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Anne Lanham, Lillian Mwanri

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Diagnosis and Management of Neurogenic Bladder Dysfunction

Jehad Nabeel Qutub*, Mohammed Ahmed Alamoudi, Amr Ibrahim Serage, Ahmed Awad Mobaraki, ‏Mohammed Siraj Alghamdi, Abdulrahman Ali Alamri

Mbbs, Urology Resident, king Fahad Hospital, Jeddah, KSA

Abstract: Background: The function of the LUT is mainly storage and voiding of urine, which is regulated by the nervous system that coordinates the activity of the urinary bladder and bladder outlet. The part of the nervous system that regulates LUT function is disseminated from the peripheral nerves in the pelvis to highly specialized cortical areas. Any disturbance of the nervous system involved, can result in neuro-urological symptoms [1]. Methods: this article was done after retrospective longitudinal and observational study including patients with neurogenic bladder and reviewing national and international recent and related literatures to overview neurogenic bladder and most advanced medical and surgical diagnostic procedures and treatment modalities of neurogenic bladder. Results: Among patients included, 52% had an early referral. The majority were diagnosed as neurogenic bladder with high bladder pressure and low bladder compliance and were treated with oxybutynin and intermittent catheterization. Urodynamic follow-up results showed 68% of improvement at the second urodynamic examination decreasing bladder pressure and increasing bladder capacity and compliance. The percentage of incontinence and urinary tract infections decreased over treatment. Conclusion: Multiple conservative modalities, i.e pharmacologic agents, medical devices and neuro modulation, should be promoted before undertaking surgical interventions. Intermittent catheterization and drug therapy are usually sufficient for maintaining continence and preserving upper tracts. Surgical procedures should be considered if conservative measures fail to achieve continence between catheterizations or preserve upper tracts. However today the improvement of Quality of life is the final goal.

Keywords: neurogenic bladder, neurogenic lower urinary tract dysfunction, neurogenic bladder, surgical management, urinary incontinence. urinary retention, voiding dysfunction

Received August 04, 2020; Revised September 05, 2020; Accepted September 14, 2020

Citation: Jehad Nabeel Qutub, Mohammed Ahmed Alamoudi, Amr Ibrahim Serage, Ahmed Awad Mobaraki, ‏Mohammed Siraj Alghamdi, Abdulrahman Ali Alamri, Diagnosis and Management of Neurogenic Bladder Dysfunction. American Journal of Medical Sciences and Medicine, 8 (4). 157-163. January 2020. doi:10.12691/ajmsm-8-4-4

1. Introduction

Chronic kidney disease (CKD) is a worldwide public health problem. Evidence has confirmed the increase in cases, with millions of individuals being treated by renal replacement therapy, dialysis or kidney transplantation. Its prevalence in the world’s population exceeds 10% and may reach 50% in high-risk subpopulations, including patients with neurogenic bladder, a neurological dysfunction of the lower urinary system that changes the phases of filling and emptying of the bladder. Neural tube congenital malformations, such as myelomeningocele, are the most frequent causes of neurogenic bladder in childhood. At least 25% of the most severe symptoms in pediatric urology are associated with neurogenic bladder. Approximately 40% of children with neurogenic bladder develop some degree of renal impairment [2].

The appropriate process of urination depends on the synergy between the bladder and the urinary sphincter complex. This allows the bladder to remain relaxed and under low pressure during the filling phase, which characterizes bladder compliance. The emptying phase begins when the bladder capacity is reached, which generates a contraction of the bladder with elevation of the intravesical pressure, ideally up to 40cmH₂O, accompanied by sphincter relaxation, allowing complete emptying without post-void urinary residue [3].

The main risk factors for renal impairment related to the diagnosis of neurogenic bladder are increased pressure, reduced bladder capacity and compliance, detrusor sphincter dysynergia, and post-void residue. To reduce renal morbidity, it is necessary to identify and treat these risk factors as early as possible. The urodynamic evaluation is recognized as the gold standard diagnostic method, because it is the only examination capable of safely identifying these risk factors, assessing the coordination and pressure variations between the bladder, urethra, and sphincter complex and the integration between the bladder filling and emptying phases, identifying the causes of dysfunction, and guiding the appropriate treatment and follow-up of the disease [4].

