Chapter Outline
Neurophysiology of Micturition
Evaluation of Voiding Dysfunction
Classification of Voiding Dysfunction
Specific Causes of Voiding Dysfunction: Diagnosis and Management
Neurogenic Voiding Dysfunction
Nonneurogenic Voiding Dysfunction
Voiding dysfunction or lower urinary tract emptying dysfunction are terms used to describe various problems related to the bladder’s ability to store or empty urine. Urinary retention is the inability to complete the voiding phase of the micturition cycle and, often times, represents the end stage of voiding dysfunction. Physiologically, a problem may be present with either the bladder or the outlet, or both. Voiding dysfunction manifest clinically in lower urinary tract symptoms (LUTS), which may be associated with storage symptoms (frequency, urgency, nocturia, and urge incontinence) as well as voiding or emptying symptoms (decreased force of stream, incomplete emptying, hesitancy, straining to void, and urinary retention). Symptoms do not always correlate with the underlying pathology, and numerous conditions may exist that can have similar presentations. Thus, an often-challenging task is to determine the specific etiology involved. In many cases, voiding dysfunction can be explained by neurologic disease; learned behavioral patterns; or congenital, acquired, or iatrogenic bladder outlet obstruction. In this chapter, we discuss normal voiding and the pathophysiologic events that lead to abnormal voiding as well as the evaluation, management, and treatment of women with specific types of voiding problems.
Neurophysiology of Micturition
Normal voiding is accomplished by activation of the “micturition reflex” ( Fig. 38.1 ). This is a coordinated event characterized by relaxation of the striated urethral sphincter, contraction of the detrusor, opening of the vesical neck and urethra, and onset of urine flow ( Fig. 38.2 ). This reflex is integrated in the pontine micturition center, which is located in the rostral brainstem. Also, a sacral micturition center is located at S2-S4, through which the bladder can contract independent of cortical and pontine input. The pontine micturition center , through its neural pathways to the sacral micturition center, is responsible for coordinated and voluntary voiding. Both the autonomic and somatic nervous systems play a crucial role in lower urinary tract function. Normal voiding occurs when the bladder responds to threshold tension via its mechanoreceptors. To avoid a random occurrence, central nervous system inhibitory and facilitatory pathways are involved in coordination of urine storage and micturition.
Micturition depends on a spinobulbospinal reflex that is relayed through the pontine micturition center, which receives input from the cerebral cortex, cerebellum, basal ganglia, thalamus, and hypothalamus, and is the final common pathway to the bladder motor neurons. Much of the input from suprapontine centers appears to be inhibitory, although some facilitatory influences are involved. The central facilitatory areas are the anterior pons and the posterior hypothalamus, and the inhibitory areas include the cerebral cortex, basal ganglia, and cerebellum. The cerebellum also is implicated in the maintenance of tone in the pelvic floor striated musculature and coordination between bladder contraction and periurethral striated muscle relaxation. Because most of the suprapontine input to the pontine micturition center is inhibitory, interruption of this input (e.g. cerebrovascular accident, cerebral atrophy, Parkinson’s disease, brain tumor, or trauma) often results in uncontrolled detrusor activity, or involuntary contractions, but the “micturition reflex” is intact. When micturition is affected by suprapontine lesions, it usually is characterized by loss of voluntary control. Uninhibited detrusor contractions may result in urinary frequency, urgency, and urgency incontinence. Little risk is present for developing urologic complications because voiding is coordinated, even if not voluntary.
Anatomically, the two areas of the spinal cord responsible for transmitting afferent input from the lower urinary tract are the lateral spinothalamic tracts and the posterior columns. The lateral spinothalamic tracts contain ascending routes responsible for transmitting bladder sensation and triggering voiding. Proprioceptive sensory impulses generated in bladder muscle and periurethral striated muscle travel in the posterior columns. The pontine micturition center controls efferent input to the bladder and external sphincter via two separate regions. The medial region is responsible for motor input to the bladder detrusor muscle via the reticulospinal tracts to the sacral intermediolateral cell groups, which contain preganglionic parasympathetic neurons that form the motor supply of the bladder detrusor muscle. Electrical stimulation of this region results in a prompt decrease in pelvic floor electromyography (EMG) and urethral pressure followed by an increase in intravesical pressure (normal voiding). The lateral region has specific projections via the corticospinal tracts to the nucleus of Onuf in the sacral cord that contains motor neurons innervating the pelvic floor, including the urethral and anal sphincters. Electrical stimulation of this region results in a rapid increase in urethral pressure and pelvic floor EMG but little increase in intravesical pressure (normal storage).
