Neurogenic Bladder and Neurogenic Lower Urinary Tract Dysfunction

Etiology

There are multiple conditions in which neurogenic bladder can develop.[5] Some of these appear in the list below:

• Normal-pressure hydrocephalus
• Spinal cord injuries
• Cerebral palsy
• Traumatic brain injury
• Stroke
• Parkinson disease
• Multiple sclerosis
• Meningomyelocele
• Spina Bifida
• Diabetes mellitus
• Dementia
• Guillain-Barre syndrome
• Tumors involving the central nervous system or spine

Epidemiology

The mean age of neurogenic bladder patients is 62.5 (standard deviation of 19.6.)[6] 

In the United States, a neurogenic bladder is found in 40% to 90% of persons with multiple sclerosis (with detrusor hyperreflexia in 50% to 90% of cases), 37% to 72% in patients with Parkinson disease, and 15% of all stroke patients.[4] 

Research shows that 70% to 84% of patients with spinal cord injuries have neurogenic bladder dysfunction at some point in their lives.

The worldwide yearly incidence of spinal cord injuries resulting in neurogenic bladder dysfunction has been estimated at between 12 to more than 65 cases/million population.[7]

About 1427 babies are born in the United States with spina bifida; roughly one out of 2758 live births.[8] In these patients, some kind of bladder dysfunction is present permanently.[4][6] Vesicoureteral reflux is present in up to 40% of the cases in children by age 5, and up to 60.9% of adults with spina bifida experience some degree of urinary incontinence.[9] Possible voiding dysfunctions include a flaccid or spastic pelvic floor, detrusor overactivity, detrusor sphincter dyssynergia, or some combination of these disorders. When associated with high bladder pressures, there is an increased risk of developing vesicoureteral reflux with subsequent renal deterioration.[10]

History and Physical

A thorough history is always the first step in evaluating a neurogenic bladder. By definition, a neurogenic bladder involves some disorder or problem with the nerve control of continence and voiding function. Therefore, the history should focus on urinary tract issues and any neurological symptoms. The timing and clinical course of the voiding dysfunction should be documented as well as any bowel issues, sexual dysfunction, or neurological deficits. A questionnaire about voiding habits can be used for all patients (frequency, number of voiding episodes, voiding volume, sense of incomplete evacuation or not, symptoms of a UTI ( burning, associated fever), anorectal issues (constipation, stool impaction, bowel incontinence). Usual voiding habits should be noted, particularly if there was a significant change at a specific time. 

All potential traumas, associated diseases such as diabetes or Parkinson's, medications, significant family medical history, and all surgical procedures should be reviewed and documented. 

The patient's overall health, mobility, cognitive ability, hand function (strength, coordination, and control), and social support network should be assessed. These factors will help determine the range of available treatment options. 

The physical examination should include an abdominal exam and the external genitalia in men, as well as a pelvic examination in women to check for prolapse. A rectal exam can identify changes in anal sphincter tone. A focused neurological examination is also recommended. Cognitive ability, ambulation, hand functionality, urogenital area sensation, and reflexes should be assessed. 

A urological evaluation for spinal cord injured patients should occur after the period of spinal shock has expired, preferably at three months but no longer than six months after the initial injury; sooner is recommended.[11][12] Significant bladder dysfunction can develop very soon after a spinal cord injury, even in ambulatory patients who may be asymptomatic.[13][14]

Evaluation

A "urine dipstick" evaluation is recommended for all patients with new urinary symptoms as an initial test. It has a very high negative predictive value (98%) but a low positive predictive value (50%) for urinary tract infections.[15] A baseline blood test for renal function (creatinine) and an estimated glomerular filtration rate (GFR) should be performed. 

It is also necessary to determine their bladder emptying ability (post-void residual urine volume) for patients who can void spontaneously by ultrasonography (preferred) or catheterization.[16] A 24-hour voiding diary (preferably for 2 or 3 days) indicating the time of voiding and the amounts is essential in determining the patient's voiding pattern.[11][16][17]

Quality of life assessment (usually based on the specific and validated in multiple sclerosis and spinal cord injury) may be useful.[18]

Evaluating the upper urinary tracts is generally recommended for all newly diagnosed neurogenic bladder patients. American Urological Association Guidelines now suggest that this may be omitted in selected patients identified as low risk.[19] This is typically done with either a renal ultrasound or an abdominal CT scan examination. It is recommended that patients with spinal cord injuries have an evaluation of the upper urinary tracts every 12 months. There are no specific recommendations for follow-up upper tract imaging for patients with other types of neurogenic bladder, but periodic (yearly) rechecks are reasonable in high-risk patients, especially if there is a change in renal function or symptoms. In moderate-risk patients, imaging is recommended every 1 to 2 years.[19]

Other initial tests such as uroflowmetry and cystoscopy should be performed as necessary.[16][20] For example, high bladder pressure with low urinary flow suggests a mechanical obstruction such as benign prostatic hyperplasia or urethral strictures.

