder every 6 \200\22312 months have produced impressive re ductions in bladder pressure and increases in volume (bladder capacity), with a low risk of side effects. As a consequence, surgical augmentation is nowadays only rarely done, being reserved for cases where botox has failed to work (where the patient is still wet between p assing ISC catheters or where there is persistent hydronephrosis). Botulinum toxin is a potent neurotoxin produced by the Gram-negative anaerobic bacterium Cl ostridium botulinum. Of the seven serotypes, only types A (BoNT-A) ( \200\230Botox \200 \231, Allergan, CA in the United States; \200\230Dysport \200\231, Ipsen, Slough, UK) an d B ( \200\230Myobloc \200\231, Elan Pharmaceuticals, NJ, United States) are used clinica lly. BoNT-A is synthesized as an inactive single chain of 1285 amino acid polypeptide and i s activated when cleaved by Clostridial protease into a two-chain polypeptide (50kDa light chain, 100kDa heavy chain). Botulinum toxin type A ( \200\230Botox \200\231 or \200\230Dysport \200\231) binds to the SV2 recep- tor (synaptic vesicle protein) on the presynaptic nerve terminal where it is internalized by endocytosis. It causes proteolysis of the synaptosomal associated protein, SNAP-25, which is one of a group of SNARE pro- teins \200\224with neuronal cell membranes (BoNT-B cleaves synaptobrevin). Thus, botulinum toxin inhibits neurotransmission at motor c holinergic, noradrenergic, and other (sensory) nerve terminals. It also reduces the express ion of the vanilloid receptor, TPRV1, and the purinoreceptor, P2X3, both of which are senso ry neuron receptors. Thus, while we tend to think of botulinum toxin type A as inhibiting neu- romuscular nerve transmission and, therefore, as a muscle paralyzing agent, it is likely that it also has ef fects on sensory nerve transmission. BoNT-A inhibits the release of calcitonin gene-related peptide, substance P, gluta- mate, nerve growth factor, and ATP, which are neurotransmitte rs involved in pain pathways. In rat pain models, BoNT-A reduces pain behavior.5,6 How this effect on sensory nerve function translates into a role, if any, in the management of sens ory urological conditions (sensory urgency, inter- stitial cystitis) remains to be establis hed. Recovery of neurotransmission requires removal of BoNT and restora- tion of intact SNARE proteins. Intravesical botox injections can be administered using a \202 exible cys- toscope (with a \202 exible injection needle) or a rigid scope. Multiple tech- niques of injection have been described and all seem to be effective. Some surgeons dilute the botox in 5mL of sali ne whereas others use the same number of units in 10 or 20mL of saline. Some use \200\230D ysport \200\231 (Ipsen) while BLADDER MANAGEMENT TECHNIQUES 617 others use \200\230Botox \200\231 (Allergan). Some inject in ten sites, others in 20 sit es, while others make 50 injections. Whether one technique or concentration or formulation of botox is superior to any other remains to be established. Precisely where the botox is a ctually administered (into the detrusor mus- cle or into the suburothelium) is debatable (t he bladder wall is thin). For intravesical injection in neuropathic patients (e.g. those with SCI or MS), the author uses a standard dose of 1000 units of Dysport (though not infrequently between 1000 and 1 500 units in those failing to respond for an adequate duration with 1000 units), diluted in 10mL of saline, and injects 0.33mL per site (three doses per 1mL syringe) in approximately 30 sites (roughly 30 \200\22335 units per site), using (usually) a \202 exible cysto- sc ope and \202 exible injection needle. Some surgeons spare the trigone (i.e. avoid injecti ng the trigone), the theory (not proven) being that this avoids disrupting the valve mechan ism of the VUJ. Other surgeons (the author included) inject in the trigone. Since the trigo ne has a dense sensory inner- vation, trigonal injections may (unproven) be more effective for sensory or painful bladder syndromes. Intravesical botox injections are indicated for hydronephrosis which has failed to respond to increased frequency of ISC combined with oral anti- cholinergic medication; inter-ISC le akage which has failed to respond