14 Neuropathic bladder

Preganglionic, parasympathetic nerve cell bodies are located in the intermediolateral column of spinal segments S2–4. These preganglionic, parasympathetic fibres 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 preganglionic, parasympathetic fibres synapse within ganglia with the cell bodies of the post-ganglionic parasympathetic 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 post-ganglionic axons provide cholinergic excitatory input to the smooth muscle of the bladder.

In the male, preganglionic sympathetic nerve fibres arise from the intermediolateral column of T10–12 and L1–2. These preganglionic neurons synapse in the sympathetic chain and post-ganglionic sympathetic nerve fibres travel as the hypogastric nerves to innervate the trigone, blood vessels of the bladder, and the smooth muscle of the prostate and preprostatic sphincter (i.e. the 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 ganglia (in the adventitia surrounding the bladder and within the bladder wall) and exert an inhibitory effect on bladder smooth muscle contraction.

Afferent nerves from receptors throughout the bladder ascend with parasympathetic neurons back to the cord and from there, up to the pontine storage and micturition centres or to the cerebral cortex. They sense bladder filling.

Other receptors are located in the trigone and afferent neurons from these neurons ascend with sympathetic neurons up to the thoracolumbar cord and thence to the pons and cerebral cortex.

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.

Anatomically, this is located slightly distal to the apex of the prostate in the male (between the verumontanum and proximal bulbar urethra) and in the mid-urethra in the female. It has three components:

Preganglionic somatic nerve fibres (i.e. neurons which innervate striated muscle) are, along with parasympathetic nerve fibres (which innervate the bladder), derived from spinal segments S2–4, specifically from Onuf’s nucleus (also known as spinal nucleus X) which lies in the medial part of the anterior horn of the spinal cord. (Onuf’s nucleus is the location of the cell bodies of somatic motoneurons that provide motor input to the striated muscle of the pelvic floor—the external urethral and anal sphincters.) These somatomotor nerves travel to the rhabdosphincter via the perineal branch of the pudendal nerve (documented by direct stimulation studies and horseradish peroxidase (HRP) tracing—accumulates in Onuf’s 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 (specifically the inferior hypogastric plexus) via pelvic nerves. In dogs, complete silence of the rhabdosphincter is seen only if both the pudendal and pelvic efferents are sectioned. Thus, pudendal nerve block or pudendal neurectomy does not cause incontinence.

The nerve fibres that pass distally to the distal sphincter mechanism are located in a dorsolateral position (5 and 7 o’clock). More distally, they adopt a more lateral position.

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 horn of the spinal cord at S2–4, connecting with neurons that relay sensory information to the brainstem and cerebral cortex.

The pudendal nerve (a somatic nerve derived from spinal segments S2–4) innervates striated muscle of the pelvic floor (levator ani, i.e. the pubo-urethral sling). Bilateral pudendal nerve block¹ does not lead to incontinence because of maintenance of internal (sympathetic innervation) and external sphincter function (somatic innervation, S2–4, nerve fibres travelling to the external sphincter alongside parasympathetic neurons in the nervi erigentes).

During bladder filling, bladder pressure remains low despite a substantial increase in volume. The bladder is thus highly compliant. Its high compliance is partly due to the elastic properties (viscoelasticity) of the connective 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 is able to do this as a consequence of prevention of transmission of activity from preganglionic parasympathetic neurons to post-ganglionic efferent neurons—a so-called ‘gating’ mechanism within the parasympathetic ganglia. In addition, inhibitory interneuron activity in the spinal cord prevents transmission of afferent activity from sensors of bladder filling.

A spino-bulbar-spinal reflex, coordinated in the pontine micturition centre in the brainstem (also known as Barrington’s nucleus or the M region), results in simultaneous detrusor contraction, urethral relaxation, and subsequent micturition. Receptors located in the bladder wall sense increasing tension as the bladder fills (rather than stretch). This information is relayed, by afferent neurons to the dorsal horn of the sacral cord. Neurons project from here to the periaqueductal grey (PAG) matter in the pons. The PAG is thus informed about the state of bladder filling. The PAG and other areas of the brain (limbic system orbitofrontal cortex) input into the pontine micturition centre (PMC) and determine whether it is appropriate to start micturition.