Urodynamics is extremely helpful in assessing bladder and urethral function in patients with real or suspected neurogenic bladder. It is particularly useful in detecting those patients with neurogenic bladders who might be at risk for upper tract renal deterioration as this may occur without any clinical symptoms. Both the American Urological Association and the Society of Urodynamics, Female Pelvic Medicine, and Urogenital Reconstruction Guidelines recommend that all patients with a diagnosis of neurogenic bladder should receive a post-void residual (PVR) determination, a complex cystometrogram (CMG), a pressure-flow analysis, electromyography (EMG), and video urodynamics when available. The urodynamic assessment should include bladder sensation (first sensation of filling), bladder compliance during filling, voluntary detrusor pressure, involuntary detrusor contractions, maximum bladder capacity, a pressure-flow study, and sphincteric function during filling and voiding.[21][22] (See our companion article on Urodynamics Testing and Evaluation.)[23]

Special precautions may be needed when performing urodynamics on patients at risk for autonomic dysreflexia, including hemodynamic monitoring and having emergency supplies available to manage extreme hypertension.[24]

When high-risk factors are present, such as sustained high bladder pressures during the filling phase or voiding, specific investigations should be performed (CT scan, cystoscopy, and sometimes renal scintigraphy when the creatinine clearance is abnormal).[25] Detrusor leak point pressures or sustained bladder pressures of more than 40 cm of water on urodynamic testing greatly increase the risk for upper urinary tract deterioration.[26][27]

ClassificationAbnormal bladder function can be most easily categorized as either a failure to store or a failure to empty. In its simplest form, bladder function can be considered normal, overactive, or hypoactive/atonic. Similarly, the urethral function can be normal and appropriate, hypotonic, or dysfunctional.  

There is no absolute requirement to specifically classify the exact type of neurogenic bladder. While helpful at times, no single classification system ideally suits all neurogenic bladder disorders or situations. 

There are several classification systems for neurogenic bladder, including functional systems, urodynamic classifications, the Bors-Comarr classification (useful primarily for spinal cord injuries only), the Hald-Bradley system, and the Bradley classification, among others. The most clinically valuable systems are the International Continence Society Classification, the Lapides Classification, and the General Guide to Neurologic Disease and Urinary Tract Dysfunction.

The International Continence Society Classification system is based on the urodynamic type of classification and divides bladder function into the storage phase and the voiding phase. Each bladder characteristic (function, activity, sensation, capacity, compliance, etc.) is measured and identified for both storage and voiding. It is useful for both neurogenic and non-neurogenic bladder dysfunctions.

International Continence Society ClassificationStorage Phase

• Bladder Function: Normal (Stable) or Overactive
• Bladder Sensation: Normal, Hypersensitive, Hyposensitive (Reduced), or Absent
• Bladder Capacity: Normal, Above Normal, or Below Normal
• Bladder Compliance: Normal, High, or Low
• Urethral Function: Normal Closure Function or Incompetent Closure Function

Voiding Phase

• Bladder Function: Normal, Underactive, Acontractile, Areflexic
• Urethral Function: Normal, Mechanically Obstructed, Overactive, Dysfunctional, Detrusor Sphincter Dyssynergia, or Nonrelaxing Urethral Sphincter Dysfunction

Lapides Classification: The Lapides Classification is perhaps the most straightforward and recognizable, but many patients do not fit precisely into these categories, and it does not include urethral function. It is useful only in neurogenic bladder dysfunctions. 

• Sensory neurogenic bladder is due to neurological processes that specifically disrupt afferent fibers to the brain or bladder sensory nerves. Motor function is spared. Diabetes, tabes dorsalis, and pernicious anemia would be examples. Over time, this causes chronic overdistension resulting in a hypotonic bladder. 
• Motor paralytic neurogenic bladder is due to a loss of parasympathetic motor innervation to the detrusor, such as from trauma, extensive surgery, or Herpes zoster. Chronic overdistension tends to lead to a large capacity bladder with low detrusor voiding pressures and high post-void residual volumes. 
• Uninhibited neurogenic bladder is most often associated with a stroke, brain tumor, spinal lesion, Parkinson or a demyelinating disease are the most common causes. Symptoms are typically frequency, urgency, and urge incontinence. There is normal bladder sensation but frequently, early, uninhibited detrusor contractions at low bladder volumes. Post-void residual urine volumes are usually low.  
• Reflex neurogenic bladder is most often seen after traumatic spinal cord injuries, transverse myelitis, extensive demyelinating disease, or any significant supraspinal spinal cord disease. There are low volume uninhibited contractions, but there are no voluntary detrusor contractions and no sensation of fullness. A reflex neurogenic bladder can be thought of as the result of a complete upper motor neuron lesion. Detrusor sphincter dyssynergia would be common with this type of neurogenic bladder.
• Autonomous neurogenic bladder represents a complete disruption of both motor and sensory nervous system control over the bladder. This is most commonly seen in disease processes affecting the sacral spinal cord or pelvic nerves. There is no ability to initiate voiding, no voiding reflexes, and no sensation of bladder fullness. An autonomous neurogenic bladder would result from a complete lower motor neuron bladder. Urodynamically, this causes a large bladder capacity with low detrusor pressures, often associated with decreased compliance.  

General Guide to Neurologic Disease and Urinary Tract Dysfunction: This guide is based on the anatomical location of the underlying neurological defect. (Modified from Panicker.)[28]

      Suprapontine Lesions

• Usually, a urinary storage problem
• Post-void residual urine volumes are usually low
• The detrusor is overactive
• The urethral tone is normal

      Spinal Lesions (Infrapontine-Suprasacral)

• Both urinary storage and voiding symptoms
• Post-void residual urine volumes are increased
• The detrusor is overactive; possible detrusor sphincter dyssynergia or areflexia
• The urethral tone is overactive
• Compliance decreased
• Possible autonomic dysreflexia if the lesion is at T-6 or higher

      Sacral and Infrasacral Lesions

• Usually just voiding issues
• Post-void residual urine volumes are high
• The detrusor is hypoactive or atonic
• The urethral tone is normal or hypoactive
• Possible cauda equina syndrome

The clinical findings typically correlate with the location of the neurological lesion along the efferent (motor) or afferent (sensory) portions of the sacral arc pathway, either alone or in combination. Classic presentations include patients with a preserved sensation of bladder fullness and an inability to empty (motor neurogenic bladder) and patients who can void but have decreased sensation (sensory neurogenic bladder). The patients with the former lesion have an injury of the efferent sacral nerves or a conus medullaris lesion that selectively spares afferent transmission to supraspinal centers, and the patients with the latter type of injury are expected to have a pure afferent lesion.