Patients with neurologic disease can be a challenging population for medical providers. As the nervous system is integral to every major organ system, the effects of neurologic disease can be severe and widespread. From an urologist’s perspective, neurologic diseases have the potential to significantly impact urine storage and emptying. This can result in symptoms of urinary incontinence or urinary retention, which are common presenting symptoms [5].

The storage and voiding functions of the bladder are regulated by a complex neural control system, which acts like a switching circuit to maintain a reciprocal relationship between the reservoir function of the bladder and the sphincteric function of the urethra. The pontine micturition centre controls this system and it in turn receives input from higher centres, including regions of the frontal lobes (Figure 1). Disruption of the spinobulbospinal micturition pathway results in both impaired storage and voiding, which is associated with significant impairment of quality of life and can predispose to potentially life-threatening complications [35].

The ultimate goal is to preserve the upper urinary tract and long-term kidney function. Safe bladder management is also achieved by ensuring a compliant bladder with adequate bladder capacity for urine storage and confirming adequate bladder emptying. By allowing for adequate storage and emptying of the bladder, over distension or retention is avoided, urinary tract infections and stones are prevented, and complications associated with long-term urethral catheter placement can be avoided.

1.1. Review

Neurogenic bladder dysfunction may complicate a variety of neurologic conditions. In the United States, neurogenic bladder aﬀects 40-90% of persons with multiple sclerosis, 37-72% of those with Parkinsonism, and 15% of those with stroke . Detrusor hyperreﬂexia is seen in 50-90% of persons with multiple sclerosis, while another 20-30% have detrusor areﬂexia. There are more than 200,000persons with spinal cord injuries, and 70-84% of these individuals have at least some degree of bladder dysfunc-tion [6].

Figure 1. Innervations of the lower urinary tract

Figure 2. Classification system for neurogenic bladder voiding dysfunction

1.2. Classification

Neurogenic bladder, like other types of voiding dysfunction, can be classified, based on the description by Wein [31], as a failure to store or a failure to empty. Failure to store or empty can be further classified by bladder anomalies, outlet anomalies, or a combination of both. Anomalies of the bladder include altered compliance, altered sensation, or altered detrusor contractions. Anomalies of the outlet include decreased resistance or increased resistance from anatomic obstruction, sphincter dyssynergia, or sphincter dysfunction. A classification system for neurogenic bladder voiding dysfunction is shown in (Figure 2). A patient with neurogenic bladder may present with complex urinary symptoms, and Wein’s classification scheme, presented here, helps identify the basic components of the problem that will direct management.

Neuro-urological symptoms can cause a variety of long-term complications; the most significant being deterioration of renal function. Since symptoms and long-term complications do not correlate, it is important to identify patients with neuro-urological symptoms, and establish if they have a low or high-risk of subsequent complications. The risk of developing upper urinary tract damage and renal failure is much lower in patients with slowly progressive non-traumatic neurological disorders than in those with spinal cord injury or spina bifida [33].

2. Causes of Neuropathic Bladder Dysfunction

2.1. Spinal Cord Injury

All patients with spinal cord injury have bladder dysfunction. Detrusor overactivity and detrusor sphincter dyssynergia are the most common abnormalities, especially in cases of suprasacral lesions. Patients with spinal cord injury are prone to develop upper tract damage and renal disease due to high intravesical pressure, vesicoureteral refl ux and hydronephrosis; they have five times the age-standardised risk of renal failure compared to the general adult population.2 UK and European guidelines are available for management [35].

2.2. Multiple Sclerosis and Other Demyelinating Disorders

Bladder dysfunction is very common in patients with multiple sclerosis (MS), particularly as spinal cord involvement increases. It has been reported that up to 80 per cent of these patients have bladder symptoms if the duration is greater than ten years, and symptoms occur on average six years into the illness [7]. Complications can occur in up to 30 per cent of patients, most commonly lower urinary tract infections. For reasons that are still unclear, the incidence of upper urinary tract damage and renal failure is low in patients with MS, and bladder symptoms, particularly in the early stage of the disease, can be regarded as medically manageable. Practical guidelines for management and follow-up of neurogenic bladder in patients with MS have been proposed. 6 Lower urinary tract dysfunction has been shown to occur in other demyelinating disorders such as acute disseminated encephalomyelitis or transverse myelitis; this may persist after other neurological deficites have resolved [8].

