Lower Urinary Tract Management in Patients with Neurological Disease

ABSTRACT

Lower urinary tract dysfunction is common in patients with neurological disease. Storage and/or voiding function can be affected, leading to bothersome symptoms. However, preventing upper urinary tract deterioration is a greater clinical priority, requiring identification of patients at risk, early intervention where indicated, and ongoing surveillance. An initial assessment requires a comprehensive evaluation, including wider issues such as aspirations for independent living, cognitive function, manual dexterity, and mobility. Measures to improve urine storage include antimuscarinic drugs, botulinum injections, or surgical procedures. For voiding dysfunction, intermittent catheterization is by far the most effective and most widely applicable approach, with additional benefits for urinary storage. The assessment of urinary tract function and treatment selection requires a multidisciplinary approach in the context of full rehabilitation or support.


Marcus J Drake, Francisco MJ Cruz

Date Received: April 26, 2011 Accepted on: January 17, 2012


KEYWORDS: Neurourology; Detrusor overactivity; Urodynamics; Antimuscarinics; Botulinum toxin A

CORRESPONDENCE: Marcus J Drake, MA, DM, FRCS (Urology), University of Bristol, Bristol Urological Institute, Southmead Hospital, Bristol, BS10 5NB, United Kingdom ().

CITATION:UroToday Int J. 2012 Feb;5(1):art 95. http://dx.doi.org/10.3834/uij.1944-5784.2012.02.13

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INTRODUCTION

The initial clinical evaluation of the urinary tract in a patient with neurological disease is crucial as presentations and prognoses vary, and the outcome is dependent on an accurate assessment. The key aims are: 1) to detect risk factors for the future (especially renal failure), 2) to optimize life expectancy, and 3) to evaluate symptoms, thereby guiding management to optimize quality of life.

There are useful guidelines published by international organizations, such as the International Consultation on Incontinence and the European Association of Urology [1,2]. National consensus statements have also been developed (for example [3,4]).

Fundamentally, neurological patients should be assessed by a suitably trained health care professional who has specialized knowledge of lower urinary tract dysfunction, and the appropriate follow-up surveillance is needed at intervals. Lower urinary tract (LUT) issues have to be managed in the context of the wider health issues of the individual. These include directly relevant aspects, such as bowel and sexual function, and the impact of LUT dysfunction on psychological, domestic, social, and employment rehabilitation. Accordingly, multidisciplinary expertise is needed in medical teams managing patients with neurological disease, where the urological element is one of several important aspects.

CLINICAL EVALUATION

Medical History

The neurological diseases a urologist sees most commonly are spinal cord injury (SCI), multiple sclerosis (MS), and spina bifida (myelomeningocele). The range of possible neurological diseases is substantial, with many unfamiliar to the urologist. In general, they can be considered as follows:

  • Level(s) of nervous system affected: brain, upper motor neuron spinal, lower motor neuron spinal, peripheral, and combination of the above
  • Sensory and/or motor deficit
  • Complete or incomplete neurological impairment
  • Cognition
  • Possible progression of neurology

After the neurological disease has been understood, the general history covers: 1) social factors and the patient’s motivation, 2) relevant surgery, 3) drug history, 4) bowel function, 5) gynecological/obstetric history and hopes for future fertility, and 6) sexual function.

Additionally, urinary tract history covers: 1) possible alarm signs, such as pain, urinary tract infection, hematuria, and fever that warrants further specific diagnosis, 2) LUT symptoms related to storage and voiding phases, including urinary incontinence and bladder sensation, 3) current bladder management methods, including intermittent catheterization, and 4) urinary infections (remembering the symptoms are unreliable where sensation below the neurological lesion is impaired [5]).

Symptom assessment tools are important to catalogue problems and their severity [6]. A bladder diary gives information about frequency, daytime and nighttime voiding frequency, voiding volume, incontinence, and urgency episodes [7]. This is useful for making treatment decisions and assessing response.