In clinical practice, patients usually have a mixture of symptoms that involve both pathways. Patients with sacral or infrasacral lesions often complain of alterations in erectile function. Reflexogenic erections, like bladder and external sphincter contractility, rely on the somatic function of the pudendal nerve and the autonomic function of the pelvic nerve. These pathways may become disrupted in patients with infrasacral or CONUS lesions, but 95% of patients with suprasacral lesions have reflexogenic erections. The physical examination of patients with lesions at or below the conus medullaris typically reveals skeletal muscle flaccidity of the lower extremities. A number of reflexes reflect the status of the sacral cord and nerves S2 through S4 (Table 2).

The status of these reflexes provides significant information regarding detrusor and external sphincter function because the pudendal nerve and the preganglionic parasympathetic motor fibers also originate from these levels. The absence of a sacral reflex is highly suggestive of a neurologic lesion involving the conus medullaris, cauda equina, or a peripheral nerve. However, the presence of a sacral reflex does not exclude such a lesion and, when present in a patient with an areflexic bladder, suggests an incomplete lower motor neuron lesion. Patients with isolated lesions of the conus medullaris or the pudendal nerve may have areflexic bladders and absent sacral reflexes, but the Achilles deep tendon reflex (L5-S2) and the knee-jerk reflex (L2-L4) should be present because these reflex arcs originate more superiorly on the cord.[29]

Cauda equina syndrome is usually caused by a spinal fracture, disk protrusion, spinal surgery, and sacral tumors. It is characterized by both motor and sensory deficits involving bladder function, bowel habits, and sexual difficulties. Neurological deficits may affect the perineum, lower extremities, and buttocks. The typical urinary symptom is urinary retention due to a loss of bladder sensation and decreased detrusor activity. Other possible symptoms include overflow incontinence, detrusor overactivity, and loss of bladder compliance. Symptoms occur immediately after the neurological insult.[30][31] (See our companion article on Cauda Equina and Conus Medullaris syndromes.)[31]

Detrusor sphincter dyssynergia describes the condition where there is an involuntary contraction of the urethral sphincter and/or the periurethral musculature during a detrusor contraction. The result is the bladder contracting and trying to empty while the urethral sphincter is tightening and closing instead of opening.[32] This causes inadequate emptying with high detrusor pressures leading to bladder damage over time, including loss of compliance, vesicoureteral reflux, urolithiasis, and renal damage, particularly if sustained detrusor pressures are over 40 cm of water pressure.[26][27][32][33] The condition occurs when there is a neurologic disruption between the pontine micturition center and Onuf's nucleus in the sacral spinal cord (S2-4). Without correct treatment, over 50% of men known to have detrusor sphincter dyssynergia will develop significant urological complications, as noted above.[34] Detrusor sphincter dyssynergia is often associated with multiple sclerosis, myelomeningocele, transverse myelitis, and spinal cord injuries.[32] (See our companion article on Bladder Sphincter Dyssynergia.)[32]

Evaluation Summary

• Complete history focusing on urological and neurological history, symptoms, and physical findings
• Assessment of patient's cognitive ability, mobility, and hand functionality
• Quality of life score
• Baseline urinalysis and renal function laboratories
• 24-hour voiding diary (2 or 3 days is recommended)
• Post-void residual urine determinations
• Initial imaging of upper urinary tracts by ultrasonography or CT scan
• Urodynamics and video urodynamics to include CMG, pressure-flow analysis, and electromyography
• The specific classification is not important but may be helpful if a particular category or type can be diagnosed
• Identify specific functional voiding issues regarding detrusor activity (overactive, normal, hypoactive, or atonic) and sphincteric tone (normal, abnormal, or dyssynergia)
• Diagnose or rule out cauda equina syndrome and detrusor sphincter dyssynergia early

Treatment / Management

The primary goal of treating neurogenic bladder is to protect the upper urinary tract from damage and minimize permanent harm to the bladder. A secondary goal is maintaining urinary continence and improving the patient's quality of life.[35] The specific treatments selected will depend on the etiology of the neurogenic bladder, patient preferences, comorbidities, and the patient's ability to implement therapy when necessary. Treatment is generally broken down into behavioral interventions, medications, catheters, neuromodulation, and surgery, either alone or in combination.

Behavioral and conservative measures can be helpful in selected individuals, such as those with cognitive impairment. The treatments include timed voidings (especially for sensory neurogenic bladder patients), habit retraining, verbal prompting, prompted voiding, pelvic floor exercises, and pelvic floor physiotherapy. Pelvic floor physiotherapy, for example, has shown some benefits, especially in women with multiple sclerosis.[36] In spinal cord injured patients, reflex-triggered voiding, as well as Valsalva and Crede maneuvers, are not recommended (except in sacral and infrasacral lesions where bladder pressures are typically low) as the higher detrusor pressures created can increase the potential risk of kidney damage and renal failure.[11][37][38][39]

Medications

Alpha-blocker medications, both selective and non-selective, can be partially successful in selected neurogenic bladder situations as they decrease bladder outlet resistance, lower urine residual volume, reduce incontinence, improve bladder capacity, and may help reduce or somewhat mitigate autonomic dysreflexia.[19][24][40][41] (See our companion article on Autonomic Dysreflexia.)[24] If there is true outlet obstruction, as with benign prostatic hyperplasia, a surgical approach, such as transurethral prostate resection, may be preferred. (See our companion article on Alpha-blocker Medications.)[42](A1)