At times when it is appropriate to void, micturition is initiated by relaxation of the external urethral sphincter and pelvic floor. Urine enters the posterior urethra and this, combined with pelvic floor relaxation, activates afferent neurons, which results in stimulation of the PMC (located in the brainstem). Activation of the PMC switches on a detrusor 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 S2–4. At the same time that the detrusor contracts, the urethra (the external sphincter) relaxes. The PMC inhibits the somatic motoneurons located in Onuf’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 sacral cord, which in turn project to the motoneurons in Onuf’s nucleus. In this way, the PMC relaxes the external sphincter.

Micturition is an example of a positive feedback loop, the aim being to maintain bladder contraction until the bladder is empty. As the detrusor contracts, tension in the bladder wall rises. The bladder wall tension receptors are stimulated and the detrusor contraction is driven harder. One of the problems of positive feedback loops is their instability. Several inhibitory pathways exist to stabilize the storage–micturition ‘loop’.

Excitatory neurotransmission in the normal detrusor is exclusively cholinergic and reciprocal relaxation of the urethral sphincter and bladder neck is mediated by NO released from post-ganglionic parasympathetic neurons.

A variety of neurological conditions are associated with abnormal bladder and sphincter function (e.g. SCI, spina bifida (myelomeningocele), MS). The bladder and sphincters of such patients are described as ‘neuropathic’.

They may have abnormal bladder function or abnormal sphincter function 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. ‘Activity’ here means bladder and sphincter pressure.

In the normal LUT during bladder filling, the detrusor muscle is inactive and the sphincter pressure is high. Bladder pressure is, therefore, low and the high sphincter pressure maintains continence. During voiding, the sphincter relaxes and the detrusor contracts. This leads to a short-lived increase in bladder pressure, sustained until the bladder is completely empty. The detrusor and sphincter thus function in synergy—when the sphincter is active, the detrusor is relaxed (storage phase) and when the detrusor contracts, the sphincter relaxes (voiding phase).

An overactive bladder is one that intermittently contracts during bladder filling so developing high pressures when normally bladder pressure should be low. In between these waves of contraction, bladder pressure returns to normal or near normal levels. In a patient with an underlying neurological problem, bladder overactivity is called detrusor hyperreflexia (DH). In other patients, the bladder wall is stiffer than normal, a condition known as poor compliance. Bladder pressure rises progressively during filling, such bladders being unable to store urine at low pressures. Some patients have a combination of DH and poor compliance. The other end of the spectrum of bladder behaviour is the underactive bladder which is low pressure during filling and voiding. This is called detrusor areflexia.

An overactive sphincter generates high pressure during bladder filling, but it also does so during voiding when normally it should relax. This is known as detrusor–external sphincter dyssynergia (DESD or DSD; Fig. 14.1). During EMG recording, activity in the external sphincter increases during attempted voiding (the external sphincter should normally be ‘quiet’ during voiding; see Fig. 3.16). An underactive sphincter is unable to maintain enough pressure in the face of normal bladder pressures to prevent leakage of urine.

Neuropathic patients experience two broad categories of problems— bladder filling and emptying—depending on the balance between bladder and sphincter pressures during filling and emptying. The effects of these bladder filling and emptying problems include incontinence, retention, recurrent UTIs, and renal failure.

If the bladder is overactive (detrusor hyperreflexia) or poorly compliant, bladder pressures during filling are high. The kidneys 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 (incontinence). If the sphincter pressure is higher than the bladder pressure during voiding (DSD), bladder emptying is inefficient (retention, recurrent UTIs).

If the bladder is underactive (detrusor areflexia), pressure during filling is low. The bladder simply fills up—it is unable to generate enough pressure to empty (retention, recurrent UTIs). Urine leaks at times if the bladder pressure becomes higher than the sphincter pressure (incontinence), but this may occur only at very high bladder volumes or not at all.

If the detrusor is hyperreflexic or poorly compliant, the bladder will only be able to hold low volumes of urine before leaking (incontinence).

If the detrusor is areflexic such that it cannot develop high pressures, the patient may be dry for much of the time. They may, however, leak urine (incontinence) 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 bladder emptying (recurrent UTIs).