2.3. Movement Disorders

Bladder symptoms are common but not inevitable in Parkinson’s disease, and patients most often report urgency, frequency and urgency incontinence secondary to detrusor over activity. Bladder dysfunction tends to correlate with neurological disability.8 Voiding dysfunction may occur due to pelvic floor rigidity and bradykinesia. However, ‘diagnostic shadowing’ should not be allowed to obscure the fact that men may have out flow obstruction of prostatic origin amenable to treatment. In multiple system atrophy, incontinence usually arises from detrusor over activity and external sphincter weakness [5].

As the disease progresses, emptying becomes increasingly abnormal. Spina bifi da, especially when it is associated with myelomeningocele, is the commonest congenital cause of neurogenic voiding dysfunction. Studies suggest that more than 90 per cent of children with spina bifi da have bladder dysfunction. The incidence of upper urinary tract damage tends to increase with age12 Adults with spina bifi da have eight times the age-standardised risk of renal failure compared to the general adult population, and a retrospective chart review suggests this may be the leading cause of death in adults with spina bifi da [32].

3. Cauda Equina Syndrome and Peripheral Neuropathy

Lower motor neuron disturbance of the bladder in patients with polyradiculopathy or peripheral neuropathy is unpredictable. Generally, bladder dysfunction results in reduced or absent detrusor contractions. Patients notice reduced sensation of bladder fullness, inability to initiate micturition voluntarily, and have bladder distension to the point of over flow incontinence. However, detrusor over activity may occur as well, resulting in symptoms of storage dysfunction [9].

3.1. Dementia

Incontinence is often a prominent symptom and may occur at variable times during the natural history of dementia. It tends to occur early in normal pressure hydrocephalus, dementia with Lewy bodies, vascular dementia and frontotemporal dementia. On the other hand, urinary incontinence generally occurs only in the advanced stages of Alzheimer’s disease. Also, Stroke is another cause. More than 50 per cent of stroke patients may have urinary incontinence during the acute phase, and this is a strong indicator of prognosis. Approximately 70 per cent of survivors of hemispheric strokes suffer transient urinary incontinence. Risk factors for incontinence include lesion size, presence of comorbid illnesses such as diabetes, and age [9].

3.2. Diagnostic Evaluation

The normal physiological function of the LUT depends on an intricate interplay between the sensory and motor nervous systems. When diagnosing neuro-urological symptoms, the aim is to describe the type of dysfunction involved. A thorough medical history, physical examination and bladder diary are mandatory before any additional diagnostic investigations can be planned. Results of the initial evaluation are used to decide the patient’s long-term treatment and follow-up.

3.3. Patient history

History taking should include past and present symptoms and disorders. It is the cornerstone of evaluation, as the answers will aid in diagnostic investigations and treatment options. In non-traumatic neuro-urological patients with an insidious onset, a detailed history may find that the condition started in childhood or adolescence. Urinary history consists of symptoms associated with both urine storage and emptying .bowel history is important because patients with neuro-urological symptoms may also have related neurogenic bowel dysfunction, Sexual function may be impaired because of the neuro-urological condition. Special attention should be paid to possible warning signs and symptoms (e.g. pain, infection, haematuria and fever) requiring further investigation. The presence of urinary, bowel and sexual symptoms without neurological symptoms could be suggestive for an underlying neurological disease or condition [10].

3.4. Physical Examination

In addition to a detailed patient history, attention should be paid to possible physical and intellectual disabilities with respect to the planned investigations. Neuro-urological status should be described as completely as possible. Patients with a high spinal cord or supraspinal neurological lesions may suffer from a significant drop in blood pressure when moved into a sitting or standing position. All sensations and reflexes in the urogenital area must be tested. Furthermore, detailed testing of the anal sphincter and pelvic floor functions must be performed. It is essential to have this clinical information to reliably interpret later diagnostic investigations [11].

