Neurogenic bladder (NB) or neurogenic lower urinary tract dysfunction (NLUTD), a dysfunction of the urinary bladder and urethra due to disease of the central or peripheral nervous system. Various neurological diseases like stroke, dementias, Parkinson's disease, spinal injuries, spinal tumors, congenital lesions like spinal dysraphism and diabetes can produce NB/NLUTD. The neurogenic dysfunction manifest as over active or underactive bladder which depends on extent and level of neural lesion. It is not only a medical problem but also a major social issue.1
ANATOMY OF BLADDER INNERVATION (FIG. 1)
- Parasympathetic: S2- S4 motor to detrusor, inhibitory to internal sphincter
- Sympathetic: D10-L2 motor to sphincter, inhibitory to detrusor
- Origin: Intermediolateral grey column.
- Pudendal nerve (S2, S3, S4)
- Origin: Nucleus of Onuf/Ventral horn.
Cortical Micturition Center:
- Second frontal gyrus (Paracentral lobule) inhibitory to PMC.
Pontine Micturition Centre:
- Supraspinal regulation of micturition.
Briefly, neurologic voiding dysfunctions can be classified as (Fig. 2):
- Suprapontine lesions
- Suprasacral spinal cord lesions
- Sacral spinal cord lesions
The suprapontine areas are responsible for providing inhibitory signals to the pontine micturition center, which provides signals for regulating micturition. Suprapontine lesions such as dementias, CVAs, and brain tumors can therefore cause loss in inhibitory signals to the pontine center, resulting in urinary frequency, urgency, urge incontinence, and uninhibited voiding. But there is no impact on the coordination of the bladder and sphincter.
Suprasacral spinal cord lesions result in the loss of supraspinal input. This loss of input typically results in uncontrolled activation of the micturition reflex, via afferent fiber stimulation, causing uninhibited detrusor contractions. Signals from the pons that help to coordinate bladder and sphincter activity can be affected, resulting in detrusor-sphincter dyssynergia (DSD). Detrusor-sphincter dyssynergia occurs more frequently with higher spinal lesions.
Sacral spinal cord lesions can manifest with varying degrees of upper and lower motor neuron damage. This can result in different clinical manifestations, including detrusor hyper-reflexia and areflexia. Similarly, the external sphincter can be affected in different ways, ranging from complete loss of function to DSD.
Lesions that are distal to the sacral spinal cord, such as those present in myelodysplasia, cauda equina injury, radical pelvic surgery, or pelvic plexus injury can result in an areflexic, hypotonic, or flaccid bladder and a denervated sphincter. The external sphincter can be in a fixed position, resulting in chronic obstruction and consequent loss of bladder compliance.
Functional Classification of Neurogenic Bladder Dysfunction (Box 1)
The functional system is perhaps the most simple and widely accepted classification system for lower urinary tract disorders. First proposed by F. Brantley Scott's group in 1968,2 this system was later popularized by Alan J. Wein.3 In its essence, this system describes whether the deficit is primarily one of:
- The filling/storage or
- The emptying/voiding phases of micturition.
A failure of filling/storage and failure of emptying/voiding can result from either bladder or outlet abnormalities, or a combination of both.
This classification is useful and easy for understanding and remembering. But some patient may not fit into any one category.
EVALUATION (TABLE 2)
As always the patient history is an essential part of the diagnosis. Duration and level of lesion and previous medical histories are important data. The special history includes a complete review on the general neurological, specific somatic and sensory, urinary, anorectal, sexual, gynecological symptoms and signs. Sensations of bladder filling have to be asked for. Autonomic dysreflexia has to be investigated if a spinal lesion above T6 has occurred. The way bladder emptying has been done so far, the eventual presence of incontinence, and any usage of catheter or appliances are important. Evaluation following soinal cord injury is summarized in flow chart 1.
The main objectives for current strategies in the management of NB are:
- Protection of the upper urinary tract
- Restoration of the lower urinary tract function
- Improvement of urinary continence
Most widely applied treatment modality in NB. Conservative treatment is cheap, easily available even in periphery where urologists not available with less complications. The goals are to achieve a good bladder storage/voiding cycle, with low intravesical pressure with maintenance of urinary continence and little or no residual urine. These techniques includes:
- Behavioral techniques
- Intermittent catheterization and intermittent self-catheterization
- Transurethral and suprapubic catheters
- Appliances (condom catheters and penile clamp).