A variety of techniques and procedures are used to treat retention, incontinence, recurrent UTIs, and hydronephrosis in the patient with a neuropathic bladder. Each of the techniques described here can be used for a variety of clinical problems. Thus, a patient with a high-pressure, hyperreflexic bladder that is causing incontinence can be managed with an ISC (with intravesical botox injections, if necessary) or an SPC or by sphincterotomy 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’s clinical problem, their hand function, their lifestyle, and other ‘personal’ factors such as body image, sexual function, etc. Some patients will opt for an SPC as a simple, generally safe, generally very convenient, and effective form of bladder drainage. Others wish to be free of external appliances and devices because of an understandable desire to look and ‘feel’ normal. They might opt for deafferentation with a SARS.

See  p. 622.

See  p. 622.

Deliberate division of the external sphincter to convert the high-pressure, poorly emptying bladder due to DSD to a low-pressure, efficiently emptying bladder. Indications: retention, recurrent UTIs, hydronephrosis.

Technique of increasing bladder volume to lower pressure by implanting detubularized small bowel into the bivalved bladder (‘clam’ ileocystoplasty) (Fig. 14.2) or by removing a disc of muscle from the dome of the bladder (auto-augmentation or detrusor myectomy). In the botox era, augmentation is becoming less and less frequently used because repeat (every 6–12 months) botox injections are often all that is required to achieve an acceptable level of continence, but also because of the short- and long-term morbidity of augmentation (bladder stones in 15%, bladder perforation, 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).

Recently, intravesical botulinum toxin type A injections at multiple sites in the bladder every 6–12 months have produced impressive reductions 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 passing ISC catheters or where there is persistent hydronephrosis).

Botulinum toxin is a potent neurotoxin produced by the Gram-negative anaerobic bacterium Clostridium botulinum. Of the seven serotypes, only types A (BoNT-A) (‘Botox^®’, Allergan, CA in the United States; ‘Dysport^®’, Ipsen, Slough, UK) and B (‘Myobloc^®’, Elan Pharmaceuticals, NJ, United States) are used clinically. BoNT-A is synthesized as an inactive single chain of 1285 amino acid polypeptide and is activated when cleaved by Clostridial protease into a two-chain polypeptide (50kDa light chain, 100kDa heavy chain).

Botulinum toxin type A (‘Botox^®’ or ‘Dysport^®’) binds to the SV2 receptor (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 proteins—with neuronal cell membranes (BoNT-B cleaves synaptobrevin). Thus, botulinum toxin inhibits neurotransmission at motor cholinergic, noradrenergic, and other (sensory) nerve terminals. It also reduces the expression of the vanilloid receptor, TPRV1, and the purinoreceptor, P2X3, both of which are sensory neuron receptors.

Thus, while we tend to think of botulinum toxin type A as inhibiting neuromuscular nerve transmission and, therefore, as a muscle paralysing agent, it is likely that it also has effects on sensory nerve transmission. BoNT-A inhibits the release of calcitonin gene-related peptide, substance P, glutamate, nerve growth factor, and ATP, which are neurotransmitters involved in pain pathways. In rat pain models, BoNT-A reduces pain behaviour.^5,6 How this effect on sensory nerve function translates into a role, if any, in the management of sensory urological conditions (sensory urgency, interstitial cystitis) remains to be established.

Recovery of neurotransmission requires removal of BoNT and restoration of intact SNARE proteins.

Intravesical botox injections can be administered using a flexible cystoscope (with a flexible injection needle) or a rigid scope. Multiple techniques of injection have been described and all seem to be effective. Some surgeons dilute the botox in 5mL of saline whereas others use the same number of units in 10 or 20mL of saline. Some use ‘Dysport^®’ (Ipsen) while others use ‘Botox^®’ (Allergan). Some inject in ten sites, others in 20 sites, 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 actually administered (into the detrusor muscle or into the suburothelium) is debatable (the 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 1500 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 30–35 units per site), using (usually) a flexible cystoscope and flexible injection needle. Some surgeons spare the trigone (i.e. avoid injecting the trigone), the theory (not proven) being that this avoids disrupting the valve mechanism of the VUJ. Other surgeons (the author included) inject in the trigone. Since the trigone has a dense sensory innervation, 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 anticholinergic medication; inter-ISC leakage which has failed to respond to increased frequency of ISC combined with oral anticholinergic medication; urethral leakage in patients with SPC where the leakage is thought to be due to uninhibited bladder contractions.