Anticholinergic medications have been the mainstay of treatment for patients with detrusor overactivity and are generally considered first-line therapy for this neurogenic condition. They work by interfering with the muscarinic acetylcholinergic receptors of the detrusor muscle and cause bladder muscle relaxation with reduced intravesical pressures and improved storage. Maximal detrusor pressures are reduced by 30% to 40%, while bladder capacity is increased by a similar amount.[43]

In some individuals, anticholinergic medications may unacceptably increase post-void residual urine volumes. Patients with Parkinson's, post-stroke, and multiple sclerosis are the most likely to develop this complication.[44] Post-void residual urine determinations should be reviewed periodically to avoid urinary retention or unacceptable problems with bladder emptying.[45] (B3)

Anticholinergic medications are usually started at a low dose and then gradually increased (after 4 to 6 weeks) to optimize symptoms or urodynamic parameters until maximum tolerability is achieved.[11] Supratherapeutic dosages may sometimes be considered but should be used cautiously.[46] Combination therapy with several anticholinergic agents can be helpful in patients where a single drug alone provides inadequate symptom relief.[11][47][48](A1)

Anticholinergic therapy can also be used to reduce bladder spasms and leakage in patients with indwelling catheters, minimize the risk of kidney damage, hydronephrosis, or renal failure, and reduce episodes of autonomic dysreflexia due to uninhibited detrusor contractions.[24][49][50] They may also be used intravesically, which is particularly useful for patients performing clean intermittent self-catheterization.[11](B2)

Anticholinergic therapy's most common side effects typically include constipation and dry mouth. Other side effects of this class of medication include tachycardia, mental confusion, and short-term memory loss. Specific drugs in this class will have different side effects, which should be considered when selecting a particular medication for individual patients. For elderly patients and individuals with memory or cognitive issues, anticholinergic drug selection should include medications that do not significantly affect brain activity (such as trospium and darifenacin) or use a beta-3 adrenoreceptor agonist as described below.[20][51][52][53] (See our companion article on Anticholinergic Medications.)[54](B3)

Underutilized Anticholinergic Medications

• Oxybutynin is available as a transdermal patch which has minimal side effects. It is often marketed "for women" and can be expensive, although it is available commercially for about $30 per month.
• Oxybutynin is also available as a liquid for patients who cannot take pills or tablets.
• Intravesical anticholinergic therapy should be considered in patients doing self-catheterization to minimize side effects.
• Trospium is a relatively underutilized anticholinergic medication with many favorable qualities; it is generic, relatively inexpensive, and has no brain or adverse cognitive effects. However, it is not covered by many commercial insurance plans and is therefore frequently overlooked.
• Darifenacin is an effective anticholinergic that also does not affect memory or cognitive functions as well as being extremely safe but has a relatively high rate of constipation, making it unsuitable for some patients. 

Beta-3 adrenoreceptor agonists (mirabegron and vibegron) are newer agents designed to relax overactive detrusor activity. By targeting and stimulating the bladder's natural sympathetic nerve-calming mechanism, they effectively relax detrusor activity without the complications associated with anticholinergic medications.[53][55][56] Overall effectiveness in reducing bladder overactivity is roughly equivalent to anticholinergics. Side effects are typically minimal and include a modest increase in heart rate and blood pressure.[57] A meta-analysis of the available data on their use in neurogenic bladder indicates that adrenoreceptor agonists significantly improve clinical symptoms, quality of life scores, and urodynamic parameters in neurogenic bladder patients with detrusor overactivity.[58] They also offer a significantly reduced complication rate compared to anticholinergics, fewer side effects, greater safety, and increased patient compliance.[58] Beta-3 adrenoreceptor agonists and anticholinergic medications can be used together if necessary in neurogenic bladder patients with detrusor overactivity not responsive to single agents. They are approved for use in both adults and children.(A1)

Desmopressin is a synthetic form of vasopressin that reduces urine production by promoting water reabsorption in the distal and collecting tubules of the kidney. It has no direct effect on bladder function but is useful for patients with nocturnal polyuria and volume-dependent detrusor overactivity symptoms, particularly for those individuals with multiple sclerosis, Parkinson's, or high spinal cord disorders that are associated with increased urine production overnight.[20][59][60] While useful in selected cases, there are potential risks such as hyponatremia, hypertension, and congestive heart failure. Sodium and creatinine levels should be monitored periodically. It should be used cautiously in patients with pre-existing hyponatremia, renal failure, congestive heart failure, dependent leg edema, and patients over 65 years of age.[20] (See our companion article on Desmopressin.)[61](A1)

Onabotulinumtoxin A (botulinum toxin) detrusor injections were first used in 2000 for intractable bladder overactivity that was unresponsive to anticholinergic medications.[62] Botulinum toxin is a neurotoxic protein produced by Clostridium botulinum. It blocks the release of acetylcholine from axons in neuromuscular junctions resulting in muscle paralysis. More specifically, it disrupts synaptosome-associated protein 25 kD (SNAP-25), which is necessary for the release of intracytoplasmic synaptic vesicles containing acetylcholine from the axon terminals in the neuromuscular junctions.[63][64] Botulinum toxin has also been found to reduce C-fiber stimulation (which can otherwise cause uninhibited detrusor contractions and bladder overactivity) by inhibiting urothelial sensory nerve function.[65][66] Botulinum toxin detrusor injections have been extensively studied and are recommended for overactive neurogenic bladder conditions when standard pharmacotherapy has failed.[67][68][69][70][71][72] The injections may be combined with other treatments, such as oral medications, as necessary.(A1)