Storage and evacuation of urine depend on neural integration at the peripheral, spinal cord, and central levels. Normally, bladder distension will cause low-level firing of afferent nerves. This will cause a reflex inhibitory response to the bladder via the hypogastric nerve and stimulatory response to the external sphincter from the pudendal nerve. With further distension, myelinated A delta fiber afferents are activated. Afferents travel up the spinal cord to the pontine micturition center. Here central input, mostly inhibitory, is received from suprapontine centers. If voiding is not desired, the voiding reflex can be suppressed or interrupted. If voiding is desired, efferent output to the pelvic plexus at S2-S4 via the spinal cord is initiated. Ultimately, the stimulatory message is sent to the bladder via the pelvic nerve. At the same time, inhibitory messages are sent to the hypogastric and pudendal pathways to allow for relaxation of the urethral sphincter mechanisms and coordinated voiding.
Peripheral innervation to the bladder and to the internal and external sphincters is provided by the pelvic, hypogastric, and pudendal nerves. Parasympathetic efferent input to the bladder arises from the intermediolateral cell column of S2-S4 and travels as preganglionic fibers via the pelvic nerve to the pelvic plexus located on both sides of the rectum, from which postganglionic fibers innervate the bladder. Efferent sympathetic nerves to the bladder and urethra arise from the intermediolateral cell column of T10 to L2 as preganglionic fibers that travel to ganglia located in the superior hypogastric plexus, from which arises the hypogastric nerve that contains the postganglionic sympathetic efferents to the bladder and urethra. The pudendal nerve carries the somatic input from S2-S4 to the external sphincter. Injury to any one of these nerves or their branches can result in a partial or complete denervation to the involved end organ.
In addition to the neurophysiologic pathways, other pharmacologic factors are responsible for normal voiding. The lower urinary tract is rich in both cholinergic and adrenergic receptors. Muscarinic receptors are located in the body of the bladder, and they are activated by parasympathetic release of acetylcholine to induce bladder contraction. Also, β-adrenergic receptors in the detrusor cause relaxation in response to increasing levels of cyclic adenosine monophosphate (AMP). In the bladder neck and urethra, α-adrenergic receptors are responsible for the increase in urethral tone and rise in intraurethral pressure during sympathetic stimulation via the hypogastric nerve. Each of these receptor types have been the basis for pharmacologic therapy of the lower urinary tract.
Anticholinergic medications are able to cause bladder relaxation by inhibiting parasympathetic pathways; β-adrenergics also treat bladder overactivity by stimulating adrenoreceptors and causing detrusor relaxation. α-Agonist medications have been used to treat stress incontinence, whereas α-blockers can facilitate emptying by relaxation of bladder neck smooth muscle.
Evaluation of Voiding Dysfunction
The evaluation of LUTS in women starts with a thorough history. This evaluation should focus on the type and duration of symptoms and voiding habits over time. Historically, women have fewer reported classic voiding (obstructive) symptoms and more commonly present with storage symptoms and recurrent urinary tract infections. Two studies showed that with a high index of suspicion and careful questioning, voiding symptoms are noted in 71% to 76% and storage symptoms were present in 79% to 92% of women with obstruction; therefore, voiding symptoms should not be overlooked when evaluating a woman who complains primarily of storage symptoms. A complete medical, surgical, obstetric-gynecologic, neurologic, and urologic history may uncover possible causes of voiding dysfunction. Any inciting events, such as surgeries to treat stress urinary incontinence or any other procedures in the lower urinary tract or vagina, must be recorded. Other relevant information that may aid in the diagnosis of obstruction include history of urogenital trauma, history of falls, back injury or surgery, and other medical conditions, such as diabetes, neurological disease, or psychiatric conditions. If symptoms are acute, and the cause of acute obstruction is clear, treatment should be directed toward alleviating the obvious cause.