Bladder botox injections reduced incontinence episodes by a mean of 50% in patients with SCI when compared with placebo⁷ and markedly improve continence in patients with MS where 80% are wet before botox, approximately 80% being dry afterwards, and remaining so for a median of 12–13 months.⁸

In non-neuropathic patients, three randomized placebo-controlled trials have shown that patients treated with 200–300 units of Botox^® dissolved in between 2.5 to 20mL of saline and given at 10–20 sites had reduced urinary frequency and on average 3.88 fewer incontinence episodes per day.⁹ The botox took effect within 3–14 days and lasted for a median of 307 days.

There have been few studies to determine the ‘correct’ dose of botox either in neuropaths or non-neuropaths, e.g. the minimal 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 times a day, knowledge of the undoubted efficacy of intravesical botox injections makes it is difficult to decide to enter a placebo-controlled study or one where a low, possibly ineffective, dose might be used.

In the neuropathic patient, there appears to be no significant difference in clinical and urodynamic outcomes in patients (mainly spinal injury or MS and almost all doing ISC) randomized to 500 vs 750 units of Dysport^® (5mL saline, 20 injection sites).¹⁰ Complete continence was achieved in 56% and 74%, respectively (no significant dose difference). Reappearance of incontinence occurred at a median of 168 days (5.5 months). The bladder volume at which a reflex bladder contraction occurred increased by a mean of approximately 150mL and maximum cystometric capacity increased by a median of 192mL (500 units) to 243mL (750 units) (no significant dose difference, but a trend towards a better symptomatic and urodynamic improvement in those receiving 750 units).

In the author’s experience, intravesical botox injections are most successful for the neuropathic patient with inter-ISC leakage, but they are also a very effective treatment for the symptoms of frequency, nocturia, urgency, and urge incontinence caused by non-neuropathic detrusor overactivity. They last for somewhere between 6 and 12 months and the efficacy and duration of effect of the botulinum toxin does not appear to diminish with repeat injections in both the neuropath or non-neuropath over, at present, 10y of follow-up, an experience shared by others.^8,11

The principle side effect is urinary retention, a retention volume of >150–200mL of urine occurring in approximately 40% of individuals (in the non-neuropathic patient); in the neuropathic patient, the deliberate aim is to achieve retention so that the patient becomes completely continent between doing ISC. Up to 41% of patients were said to ‘require’ 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 definition of urinary retention based solely on a post-void residual urine volume of >150–200mL, but in the absence of symptoms, is, in the authors’ opinion, an unnecessary imposition. 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 while retaining the bulk of their urine production, or (c) has complete painless retention (painless inability to pass any urine—very unusual), or (d) develop symptomatic, recurrent UTI in the post-botox period. The author recommends the patient discontinue ISC once they feel comfortable to do so which, empirically, is usually when the balance between voided urine volume and retained urine volume shifts in favour of the former.¹⁰

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 injections and is almost always self-limiting (very occasionally, admission for a bladder washout of clots and irrigation via a 3-way catheter is required, but this is rare—two cases in 10y in the author’s experience). Occasionally, systemic side effects can occur. These are uncommon, but can be disabling, particularly in the patient with pre-existing neurological disease. The author warns patients of the risks of generalized weakness which occurs in approximately 1 in 100 patients (lower risk after bladder injections; higher risk after external sphincter injections) and can impair the ability to transfer on and off a wheelchair and affect daily living and working activities; blurring of vision (due to intraocular muscle effects—very rare, but very disabling); and difficulty taking a deep breath and/or swallowing (two cases in 10y in the author’s experience, both resolving spontaneously within 2–3 weeks and neither required in-hospital observation). All of these side effects are uncommon, will last weeks or a few months, require no specific treatment, and usually do not recur with subsequent repeat injections.

Division of dorsal spinal nerve roots of S2–4 to convert the hyperreflexic, high-pressure bladder into an areflexic, low-pressure one. Can be used where the hyperreflexic bladder is the cause of incontinence or hydronephrosis. Bladder emptying can subsequently be achieved by ISC or implantation of a nerve stimulator placed on ventral roots (efferent nerves) of S2–4 to ‘drive’ micturition when the patient wants to void (a pager-sized externally applied radiotransmitter activates micturition (Figs. 14.3 and 14.4). Also useful for DSD/incomplete bladder emptying causing recurrent UTIs and retention.