Botulinum toxin injection therapy has been shown to reduce the mean detrusor pressure by 40% to 60% and significantly reduce incontinence and bladder overactivity.[67][69] The typical dose is 200 to 300 units.[69] Botulinum toxin therapy is particularly helpful when detrusor overactivity and autonomic dysreflexia are present simultaneously.[73] Side effects include increased post-void residual urine volumes and urinary retention requiring clean intermittent self-catheterization. Patients who are unable or unwilling to perform self-catheterization may not be ideal candidates for botulinum toxin therapy as they will require a Foley catheter until bladder function returns. The botulinum toxin treatment eventually wears off, usually after 6 to 9 months, and must be repeated to maintain efficacy.(A1)

Catheters

Clean intermittent self-catheterization is the gold standard and recommended first-choice therapy for neurogenic bladder patients who exhibit urinary retention, an inability to adequately drain their bladders, or have larger post-void residual volumes (typically >200 mL). It is most useful in patients with the manual dexterity, strength, and cognitive ability to perform self-catheterization independently.[22] While technically, having a willing caregiver to perform the catheterizations is equivalent, in practice, this is usually not desirable long-term as it places a significant responsibility and undue burden on family and support staff. Clean intermittent self-catheterization is preferred over other methods of catheter-assisted bladder drainage as it has fewer long-term complications such as renal deterioration, urolithiasis, and autonomic dysreflexia.[74] Clean intermittent self-catheterization will not work well in patients with abnormal urethral anatomy, small bladder capacities (<200 mL), autonomic dysreflexia, poor cognition, dementia, inadequate motivation, or an unwillingness or inability to adhere to a strict daily schedule. Potential complications include urethral strictures, hematuria, bladder overdistension, urinary tract infections, urethral strictures, incontinence, urolithiasis, and autonomic dysreflexia.(B2)

Clean intermittent self-catheterization combined with anti-muscarinic agents, beta-3 adrenoreceptor agonists, botulinum toxin, or sacral neuromodulation is the preferred gold standard for complicated neurogenic bladder disorders with both detrusor overactivity and incomplete bladder emptying not adequately managed adequately or safely with single-modality therapy.[75][76] It is based on the theory that even a very complex neurogenic bladder disorder can be converted to incomplete emptying with various therapies and then treated with intermittent clean catheterization.

Foley catheters are used in those situations where there is no other reasonable choice, and intermittent catheterization is not possible. Typical situations would be urinary retention or sustained high post-void residual volumes in selected patients with poor hand function, dementia, active substance abuse, high detrusor pressures, vesicoureteral reflux, failure of other treatment modalities which are not candidates for any surgical options, and those with limited help available support staff, family, or caregivers. Urethral catheters are contraindicated for urge incontinence with uncontrolled detrusor overactivity. Long-term catheterization should be avoided whenever possible as it has been associated with a three-fold increase in mortality in nursing home patients compared to those without catheters.[77]

Suprapubic tubes are generally preferred over urethral Foley catheters if it appears that catheter drainage will be a long-term therapy. Compared to a standard Foley catheter, a suprapubic tube reduces urethral irritation, eliminates discomfort at the urethral meatus, avoids ventral penile erosions, is easier to change, allows for the use of larger-sized catheters, is far more comfortable for the patient, and decreases the risk of urinary tract infections.[22][78] Bladder spasms and overactivity can be treated with anticholinergics, beta-3 adrenergic agents, botulinum toxin detrusor injections, or neuromodulation. If the suprapubic catheter falls out, it should be replaced on an urgent basis, or the cystostomy opening will close. (See our companion article on Suprapubic Tube Catheterization.)[79]

Asymptomatic bacteriuria should not be treated in patients with neurogenic bladder or catheters unless they have pyuria and signs or symptoms of an infection.[11] These would include leakage around the catheter, fever, lethargy, back or bladder pain, dysuria, or evidence of autonomic dysreflexia.[11] Cloudy or odoriferous urine is not sufficient to make a diagnosis of a UTI.[11] Urine cultures should always be done prior to starting UTI treatment, and a typical course of therapy would typically be at least seven days in these higher-risk individuals.[11] Neither routine urinalyses nor antibiotic prophylaxis is recommended in patients with catheters nor most patients with neurogenic bladders.[11]

Cystoscopic screening of patients with long-term catheters has been recommended historically, but there is no clear evidence that such surveillance is effective.[11][80] A 2017 meta-analysis of spinal cord injured patients managed with Foley catheters found an overall bladder cancer risk of only 6%, with an average duration of catheterization of 16 years.[80][81](A1)

Sacral Neuromodulation

Sacral neuromodulation is a safe and effective, minimally invasive therapy that moderates poorly regulated or unregulated spinal cord reflexes and activity by blocking afferent input to the sacral spinal, primarily through S3 stimulation.[82][83] It is also thought that sacral neuromodulation may block C fiber activity which would reduce uninhibited detrusor contractions, block the urethral guarding reflex (which would induce voiding for patients with retention), and relax the pelvic floor musculature, which would help initiate micturition.[82][83][84][85][86] This results in significant clinical relief of various disorders, including urinary urgency, incontinence, frequency, and urinary retention in patients who have failed standard pharmacologic and behavioral therapy.[83][87][88] Sacral neuromodulation requires the percutaneous placement of a very small, tined electrode wire along the S3 nerve root through the S3 foramen under fluoroscopic guidance and then stimulating the nerve with a minute electrical current from an implanted battery.[82] A test period of 2 to 4 weeks allows for an assessment of the efficacy of the treatment before a permanent battery pack is implanted.(B3)

Overall success rates with sacral neuromodulation have been reported at about 80%, and it may be combined with other treatment modalities as needed.[87][89][90] Overall, studies on the use of sacral neuromodulation are small, often demonstrate a selection bias, are not prospective trials, specifically exclude patients with neurogenic bladders, lack long-term follow-up, or have other statistical problems.[87][91] Larger, randomized, prospective trials with long-term follow-up are required to better predict outcomes with this modality in specific patient populations.[87] (A1)