A complete physical examination is the next part of the evaluation. Particular attention should be paid to a systematic examination of the vagina and pelvis. An abdominal examination is performed to evaluate for abdominal masses or a palpable distended bladder. A pelvic examination then is performed and one should first inspect the vagina and the mucosa for atrophic changes as well as signs of previous surgery. Also, the position of the urethra, bladder neck, and bladder can be observed at rest and with straining by visualizing the amount of anterior vaginal wall prolapse (urethral hypermobility and cystocele). One should also inspect for existing scars or hypersuspension caused by prior surgery. We like to use the posterior blade of a small vaginal speculum to retract the posterior vaginal wall to view the anterior wall. The cotton swab test can be used to quantify urethral hypermobility when needed. The patient also should be assessed for stress urinary incontinence (SUI). Palpation of the uterus and cervix should be done to determine its size, length, position, and support. In cases of previous hysterectomy, vaginal apex support and position are important, as uterine or apical prolapse are potential causes of obstruction. After examination of the anterior vaginal wall is completed, the blade of the speculum is rotated and the posterior wall and apex are inspected. Similar to other forms of prolapse, posterior vaginal wall prolapse, including rectocele and posterior enterocele, can cause obstruction and voiding dysfunction. Bimanual examination is performed to determine the presence of pelvic masses, including fibroids, which may cause or contribute to voiding dysfunction. In patients with LUTS, a focused neurologic examination should also be performed. Attention should be paid to the sensory and motor functions of the sacral nerves, including anal sphincter tone, perineal sensation, bulbocavernosus and anal wink reflexes, strength of lower extremities, and deep tendon reflexes (knee and ankle). A careful neurologic examination may help to confirm suspected disease or uncover an unknown lesion.
In addition to history and physical examination, several simple tests can give insight to the cause of LUTS. Urine analysis (and culture, if indicated) is done routinely. Intake and voiding diaries are helpful in quantifying symptoms, voiding habits, and urine production. Diaries log the number of incontinence episodes and type (stress, urgency, insensible). Noninvasive uroflow and postvoid residual (PVR) volume determination are good noninvasive methods to screen for disorders of bladder emptying. A PVR can be performed initially as a safety measure to rule out urinary retention, and later to monitor changes in bladder emptying ability, especially in neurologic conditions as patients may develop bladder dysfunction at any point in their disease process. There is no agreed standard definition as to what constitutes an elevated PVR. According to some studies, the suggested upper limit of a normal PVR (within 60 s of voiding) in both symptomatic and asymptomatic women is 30 mL. No data suggest, however, that higher residuals indicate pathological conditions.
Acute urinary retention is defined as a painful, palpable, or percussible bladder, when the patient is unable to pass urine. Chronic retention is less specifically defined but usually presents as an elevated PVR of at least 250 mL without pain. Individuals with chronically elevated PVRs may be at increased risk of ongoing voiding dysfunction, recurrent UTIs, and stone disease. Many such woman, however, are asymptomatic and do not require treatment. Although these tests cannot determine why voiding or emptying are abnormal (e.g. impaired detrusor function versus obstruction), they may prompt more thorough evaluation with urodynamics. Thus, we consider uroflow and PVR to be good “screening tests” for a woman with LUTS. A single elevated PVR should not be considered the sole assessment of bladder emptying ability and should be confirmed with a repeat measurement on a follow-up visit. PVR should be interpreted with respect to LUTS, urinary tract infections, and other symptoms.
Urodynamic testing can be an important part of the evaluation of female voiding dysfunction. We must keep in mind, however, that it is only part of the evaluation and should be used in conjunction with the rest of the assessment. The clinician always should have a clear question and an indication for performing the test. Urodynamic findings inconsistent with patient symptoms or events occurring during testing that are uncharacteristic for patients during normal activity outside of the urodynamics lab should be interpreted with caution. Urodynamics should be performed in patients in whom additional information is needed to make an accurate diagnosis and to guide therapy, and in those patients whose condition has the potential to cause deleterious and irreversible effects on the upper urinary tract. We always advocate the use of multichannel urodynamics with simultaneous measurement of vesical and abdominal pressure and “subtracted” detrusor pressure during filling and voiding (see Fig. 38.2 ). The filling phase (cystometry) evaluates the ability of the bladder to effectively store urine by assessing bladder stability, compliance, and capacity. Pressure-flow analysis during voiding assesses bladder contractility and bladder outlet resistance. EMG may be added to assess the pelvic floor musculature and external sphincter. We have found videourodynamics to be particularly helpful in confirming and localizing anatomic or functional obstruction. The addition of simultaneous fluoroscopy of the bladder outlet often will discover an obstruction that would not have been made on the basis of multichannel urodynamics alone. When videourodynamics are not available, radiographic evaluation may be useful in evaluating incomplete emptying. A standing cystogram in the anterior–posterior, oblique, and lateral positions, with and without straining, assesses the degree of bladder and urethral prolapse and displacement or distortion of the bladder. A voiding cystourethrogram examines the bladder, bladder neck, and urethra during voiding and is important in uncovering anatomic abnormalities.
