Multiple Sclerosis

Multiple sclerosis (MS) is a disease of unknown etiology that usually affects patients between 20 and 40 years of age. Demyelinating plaques in the white matter of the cerebral cortex, cerebellum, brainstem, spinal cord, and optic nerve produce varied neurologic dysfunction and symptoms. MS is characterized by multiple lesions and usually a progressive course of bladder dysfunction. Plaques in the frontal lobe of the cerebral cortex or in the lateral columns of the spinal cord usually produce lower urinary tract dysfunction.

Bladder dysfunction as an initial symptom leading to the diagnosis of MS occurs in only 5% of patients; however, up to 90% of patients with MS have bladder dysfunction during the course of their disease. Approximately 60% of patients with lower urinary tract dysfunction show detrusor contractions on cystometry. Up to half of these patients demonstrate detrusor sphincter dyssynergia, whereas the other half demonstrates adequate and appropriate sphincter relaxation. Approximately 30% of patients have an underactive or areflexic detrusor.

Cerebrovascular Disease

Based on the 1990 to 1992 National Health interview surveys, the prevalence of persons in the United States who report a medical history of stroke increases with age from 1.7% for those aged 45 to 64 to 8.1% of those greater than age 75. It is associated with varying degrees of chronic disability, including bladder dysfunction. Atherosclerosis, arteritis, intracranial hemorrhage, and arterial malformations may be etiologic factors. Infarction of discrete areas of the frontal lobe of the cerebral cortex, internal capsule (which sends axons between the thalamus and cerebral cortex), brainstem, or cerebellum can result in bladder dysfunction. During the initial phase of a cerebrovascular accident, urinary retention secondary to detrusor areflexia is common. During recovery, detrusor overactivity with an appropriate sphincteric response usually occurs. Very rarely, detrusor sphincter dyssynergia can result.

Parkinson Disease

Parkinson disease is estimated to occur in 1 to 2 per 1000 persons in the United States. Onset usually occurs after age 50, and the course of the disease is progressive. The occurrence of bladder dysfunction ranges from 40% to 70%. The extrapyramidal system is believed to inhibit the micturition center, so loss of dopaminergic activity in the substantia nigra, caudate, putamen, and globus pallidus results in loss of detrusor inhibition. However, this theory has been challenged by , who performed urodynamic studies on 2526 patients, of whom 76 had Parkinson disease. They found no evidence of a disease-specific “Parkinsonian bladder,” suggesting that changes seen in such patients are age-related phenomena. Obstructive symptoms can occasionally result from therapy with anti-Parkinsonian agents.

Dementia

Dementia is a diffuse deterioration in intellectual function manifested primarily by memory deficits and secondarily by changes in conduct. The causes of dementia include aging, severe head injury, encephalitis, presenile dementias (including Alzheimer disease, Pick disease, and Jakob-Creutzfeldt disease), hydrocephalus, and syphilis. The mechanism of bladder dysfunction can be direct involvement of the cerebrocortical areas concerned with bladder control or from the loss or inability to control socially appropriate behavior. Detrusor overactivity or areflexia may occur, depending on the cause and severity of the dementia.

Neoplasia

Brain tumors in the superior medial frontal lobe can result in bladder dysfunction, which may manifest as irritative voiding symptoms, including detrusor overactivity. Spinal cord tumors above the level of the conus medullaris and cervical spondylosis can also produce detrusor overactivity.

Spinal Cord Injury

Spinal cord injury is a common cause of detrusor overactivity. All cord injuries that are complete and spare S2, S3, and S4 segments eventually produce upper motor neuron lesions with resultant detrusor overactivity. However, during the initial phase of spinal shock after suprasacral spinal cord injury, the bladder is areflexic, resulting in urinary retention and overflow incontinence.

Urinary Tract Infection

Inflammation of the bladder epithelium, with or without associated bacteriuria, has been suggested as a cause of bladder overactivity. performed urodynamic studies on women with acute UTIs before treatment. Half of those with urodynamic evidence of detrusor overactivity before treatment had stable cystometrograms after the infection was treated. However, reported on more than 2000 patients examined by videocystography on whom culture and sensitivity studies of midstream urine specimens were performed. They found that of the 35 patients infected at the time of the study, only three had non-neuropathic detrusor overactivity.