Behavioral therapy is important in all patients. It is most valuable in patients with some amount of bladder control and intact bladder sensation. It is helpful in patients like CVA, multiple sclerosis (MS), dementia, Parkinson's, incomplete spinal cord injury (SCI) and transverse myelitis.
- Timed voiding: Chronic/frequent over distension leads to flaccid, large capacity, permanent paralytic bladder. Timed voiding means maintaining fixed interval between episodes of urination/toileting. The primary goal of timed voiding is to void before urinary urgency and occurrence of incontinence. It is done by frequent voiding to lower the residual urine or by increasing the voiding interval to reduce frequency. This type of “bladder drill” helps to hold more urine and inhibit inappropriate detrusor contractions during the filling phase of bladder
- Modifying/Adapting drinking habits: Includes balanced fluid intake/restricting caffeinated beverages and bladder irritants. Toilet facility should be nearby to the patient which improves the mobility. Planning a fluid schedule is an important initial event in the management. The recommended fluid schedule is 400 cc with meals; 200 cc at 10 AM, 2 PM, and 4 PM; and only sips of fluid after the evening meal (1800 cc/day total). This schedule limits the urine formation about 1500 cc with insensible fluid loss.
Patient is also instructed to keep a voiding diary—helps to know functional bladder capacity, sensation.
Detrusor over activity from defective central inhibition or increased detrusor afferent activity can be improved by reinforcing inhibitory pathways. Pelvic floor muscle training should benefit patients with weak pelvic musculature. To activate this myotomes a simple technique like standing on tiptoes can suppress urgency.5
The activation of sacral dermatomes particularly glans penis, clitoris and anus can inhibit detrusor activity by enhancing sympathetic neurons and inhibiting preganglionic bladder motor neurons.
The bladder drill for urgency and urge incontinence, consists of teaching the patients to sit down on a rolled-up towel and press on or squeeze the clitoris/glans penis to activate the appropriate dermatomes. This type of training reduces urgency by inhibiting the bladder contraction and increase the functional bladder capacity.
Transcutaneous electrical nerve stimulation over sacral dermatomes (s2–s4) reduces urgency and urge incontinence. Various studies proved that electrode placed over s3 dermatome and stimulation of this electrodes in the range of 2–10 Hz has shown significant positive response in the form of reduction in bladder urgency, improvement in bladder capacity and reduction of bladder pressure compared to pre- stimulation.
- Physiotherapy for detrusor hypoactivity: Detrusor overactivity can be enhanced by pressing or tapping over the bladder wall which will activate stretch receptors. Other techniques like bending forward and straining can also activate bladder contraction. Pelvic floor relaxation helps bladder emptying.Pelvic floor muscle electric stimulation is very useful in patients with DSD with urinary retention. Plevnik et al.6 treated six patients with spinal cord lesions from C5 to T4,using anal or vaginal electrodes monophasic square pulses of 1 ms, frequency of 20 Hz and 50–90 mA, a reduction in maximal urethral pressure was reported.Intravesical transurethral bladder stimulation uses the procedure of combining direct stimulation of bladder receptors with visual feedback using patient observance of cystometric pressure changes. It is useful in patients with bladder underactivity due to neuromuscular weakness
- Triggered reflex voiding: It consists of bladder reflex triggering maneuvers performed by patient to elicit reflex detrusor contractions by external stimuli. These are suprapubic tapping, thigh scratching, squeezing the glans penis and the scrotal skin, pulling on the crines pubis, anal/rectal manipulation. Only in a minority these methods are useful
- Bladder expression: Comprises various maneuvers like Valsalva (abdominal straining) and the Credé (manual compression of the lower abdomen) maneuvers. These methods are useful in patients with lower motor neuron lesions where combination of an underactive detrusor with an underactive sphincter or with an incompetent urethral closure mechanism of other origin.