The final component of the evaluation is cystourethroscopy, when indicated. Scarring, kinking, or deviation of the urethra, especially after previous surgery, may be responsible for incomplete emptying. Rarely, a urethral lesion responsible for obstruction may be found. Examination of the bladder may uncover a lesion, such as a tumor or stone, and may identify some of the changes associated with obstruction or retention.
Classification of Voiding Dysfunction
Many complex classification systems for voiding dysfunction have been proposed; however, they failed to be diagnostically and therapeutically oriented. We have found the functional classification system, proposed by to be the most useful (see Chapter 8 ). This simple and practical classification system can be applied easily to our diagnostic criteria (e.g. urodynamics). Of equal importance is that treatment options can be chosen based on the classification.
Wein’s functional classification is based on a simple understanding of urine storage and micturition. For normal urine storage and voiding to occur, there must be proper and coordinated functioning of the bladder and the bladder outlet. Therefore, in simple anatomic terms, voiding dysfunction can be divided into the following:
- 1.
Bladder dysfunction
- 2.
Bladder outlet dysfunction (bladder neck, urethra, external sphincter)
- 3.
Combined bladder and outlet dysfunction
Similarly, the effects of these problems can be classified as follows:
- 1.
Failure to store urine
- 2.
Failure to empty urine
- 3.
Failure to store and empty urine
In this chapter we will divide voiding dysfunction into neurogenic and non-neurogenic. Furthermore, non-neurogenic voiding dysfunction and obstruction can be classified as functional or anatomic.
Specific Causes of Voiding Dysfunction: Diagnosis and Management
Treatment of voiding dysfunction is dictated by several factors. First and foremost is the potential danger to the upper urinary tract associated with high storage pressures or the inability to empty the bladder. Although this is less common in non-neurogenic voiding dysfunction, any evidence of upper tract decompensation (hydronephrosis, elevated blood urea nitrogen (BUN) and creatinine) should be given immediate attention as well as infectious complications secondary to alterations in storage and emptying. Second is the degree of bother of the patient’s symptoms. In many cases, empiric therapy is an appropriate first step for patients with symptoms caused by voiding dysfunction. In patients without neurologic disease whose primary complaints are storage symptoms, such as urgency incontinence, and who demonstrate an ability to empty, behavioral modification, with pelvic floor muscle exercises or anticholinergic therapy, is effective in relieving overactive bladder symptoms. In cases in which the diagnosis is not clear, or when abnormal emptying and storage coexist, a more comprehensive workup is necessary. The same can be said when empiric therapy fails and for cases of voiding dysfunction associated with neurologic disease. In all such cases, further investigation with urodynamic testing usually is indicated. In these instances, the specific cause for the voiding dysfunction will direct treatment. On the other hand if a patient presents with an incidental finding of an elevated PVR, no further testing might be necessary. For example, an asymptomatic 60-year-old patient presents to the office after a routine pelvic ultrasound that showed a PVR of 200 mL. If there is no compromise of the upper urinary tract and she remains asymptomatic, further diagnostic studies are unnecessary and monitoring of annual or biannual PVRs may be sufficient.
Distinguishing neurogenic from non-neurogenic voiding dysfunction is important. The latter category often is caused by bladder outlet obstruction, and this may be functional, as in the case of dysfunctional voiding and primary bladder neck obstruction (PBNO), or anatomic, as in the case of pelvic floor prolapse or postsurgical obstruction. A complete list of causes for bladder outlet obstruction in women is shown in Table 38.1 .
| Anatomic Obstruction | Functional Obstruction |
|---|---|
|
|
|
|
|
|
| |
| |
|
Neurogenic Voiding Dysfunction
Neurologic disease can have a profound effect on the urinary system, including both the upper and lower urinary tracts. The term neurogenic bladder often is used loosely by many clinicians to describe a bladder that is not functioning normally. In the evaluation of neurogenic voiding dysfunction, however, it is critical to be more precise in assessment and classification. Ideally, this should be done in such a way that it is practical for diagnostic and therapeutic purposes. Thus, the goals in assessing patients with neurogenic voiding dysfunction are to determine the effects of the neurologic disease on the entire urinary tract (not just the bladder) in such a way that treatment can be implemented to relieve symptoms and prevent damage to the upper and lower urinary tracts. For the patient with neurologic disease, it is important to keep in mind that symptoms do not always indicate the magnitude to which the disease is affecting the urinary tract.