Hypersensitive Bladder Disorders

Pain is not a common symptom of women with OAB. Pain with a full bladder in conjunction with urgency and frequency suggests a hypersensitive bladder condition, such as interstitial cystitis. Women who have had previous pelvic radiation and those with significant urogenital atrophy may also complain of OAB symptoms.

Urodynamic Conditions

Urethral instability is defined as a spontaneous fall in maximum urethral pressure exceeding one third of the resting maximum urethral pressure in the absence of detrusor activity. If simultaneous urethrocystometry is performed during filling, the diagnosis of urethral instability or uninhibited urethral relaxation can be made. Although the clinical significance of urethral instability is not fully appreciated, some investigators have correlated this finding with symptoms of frequency and urgency.

noted a subgroup of elderly women with detrusor overactivity resulting in incontinence who could not effectively empty their bladders when attempting to void. Urodynamic testing revealed that impaired contractility caused impaired emptying. They named the condition detrusor overactivity with impaired contractility and hypothesized that this may represent the last stage of detrusor overactivity, in which detrusor function deteriorates.

Structural or Anatomic Conditions

At the level of the urethra, urgency incontinence can occur with outlet obstruction. This is a well-known problem in men with benign prostatic hyperplasia and in younger men and women with spinal cord injuries or multiple sclerosis. In women, bladder outlet resistance from previous anti-incontinence surgery can result in irritative symptoms and urgency incontinence. Idiopathic bladder outlet obstruction is rare in women. Abnormal voiding is usually caused by poor detrusor function rather than physical obstruction. However, obstructive voiding sometimes occurs with advanced pelvic organ prolapse and after operations for stress incontinence.

The correlation between detrusor overactivity and pelvic surgery is confusing and, at times, unexplainable. Studies on patients operated on for stress incontinence who had stable preoperative cystometrograms note that 7% to 27% develop postoperative detrusor overactivity. Women with mixed symptoms of stress incontinence and OAB will have a resolution of their OAB symptoms in approximately 50% of cases after an anti-incontinence procedure. The remaining 50% may have persistence or worsening of their symptoms. Postoperative detrusor overactivity or persistence or worsening of symptoms seems to be more common in patients with previous bladder neck surgery and in those with coexistent detrusor overactivity and preoperative sphincteric incompetence.

Radical pelvic surgery can result in an OAB. Partial denervation of the bladder during the operative process with subsequent development of detrusor dysfunction is currently the most accepted theory.

Other conditions that can impact the lower urinary tract and result in OAB symptoms include pregnancy, pelvic mass, urethral diverticulum, and intravesical lesions.

Orgasm

Orgasm may cause detrusor overactivity. The pathogenesis is unknown, but women sometimes experience urinary urgency or urgency incontinence with a gush of urine during climax. Treatment is the same as for detrusor overactivity; sexual counseling and education are often helpful.

Mixed Incontinence

Detrusor overactivity can coexist with stress incontinence in up to 30% of patients. Whether this is a coincidental finding or some underlying relationship between these two conditions is unknown. In women with mixed stress and urgency incontinence, a deficient urethral sphincter may result in urgency incontinence, if leakage of urine into the proximal urethra stimulates urethral afferents that induce involuntary voiding reflexes. Interestingly, after anti-incontinence surgery, detrusor overactivity may disappear, remain the same, or worsen.

In a matched control study, noted that 95% of their patients were cured of stress incontinence after a Burch urethropexy was performed if they had a stable preoperative cystometrogram. On the other hand, only 75% were cured if, preoperatively, they had low compliance or uninhibited bladder contractions.

Women may condition themselves to have urgency and frequency by becoming habitual frequent voiders. This can be seen in women with long-standing stress incontinence because these women will consciously or subconsciously void more frequently to avoid or reduce leakage. Over time, it has been proposed that functional bladder capacity is reduced, and the bladder becomes more sensitive at lower volumes of urine, thus resulting in frequency and urgency (OAB dry). This same phenomenon can occur in women with urgency incontinence, resulting in more severe frequency. This can be viewed as a cycle in which symptoms continue to worsen unless intervention is undertaken ( Fig. 35.7 ).