Potential candidates for sacral neuromodulation must have failed behavioral measures and maximum tolerable pharmacological therapy for at least 8 to 12 weeks.[92] They are instructed to maintain a voiding diary during this period to monitor the efficacy of the treatment. An improvement of 50% or more is considered a success.[93] 

A relative contraindication would be a rapidly progressive or severe neurological disease.[94] Specific contraindications would include active pelvic infections, urinary or bladder outlet obstruction, or an inability of the patient to operate the program.[82][94][95] There is evidence that patients older than 55 years with significant comorbidities (three or more chronic medical conditions) enjoy a lower success rate with sacral neuromodulation for bladder and urinary control.[96]

The American Urological Association Guideline on Adult Neurogenic Lower Urinary Tract Dysfunction (2021) does not generally recommend sacral neuromodulation for spina bifida or spinal cord injured patients due to the high degree of variability in disease progression and bladder dysfunction in this population.[19] However, they do recommend offering sacral neuromodulation to other neurogenic bladder patients with otherwise intractable detrusor overactivity causing severe urinary urgency, frequency, and urge incontinence that is unresponsive to more conservative measures.[19]

Early use of sacral neuromodulation in a small number of spinal cord injured patients appears to have prevented the development of detrusor overactivity and incontinence, allowing for a normal bladder capacity and preservation of erectile function as well as bowel function.[97][98][99] Although this approach appears promising, the early use of sacral neuromodulation to change the usual progression of a spinal cord injury must still be considered investigational.[100] More data and studies are needed to identify which patients in this population might benefit from neuromodulation.(A1)

Randomized studies, including adequate numbers of patients with long-term follow-up, are required to better identify and predict the response of various neurogenic bladder patients to neuromodulation therapy either alone or in combination with other treatments.[87] (See our companion article on Sacral Neuromodulation.)[82]

Percutaneous tibial nerve stimulation has been shown to improve symptoms and urodynamic parameters in Parkinson disease and multiple sclerosis.[101][102][103][104] The treatment involves the temporary, percutaneous placement of a fine needle near the end of the tibial nerve at the ankle. A very small, fixed-frequency electrical current is then used to stimulate the nerve for 30 minutes. This is repeated for 12 weekly sessions, which can be followed by monthly maintenance therapy. The treatment is considered minimally invasive and has no serious side effects or complications. It is most effective for patients with mild to moderate overactive bladder voiding issues as it is generally not as effective overall as botulinum toxin injections or sacral neuromodulation.[20] Pudendal neuromodulation is another potential treatment for neurogenic bladder overactivity, especially immediately after a spinal cord injury.[105][106](A1)

Surgery

Augmentation cystoplasty is no longer recommended by some experts for intractable neurogenic bladder dysfunction due to detrusor overactivity in adults because of poor long-term reported success rates and significant complications in over 10% of patients.[107][108] However, modern studies are showing good results in selected patients, but not without some long-term issues.[109][110] The American Urological Association Guideline on Adult Neurogenic Lower Urinary Tract Dysfunction (2021) recommends augmentation cystoplasty in neurogenic bladder patients with reduced bladder capacity, compliance, or intractable overactivity that is not responsive to pharmacotherapy or botulinum toxin detrusor injections.[19] The main benefit of augmentation cystoplasty is good continence control and protection of the upper urinary tracts.[19] An ileal cystoplasty is currently the preferred type.[11] The problems associated with the procedure include the high likelihood of follow-up surgeries to manage complications (bladder stones, renal calculi, hematuria, perforation, bowel dysfunction, pouch mucus production, scarring with outlet obstruction) and the need for permanent urological follow-up.[19] Patients need sufficient hand strength and coordination to perform self-catheterization and the willingness, cognitive ability, and motivation necessary to do so indefinitely.[19] (B2)

Modern bioengineering technology is looking at creating a suitable, functional tissue suitable for bladder augmentation. This requires a high degree of biocompatibility, compliance similar to normal bladder tissue, and a urothelial layer to prevent extravasation, leakage, encrustation, stone development, and upper urinary tract deterioration.[111](B3)

Sphincterotomy is a destructive procedure in which the external urinary sphincter is incised, rendering it useless. The benefit is substantially lower bladder pressure which protects the upper urinary tracts, minimizes reflux, and reduces episodes of autonomic dysreflexia, but it causes continuous, uncontrollable urinary incontinence, which is irreversible. The incontinence is best managed with a condom catheter, usually preferable over Foley catheters or pads.[112] This drastic procedure is intended for patients with significant detrusor sphincter dyssynergia and bladder overactivity who have failed medical therapy and in selected patients unable or unwilling to perform self-catheterization. Potential complications include inadequate sphincteric disruption, bleeding, infection, and erectile dysfunction. Due to its inherent irreversible nature, the procedure should only be performed on carefully selected patients who fully understand and appreciate the consequences. Maximum detrusor pressure over 40 cm of water pressure has been found to be a good predictor of success in sphincterotomy procedures, with success defined as a consistent post-void residual volume of <150 mL.[113][114] Urodynamics may be used to assess the success of the sphincterotomy.[19] An alternative solution would be to use botulinum injections into the sphincter, usually at the 12, 3, 6, and 9 o'clock positions.[115](A1)