Examination

The examination aims to: 1) locate neurological lesions, 2) establish if other organ systems are affected; e.g., bowels, 3) establish lower urinary tract function (storage, voiding), 4) detect unexpected problems; e.g., lower motor neuron deficits may point towards secondary changes needing early intervention (e.g., syringomyelia in spinal cord injuries), and 5) influence further management options (coordination and cognitive tests are rarely untaken but may be appropriate as they influence the choice of management options).

A general urological examination looks for distended bladder/hydronephrosis, prostate size, pelvic organ prolapse (POP), continence/fecal impaction, and sacral/dependent sores. A focused neurological examination looks at key features, such as: 1) lower limb reflexes and bulbocavernosus reflexes, sensory dermatomes (fine touch and pin prick) of the lower limbs, and perianal effects, to see which spinal cord segments are affected, 2) anal tone and voluntary pelvic-floor squeeze, and 3) the evaluation of other facets; for example, coordination or blood pressure (lying and standing) should be considered.

INVESTIGATION

Urinalysis

Asymptomatic bacteriuria may subsequently turn into a urinary tract infection, which may become severe due to a lack of awareness of early symptoms in people with impaired sensory function.

Serum Tests of Renal Function

Allowance has to be made for muscle mass, considering disease is often lower in able-bodied individuals, and it will influence the normal range for serum creatinine values.

Imaging Tests

Specific tests depend on the findings of a clinical evaluation. In most cases, the following are appropriate: 1) ultrasound, to look for upper urinary tract (UUT) changes, 2) hydronephrosis, post-void residual, calcification, and other lesions, and 3) flow rate testing.

Flow rate patterns include normal, interrupted, prostatic, or stricture. The interrupted pattern is commonly seen in neurological patients and signifies poorly sustained detrusor contractions, straining, or dyssynergia. Artifacts have to be excluded.

Other tests are required, according to specific clinical requirements:

  • IVU / CTU: many neurological patients are at risk of forming urinary tract stones, and
  • spine/brain imaging: if there is doubt as to neurological lesion location or progression; however, this is most appropriately discussed with the relevant neurologist.

URODYNAMICS

Urodynamics is an invasive test with risks attached, so careful consideration is needed before proceeding with formal filling cystometry and pressure/flow studies. The EAU guidelines make a grade A recommendation that urodynamic investigation is necessary to document the (dys)function of the LUT.

Key urodynamic questions can be addressed by videourodynamics (VUDS):

  • Are the patient’s kidneys at risk because of LUT dysfunction?
  • What is the cause of a patient’s LUT symptoms?

Certain neurological patients may be considered at risk of LUT deterioration (especially SCI and spina bifida). They will generally need pressure flow studies. Those neurourological patients who, in the opinion of the managing clinician, are at a lower risk of renal dysfunction, and who have LUT symptoms, should only have invasive pressure flow studies if conservative treatment has failed, the patient is bothered by the symptoms, and they are fit for management interventions.

Invasive urodynamic tests should be in accordance with the International Continence Society good urodynamic practices [8]. Key issues are: use a slow filling rate (at least at the start of filling), and minimize the risk of artifactual reduction in compliance. The use of video screening is important because of the range of apparent filling and voiding abnormalities. In most cases, the bladder should be emptied at the start of filling, though the investigator may vary this according to the circumstances.

  • Filling cystometry
  • To detect detrusor overactivity
  • To ascertain the cause of incontinence
  • To check leak point pressures
  • To look for vesicoureteric reflux
  • To check compliance
  • To find cystometric capacity
  • To evaluate pelvic-floor support
  • Voiding studies
  • To exclude bladder outlet obstruction or identify its site, if present
  • To gauge detrusor contractility
  • To look at problems of coordination of outlet and bladder contraction (DSD)
  • Post-void residual

Detrusor leak point pressure (DLPP) is assessed in patients with reduced filling compliance (for example, patients with myelomeningocele, or where there is a neurological lesion of the sacral spinal cord). The DLPP is the detrusor pressure associated with leakage. When the compliance curve exceeds the outlet resistance, high values cause anxiety for future upper urinary tract function [9]. (Abdominal leak point pressure is a different concept, unrelated to the risk of renal impairment, giving an indication of incontinence severity in patients with normal bladder compliance).