3.5. Laboratory and Urinalysis

After the first week of life, renal function should be tested, for example, by plasma creatinine levels; cystatin C can be a useful marker. In patients with impaired renal function, treatment should be optimized as much as possible. Urine samples can be easily obtained by catheterization as most patients perform CIC. Only in patients with asymptomatic/febrile proven UTI, antibiotic treatment should be started. In most patient’s asymptomatic bacteriuria can be detected, which requires no treatment [12].

3.6. Ultrasound

At birth, ultrasound of the kidneys and bladder should be performed and then repeated. Dilatation of the upper urinary tract should be recorded according to the classification system of the Society of Fetal Urology including the measurement of caliceal dilatation and anterior-posterior diameter of the renal pelvis. Bladder wall thickness has been shown not to be predictive of high pressures in the bladder, but may be mentioned in the ultrasound report [13].

3.7. Urodynamic Studies

Urodynamic studies (UDS) are one of the most important diagnostic tools in patients with a neurogenic bladder. In patients with postnatal closure of the spina bifida, the first UDS should be performed after the phase of the spinal shock, usually between the second and third months of life. In those patients with prenatal closure, UDS are recommended to be performed before the child is discharged from hospital, because the phase of spinal shock occurred already intrauterine—mostly 2 to 3 months before. In all other patients (see above) UDS should be performed as soon as there is a strong suspicion of a neurogenic bladder (eg, voiding pattern, changes of the upper or LUT). Especially in the newborn age, interpretation of UDS may be difficult, and normal values do not exist. During and after puberty there should be increased attention to bladder and sphincter behavior as bladder significantly during this time period [14].

3.8. Electromyography (EMG)

This reflects the activity of the external urethral sphincter, the peri-urethral striated musculature, the anal sphincter, and the striated pelvic floor muscles. Correct interpretation may be difficult due to artefacts introduced by other equipment. In the urodynamic setting, an EMG is useful as a gross indication of the patient’s ability to control the pelvic floor. Possible pathological findings include inadequate recruitment upon specific stimuli (e.g. bladder filling, involuntary detrusor contractions, onset of voiding, coughing, Valsalva manoeuvre) suggesting a diagnosis of DSD [15].

3.9. Treatment

Clinicians managing patients with neurogenic bladder (NGB) and neurogenic detrusor over activity (NDO) are faced with a myriad of complex choices when deciding on appropriate medical and/or surgical interventions to relieve bothersome symptoms associated with NGB and NDO, especially urinary incontinence. Therapies must provide maximum benefits while minimizing patients’ risk for adverse events. A thorough knowledge and understanding of available and emerging medical and surgical treatment options for NGB/NDO is vital to assist clinicians in choosing appropriate treatment pathways and optimize response to therapy and individual outcomes. Individualized treatment of NGB will depend on the type of neurologic disease underlying the lower urinary tract dysfunction and its general evolution (prognosis, degree of disability, progression), patient symptoms, urodynamic findings, and also on the general health and condition of the patients and available resources [16].

3.10. Conservative and Lifestyle-Based Therapies

Regular and adequate emptying of the bladder is a critical component of optimal healthcare for patients with NGB. Regular bladder emptying (through self-catheterization or other means) reduces intra vesical bladder pressure and allows for appropriate cycling of bladder contents to lower patient risk for UTIs. Behavioral training is a frequent component of urologic management in patients with neurologic disorders for patients with neurologic lesions involving the brain such as cerebrovascular disease, Parkinson’s disease, multiple system atrophy, dementia, and cerebral palsy, as well as for patients with MS, incomplete SCI, transverse myelitis, and diabetes mellitus.The most common techniques used are Valsalva (abdominal straining) and Crédé maneuver (manual compression of the lower abdomen). Although bladder expression techniques can be effective in bladder emptying, they can be complicated by potential urine reflux into the upper urinary tract, genital-rectal prolapse, hemorrhoids, and incomplete emptying [16].

3.11. Intermittent Catheterization

The purpose of catheterization is to empty the bladder of urine. Clean, intermittent catheterization (IC) is the preferred bladder management technique for patients with NGB dysfunction who experience complete or partial urinary retention. The purpose of IC is to resume normal bladder storage and regularly complete bladder emptying and urine evacuation. Self-administered IC enhances patient self-care and independence and reduces barriers to activity and sexual functioning compared with use of an indwelling catheter [16].