Many patients manage their bladders by intermittent catheterization (IC) done by themselves (ISC) or by a carer if their hand function is inadequate, as is the case with most (though remarkably not all) tetraplegics. Many others manage their bladders with an indwelling catheter (urethral or suprapubic). Both methods can be effective for managing incontinence, recurrent UTIs, and BOO causing hydronephrosis.

Requires adequate hand function. The technique is a ‘clean’ one (simple handwashing prior to catheterization) rather than ‘sterile’. Gel-coated catheters become slippery when in contact with water so providing lubrication. Usually done 3–4 hourly.

Some patients prefer the convenience of a long-term catheter. Others regard it as a last resort when other methods of bladder drainage have failed. The suprapubic route (SPC) is preferred over the urethral because of pressure necrosis of the ventral surface of the distal penile urethra in men (acquired hypospadias—‘kippering’ of the penis) and pressure necrosis of the bladder neck in women which becomes wider and wider until urine leaks around the catheter (‘patulous’ urethra) or frequent expulsion of the catheter occurs with the balloon inflated.

Problems and complications of long-term catheters

These are an externally worn urine collection device, consisting of a tubular sheath applied over the glans and shaft of the penis (just like a contraceptive condom, only without the lubrication to prevent it slipping off). Usually made of silicone rubber with a tube attached to the distal end to allow urine drainage into a leg bag. They are used as a convenient way of preventing leakage of urine, but are obviously only suitable for men. Detachment of the sheath from the penis is prevented by using adhesive gels and tapes. They are used for patients with reflex voiding (where the hyperreflexic bladder spontaneously empties and where bladder pressure between voids never reaches a high enough level to compromise kidney function). They are also used as a urine collection device for patients after external sphincterotomy (for combined detrusor hyperreflexia and sphincter dysynergia where incomplete bladder emptying leads to recurrent UTIs and/or hydronephrosis).

The principal problem experienced by some patients is sheath detachment. Despite the fact that a man walked on the moon 30y ago, we have been unable to design a condom sheath that will consistently prevent urine leakage in all men. This can be a major problem and in some cases, requires a complete change of bladder management. Skin reactions sometimes occur.

High-pressure bladder (detrusor hyperreflexia, reduced bladder compliance); sphincter weakness; UTI; bladder stones; rarely, bladder cancer (enquire for UTI symptoms and haematuria). Hyperreflexic peripheral reflexes suggest bladder may be hyperreflexic (increased ankle jerk reflexes, S1–2, and a positive bulbocavernosus reflex indicating an intact sacral reflex arc, i.e. S2–4 intact). Absent peripheral reflexes suggest the bladder and sphincter may be areflexic (i.e. sphincter unable to generate pressures adequate for maintaining continence).

Urine culture (for infection); KUB X-ray for bladder stones; bladder and renal USS for residual urine volume and to detect hydronephrosis; cytology and cystoscopy if bladder cancer suspected.

Start with simple treatments. If the bladder residual volume is large, regular ISC may lower bladder pressure and achieve continence. Try an anticholinergic drug (e.g. oxybutynin, tolterodine). Many SCI patients are already doing ISC and simply increasing ISC frequency to 3–4 hourly may achieve continence. ISC more frequently than 3-hourly is usually impractical, particularly for paraplegic women who usually have to transfer from their wheelchair onto a toilet and then back onto their wheelchair (Table 14.1).

Determined by videocystourethrography (VCUG) to assess bladder and sphincter behaviour.

High-pressure sphincter (i.e. DSD): treating the high-pressure bladder is usually enough to achieve continence.

Low-pressure sphincter. Treat the bladder first. If bladder treatment alone fails, consider a urethral bulking agent, a transvaginal tape (TVT) or bladder neck closure in women, or an artificial urinary sphincter in either sex (Fig. 14.5).

The AUS essentially consists of two balloons connected by tubing to a control pump. One of the balloons is configured as a cuff around the bulbar urethra or bladder neck. The other balloon (placed deep to the rectus muscle) applies a constant pressure (usually 61–70cmH₂O pressure) to the cuff via a control pump located in the scrotum or labia (Fig. 14.5; The AMS (American Medical Systems) 800 AUS). Pressure in the cuff is maintained until the control pump is squeezed by the patient. This forces fluid from the cuff (so it temporarily no longer occludes the urethra) into the balloon. Pressure from the balloon then refills the cuff via delay resistors in the control pump over a minute or so.