Cycle of bladder dysfunction. OAB, overactive bladder.

Lifestyle

Interestingly, a study by found that lifestyle factors that predispose to obesity and diabetes also may predispose to OAB. Over 3411 women without OAB at baseline were included in their analysis and 277 subjects developed OAB at 1 year. The authors suggest that further studies are needed to demonstrate a link between lifestyle and OAB.

Urinalysis and Culture

Because the symptoms of UTI and other irritative bladder conditions commonly mimic OAB, urinalysis should be performed before further investigations are initiated. As previously mentioned, bacteriuria may cause detrusor overactivity, which sometimes resolves after the infection has been treated. Urine cytology should be performed to rule out neoplasia in patients with chronic irritative bladder symptoms, particularly in elderly patients and those with microscopic hematuria.

Voiding Diary

In addition to history-taking, patients can be mailed or given a voiding diary to fill out 48 h before their office visit, usually over a weekend to avoid the possible interference of work. A chart of the timing and volume of intake and output is indispensable for corroborating the patient’s history and symptoms. Patients’ interpretation of problems does not always correlate with their voiding diary. Also, significant changes can be made with daily fluid intake and medication to decrease urinary loss. Follow-up charts are useful to provide evidence to both patient and clinician of treatment response, particularly when bladder retraining is used.

evaluated bladder diary parameters in a group of 161 women aged 19 to 81 years. The volume voided in 24 h was a mean of 1730 mL (range 437-3861 mL) and the mean frequency was 7 (range 2-13) voids per day. One of the interesting findings from this study was that a linear relationship was found between the functional bladder capacity and the volume voided in 24 h. The authors speculate that an increased bladder capacity may be a way to compensate for increased volume without increasing voiding frequency.

Urodynamic Tests

Cystometry

Cystometry is the mainstay of investigation for bladder storage function and is the only method of objectively diagnosing detrusor contractions. Figure 35.8 reviews the various cystometric patterns that may be seen in patients with detrusor overactivity.

Various cystometric patterns noted in patients with detrusor instability. A , Normal filling cystometry with voluntary terminal contraction. B , Phasic involuntary detrusor contractions that return to baseline. C , Cough-provoked detrusor instability (intravesical instead of true detrusor pressure is depicted here). D , Phasic contractions with steady rise in detrusor pressure. E , Steady rise in detrusor pressure (low-compliance bladder). F , Subthreshold detrusor instability with voluntary terminal contraction.

During the cystometric evaluation of patients with suspected OAB, one must use provocative stimuli if detrusor contractions are not elicited during filling. Sometimes, the provocation needed to reproduce a detrusor contraction cannot be performed in a laboratory setting. This problem has been demonstrated in numerous ambulatory monitoring studies in which symptomatic patients had a stable detrusor during filling in the urodynamic laboratory but had uninhibited contractions when monitored on a continuous basis.

Testing should always be performed with the patient in a sitting or erect position because supine filling cystometry alone fails to uncover a significant proportion of bladder overactivity. Other provoking factors that can be performed during the testing session include coughing, straining, heel-bouncing, jogging in place, listening to running water, and placing the patient’s hands under running water.

Per the American Urological Association (AUA) Guidelines ( ), “Clinicians may perform multi-channel filling cystometry when it is important to determine if altered compliance, detrusor overactivity or other urodynamic abnormalities are present (or not) in patients with urgency incontinence in whom invasive, potentially morbid or irreversible treatments are considered.” The guidelines go on to state that “Clinicians may perform pressure flow studies (PFS) in patients with urgency incontinence after bladder outlet procedures to evaluate for bladder outlet obstruction.” This statement is based on expert opinion. Finally, the guidelines specifically state that patients should be counseled that the absence of detrusor overactivity on urodynamics does not exclude the diagnosis of OAB. In fact, detrusor overactivity is often not seen during a cystometrogram in a patient with a diagnosis of OAB. Figure 35.9 reviews the diagnosis and treatment algorithm from the AUA Guidelines on Non-Neurogenic Overactive Bladder in Adults.