CIC is important in avoiding the complications of neuropathic bladder dysfunction, and nighttime continuous catheterization may be recommended to those patients who are under increased risk for upper tract changes. In patients who are resistant to anticholinergic treatment, intra vesical applications, electrostimulation or neuro modulation may also be added to the treatment regimen. Intra vesical Botox© injection is regarded as a second option for a therapy resistant overactive bladder in spina bifida patients. However, its effect disappears after 6-12 months and relaxation is difficult to achieve in noncompliant fibrotic bladders [36].

4. Pharmacologic Therapies for Neurogenic Bladder

4.1. Antimuscarinics

Antimuscarinic drugs comprise the foundation of first-line treatments for patients with NGB/NDO.5 The physiologic basis for treating bladder over activity with these agents is that detrusor contractions are primarily mediated by muscarinic receptors. It inhibit acetylcholine at the muscarinic receptors, leading to relaxation of the detrusor and improved bladder storage.5 By blocking the action of acetylcholine, these agents stabilize the detrusor, rendering it refractory to parasympathetic nerve impulses. This results in increased bladder capacity and a delay in the urge to void [18].

4.2. α-Blockers

In some patients with NB, non-selective and selective α-blockers have been partially successful for decreasing bladder outlet resistance, residual urine, and autonomic dysreflexia [19].

4.3. β3-Adrenergic Receptor Agonist

The β3 receptor agonist has recently been introduced and evaluated in patients with over activity bladder (OAB), but clinical experience in neuro-urologic patients is limited and it is safe and effective in the future [20].

4.4. Phosphodiesterase Inhibitors (PDE5Is)

PDE5Is have been shown to have significant effects and become alternatives or adjuncts to anti-muscarinic treatment in the future. Recently, nitric oxide (NO) has been shown to participate in the neural pathways that control the LUT [21].

4.5. Surgical Interventions for Neurogenic Bladder

Surgical interventions are usually reserved for cases in which nonpharmacologic and pharmacologic interventions fail to control NDO in patients with neurologic disorders. Surgical treatment of urological complications is limited to the patients who have breakthrough UTI with upper urinary tract deterioration. Exact indications for surgical interventions are; bladders with high pressure, low compliance and low capacity, upper urinary tract deterioration because of high grade VUR and incontinence after school age due to low sphincter resistance. Although most of the cases can be managed conservatively, some patients may need surgical interventions [22].

4.6. Neuromodulation Sacral Neuromodulation (SNM)

Involves unilateral or bilateral sacral nerve root stimulation. SNM has been used to treat OAB and has been approved by the FDA for treatment of urge incontinence, urinary urgency and frequency, and non-obstructive urinary retention. SNM uses electrical stimulation to modulate signaling from somatic and afferent nerves involved in the micturition reflex pathway. Original trials excluded patients with NGB because it was initially believed that intact spinal pathways were required for neuromodulation to occur. This therapy is considered (though not yet approved by the FDA) in patients with NGB/NDO who have used conservative therapies including lifestyle changes and bladder training plus antimuscarinic therapy but have not achieved adequate relief from symptoms [23].

4.7. Other Surgical Interventions

The most effective surgical method to optimize bladder capacity is enterocystoplasty. This involves the harvesting of a piece of bowel that is configured into a patch, which is placed on a bivalved bladder. Patients undergoing bladder augmentation would be expected to have an appropriate increase in bladder capacity and decrease in bladder storage pressures. Risks of these procedures include bladder stone, UTI, bladder perforation, change in bowel habits, and cancer. For patients who are interested in lower urinary tract reconstruction but are unable or unwilling to perform IC per their native urethra, a continent urinary stoma can be constructed to the skin [24].

4.8. Artificial Urinary Sphincter (AUS)

Artificial urinary sphincter (AUS) implantation plays an important role in urinary tract reconstruction (UTR) for patients with complex urinary incontinence (UI), including neurogenic UI. Patients with NB have low bladder outlet resistance and AUS can offer such patients the possibility of spontaneous voiding. The primary sources for AUS implantation in China are unique, and the procedure is an effective treatment as a key procedure for UTR, especially in neurogenic UI cases. Cuff erosion, urethral atrophy, and mechanical device failure are the well-known complications during the long-term follow up, all of which require revision surgery [25].