Incontinence

Bulbar cuff placement: for post-radical prostatectomy incontinence, previous surgery or trauma (pelvic fracture) in the region of bladder neck (increased risk of rectal perforation).

Bladder neck cuff placement: women (obviously), children (bulbar urethra too small for the available cuff sizes), men who wish to maintain fertility by preserving antegrade ejaculation, neuropathic patients where ISC is or may be required.

A deactivation button prevents return of fluid from the balloon to the cuff so allowing catheterization or instrumentation.

Improved continence in 60–90%. Complications in 5–30%—infection, urethral erosion, urethral loosening under the cuff (atrophy), device (‘mechanical’) failure.¹

What the patient interprets as a UTI may be different from your definition of UTI. The neuropathic bladder is frequently colonized with bacteria and often contains pus cells (pyuria). From time to time, it becomes cloudy due to the precipitation of calcium, magnesium, and phosphate salts in the absence of active infection. The presence of bacteria, pus cells, or cloudy urine in the presence of non-specific symptoms (abdominal pain, tiredness, headaches, feeling ‘under the weather’) is frequently interpreted as a UTI.

It is impossible to eradicate bacteria or pus cells from the urine in the presence of a foreign body (e.g. a catheter). In the absence of fever and cloudy smelly urine, we do not prescribe antibiotics, the indiscriminate use of which encourages growth of antibiotic-resistant organisms. We prescribe antibiotics to the chronically catheterized patient where there is a combination of fever, cloudy, smelly urine and where the patient feels unwell. Culture urine and immediately start empirical antibiotic therapy with nitrofurantoin, ciprofoxacin, or trimethoprim (the antibiotics sensitivities of our local ‘bacterial flora’), changing to a more specific antibiotic if the organism is resistant to the prescribed one.

For recurrent UTIs (= frequent episodes of fever, cloudy, smelly urine and feeling unwell), organize the following:

In the presence of fever and cloudy, smelly urine, culture the urine and start antibiotics empirically (e.g. trimethoprim, nitrofurantoin, amoxicillin, ciprofloxacin), changing the antibiotic if the culture result suggests resistance to your empirical choice. ‘Response’ to treatment is suggested by the patient feeling better and their urine clearing and becoming non-offensive to smell. Persistent fever with constitutional symptoms (malaise, rigors) despite treatment with a specific oral antibiotic in an adequate dose is an indication for admission for treatment with intravenous antibiotics.

If there is residual urine present, optimize bladder emptying by IC (males, females) or external sphincterotomy for DSD (males). IC can be done by the patient (ISC) if hand function is good (paraplegic) or by a carer if tetraplegic. An indwelling catheter is an option, but the presence of a foreign body in the bladder may itself cause recurrent UTIs (though in some, it seems to reduce UTI frequency).

An overactive bladder (detrusor hyperreflexia) or poorly compliant bladder is frequently combined with a high-pressure sphincter (DSD). Bladder pressures during both filling and voiding are high. At times, the bladder pressure may overcome the sphincter pressure and the patient leaks small quantities of urine. For much of the time, however, the sphincter pressures are higher than the bladder pressures and the kidneys are chronically exposed to these high pressures. They are hydronephrotic on USS and renal function slowly, but inexorably, deteriorate.

Seventy-five percent of patients with MS have spinal cord involvement and in these patients, bladder dysfunction is common. The most common symptoms in patients with MS are urgency, frequency, nocturia, and urge incontinence (due to DH) occurring in 32–97% of individuals, depending on the duration and severity of their MS.¹ Bladder pressures are rarely high enough to cause upper tract problems (hydronephrosis). The mainstays of treatment are anticholinergics, ISC, and bladder botox injections.

PD is a cause of parkinsonism (tremor, rigidity, bradykinesis—slow movements) and is due to the degeneration of dopaminergic neurons in the substantia nigra in the basal ganglia. The principal urological manifestation of PD is the development of LUTS, affecting 30–40% of patients with PD.² In the 30–40% of patients with PD and LUTS, nocturia is reported by 90%, urinary frequency and urgency by 70%, and urge incontinence by >40% (the symptoms that classically respond least well to TURP).