Urinary diversion surgery can be done to divert urine from the urinary bladder altogether. These major surgeries are intended for the most difficult and intractable neurogenic bladder situations not adequately managed with other treatment modalities. Continent diversions utilize either a pouch, which acts as an internal reservoir, or a bladder substitute for internal urinary storage. These can then be emptied periodically, usually by intermittent self-catheterization. A cutaneous stoma may be used to allow catheter access to the reservoir.[116] A number of variations on this basic procedure exist, including the Mitrofanoff appendicovesicostomy in which the appendix is used for stomal access, the Yang-Monti ileovesicostomy, the Indiana pouch, the Miami pouch, and several others.[116][117][118][119][120] In a bladder substitution (orthotopic neobladder), a bowel segment is reformed into a pouch and attached directly to the ureters and urethra. It has the advantage of not needing a continent stoma as the urethral sphincter is left intact.[121] Continent diversions are more complicated and time-consuming to surgical construct but are generally preferred, whenever possible, over incontinent diversions, especially in younger patients.[116](B2)

Incontinent urinary diversions use a portion of the bowel or intestine, usually the ileum, to create a passage to the skin surface, where it is used to create a continuously draining stoma. Patients who cannot tolerate longer surgeries, have pre-existing renal failure, or are unable to manage continent stomas are potential candidates for incontinent diversions.[37][122] The traditional version of this type of diversion is an ileal conduit. A straight urostomy, where the ureters are brought directly to the skin surface, is rarely used due to the high reported rate of stricture and stenosis.[116] An ileovesicostomy is a variation of the standard surgery in which the ileal conduit is attached to the bladder instead of directly to the ureters; it is used when there is a concern about potential stricture development if the ureters were anastomosed directly to the ileum.[118] It is not optimal for obese patients and tends to have a very high complication and follow-up surgery rate.[19] (See our companion article on Urinary Diversions and Neobladders.)[123](B2)

Special Cases

Autonomic dysreflexia patients will require special attention during urodynamics and other procedures. Extra attention may be necessary to avoid bladder overactivity, spasms, distension, urinary retention, and high detrusor pressures. Botulinum toxin detrusor injections should be considered in patients with bladder spasms or overactivity not responding well to oral pharmacotherapy.[24] (See our companion article on Autonomic Dysreflexia.)[24]

Cauda equina syndrome will usually develop quickly after an injury. It will demonstrate urinary retention and require clean, intermittent self-catheterization.[31] (See our companion article on Cauda Equina Syndrome.)[31]

Detrusor dyssynergia patients may respond to oral therapy with baclofen or diazepam, but most will require intermittent self-catheterization, detrusor overactivity pharmacotherapy, botulinum toxin sphincteric injections, sphincterotomy, permanent catheterization, or urinary diversion surgery.[32] (See our companion article on Detrusor Sphincter Dyssynergia.)[32]

Treatment Summary

• Identify patients with autonomic dysreflexia, cauda equina syndrome, and detrusor sphincter dyssynergia early so their treatment is optimized and not delayed unnecessarily.
• Patients with significant detrusor overactivity should initially be treated with behavioral modifications and pharmacotherapy, including anticholinergics and/or beta-3 adrenoreceptor agonists.
• Beta-3 adrenoreceptor agonists are generally preferred if possible due to their improved efficacy and low side effect profile.
• Bladder relaxing medications should be given at least 4 to 6 weeks before readjusting.
• Dosages of oral pharmaceuticals for bladder relaxation should be adjusted for efficacy and tolerability.
• Physicians should be familiar with the individual characteristics and costs of these medications to optimize their use for specific patient populations and individual patients.
• Combination therapy is encouraged when a single medication is inadequate to control symptoms or urodynamic parameters.
• Alpha-blocker medications may be of some use in patients able to void but who still have high post-void residual levels.
• Desmopressin can be used to diminish nocturnal polyuria but may cause fluid retention and hyponatremia, so it should be used with caution in elderly patients and those prone to congestive heart failure.
• Periodic 24-hour voiding diaries and post-void residual determinations can help monitor progress.
• Self-catheterization schedules should be adjusted so that the maximum urinary volumes drained should optimally not exceed 500 mL.
• Post-void residual volumes should be as low as possible but are generally considered "acceptable" at 200 mL or less.
• Botulinum toxin detrusor injections and sacral neuromodulation should be considered in patients with detrusor overactivity refractory to pharmacotherapy alone.
• Clean intermittent self-catheterization is the first-line recommended therapy for incomplete bladder emptying or urinary retention due to neurogenic bladder disorders.
• Patients unable to perform self-catheterization will need alternate therapy, such as an indwelling catheter.
• Suprapubic tubes are recommended over urethral Foleys if long-term urinary catheter drainage is required.
• Bladder relaxing therapy with oral pharmaceuticals, intravesical anticholinergics, botulinum toxin detrusor injections, or sacral neuromodulation can suppress bladder spasms in patients with permanent indwelling catheters.
• Even very complicated neurogenic bladders can usually be managed with a combination of bladder relaxation treatments and self-catheterization.
• Persistent detrusor pressures over 40 cm of water are likely to cause upper urinary tract damage if they cannot be controlled with bladder relaxing treatment modalities.
• For intractable cases, sphincterotomy, augmentation cystoplasty, or urinary diversion surgery may need to be considered, as the primary goal of neurogenic bladder treatment is to maintain kidney function and prevent renal failure.
• An individualized, patient-tailored approach is required for the optimal management of lower urinary tract dysfunction in this unique population.

Differential Diagnosis

The timely diagnosis of neurogenic bladder is crucial, and it significantly impacts patient outcomes. A careful history and review of systems, along with a thorough, focused neurological examination, play a key role in identifying the underlying cause of the neurogenic bladder. Laboratory evaluation is also helpful in reaching a final diagnosis.[124][125]

A neurogenic bladder can have many differentials, the most important of which is a spinal cord injury or tumor. Any injury to the spinal cord, including blunt, degenerative, developmental, vascular, infectious, traumatic, iatrogenic, radiation-induced, and idiopathic damage, can disturb normal micturition and result in urinary incontinence. Remember that patients with lesions at or above T-6 are at risk for autonomic dysreflexia. 