Electromyography (EMG) can register the activity of the external urethral sphincter, the periurethral striated musculature, the anal sphincter, or the striated pelvic-floor muscles. It signifies the patient’s ability to control the pelvic floor and objectively identifies DSD, though the pressure trace alone can be used to deduce the presence of DSD in the absence of EMG recording

Ambulatory urodynamics uses natural filling by the kidneys. It can be used where conventional VUDS fails to reproduce a patient’s symptoms. For example, wheelchair users with stress incontinence symptoms may not be able to exert themselves sufficiently to elicit stress incontinence in the confines of a standard urodynamic test. Ambulatory testing should allow them the freedom to undertake the activity that reliably elicits symptoms.

The ice water test is fast-filling cystometry with cooled saline. The ice water test has reportedly distinguished between an upper motor neuron lesion (UMNL) and lower motor neuron lesion (LMNL) [10]. It is not widely used outside a research setting.

Safety for the Patient During UDS

Specific issues require caution when undertaking a VUDS test in neuropathic patients.

  • UTI: Urine should be screened before filling cystometry. If bacteriuria is present, the test should be deferred until resolved, or prophylaxis should be administered.
  • Autonomic dysreflexia [11]: A life-threatening complication of SCI above T6, in which extreme hypertension arises acutely in response to a noxious stimulus below the injury level. Severe headache can be followed by intracerebral hemorrhage and death. If the patient complains of headache, the bladder should be emptied. Other stimuli should be excluded (i.e., any additional noxious stimulus below the neurological level), antihypertensives should be administered (e.g., sublingual nifedipine), and monitoring instituted.
  • Latex allergies: Neuropathic patients are at risk of a latex allergy [12] and may manifest an anaphylactic response [13]. Latex-free settings for VUDS are important, as a remarkably small level of exposure can trigger an anaphylactic response.
  • Erroneous conclusions: If VUDS is not carried out satisfactorily, inappropriate management decisions may result.

TREATMENT

Treatments are often a compromise between 2 main objectives: firstly, the protection of the upper urinary tract from deleterious effects of high intravesical pressures, and secondly, the improvement of storage and voiding symptoms. Restoration of nervous system function is not currently possible, but it is a hope for many patients.

Risk of Renal Failure in Neurological Disease

Upper urinary tract deterioration, which may be clinically “silent” until advanced, is a crucial factor in neurourological management. Four main risk factors have been identified for upper urinary tract damage in MS [14]: 1) the duration of MS, 2) the presence of an indwelling catheter, 3) high-amplitude neurogenic detrusor contractions, 4) permanent high detrusor pressure, and 5) detrusor-sphincter dyssynergia (DSD).

Accordingly, these factors warrant consideration of more active surveillance of the upper urinary tract. However, the factors are debatable in context. There is a paucity of irrefutable evidence relating to the risk factors of renal deterioration in modern practice, and for the range of neurological diseases. For example, in SCI, an indwelling catheter protects against subsequent deterioration [15].

BEHAVIORAL TREATMENT

Triggered Reflex Voiding

Triggered reflex voiding comprises maneuvers performed by the patient to trigger reflex detrusor contractions, such as suprapubic percussion. The integrity of the sacral reflex pathways is a requirement. Patients who may benefit are those with suprasacral spinal cord lesions who are able to collect urine in a socially acceptable way. The presence of severe DSD must be excluded.

Bladder Expression (Credé and Valsalva Maneuvers)

Bladder expression has been recommended to patients with an underactive detrusor combined with an underactive sphincteric mechanism. It is no longer supported by most clinicians due to the risk of infection, vesicoureteral reflux, hernias, and rectogenital prolapses.