Pathologic processes at each level of innervation must be considered when evaluating neurogenic voiding dysfunction ( Table 38.2 ). For example, suprapontine lesions (e.g. cerebral atrophy, cerebrovascular accident, brain tumor) cause a loss of inhibitory input to the pontine micturition center and subsequent uninhibited bladder contractions, a condition known as neurogenic detrusor overactivity (NDO) when evaluated urodynamically. Sphincter reflexes are not affected, and coordinated uninhibited voiding can result.
| Suprapontine Lesions |
| Cerebrovascular disease |
| Parkinson’s disease |
| Multiple sclerosis |
| Concussion |
| Brain tumor |
| Shy-Drager syndrome |
| Normal pressure hydrocephalus |
| Pontine-Sacral Spinal Cord Lesions |
| Spinovascular disease |
| Spinal cord injury |
| Multiple sclerosis |
| Spinal dysraphism |
| Tabes dorsalis |
| Spinal stenosis |
| Disk herniation |
| Infrasacral/Peripheral Lesions |
| Sacral agenesis |
| Low spinal cord tumor |
| Spinal cord injury |
| Cauda equina syndrome |
| Diabetes |
| Herpes zoster |
| Tabes dorsalis |
| Radical pelvic surgery |
Clinically, interruption of the neural pathways connecting the pontine micturition center to the sacral micturition center (e.g. spinal cord injuries or lesions) usually results in uninhibited bladder contractions (NDO) and a dyscoordination of the bladder and external sphincter or detrusor-external sphincter dyssynergia (DESD). DESD is characterized by simultaneous contractions of the detrusor and external sphincter. The involuntary detrusor contractions cause incontinence and the involuntary sphincter contractions cause bladder outlet obstruction and retention of urine. DESD commonly is seen in suprasacral spinal cord lesions, multiple sclerosis, and, less commonly, myelodysplasia and lumbosacral lesions. Untreated DESD can result in high storage pressures (loss of bladder compliance) and resultant vesicoureteral reflux, hydronephrosis, urolithiasis, and urosepsis. Suprasacral spinal cord lesions also result in loss of supraspinal input; however, the complexity of the resulting voiding dysfunction depends on the level and completeness of the lesion. Also, input to the sphincters may be disrupted, resulting in DESD. A complete spinal cord lesion will result in the development of a spinal micturition reflex. Unmyelinated C-fiber afferents excite sacral neurons and trigger a bladder contraction. In addition, incomplete relaxation of the external sphincter results in a contraction against a closed outlet with subsequent incontinence, retention, and eventual loss of bladder compliance.
Infrasacral cord and peripheral nerve lesions generally result in loss of sensation and contractility, leading to a large, supercompliant, areflexic bladder. The external sphincter also may be deficient of contractility and tone. Neurologic lesions that interfere with the sacral reflex arc most often are seen in patients with myelodysplasia, diabetic cystopathy, ruptured discs, and low spinal cord tumors. These can take away reflex voiding and result in various degrees and combinations of detrusor areflexia, intrinsic urethral sphincter deficiency, and paralysis of the external urethral striated sphincter.
The previous information is useful when evaluating patients with particular neurologic diseases. The clinician, however, must always keep in mind that neurologic lesions can be “complete” or “incomplete.” Therefore, the exact manifestations of a particular disease or lesion on a given patient are not absolutely predictable. A complete urologic evaluation for patients with neurogenic voiding dysfunction therefore is recommended. A good example of a disease that can affect the lower urinary tract in various ways is multiple sclerosis (MS), a disease common in young and middle-age women. Because it can affect multiple areas of the central nervous system (CNS), urologic presentations include detrusor overactivity, detrusor overactivity with DESD, and impaired or absent detrusor contractility. The latter two presentations can lead to problems with bladder emptying.