The most common urodynamic abnormality is DH (the basal ganglia may have an inhibitory effect on the micturition reflex). L-dopa seems to have a variable effect on these symptoms and DH, improving symptoms in some and making them worse in others. Impaired detrusor contractility can also occur, albeit uncommonly. Sphincter function during spontaneous (desired) voiding is synergic, i.e. there is no sphincter dyssynergia. Thus, the patient with PD has unobstructed voiding, unless they have coexistent benign prostatic obstruction. Poor striated sphincter function can also occur. Both DH and poor striated sphincter function can predispose to post-TURP incontinence.³

Urological lore is that patients with PD have had a poor outcome after TURP³ (de novo urinary incontinence rate of 20%). However, this is probably because of inclusion of patients with multisystem atrophy in previous studies,³ which is associated with a particularly poor outcome after TURP.⁴ If a patient with PD has urodynamically proven BOO, symptomatic outcomes after TURP can be good⁴, at least in patients with mild PD of less than 5y duration.

A cause of parkinsonism characterized clinically by postural hypotension and detrusor areflexia. Loss of cells in the pons leads to DH (symptoms of bladder overactivity), loss of parasympathetic neurons due to cell loss in the intermediolateral cell column of the sacral cord causes poor bladder emptying, and loss of neurons in Onuf’s nucleus in the sacral anterior horns leads to denervation of the striated sphincter causing incontinence. The presentation is usually with DH (i.e. symptoms of bladder overactivity), followed over the course of several years by worsening bladder emptying.

The term ‘spina bifida’ (more correctly, spinal dysraphism) describes the clinical manifestations arising from the failure of fusion of the neural and bony elements of the spine. The entity of spina bifida includes spina bifida cystica (myelomeningocele and meningocele) and spina bifida occulta (lipomeningocele, intradural lipoma, and tethered cord).

Urinary incontinence, recurrent UTI, bladder and renal stone formation, and reflux nephropathy are common problems.

McGuire introduced the concept of detrusor leak point pressure as an indicator of risk of upper tract deterioration in spina bifida patients.⁵ In 42 patients with myelodysplasia followed over 15y, urethral urine leakage occurred in 20 patients at intravesical pressures <40cmH₂O (the detrusor leak point pressure) and in 22 at pressures >40cmH₂O. While no patient with a leak point pressure <40cmH₂O had VUR and only two had ureteral dilatation on intravenous urography, in contrast, VUR was present in 15 patients (68%) and ureteral dilatation in 18 (81%) in those patients with a leak point pressure >40cmH₂O. As a result of this study (later supported by others), an end fill pressure <40cmH₂O is taken as an indication that upper tract deterioration will not occur and an end fill pressure >40cmH₂O is taken as an indication of the potential for upper tract deterioration.

The hallmark urodynamic finding in spina bifida is loss of bladder compliance combined with increased outlet resistance secondary to abnormal bladder neck function or DSD⁶ (62% of patients; 38% had what was described as detrusor areflexia which, in reality, described a group of 34 patients, 30 of who had poor bladder compliance with high end fill pressures). Most patients have a fixed (static) external sphincter and 10–15% of patients have DESD.

The mainstay of management is directed towards maintaining a low-pressure, continent bladder with anticholinergics combined with ISC.⁷ In those with increased detrusor leak point pressures, this decreases the probability of upper tract deterioration.⁸ Where anticholinergics fail to achieve continence or fail to eliminate hydronephrosis, the next step is to try bladder botox injections combined with ISC, though the poorly compliant bladder that is so characteristic of spina bifida seems to be more resistant to botox than the purely hyperreflexic bladder.

If anticholinergics or botox combined with ISC are not be able to achieve safe storage pressures in the small capacity, poorly compliant bladder augmentation cystoplasty with or without a Mitrofanoff stoma to make ISC easier (especially in the wheelchair-bound patient) may be required to achieve safe lowering of bladder pressure. Where continence cannot be achieved by reducing bladder pressure alone, bladder neck closure, urethral support (e.g. a TVT in women), or an artificial sphincter may be required. Leak point pressure can predict (with reasonable accuracy) those patients who have adequate bladder outlet resistance (those with a leak point pressure >40cmH₂O generally) to obviate the need for bladder outlet surgery.