to increased frequency of ISC combined with oral antichol inergic medication; urethral leakage in patients with SPC where the leakage is thought to b e due to uninhibited bladder contractions. Outcomes of bladder botulinum toxin injections in the neuropathic patient Bladder botox inj ections reduced incontinence episodes by a mean of 50% in patients with SCI when compared w ith placebo7 and markedly improve continence in patients with MS where 80% are wet before b otox, approxi- mately 80% being dry afterwards, and remaining so for a median of 12 \200 \22313 months.8 Outcomes of bladder botulinum toxin injections in the non-neuropathic patient In non-neurop athic patients, three randomized placebo-controlled trials have shown that patients treated with 200 \200\223300 units of Botox dissolved in between 2.5 to 20mL of saline and given at 10 \200\22320 sites had reduced urinary frequency and on average 3.88 fewer incontinenc e episodes per day.9 The botox took effect within 3 \200\22314 days and lasted for a median of 307 days. What dose of bladder botulinum should be used? There have been few studies to determine the \200\230correct \200\231 dose of botox either in neuropaths or non-neuropaths, e.g. the m inimal effective dose or the dose giving an adequate duration of effect (balanced against a low frequency of side effects). For the patient who has to change their clothes several ti mes a day, knowledge of the undoubted ef \201 cacy of intravesical botox injections makes it is dif \201 cult to decide to enter a placebo-control- led study or one where a low, po ssibly ineffective, dose might be used. In the neuropathic patient, there appears to be no signi \201 cant difference in clinical and urodynamic outcomes in patients (mainly spinal injury or MS and almost all doing ISC) r andomized to 500 vs 750 units of Dysport CHAPTER 14 Neuropathic bladder 618 (5mL saline, 20 injection sites).10 Complete continence was achieved in 56% and 74%, respec tively (no signi \201 cant dose difference). Reappearance of incontinence occurred at a me dian of 168 days (5.5 months). The blad- der volume at which a re \202 ex bladder contract ion occurred increased by a mean of approximately 150mL and maximum cystometric capacity in creased by a median of 192mL (500 units) to 243mL (750 units) (no signi \201 cant dose dif ference, but a trend towards a better symptomatic and urodynamic improvement in those recei ving 750 units). In the author \200\231s experience, intravesical botox injections are most suc- cessful for the neuropathic patient with inter-ISC leakage, but they are also a very effective treatme nt for the symptoms of frequency, noctu- ria, urgency, and urge incontinence caused by non- neuropathic detrusor overactivity. They last for somewhere between 6 and 12 months and the ef \201 cacy and duration of effect of the botulinum toxin does not appear to diminish wit h repeat injections in both the neuropath or non-neuropath over, at present, 10y of follow- up, an experience shared by others.8,11 Side effects of botulinum toxin type A The principle side effect is urinary retention, a re tention volume of >150 \200\223200mL of urine occurring in approximately 40% of individuals (in the non-neuropathic patient); in the neuropathic patient, the deliberate aim is to ach ieve retention so that the patient becomes completely continent between doing ISC. Up to 41 % of patients were said to \200\230require \200\231 ISC for up to 6 months.9 Committing a patient to ISC for as long as 6 months after botox injections according to a rigid de \201 nition of urinary retention based solely on a post-void residual urine volume of >150 \200 \223200mL, but in the absence of symptoms, is, in the authors \200\231 opinion, an unnecess ary imposi- tion. The author has a less rigid practice and places a patient on ISC only if they have (a) painful, complete urinary retention (painful inability to pass any urine, the pain being relieved by catheterization), or (b) are able to void only a few mL of urine wh ile retaining the bulk of their urine produc- tion, or (c) has complete painless retention (painless inability to pass any urine \200\224very unusual), or (d) develop symptomatic, re current UTI in the post-botox