Diagnosis and treatment algorithm from the American Urological Association (AUA) guideline on non-neurogenic overactive bladder in adults. OAB, overactive bladder; FDA, Food and Drug Administration.

(The complete OAB guideline is available at www.AUAnet.org/Guidelines . This resource is supported by an educational grant from Astellas Scientific and Medical Affairs, Inc.)

found an overall incidence of detrusor overactivity in 76.1% of male patients and 58.7% of female patients with OAB. A higher percentage of patients (93% of men, 69.8% of women) were found to have detrusor overactivity when they had both symptoms of urgency and urgency urinary incontinence. Overall, a combination of LUTS resulted in a higher likelihood of actually seeing detrusor overactivity on urodynamics.

explored the relationship between the finding of detrusor overactivity on urodynamics and the response to treatment with anticholinergics in patients with OAB. This study demonstrated that detrusor overactivity is not found in all subjects with OAB but, when found, those patients respond more favorably to anticholinergic treatment. The author suggests that anticholinergic therapy is most effective in patients with demonstrated detrusor overactivity and, thus, urodynamics should be considered in all patients with OAB as a predictor for success of therapy.

In conclusion, the evidence to support or refute the routine use of urodynamics for OAB is unclear. Certain scenarios or clinical presentations may warrant urodynamic testing, but it is still controversial whether or not testing is needed in all cases of OAB. Further data is needed to determine if the cost, invasiveness, and potential morbidity outweighs the benefits and risks of empiric treatment. In the author’s opinion, initiating treatment without a prior urodynamic study in a patient with uncomplicated (i.e., non-neurogenic) OAB is reasonable, reserving urodynamic studies for refractory or complicated cases.

Urethral Pressure Studies

Urethral pressure studies add little to the diagnosis of detrusor overactivity or to the differentiation of patients with stress incontinence from those with urgency incontinence.

Detrusor contractions are almost always preceded by a drop in urethral pressure ( Fig. 35.10 ). studied urethral pressure tracings in 72 women with detrusor overactivity to learn whether urethral pressure changes may be the cause, rather than the effect, of bladder contractions. Patients who had urethral relaxation before detrusor contractions responded better to sympathomimetic drugs, whereas patients without urethral pressure changes responded more favorably to anticholinergic drugs.

Multichannel substracted urethrocystometry showing detrusor instability. Note urethral relaxation and quieting of electromyography (EMG) activity.

In another study, urethral instability occurred in 42% of patients with detrusor overactivity and was strongly associated with the sequence of urethral relaxation before an unprovoked contraction. This study concluded that, based on a urethral response, two subgroups of detrusor overactivity may exist.

Electromyography

Electromyography (EMG) gives information on the activity of the external striated urethral sphincter muscles. Its potential value in patients with detrusor overactivity is to document voluntary control of this sphincter, as well as to demonstrate that the external sphincter and detrusor muscle function in a coordinated fashion (see Fig. 35.10 ). found that 48% of patients with idiopathic detrusor overactivity exhibited reflex relaxation of the sphincter at the time of a detrusor contraction. This observation is important because these patients are probably unable to voluntarily contract the external sphincter at the moment of the detrusor contraction, thus, they are unable to inhibit urine loss.

Spontaneous sphincter relaxation can also be detected during EMG studies, leading to the diagnosis of uninhibited urethral relaxation. External sphincter EMG studies are used for the diagnosis of detrusor external sphincter dyssynergia, which is a rare condition and occurs in only patients with neurologic disease ( Fig. 35.11 ). EMG adds little to the evaluation and management of neurologically intact women.

Multichannel urodynamic tracing showing detrusor–external sphincter dyssynergia. As patient tries to void, an increase in electromyography (EMG) activity is associated with a strong bladder contraction, rise in urethral pressure, and minimal urine flow.

Endoscopy

The routine use of cystourethroscopy is not indicated in the evaluation of OAB. However, certain findings during the evaluation of a patient with OAB may warrant cystoscopic examination. For example, a patient with a history of a midurethral sling placement with polypropylene mesh and new onset of OAB symptoms might be indicative of mesh erosion into the urethra or bladder (see Fig. 35.12 ). The finding on physical examination of a mass below the urethra consistent with a urethral diverticulum may be another indication for cystourethroscopy. reported an unusual case of an elderly woman with OAB and a history of lithium use for bipolar disorder. The patient was found to have suburothelial metal deposition that was felt to be related to her OAB by acting as a bladder irritant. The clinician should always pay attention to occupational exposures or medications that could potentially be bladder irritants.