Toileting Assistance

Toileting assistance aims to correct habitual patterns of liquid intake and urination, to improve bladder control under urgency, and to teach patients how to reduce incontinence episodes. Techniques include timed voiding, prompted voiding, habit retraining, bladder retraining, and a patterned response to urgency.

CATHETERS

Overall, the evidence base for catheter use in neurourology is limited [16]. Excellent intermittent catheterization (IC) outcomes in neurogenic patients with various LUT dysfunctions put it in the management forefront.

Intermittent Catheterization

Intermittent catheterization (IC) can protect renal function and facilitate the achievement of urinary continence, either alone or in combination with other treatments. The frequency of catheterizing should be tailored according to fluid intake, bladder capacity, and detrusor pressure. Frequent urinary tract infections (UTIs) can occur, but prophylactic antibiotics are not recommended, and active treatment should be confined to symptomatic UTI. One fifth of the patients on long-term IC will experience urethral complications; e.g., bleeding and stricture. Sterile IC is associated with lower bacteriuria/infection risk as opposed to clean IC. Fully sterile approaches, using entirely sterile materials, including gloves and forceps, are most frequently advocated for intensive care units. Auto-lubricated catheters, which require immersion for a few seconds in drinking water to activate the lubricating film, are catheters of 12 to 14 Fr and are suitable for most adult male and female patients.

Indwelling Urethral and Suprapubic Catheters

Short-term urethral catheterization is needed in the initial phase of spinal shock. It is not appropriate in the longer term. A dilated (“patulous”) urethra can result in women, and urethritis, trauma, and stricture can form in men. If patients cannot perform IC, a suprapubic catheter (SPC) is preferable. Due to bladder cancer risks [17], regular cystoscopy is necessary after 5 to 10 years.

PHARMACOLOGICAL TREATMENT

Drugs for Detrusor Smooth Muscle Relaxation

Antimuscarinic agents

Antimuscarinic drugs aim to decrease reflex incontinence by delaying nonvoluntary detrusor contraction in patients who void spontaneously or empty the bladder by triggered voiding. They also aim to decrease high intravesical pressure in patients with DSD. In conjunction with IC, 70% of patients with less severe neurogenic LUT dysfunction may achieve continence. The evidence base for this patient group is small. Muscarinic receptor antagonists cause a variety of side effects, including dry mouth and constipation. They are contraindicated in closed angle glaucoma. Oxybutynin, tolterodine, propiverine, and trospium are the most extensively studied in the treatment of neurogenic LUT dysfunction. They significantly reduce micturition frequency and the number of urinary incontinence episodes, and they increase maximal cystometric capacity. Often, these patients will require doses higher than those recommended by the manufacturers [18,19]. The addition of a second antimuscarinic agent may also be tried in patients for whom urinary incontinence or detrusor pressure is not adequately controlled with 1 single agent [19].

Intravesical instillation is an interesting option. Sometimes purified oxybutynin preparations are available, usually as vials containing 5 mg. In most countries, there are no such formulations. Thus, 5 mg of oxybutynin tablets are crushed and dissolved in 30 ml of distilled water or saline and instilled 2 or 3 times per day. They are left until the next voiding, as maximum effect may take 2 to 4 hours.

Acetylcholine release inhibitors

Botulinum toxin (BoNT/A) impedes the release of neurotransmitters from nerve endings. It is increasingly used in neurogenic LUT dysfunction [20,21]. In the bladder, the blockade of acetylcholine release reduces detrusor contractility, and it may affect afferent nerve function. In the sphincter, it will decrease urethral closing pressure.