Other causes of urinary dysfunction can be the following:

• Alzheimer disease
• Benign prostatic hyperplasia
• Bladder decompensation
• Brain disorders, trauma, tumors
• Cauda equina syndrome
• Decompensated bladder
• Dementia
• Diabetes mellitus
• Diabetes insipidus
• Drug side effects such as excessive anticholinergics
• Functional incontinence
• Herniated disc
• Infectious neurologic process
• Interstitial cystitis
• Mobility issues
• Morbid obesity
• Multiple sclerosis
• Myelomeningocele
• Neurosyphilis
• Overactive bladder
• Parkinson disease
• Pelvic and sacral fractures
• Pelvic surgery
• Pernicious anemia
• Radiation therapy
• Spina bifida
• Spinal and sacral tumors
• Spinal cord injury
• Stress incontinence
• Stroke
• Tabes dorsalis
• Transverse myelitis
• Urethral foreign bodies
• Urethral strictures
• Urinary tract infections

Prognosis

The goal of treatment of neurogenic bladder is primary to preserve renal function and secondarily to maintain continence. Medical management by clean intermittent self-catheterization and anticholinergics is sufficient to maintain urinary continence and preserve renal function in about 90% of the patients with neurogenic bladder. Patients require long-term follow-up to monitor renal function, measure urinary parameters, and identify possible complications requiring additional therapy.

A detailed follow-up is also useful in assessing whether the previously given treatment regimen continues to be effective in safely managing the patient's condition. In patients with neurogenic bladder sphincter dysfunction, there are no recommended guidelines on how renal function should ideally be evaluated.[126] In clinical practice, radiologic imaging (renal ultrasonography) and laboratory testing (GFR, creatinine) are generally used to assess urinary and renal function.[127] Bladder function can be assessed by a 24-hour voiding diary, urinalysis, and post-void residual urine measurements.

Follow-up Evaluations

There are no strict, universally accepted guidelines for urological follow-up for neurogenic bladder patients. A yearly assessment of symptoms, voiding pattern (24-hour voiding diary), renal function via laboratory examinations, and post-void catheterization volumes or bladder scan residual measurements is a reasonable non-invasive evaluation.

The American Urological Association (AUA) has recommended a yearly history and physical, with a symptom assessment and renal function measurements for neurogenic bladder patients deemed to have moderate risk. Renal imaging every 1-2 years is also suggested.[19] This would include all patients with indwelling catheters who are at increased risk for stones.

Routine urine cultures are not recommended in asymptomatic patients. 

Neurogenic bladder patients who develop a urinary tract infection that does not respond to antibiotic treatment should receive upper tract imaging, and those with unexplained frequent or recurrent UTIs.[19]

For high-risk patients, the AUA has recommended that upper tract imaging be done yearly in addition to the above.[19]

The Canadian Urological Association (CUA) recommends yearly renal ultrasound imaging in all patients with spinal cord injury as well as for neurogenic bladder patients at moderate or high risk.[11] They also recommend upper tract imaging for selected low-risk patients.[11] 

Any significant change in symptoms or new complications should initiate a follow-up evaluation which may need to include cystoscopy and/or urodynamic evaluations.[19]

Cystoscopy can be useful in estimating sphincteric function and checking for bladder cancer in patients with chronic catheterization, but the incidence is too low to recommend routine examinations unless there is evidence of possible pathology.

Follow-up urodynamics is recommended by the AUA only in high-risk neurogenic bladder patients and only when clinically indicated, while the CUA suggests surveillance urodynamics yearly in high-risk individuals and every 2 to 5 years for those at moderate risk.[11][19]

Global Issues with Clean Intermittent Self-Catheterization

Clean intermittent self-catheterization is generally not a problem in the more developed countries of South America and Asia, such as India, Iran, Pakistan, Turkey, Malaysia, Brazil, and Mexico.[128] Catheter access is an issue in other countries such as Kenya, Ethiopia, and Thailand. Reusable catheters dramatically lower costs and make the treatment more acceptable in many poorer regions. Often, such catheters are donated by wealthier nations or non-profit agencies. Some areas will use even use glass or metal catheters. Some countries report substantial reusability of silicone catheters, such as up to three years in Thailand.[129]

Many African and other less developed countries often find patient acceptance of self-catheterization to be problematic. There are often unfounded fears of infertility, the expectation that it might interfere with the obligatory Muslim prayer ablutions, or make them otherwise unmarriable, combined with illiteracy and cultural resistance, has resulted in low acceptance rates of self-catheterization. [129][130][131] In China, the problem is the need for long-term compliance and the perceived inconvenience. Instead, many neurogenic bladder patients with large residuals will use the Crede maneuver for emptying, while those with small or overactive bladders will use condom catheters (males) or pads (females).[132] This results in a high rate of serious complications (renal failure, death) in poorly developed countries where self-catheterization is not widely accepted by appropriate neurogenic bladder patients. Reasons given for non-compliance include the cost of catheters and anticholinergic medications, inadequate funds for transportation to medical facilities, and lack of basic sanitation measures in local communities.[128][133][134]

Complications

Complications of the neurogenic bladder may be short-term or long-term. When a neurogenic bladder is left untreated, it can lead to repeated bouts of pyelonephritis, urinary tract infections, permanent bladder damage, renal failure, urolithiasis, complete loss of bladder compliance, urethral erosions, and hematuria. Long-term complications include renal stones, refractory urinary incontinence, bladder decompensation, and rarely malignancy.[135]