period. The author recommends the patient discontinue ISC onc e they feel comfortable to do so which, empirically, is usually when the balance between vo ided urine volume and retained urine volume shifts in favor of the former. There is limited evidence suggesting retention is more likely with higher doses of Botox at 200 units leading to retention of urine compared with no retention after 100 units.12 Haematuria is almost inevitable after making multiple intravesical injec- tions and is almo st always self-limiting (very occasionally, admission for a bladder washout of clots and ir rigation via a 3-way catheter is required, but this is rare \200\224two cases in 10y in the author \200\231s experience). Occasionally, systemic side effects can occur. These are unc ommon, but can be disa- bling, particularly in the patient with pre-existing neurological d isease. The author warns patients of the risks of generalized weakness which occurs in appr oximately 1 in 100 patients (lower risk after bladder injections; higher risk after externa l sphincter injections) and can impair the ability to trans- fer on and off a wheelchair an d affect daily living and working activities; BLADDER MANAGEMENT TECHNIQUES 619 blurring of vision (due to intraocular muscle effects \200\224very rare, but very disabling ); and dif \201 culty taking a deep breath and/or swallowing (two cases in 10y in the auth or \200\231s experience, both resolving spontaneously within 2 \200\2233 weeks and neither required in-hospital observation). All of these side effects are uncommon, will last weeks or a few months, require no speci \201 c treatment, and usually do not recur with subseque nt repeat injections. Deafferentation Division of dorsal spinal nerve roots of S2 \200\2234 to convert the hyperr e \202 exic, high-pressure bladder into an are \202 exic, low-pressure one. Can be used w here the hyperre \202 exic bladder is the cause of incontinence or hydrone- phrosis. Bladd er emptying can subsequently be achieved by ISC or implanta- tion of a nerve stimulator pla ced on ventral roots (efferent nerves) of S2 \200\2234 to \200\230drive \200\231 micturiti on when the patient wants to void (a pager-sized exter- nally applied radiotransmitter acti vates micturition (Figs. 14.3 and 14.4). Also useful for DSD/incomplete bladder emptying ca using recurrent UTIs and retention. 1 Reynard JM (2003) Sphincterotomy and the treatment of detrusor \200\223sphincter dyssyner gia: cur- rent status, future prospects. Spinal Cord 41:1 \200\22311. 2 Reitz A, Knapp PA, M ntener M, Schurch B (2004) Oral nitric oxide donors: a new phar- ma cological approach to detrusor-sphincter dyssynergia in spinal cord injured patients. Eur U rol 45:516 \200\22320. 3 Mamas MA, Reynard JM, Brading AF (2001) Augmentation of external uretheral sphincter nitr ic oxide: a potential pharmacological treatment for detrusor-external sphincter dyssynergia in spinal cord injury. Lancet 357:1964 \200\2237. 4 Cain MP, Rink RC (2010) Augmentation for neuropathic bladder dysfunction \200\223 A thin g of the past? J Urol 183:2124 \200\2235. 5 Cui M, Khanijou S, Rubino J, Aoki KR (2004) Subcutaneous administration botulinum toxin t ype A reduces formalin-induced pain. Pain 107:125 \200\22333. 6 Chuang YC, Yoshimura N, Huang CC, Chiang PH, Chancellor MB (2004) Intravesical botulinum toxin A administration produces analgesia against acetic acid induced bladder pain response s in rats. J Urol 172:1529 \200\22332. 7 Schurch B, de S ze M, Denys P,et al. (2005) Botox detrusor hyper-re \202 exia study tea m. Botulinum toxin type A is safe and effective treatment for neurogenic urinary incontinen ce: results of a single treatment, randomized, placebo controlled 6 month study. J Urol 174 :196 \200\223200. 8 Khan S, Game X, Kalsi V, et al. (2011) Long term effect on quality of life of repeat detr usor injections of botulinum neurotoxin-A for detrusor overactivity in patients with multip le sclerosis. J Urol 185:1344 \200\2239. 9 Anger JT, Weinberg A, Suttorp MJ, Litwin MS, Shekelle PG (2010) Outcome of intravesical b otulinum toxin for idiopathic overactive bladder symptoms: a systematic review of the liter ature. J Urol 183:2258 \200\22364. 