BTX-A in Neurogenic Detrusor Overactivity

Schürch and colleagues [22] reported a bladder injection of BoNT/A for neurogenic detrusor overactivity (NDO) of a spinal origin resistant to anticholinergic drugs, in a patient who emptied the bladder by IC. Each patient received 300 units of onabotulinum A (Botox) diluted in saline (10 UI/ml) and injected in 30 different locations above the trigone. A significant increase in bladder capacity and a significant decrease in maximum detrusor voiding pressure were still present 36 weeks later. A multicentric European study with Botox in 200 neurogenic LUTD patients using IC or an indwelling catheter achieved continence in 73%, most benefitting at 9 months [23]. A recent and large randomized clinical trial with spinal cord injury and multiple sclerosis patients showed that 200 and 300 units of onabotulinum A were equally effective to improve or cure urinary incontinence and decrease detrusor pressure, but adverse events, mainly urinary retention and urinary tract infections, were more frequent with the 300 unit dose [24].

Patients should understand that following BoNT/A urinary retention is likely, and patients should be willing to accept a transient period of IC. A minimum interval of 3 months between BoNT/A injections might be considered to reduce the risk of antibody formation. Mild muscular weaknesses in the upper extremities of patients with complete cervical cord lesions rarely arise.

Drugs That Decrease Bladder Outlet Resistance

Alpha-1 adrenergic antagonists

Evidence to support the use of alpha-1 adrenergic blockers in neurogenic LUT dysfunction is sparse. Alpha-blockers may also contribute to decreased excessive sweating, secondary to autonomic dysreflexia [25].

Urethral sphincter injections of BTX-A

BoNT/A injected in the urethral sphincter aims to decrease bladder outlet resistance and facilitate bladder emptying, as an alternative to urethral sphincterotomy. It can be undertaken in conjunction with bladder injections [26]. Decreased urethral closure pressure, bladder pressure during voiding, and post-void residual urine are seen, and episodes of autonomic dysreflexia are reduced [27].

Central nervous system polysynaptic inhibitors

Baclofen is a GABAB receptor agonist that decreases the release of sensory neurotransmitters in the spinal cord. In theory, this may depress the activation of the bladder reflexes. However, oral baclofen has demonstrated poor efficacy in the treatment of neurogenic DO (perhaps due to poor CNS penetration). Improvement of NDO is seen with intrathecal administration of baclofen.

Substances That Decrease Sensory Input

Capsaicin extracted from hot chili peppers and resiniferatoxin (RTX) extracted from euphorbia resinifera, a cactus-like plant abundant in Northern Africa, are the most well studied compounds of the vanilloid family. These compounds have been in use clinically, and were found to have benefits. They are not commercially available, but they remain a source of potential development for future therapeutic interventions. The name “vanilloid” derives from the presence of a homovanillyl ring. Compounds with similar properties may not possess this ring. Vanilloid substances bind to a receptor belonging to the transient receptor family, a vanilloid 1 subtype (TRPV1, or VR1 or in the old terminology) that occurs in the membrane of type C, unmyelinated sensory fibers. This causes a brief excitation followed by a prolonged desensitization during which the neuron is unresponsive to natural stimuli.

SURGICAL TREATMENT

Many patients with chronic debilitating LUTS, refractory to conservative measures, will eventually require surgical procedures. Such procedures require careful evaluation of the patient. Careful urodynamic evaluation is important to establish the range of upper urinary tract dysfunctions present, so that appropriate plans can be made according to clinical need. For example, for a patient who hopes to achieve continence, the urodynamic evaluation of the bladder and the outlet enables the clinician to identify potential needs in relation to achieving sufficient stable reservoir capacity and a catheterizable continent outlet.

Operations That Decrease Outlet Resistance

DSD can be difficult to manage, and the currently available options have important limitations [28].

Sphincterotomy

Transurethral sphincterotomy (TUS) aims to reduce intravesical pressure mediated by bladder contractions against a contracted sphincter, and it may reduce episodes of autonomic dysreflexia. TUS applies to male patients, as a penile condom catheter will be needed subsequently to collect urine. Prosthesis infection and penile erosions are too high to use an implant to aid condom use. TUS is expected to be a permanent solution but there is a significant rate of failure [29], and severe bleeding or stricture formation can occur.