Polypropylene mesh eroding into the bladder of a patient who had a prior midurethral sling placement.

Definitive indications for cystourethroscopy include microscopic hematuria and abnormal urine cytology. Cystoscopy should also be considered if the diagnosis is in doubt or if the patient shows no response to appropriate behavioral and pharmacologic therapy. Box 35.3 lists indications for cystourethroscopy in patients with OAB.

Box 35.3

• 
  

  Smoker

  
  
• 
  

  Hematuria

  
  
• 
  

  Elevated postvoid residual

  
  
• 
  

  History of recurrent UTIs

  
  
• 
  

  Persistent or de novo OAB after an incontinence procedure

  
  
• 
  

  de novo OAB after pelvic surgery

  
  
• 
  

  de novo OAB after removal of indwelling Foley catheter in the absence of infection

  
  
• 
  

  Prior treatment with intravesical botulinum toxin

  
  
• 
  

  Refractory to medication (i.e., two anticholinergic agents)

  
  
• 
  

  Abnormal appearing bladder on imaging procedure

  
  
• 
  

  Positive cytology

  
  
• 
  

  Mixed symptoms with pain

  
  
• 
  

  Prior mesh placement

  
  
• 
  

  History of bladder cancer

  
  
• 
  

  Occupational exposure

OAB, overactive bladder; UTIs, urinary tract infections.

Indications for Cystourethroscopy in the Setting of OAB

Bladder Retraining Drills

Bladder retraining institutes a program of scheduled voiding with progressive increases in the interval between each void, based on the assumption that conscious efforts to suppress sensory stimuli will reestablish cortical control over an uninhibited bladder, thus reestablishing normal voiding patterns. This therapy has been studied by , and others. In several studies, Frewen reported success rates of approximately 80%. However, his protocol included primarily in-hospital behavioral management and concurrent pharmacologic therapy. Fantl et al. reported on 92 patients with objective evidence of detrusor overactivity treated by bladder drill, with or without anticholinergic therapy. Cure rates were the same in both groups: 83% in patients treated with bladder drill and drugs, and 79% in patients treated with bladder drill alone. These high cure rates with bladder retraining drills have been substantiated by other authors.

The technique used for bladder retraining involves giving the patient insight into the nature of her dysfunction. Drawings demonstrating cerebral cortical inhibitory effects over bladder reflexes can be shown to the patient to assist in explaining lower urinary tract dysfunction. The patient’s own cystometric tracing can be shown to her to illustrate the dysfunction. The patient is taught scheduled voiding at timed intervals, varying from 15 min to 1 h, based on the patient’s own frequency or incontinence intervals. We usually start patients at voiding intervals of 30 to 60 min. Patients are given preprinted cards, on which they record voiding (daily and nightly), involuntary leaking episodes, and occurrences that precipitate incontinence. Patients are instructed to make an earnest effort to follow the schedule during the day, attempting to suppress urgency and voiding only at the scheduled times regardless of the presence or absence of urinary urgency. Patients are instructed to contract their pelvic floor muscles when they feel urgency and impending urgency incontinence, to suppress involuntary bladder overactivity. Schedules are not followed during sleeping hours. Follow-up visits are scheduled every 1 to 2 weeks, at which time the cards are reviewed with the patient. Voiding intervals are increased periodically by 15 to 60 min, according to the patient’s response in reducing urgency and urgency incontinence episodes. A 6 to 12-week treatment program is anticipated in most cases.

Enthusiastic patient contact, reassurance, good long-term support, and follow-up are important. Patients must be highly motivated to improve with this therapy. The degree of patient compliance determines success. Because the success rate is so good and the therapy involves low cost bladder retraining drills should be the first line of therapy in patients with detrusor overactivity.