The urodynamic evaluation often is integral to the evaluation of patients with suspected neurologic voiding dysfunction ( Fig. 38.3 ). Incontinence, which is a common complaint of these individuals, can be secondary to NDO, decreased compliance, or sphincteric incompetence. Only multichannel urodynamics will demonstrate the underlying pathology. Incontinence secondary to bladder dysfunction may be measured by the detrusor leak-point pressure (DLPP). The DLPP is the amount of detrusor pressure, in the absence of an increase in abdominal pressure, required to cause incontinence. The DLPP is a direct reflection of the amount of resistance provided by the external sphincter; the higher the resistance, as with DESD, the higher the DLPP. High storage pressures are potentially dangerous to the upper urinary tract. showed that storage pressures of greater than 40 cm H 2 O are associated with upper tract deterioration. Incontinence secondary to sphincteric dysfunction can be measured by the Valsalva or abdominal leak-point pressure (ALPP). The ALPP is the amount of abdominal pressure, in the absence of a rise in detrusor pressure that is required to cause incontinence. The ALPP commonly is used to evaluate sphincteric function in women with SUI. Normally, no physiologic abdominal pressure will cause incontinence and therefore there is no normal ALPP. Unlike the DLPP, a high ALPP does not indicate potential danger to the upper tracts.
The evaluation of upper urinary tract function is extremely important in women with neurogenic voiding dysfunction, especially in those who are at risk for developing upper tract problems (see previous text). A renal ultrasound can be performed to assess hydronephrosis. Renal scans are best to evaluate renal function. When videourodynamic studies are not available, it may be necessary to perform a cystogram or voiding cystourethrogram to assess for vesicoureteral reflux. Also, patients with neurogenic voiding dysfunction, especially if not properly managed in the past, are at risk for developing calculi. Calculi have been reported to occur in more than 30% of patients managed with an indwelling catheter.
The main goal in the treatment of neurogenic voiding dysfunction, first and foremost, is to protect the upper urinary tract from damage. This is accomplished by maintaining low storage pressures in the lower urinary tract. Second, the goal is to alleviate the patient’s bothersome LUTS. Treatment should be directed at the specific problems uncovered during the evaluation, regardless of the neurologic disease associated with those problems.
For detrusor overactivity and impaired compliance, anticholinergic medications are the first line of therapy and, in many cases, are sufficient to lower storage pressures and reduce or abolish involuntary detrusor contractions. Sometimes, especially in cases of outlet dysfunction, like DESD, anticholinergic medication also will produce urinary retention, necessitating the patient to perform intermittent self-catheterization.
In 2011 U.S. Food and Drug Administration approved intradetrusor onabotulinumtoxinA (Botox) in patients with NDO as a treatment alternative in patients who are refractory to antimuscarinic medications. completed a multicenter randomized, double-blind, placebo-controlled trial to determine the effects of Botox on NDO. They transurethrally injected 200 or 300 U of Botox, or placebo, in the detrusor muscle at 30 sites, avoiding the trigone. At 6 weeks, mean weekly urinary incontinence episodes were reduced significantly in both the 200 U (−21.8) and 300 U (−19.4) groups compared with placebo (−13.2; p < 0.01 for both doses). There were no differences between doses. Of the patients receiving 200 and 300 U, 38% and 39.6%, respectively, were fully continent compared with 7.6% of patients who received placebo. Equally important in patients with neurologic disease, there were also significant improvements in urodynamic parameters: maximum cystometric capacity (MCC), maximum detrusor pressure during first involuntary detrusor contraction (pdetmaxIDC), and total score on the incontinence quality of life score (I-QOL). The median time to retreatment was 42.1 weeks for patients who received both doses of Botox compared with 13.1 weeks for placebo (12 weeks was the earliest that retreatment could be requested). The most common adverse effects were localized urological events, including urinary tract infections, which were similar in both the treatment and placebo groups. PVR significantly increased following injection of Botox in a dose-dependent manner. In patients who received 200 and 300 U, 30% and 42% initiated clean intermittent self-catheterization (CIC) compared with 12% of patients who received placebo. There was no difference in efficacy or duration of effect between doses. Urinary retention was highest in the 300 U group with no additional clinical benefit.
completed a double-blind, placebo-controlled trial to evaluate the efficacy of Botox in patients with NDO. They enrolled a total of 416 patients who received placebo, 200 or 300 transurethral units of Botox. After 6 weeks of treatment, the number of urinary incontinence episodes decreased by 67% in the 200 U group and 74% in the 300 U group compared with 30% by placebo. Furthermore, 36% and 41% of patients in the 200 and 300 U group achieved dry status. Each dose increased maximum cystometric capacity, pdetmaxIDC, and total I-QOL score compared with placebo. Median time to retreatment was 256 days for 200 units, 254 days for 300 units, and 92 days for placebo. The most common side effects were urinary tract infections and urinary retention. Of patients who did not catheterize at baseline, 10% of placebo patients, 35% of the 200 U dose, and 42% of the 300 U dose initiated catheterization. Efficacy and duration effect were similar for both doses, but the 300 U dose showed an increase risk in urinary retention, elevated PVR, and need to catheterize in patients who did not catheterize before the study, therefore all patients considering this treatment should be able and willing to perform CIC. further showed that Botox is a cost-effective intervention for women with NDO compared with best supportive care.