Permanent urethral stents

The application of permanent urethral stents in the area of the urethral sphincter may constitute an alternative to TUS [30]. However, stent placement may trigger autonomic dysreflexia, and migration, encrustation, infections, or fistula are problems and outcomes that are uncertain.

Operations That Decrease Detrusor Contractility

Bladder augmentation with intestine

Bladder augmentation should be undertaken only when less invasive measures fail to create a low-pressure continent reservoir of sufficient volume. Bladder augmentation with a detubularized intestinal segment is well established. In short, 20 to 30 cm of ileum is isolated and detubularized, and then sutured over a transverse cystostomy [31]. Outcomes can be reasonable but may not be sustained [32], while complications might include urine reabsorption, urolithiasis, obstruction due to mucus accumulation, frequent UTIs, bladder rupture, and some risks of cancer development in the region of the intestinal patch. Most patients will require IC.

Bladder auto augmentation

Bladder auto augmentation (detrusor myectomy) [33] involves extraperitoneally stripping the detrusor layer from the dome and anterior surface of the bladder wall to create a large epithelial diverticulum. The technique is now infrequently used.

Neuromodulation and denervation procedures

Neuromodulation of the posterior sacral roots has been investigated in idiopathic DO. Some centers have reported results in NDO, but it is not widespread. Sacral neuromodulation was recently shown to have the potential to prevent NDO in patients with spinal cord injury if initiated at the phase of spinal shock [34]. This intriguing observation was carried out in a small number of patients and requires confirmation.

Subtrigonal denervation using phenol injections provided inconsistent results and major complications, so it is no longer in use.

Operations That Increase Sphincteric Resistance

Artificial urinary sphincters have been frequently used in patients with congenital neuropathies. Success rates vary between 70 to 95%, with a revision rate of 16 to 60%. It is effective in most male patients [35]. In female patients, there can be significant problems [36].

Operations That Modulate Detrusor Contractility

Sacral anterior root stimulation to modulate detrusor contractions

Brindley and Craggs developed sacral anterior root stimulation, which is indicated in patients with suprasacral spinal cord lesions exhibiting severe DSD and autonomic dysreflexia. It comprises a posterior S2-S4 complete rhizotomy and the implantation of electrode stimulators on the intact sacral anterior roots. Anterior root stimulation activates simultaneous detrusor contractions when voiding is desired. It also activates urethral closure, but the latter fatigues quickly. Positive outcomes have been reported [37]. It can also be used to facilitate bowel emptying, and some males use it for erections.

Muscle augmentation

The restoration of bladder function by the use of an electrically stimulated muscle flap can be achieved by wrapping the latissimus dorsi muscle around the atonic bladder, retaining its innervation and blood supply [38]. The technique has not entered widespread practice.

Urinary diversion

An ileal conduit may be appropriate to prevent the deterioration of the upper urinary tract in highly selected patients. A continent reservoir may be offered to patients who have normal renal function and enough manual dexterity to catheterize the reservoir. Patients who maintain the bladder in situ have a risk of developing severe pyocystitis (pus accumulation in the dysfunctional bladder). In some women, this can be managed by vaginocystostomy.

Bladder reinnervation

Xiao and colleagues, following a series of animal experiments, reinnervated the bladder of volunteers with NDO and DSD by transferring motor nerves in the L5 ventral root onto the S2/3 ventral root. Micturition was later initiated by stimulating the L5 dermatome. However, the useful results reported [39] have yet to be reproduced by other centers, raising significant uncertainty about the procedure.

CONCLUSION

Neurourology is a challenging subspecialty requiring considerable resources. Careful specialized evaluations are needed to identify the risk factors for renal deterioration. Symptom management requires a fastidious approach to diagnosis and a realistic insight into the patient’s preserved functions in order to identify realistic options to restore bladder storage function and emptying. Patients should have access to the full range of therapeutic options, and the more complex cases should be managed in appropriate specialist centers.

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