4.9. Sphincter Dilation

The goal of sphincter dilation is to disrupt the external urethral. Dilation techniques involve using a balloon dilator at the external urethral sphincter. McFarlane [26] reported their results on a series of patients. Initially, they had good results, but at 1-year follow-up, 62% failed. Overall, 85% failed. As such, it was considered a poor long-term management strategy in these patients with DESDn [26].

4.10. Urethral Stent

Urethral stents work by providing fixed resistance at the level of the external urethral sphincter maintaining a patent membranous urethra, thereby preventing DESD. Urethral stenting has the advantage of being permanent, yet it is also described to be reversible. Contraindications to use of the urethral stents are more proximal obstruction (bladder neck pathology or BPH). For DESD, the stent should be placed such that its distal extent extends into the bulbar urethra (by at least 5 mm) and proximally covers the caudal half of the verumontanum [27].

4.11. Chemical External Sphincterotomy

Chemical sphincterotomy involves using botulinum toxin A to paralyze the external urethral sphincter. An endoscope is used to inject three 33-IU aliquots of botulinum toxin A into the external urethral sphincter at the 3-, 9-, and 12-o’clock positions. The needle is advanced approximately 1 cm into the sphincter prior to injection. There is no standard injection or reinjection protocol. Gallien et al reported significant improvements in post void residual (PVR) urine volume, voiding volume, and mean detrusor pressure compared with placebo in multiple sclerosis patients. The literature demonstrates a decrease in urethral pressures, bladder voiding pressures, and PVR after injection [28].

5. New Treatments

5.1. Stem Cell Transplantation

The mature central nervous system (CNS) cannot generate new neurons and glial cells. Consequently, recovery of bladder function is limited following SCI; however, a study suggested that transplanted neural progenitor cells or other stem cells can promote recovery of bladder function through regeneration of the injury site. In most of these studies, stem cells have been injected directly into the lesion, which carries the risk of further injury to the spinal cord. We have taken the alternative approach of intravenous injection of bone marrow stromal cells (BMSCs). These cells survive in lumbar vertebrae 3 and 4 (L3-L4) for at least four weeks, and we observed some improvements in LUT function in rats with SCI. Although the study was preliminary, it does suggest that intravenous transplantation of BMSCs has potential for the treatment of LUT dysfunction after SCI in humans. BMSCs also may become one of the early neuroprotective strategies [29].

5.2. Gene Therapy

Gene therapy has also been explored for the treatment of organ dysfunction secondary to SCI, including NB disorder. It is known that suppressing N-methyl-D-aspartate receptors (NMDARs) can improve DO in rats with SCI. We took a gene therapy approach to express kynurenic acid, the endogenous antagonist of NMDARs. We transferred the gene for human kynurenine aminotransferase II (KAT II), which synthesizes kynurenic acid, to a replication-defective herpes simplex virus vector (HSVrd) and injected the HSVrd into the bladder walls of rats. The vector was transported to the L6-S1 dorsal root ganglia, the expression of KAT II was up-regulated, and there was an improvement in DO and voiding efficiency. We also confirmed by whole-cell patch clamping of cultured rat neurons of the L6-S1 dorsal root ganglia that NMDARs are blocked by kynurenic acid present in the extracellular solution or delivered by vector-mediated gene transfer of KAT II. Therefore, HSVrd-mediated KAT II inhibits DO in rats with SCI, possibly through suppression of NMDARs in bladder afferent pathways [30].

6. Conclusion

Neurogenic bladder dysfunction can be successfully treated to achieve goals of urinary continence, prevention of renal damage from chronically high detrusor pressures, and minimizing risk of urinary tract infections or bladder over distension. A comprehensive multidisciplinary bladder retraining program can best achieve these goals utilizing patient education, instruction in catheter use/care, med-ications, and/or bladder or urethral surgical procedures. Experimental works in lumbar-to-sacral nerve rerouting and in regenerative medicine including use of stem cells to mitigate or reverse spinal cord damage producing neurogenic bladder dysfunction are still in their infancy, and more research will be needed to see if the promising results of some small pilot studies are conﬁrmed in larger, controlled studies with long-term follow up.

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