Neuromodulation for neurogenic bladder dysfunction is under investigation. One of the first reports on the use of sacral neuromodulation (SNM) was published by who reported that this was a promising treatment alternative in MS patients with refractory urgency incontinence. evaluated 24 incomplete spinal cord injury (SCI) patients to determine the safety and efficacy of SNM in neurogenic LUTS. Out of the 13 patients with urinary retention, nine patients reported at least a 50% improvement in their voiding parameters compared to baseline including a decrease in frequency and urge incontinence episodes. Follow-up was at 61 months, and at the end of the study, five (38%) patients no longer needed to use clean intermittent self-catheterization for bladder emptying. Among the 11 patients with OAB included in the study, there was an 80% reduction in mean daytime frequency. Additional parameters with significant improvement included episodes of urge incontinence, mean pad use, mean voided volume, and nocturia.
In 2002, Scheepens et al. evaluated patients with refractory urgency incontinence to look at predictive tools of success for percutaneous nerve evaluation (PNE). Of the 211 patients, 11.4% patients had neurogenic bladder dysfunction, and these patients had a four times lower chance of a positive PNE compared with patients with non-neurogenic voiding dysfunction. evaluated the effect of SNM in 27 patients with neurogenic disorders, including patients with NDO, bladder storage failure due to detrusor areflexia, and a mixed condition. In 30% of patients, lower urinary tract dysfunction symptoms were attenuated by 50% for 54 months. After this period all implants, except one, were ineffective.
conducted a systematic review and meta-analysis to evaluate the role of SNM in neurogenic lower urinary tract dysfunction. They included 357 patients in 26 heterogeneous independent studies with a low evidence levels and no randomized trials included in the analysis. The pooled success rate was 68% for the test phase, 92% for permanent SNM, pooled adverse event rate of 0% for the test phase, 24% for the permanent SNM, and a mean follow-up period of 26 months. They concluded that SNM may be effective and safe; however, further well-designed studies are required prior to widespread use of SNM in neurogenic patients. If used, it is important to keep in mind that certain patients may have significant spinal and sacral abnormalities that may limit the ability of the surgeon to place the lead. Additionally, magnetic resonance imaging (MRI) is a valuable tool in neurological disorders and MRI currently is contraindicated in patients with implantable devices, except for MRI of the head using a radiofrequency transmit–receive head coil only. There are possible hazards of performing MRI with an implantable device, and the patient’s neurologists should be informed and be part of the decision-making process. Finally, patients with ominous urodynamic findings must be monitored carefully to ensure that upper tract deterioration is avoided.
The application of pudendal nerve stimulation for patients with NDO is under investigation. evaluated 15 patients with NDO using pudendal nerve stimulation with a small qudrapolar device. Preliminary results were encouraging, showing a decrease in the number of incontinent episodes from 7 to 2.6; eight patients became continent and two patients reduced the number of incontinent episodes by 50% during screening. In 2008, Opisso et al. compared patient-controlled pudendal nerve stimulation with automatic stimulation to treat NDO. They enrolled 67 patients with neurological disorders, and 17 completed the protocol, which included three different cystometries: one without stimulation, one with automatic-controlled stimulation based on detrusor pressure, and one with patient-controlled stimulation. Automatic and patient-controlled stimulation showed a larger bladder capacity and inhibited more than an average of two detrusor contractions per filling. The authors concluded that patient-controlled stimulation could be feasible in selected patients to treat NDO, although further studies are needed.
Posterior tibial nerve stimulation also is under investigation. used transcutaneous posterior tibial nerve stimulation (PTNS) in patients with MS. Seventy patients were treated with 20-min daily sessions of PTNS in a three-month period. On the basis of bladder diaries and symptom scores, there was an 80% improvement in urgency, and it appeared to reduce urinary frequency and urgency and showed an improvement in quality of life. The authors conclude that PTNS should be considered in the treatment algorithms for neurogenic OAB. Further studies are required to demonstrate long-term efficacy of PTNS in neurogenic patients.