10 Grise P, Ruf \201 on A, Denys P, Egon G, Chartier Kastler E (2010) Ef \201 cacy and to lerability of botulinum toxin type A in patients with neurogenic detrusor overactivity and without concomitant anticholinergic therapy: comparison of two doses. Eur Urol 58:759 \200 \22366. 11 Game X, Khan S, Panicker JN, et al. (2010) Comparison of the impact on health related qu ality of life of repeated detrusor injections of botulinum toxin in patients with idiopathi c or neurogenic detrusor overactivity. BJU Int 107:1786 \200\22392. 12 Kuo HC (2006) Will suburothelial injection of a small dose of botulinum A toxin have sim ilar therapeutic effects and less adverse events for refractory detrusor overactivity. Urol ogy 68:993 \200\2237. CHAPTER 14 Neuropathic bladder 620 Fig. 14.3 A sacral anterior root stimulator used to \200\230drive \200\231 micturition fol lowing a deafferentation (external components). Fig. 14.4 KUB X-ray showing the sacral electrodes positioned on the ventral roots of S2, 3, and 4. This page intentionally left blank CHAPTER 14 Neuropathic bladder 622 Catheters and sheaths and the neuropathic patient Many patients manage their bladders by in termittent catheterization (IC) done by themselves (ISC) or by a carer if their hand functi on is inad- equate, as is the case with most (though remarkably not all) tetraplegics. Many others manage their bladders with an indwelling catheter (urethral or suprapubic). Both me thods can be effective for managing incontinence, recurrent UTIs, and BOO causing hydroneph rosis. Intermittent catheterization Requires adequate hand function. The technique is a \200\230c lean \200\231 one (simple handwashing prior to catheterization) rather than \200\230steril e \200\231. Gel-coated catheters become slippery when in contact with water so providing lu bri- cation. Usually done 3 \200\2234 hourly. Problems - - Recurrent Recurrent incontinence: check technique (adequate drainage of last few drops of u rine). Suggest increasing frequency of ISC to minimize volume of urine in the bladder (redu ces bacterial colonization and minimizes bladder pressure). If incontinence persists, consi der intravesical botulinum toxin. UTIs. Long-term catheterization Some patients prefer the convenience of a long-term catheter. Oth ers regard it as a last resort when other methods of bladder drainage have failed. The supr apubic route (SPC) is preferred over the urethral because of pressure necrosis of the ventr al surface of the distal penile urethra in men (acquired hypospadias \200\224 \200\230kippe ring \200\231 of the penis) and pressure necro- sis of the bladder neck in women which beco mes wider and wider until urine leaks around the catheter ( \200\230patulous \200\231 ureth ra) or frequent expulsion of the catheter occurs with the balloon in \202 ated. Problems and complications of long-term catheters - Recurrent source of recurrent infection. Catheter blockages are common: of the catheter wit h bacterial bio \201 lms. Proteus mirabilis, Morganella, and Providencia species secrete a polysaccharide matrix. Within this, urease-producing bacteria generate ammonia from nitrog en in urine, raising urine pH and precipitating magnesium and calcium phosphate crystals. T he matrix \200\223crystal complex blocks the catheter. Catheter blockage causes bypassing w hich soils the patient \200\231s clothes. Bladder distension can cause autonomic dysre \202 exia, leading to extreme rises in BP which can cause stroke and death! Regular bladder washouts and increased catheter size sometimes help. Impregnation of catheters with antiba cterials (e.g. triclosan) are under investigation.1 Intermittent \201 lling and emptying of the bladder using a \200\230 \202 ip- \202 ow \200\231 valve may reduce the frequency of catheter blockages. UTIs: colonization with bacteria provides a potential due to encrustation of the lumen CATHETERS AND SHEATHS AND THE NEUROPATHIC PATIENT 623 develop in 1 in 4 patients over 5y.2 chronic in \202 ammation (from bladder stones, recurr ent Bladder stones: Bladder cancer: UTIs, long-term catheterization) may increase the risk of s quamous cell carcinoma in SCI patients. Some studies report a higher incidence of bladder c ancer (whether chronically catheterized or not); others do not.3