Intermittent Catheterization and Self Intermittent Catheterization
The aim of catheterization is mainly to evacuate the bladder. In NB with partial or complete urinary retention intermittent catheterization (IC) is the technique of choice. Self-administered IC improves patient self-care, independence, decreases barriers to sexual function and daily activity. For achieving continence in patient on IC a bladder with adequate capacity, low pressure and a balance between fluid intake, residual urine and catheterization frequency is necessary. If the patient retains some voluntary control, voiding can be attempted at timed intervals or when the urge occurs. Intermittent catheterization partly aids in bladder retraining by gradually decreasing residual urine. Complications includes bacteriuria and urinary tract infection (UTI), urethritis, epididymitis, epididymorchitis, prostatitis, urethral trauma, hematuria, urethral false passages, strictures etc. Asymptomatic bacteriuria is a common finding.
In patients whom IC is not feasible, indwelling catheter may be used. This can be urethral catheter or suprapubic catheter. Commonest complication during indwelling catheter are UTIs but in a long term care setting prophylaxis against UTI is usually not advised.
Fluid intake should be generous in patients with indwelling Foleys catheter or suprapubic catheter. Long term catheterization produce bacterial colonization (biofilm) particularly at the catheter tip. Urease producing organisms elevate pH and cause calcium magnesium phosphate crystals leading to catheter obstruction. This produces or aggravates urinary tract infection. To prevent this complications urine pH must be kept alkaline (pH 8), combined with liberal fluid intake (total intake 3L/day). Increasing dietary citrate (fruit juices) to at least 11 g/day helps to keep urine pH 8 in conjunction with increasing fluid intake. Suprapubic catheter has many advantages.
- Easy to maintain catheter and hygiene
- Less tendency to kink
- Less interference with social functioning like sexual activity
- Urethral injury like erosion avoided.
This technique is mainly used in patients with poor upper extremity dexterity, as well as the presence of DSD. Other potential candidates include patients with extensive urethral damage or in whom other methods are impractical. Although open suprapubic cystostomy under anesthesia is the definitive gold-standard approach, many less invasive techniques are also available.
Condom catheters have a role in male patients with NB for short term management. In the long run, their use may lead to bacteriuria. If applied properly complications are less. In this method frequent change of condom, maintenance of good hygiene, and low bladder pressure is essential. Complications like skin maceration and ulcers may develop but compared with urethral catheters there is low incidence of infections.
Many drugs are available for NB, these include:
- Tricyclic antidepressants.
Most commonly used are antimuscarinics, mostly administered orally, rarely as intravesical instillation.
Antimuscarinic drugs are the first-line drugs for patients with NB/neurogenic detrusor overactivity (NDO).
Acetylcholine is the neurotransmitter involved in detrusor contractions, antimuscarinics inhibit at muscarinic receptor level leading to relaxation of detrusor and improved storage. This results increased bladder capacity and reduced urgency to void.
Oxybutynin is available as immediate, sustained-release oral preparations, transdermal and topical gels. Tolterodine tartrate and trospium chloride are available both immediate, and sustained-release oral formulation. Since these drugs doesn't cross blood-brain barrier they produce less cognitive side effects and dry mouth than oxybutynin.7
Overall, antimuscarinic therapy can provide substantial benefits to patients with NB and NDO. A recent meta-analysis that included a total of 960 patients with NDO in 16 randomized clinical trials (RCTs) found that antimuscarinics were associated with statistically significant better patient-reported cure or improvement, higher maximum cystometric capacity, higher volume at first detrusor contraction and lower maximum detrusor pressure when compared with placebo. Of all these drugs studied and found to be effective no one drug is superior over other. The side effects include dry mouth, constipation, nausea, and visual disturbance.
Combination therapy is considered when monotherapy has failed. Combination of two antimuscarinics at high-dosage was found to be useful when one agent has failed.
Tricyclic Antidepressant Drugs
Introduced for depressive treatment, their side effect made them second line agents. The anticholinergic side-effects of this class of drugs have been used to reduce bladder detrusor tone in neurogenic bladder dysfunction. Imipramine has strong anticholinergic effects, so it reduces bladder tone, increases internal sphincter tone which will facilitate urine storage. Amitriptyline is also used some times.