Those patients with spina bifida and impaired cognitive ability (who represent a significant proportion of the spina bifida population) may not be able to cope with the requirement for regular and frequent bladder emptying with ISC or with the use of the AUS. For such patients, an SPC may be a safer method of achieving continence and protecting renal function. Furthermore, while it is possible to improve continence with LUT reconstructive surgery, there is evidence that this may not be paralleled with substantial improvements in overall quality of life.⁹ Quality of life scores seem to be no different between patients with spina bifida who undergo successful surgery for incontinence and matched controls who do not (it is difficult to improve quality of life by correcting just one system in a complex, multisystem disability such as spina bifida).

DH occurs in 70%, DSD in 15%. Detrusor areflexia can occur.¹⁰ Frequency, nocturia, urgency, and urge incontinence are common. Retention occurs in 5% in the acute phase. Incontinence within the first 7 days after a CVA predicts poor survival.¹¹

May cause severe frequency and urgency (frontal lobe has inhibitory input to the pons).

Can cause urinary retention or bladder overactivity.

Severe tetraparesis and bladder dysfunction which often recovers to a substantial degree.

The autonomic innervation of the bladder makes it ‘vulnerable’ to the effects of peripheral neuropathies such as those occurring in diabetes mellitus and amyloidosis. The picture is usually one of reduced bladder contractility (poor bladder emptying, i.e. chronic low-pressure retention).

This is the electrical activation of afferent nerve fibres to modulate their function.

Electrical stimulation applied anywhere in the body preferentially depolarizes nerves (higher current amplitudes are required to directly depolarize muscle). In patients with LUT dysfunction, the relevant spinal segments are S2–4. Indications: urgency, frequency, urge incontinence, chronic urinary retention where behavioural and drug therapy has failed.

Several sites of stimulation are available, the electrical stimulus being applied directly to nerves or as close as possible:

PTN (L4,5; S1–3) shares common nerve roots with those innervating the bladder. PTNS can be applied transcutaneously (stick-on surface electrodes) or percutaneously (needle electrodes). Percutaneous needle systems include the SANS (Stoller) and the UrgentPC system. Stimulation is applied via an acupuncture needle inserted just above the medial malleolus with a reference (or returns) electrode—30min of stimulation per week, over 12 weeks. Thereafter, 30min of treatment every 2–3 weeks can be used to maintain the treatment effect in those who respond. PTNS has not been compared with placebo (‘sham’ stimulation) and, therefore, reported efficacy may represent a placebo response. In a single-blinded, placebo-controlled study (gastrocnemius muscle stimulation without PTNS), 71% of patients receiving PTNS (12 treatments; 3 per week over 4 weeks) reported >50% reduction in urge incontinence episodes.²

A sacral nerve stimulator (Medtronic Interstim) delivers continuous electrical pulses to S3 via an electrode inserted through the sacral foramina and connected to an electrical pulse generator which is implanted subcutaneously. Supported by NICE³ for patients with urge incontinence who have failed lifestyle modification and behaviour and drug therapy.

A test stimulation (the peripheral nerve evaluation, PNE) is performed, under local anaesthetic, by a percutaneous test electrode placed in S3 foramina to confirm an appropriate clinical response (a reduction in urgency, frequency, or incontinence episodes). A permanent implant is offered if there is a 50% reduction in frequency and urgency. This is placed in a subcutaneous pocket and is connected to the sacral electrode. It can be switched on and off and the amplitude varied within set limits. About 50–60% of patients have a successful PNE. A multicentre study, randomizing non-neuropathic patients with a successful PNE test to immediate vs delayed (for 6 months) implantation (the control group), showed significantly better symptomatic outcomes in the implant group, 50–70% reporting resolution of their urge incontinence and 80% reporting >50% reduction in incontinence episodes, persisting for at least 3–5y.⁴ Longer term follow-up studies report a durable response.^5,6 Numbers of neuropathic patients treated with SNS are too small to draw meaningful conclusions.⁵

For non-obstructive urinary retention of those responding to PNE (68 of 177, 38%) and who were subsequently implanted, 58% no longer required ISC at 18 months of follow-up,⁷ results mirrored by others (50–55% stopping ISC) at a mean of 41–43 months (70% with Fowler’s syndrome stopped ISC).^8,9

The exact mechanism of action of SNM in patients with bladder dysfunction is not known.