Although neuromodulation techniques appear to hold some promise for the treatment of detrusor overactivity in the neurogenic population, it is still considered investigational, and well-designed research in this area is needed. In addition, patients must be selected carefully, and there also must be an emphasis on upper tract preservation in those neurological patients who are at risk.
Finally, in patients who do not respond to any of the first- or second-line therapies for NDO, augmentation cystoplasty, with or without continent catheterizable stoma or complete urinary diversion, can be considered. These operations are indicated in patients with functionally decreased bladder capacities and refractory filling and storage symptoms. They are, however, major operations with obvious risks and, with the exception of an ileal conduit, they require the use of upper extremities for chronic self-catheterization.
In patients who have a problem with emptying, either secondary to DESD or impaired contractility, emptying must be facilitated in many cases. For DESD, CIC has been a mainstay of therapy and is most effective when detrusor overactivity is controlled by one of the means described previously. The same is true for retention secondary to impaired contractility because no therapies are available that increase detrusor contractility. In some cases, a catheterizable stoma can facilitate independence when neurologic disease is advanced and urethral catheterization cannot be performed independently.
Botox has been injected transurethrally for the treatment of DESD, and both open-label and controlled randomized studies have shown benefit. evaluated the effect of 100 U of Botox on the external uretheral sphincter in treatment of DESD. A total of 20 suprasacral SCI patients were evaluated. After 4 weeks of treatment, there was significant reduction in static and maximal urethral pressure, EMG activity and PVR but not in maximal detrusor pressure and detrusor leak point pressure after treatment. performed a randomized controlled study to compare 100 U of Botox versus 4 mL of 0.5% lidocaine injected endoscopically in 13 patients with urinary retention secondary to DESD. Results showed an immediate improvement in ability to void, as measured by decreased PVR volumes in the Botox group. Larger placebo-controlled trials are needed.
Urethral stents are other proposed minimally invasive approaches to treat DESD, which provides a wide lumen for drainage. Stents may be either permanent or temporary, although most available data are on the Urolome permanent stent, which initially was introduced by Shaw et al. in 1990. Several other studies have confirmed its efficacy and long-term safety. External sphincterotomy is another alternative; however, it has a high rate of complications, including life-threatening hemorrhage, incontinence, infection, and most important, failure to correct high leak point pressure in up to 65% of patients. Chronic indwelling catheters generally are not recommended for treatment of chronic retention in the neurological patient but may be used as a last resort in select patients. In situations in which this form of management is desirable and necessary, appropriate catheter care with frequent changing of the catheter is recommended. We always recommend using the smallest size catheter, usually 14-French or 16-French and a 5 mL balloon. Urinary leakage around the catheter becomes common, and there is a tendency for providers to continuously upsize the catheters causing further trauma and complications related to erosions. A propensity also exists for chronic infections, stone formation, bladder neck erosions, and the development of squamous cell carcinoma. Urethral erosions are a well-known complication of long-term indwelling catheters due to pressure and traction causing necrosis of the urethra.
Nonneurogenic Voiding Dysfunction
Dysfunctional Voiding
Dysfunctional voiding is an abnormality of bladder emptying characterized by an intermittent or fluctuating flow rate in neurologically normal individuals in which there is increased activity of external sphincter during voluntary voiding. The prevalence of dysfunctional voiding in the adult population is unknown. In 1999, Nitti et al. found dysfunctional voiding to be the most common abnormality of the voiding phase in women presenting with LUTS, and on a retrospective study, found that 2% of patients referred for urodynamic evaluation met the criteria. It is a learned behavior, which differentiates it from true DESD, which was described earlier ( Fig. 38.4 ). Thus, the terms learned voiding dysfunction and pseudodyssynergia also have been used to describe the condition. Dysfunctional voiding may result in various LUTS, both storage and emptying symptoms. investigated the presenting symptoms in patients with a urodynamic diagnosis of voiding dysfunction and found that frequency and urgency were the most common symptoms in 82% of patients, urge and stress incontinence were present in 23% and 15% of patients, respectively, and 42% of patients had a history of recurrent urinary tract infections. It also may be responsible for episodes of acute or chronic urinary retention, and in severe cases, upper and lower urinary tract decompensation.