A naturally occurring neurotoxin, derived from clostridium botulinum bacterium which produce flaccid paralysis of striated muscle by blocking presynaptic release of acetylcholine. Even though many type of botulinum toxin are available commercially, for urological condition onabotulinumtoxinA (BoNT/A) is the FDA-approved one.8
The toxin has effect mainly on efferent muscle contraction, with possible afferent effects on bladder function as well.
Injection of BoNT/A into the detrusor muscle produce dose-dependent muscle relaxation due to reduced neural signal transmission. The BoNT/A's effect on bladder smooth muscle is significantly longer than skeletal muscle. Multiple studies confirmed its effect on NB, urinary incontinence, and QoL in MS and SCI patients. At present BoNT/A is approved for patients with detrusor over activity and patients who have poor response to antimuscarinic drugs. The doses used are 200 U to 300 U. Between the used doses both are well tolerated and equally effective. The commonest adverse effect is urinary infections and urinary retention. Increased risk of retention is seen in patients who didn't perform interstitial cystitis at baseline. A dose of 200 U is commonly used because of less adverse effects.9
SURGICAL INTERVENTIONS IN NEUROGENIC BLADDER (TABLE 5)
When pharmacological and conservative managements fail surgical options can be considered. It can be of help in many ways like:
- Procedure to enhance detrusor storage
- Procedure to enhance emptying
- Bladder sphincter procedure to restrict emptying
- Bladder sphincter procedure to enhance emptying.
Some future developments in management is summarized in table 6.
Neurological disorders often cause bladder and bowel dysfunction. Most patients with NB need long term or even life-long care for optimal life expectancy and QoL. Timely recognition and treatment are essential to prevent upper and lower urinary tract damage. Evaluation of NB include detailed history, neurological assessment and appropriate investigations including urodynamic study. The neurourological management must be individualized to the patient's needs which often requires multi-disciplinary approach. Before major surgical intervention noninvasive and conservative therapies must be tried. Individual's sexual and fertility function should not be ignored.
- Liao L. Evaluation and management of neurogenic bladder: What is new in China? Int J Mol Sci. 2015;16(8):18580–600.
- Quesada E, Scott FB, Cardus D. Functional classification of neurogenic bladder dysfunction. Arch Phys Med Rehab. 1968;49:692–7.
- Wein AJ. Classification of neurogenic voiding dysfunction. J Urol. 1981;125(5): 605–9.
- Lapides J. Neuromuscular, vesical and ureteral dysfunction. In: Campbell MF, Harrison JH, editors. Urology. Philadelphia: Saunders; 1970. P. 1343-279.
- Laycock J. What can the specialist physiotherapist do? In: Wyndaele JJ, Laycock J, eds. Multidisciplinary Conservative Treatment for the Neurogenic Bladder. Wokingham: Incare, 2002. P. 14-8.
- Plevnik S, Homan G, Vrtacnik P. Short-term maximal electrical stimulation for urinary retention. Urology. 1984;24:521–3.
- Ginsberg D. Optimizing therapy and management of neurogenic bladder. Am J Manag Care. 2013;19(Suppl 10):197–204.
- Thavaseelan J. Botulinum toxin treatment for neurogenic detrusor overactivity. Incont Pelvic Floor Dysfunct. 2007;1:1–3.
- Sakamoto K, Uvelius B, Khan T, et al. Preliminary study of a genetically engineered spinal cord implant on urinary bladder after experimental spinal cord injury in rats. J Rehabil Res Dev. 2002;39(3):347–57.
- Park WB, Kim SY, Lee SH, et al. The effect of mesenchymal stem cell transplantation on the recovery of bladder and hindlimb function after spinal cord contusion in rats. BMC Neurosci. 2010;11:119.
- Lima C, Escada P, Pratas-Vital J, et al. Olfactory mucosal autografts and rehabilitation for chronic traumatic spinal cord injury. Neurorehabil Neural Repair. 2010;24(1):10–22.
- Groen J, Pannek J, Castro Diaz D, Del Popolo G, et al. Summary of European Association of Urology (EAU) Guidelines on Neuro-Urology. European Urology. 2016;69(2):324–33.