Biofeedback

Biofeedback is a form of patient reeducation, such that normally unconscious physiologic processes are made accessible by auditory, visual, or tactile signals, while attempts are made to modify the process by manipulating the signal presented to the patient. This method has been used with some success in the treatment of autonomic dysfunctions, hypertension, and cardiac dysrhythmias. As an example of how biofeedback can be used to treat detrusor overactivity, after cystometry is explained to the patient, bladder filling begins and an audible signal is used to let the patient know that her bladder pressure is rising. The tone of the signal varies by the change in bladder pressure. The patient also visualizes the urodynamic tracing throughout the test. The bladder is repeatedly filled while the patient attempts to inhibit detrusor contractions. Individual treatment sessions are approximately 1 h and are repeated weekly for up to 8 weeks.

have reported 81% subjective and objective improvement with biofeedback. They noted that biofeedback was not as successful in patients with severe detrusor overactivity, particularly in women with high-amplitude detrusor contractions occurring at small bladder volumes. In another study, patients were randomized to biofeedback-assisted behavioral training, drug treatment, or placebo. Behavioral treatment was significantly better than drug treatment or placebo. In a follow-up study, drug treatment along with biofeedback-assisted behavioral therapy was superior to either modality alone.

randomized 222 women to three different treatment arms including a biofeedback-assisted behavior training, behavioral training without biofeedback (verbal feedback based on vaginal palpation), and self-administered behavioral treatment based on a self-help booklet. No significant differences were noted in symptom improvement between the three groups, but patient satisfaction was higher in the two groups receiving behavioral training. These findings are consistent with a systematic review published in 2005 that could find no evidence that biofeedback in addition to pelvic floor muscle rehabilitation provided added benefit to pelvic floor muscle rehabilitation alone.

Many investigators use biofeedback techniques aimed at identifying and strengthening pelvic floor muscles. In addition, appropriate control of the external urethral sphincter mechanism may enhance the urethrovesical inhibitory reflex.

Functional Electrical Stimulation

Functional electrical stimulation (FES) stimulates the afferent limb of the pudendal reflex arc, increasing pelvic floor muscle and urethral striated muscle contractility, and possibly stimulating reflex inhibition of detrusor contractility. Some patients who are refractory to behavioral and pharmacologic therapies respond to FES. The main difficulty with FES is patient acceptance of intravaginal or transrectal stimulation. Originally, patients were required to use the devices for several hours daily. The results of clearly point out these limitations—94% dropout rate in a study of 36 patients using a transrectal stimulating device.

To overcome the requirement for long treatment sessions, investigators have studied the efficacy of intermittent maximal electrical stimulation in treating incontinence. With this therapy, the patient receives a short period of stimulation (for example, 30 min) at maximum tolerable intensity. Treatment is continued over several weeks. reported short-term maximal pelvic floor electrical stimulation in 48 patients with idiopathic detrusor overactivity. Each patient received 20 min of simultaneous vaginal and anal electrical stimulation for an average of seven treatments. Initial clinical and urodynamic cures were observed in 50% of patients, with significant improvement in an additional 33%. At 1-year follow-up, persistent positive therapeutic effects were found in 77% of patients. In another study, treated 30 patients with detrusor overactivity with maximal electrical stimulation at home for 20 min per day for 30 days. Cure was noted in 29%; an additional 22% reported improvement. noted significant subjective improvement in 69% of patients with detrusor overactivity, using a regimen of 15 min of maximal stimulation twice daily for 6 weeks. compared maximum electrical stimulation with oxybutynin therapy. With either treatment, symptoms were significantly reduced on visual analog scales, and diurnal frequency was reduced by voiding diary. randomized 24 postmenopausal women with urinary incontinence to intravaginal electrical stimulation or a daily Kegel exercise program. The effectiveness of FES was similar to Kegel exercises (29.2% versus 36.4%, for objective improvement, and 29.2% versus 27.3% for subjective improvement, respectively). evaluated pelvic floor muscle training with and without biofeedback-assistance and FES for 103 women with OAB. OAB symptoms were reduced in about half of women treated with FES and biofeedback-assisted pelvic muscle training, compared to 38% treated with pelvic muscle training alone (although this difference was not statistically significant).

The role of FES as therapy for detrusor overactivity is still evolving. Although currently not a first-line therapy, it may benefit certain groups of patients who have failed multiple treatments.