Kathleen c. Kobashi, MD and Gary E. Leach, MD

Multiple sclerosis (MS) involves focal neural demyelination with relative sparing of axons and resultant impaired nerve conduction. Demyelination commonly affects the posterolateral columns of the spinal cord, with the majority of patients having cervical cord involvement. Forty percent of patients have lumbar cord involvement and 18 percent have sacral cord involvement. The cerebral cortex and midbrain may also be affected. Lesions in any of these areas can affect voiding function.

Fifty percent to 90 percent of all MS patients will experience bladder dysfunction during the course of the disease (1-3), and voiding dysfunction is the presenting symptom in 10 percent of patients (3). Therefore, it is imperative that one considers MS in the differential diagnosis of patients with significant voiding complaints.

Bladder dysfunction in multiple sclerosis patients

The incidence of bladder dysfunction in MS patients is shown in Table 6-1. Urinary incontinence related to neurogenic bladder dysfunction is caused by one of three problems: (1) failure to store, (2) failure to empty, or (3) a combination of the two (Table 6-2). It is important to rule out urinary tract infection and other nonneurogenic causes, particularly in multiparous women who may have gynaecologic causes for incontinence.

Presentation and evaluation

History

The most common presenting urologic complaints are urgency, frequency, and urge incontinence. Irritative symptoms occur in approximately 65 percent of MS patients with voiding complaints (8). As mentioned previously, bladder dysfunction may be categorized as problems of urine storage and bladder emptying. Twenty-five percent present with urinary retention or obstructive symptoms, including decreased, force of stream, hesitancy, intermittency, double voiding, or straining to void. Ten percent describe a combination of both irritative and obstructive symptoms. Patients also often have a history of recurrent urinary tract infections.



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Physical Examination

A focused neurologic examination is imperative because MS patients pre- sent with variable clinical pictures and tend to have complex, unpredictable, and fluctuating courses. Anal sphincter tone, the ability to contract the anal sphincter, and the bulbocavemosal reflex should be assessed. Bulbocavemosal reflex is checked by applying pressure to the glans penis in men or the clitoris in women and observing for contraction of the anal sphincter and perineal musculature.

Blaivas reported that 98 percent of normal men and 81 percent of normal women have a clinically demonstrable bulbocavemosal reflex (9) .In his series of 299 patients, all patients with complete sacral spinal cord lesions also had an absent bulbocavernosal reflex. Patients with incomplete sacral cord injuries or lesions above the sacral level had variable presence of the bulbocavernosal reflex. Ankle and knee deep tendon reflexes should be checked, the presence or absence of clonus and the Babinski sign should be noted, and sensation to light touch and pin prick in the lumbar and sacral dermatomes should be evaluated (Figure 6-1) (10).

Finally, assessment of a patient's coordination, cognitive function, and manual dexterity is important because many MS patients may benefit from clean intermittent catheterization.

Laboratory Studies

Because 19 percent to 21 percent of MS patients have positive urine cultures before institution of medical therapy (11-13) and many have a history of recurrent urinary tract infections, one of the first steps in their evaluation is a urinalysis and a urine culture. Sirls reported that 11 percent of MS patients continued to have recurrent urinary tract infections despite medical management (3). If the urine culture is positive, the infection should be treated with appropriate antibiotics before further evaluation. A baseline serum creatinine should also be obtained. It is sufficient to check renal function annually if all baseline studies are normal

Radiologic Studies

A baseline renal ultrasound should be obtained in all MS patients with voiding dysfunction. In Sirls's series, fewer than 7 percent of MS patients with voiding dysfunction had hydronephrosis at presentation (3). Patients with hydronephrosis should be referred to a urologist. Sixty-six percent of patients who had hydronephrosis in Sirls's study had an acontractile bladder.

Hydronephrosis resolved in these three patients following institution of clean intermittent catheterization. Annual imaging studies are not necessary in patients with a normal baseline renal ultra-sound and creatinine and need only be repeated if their clinical status changes.


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Urodynamic Studies

Urodynamic studies define the cause of incontinence by providing valuable information regarding bladder and urethral function. Cystometry is useful in the evaluation of bladder function and may define detrusor hyperreflexia or acontractility. Noninvasive uroflowmetry involves measuring a patient's urinary flow rate (cc/sec). Uroflowmetry may be helpful in raising a clinical suspicion of obstruction; however, one must be aware that a decrease in flow rate may also be due to detrusor areflexia or impaired contractility. A pressure-flow study is necessary to make this determination and can be performed at the time of urodynamics. Pressure-flow studies involve the, easurement of detrusor pressures while the patient is voiding.

A primary care physician can perform "eyeball urodynamics" (14) to evaluate for detrusor hyperreflexia or acontractility, which may provide an indication of whether a patient has any detrusor instability and if he or she is adequately emptying the bladder. A urethral catheter is placed after the patient voids, and the post-void residual volume is measured. Next, a catheter-tip syringe with the plunger removed is inserted into the emptying port of the catheter. The bladder is filled with normal saline or sterile water by gravity through the syringe and catheter. The syringe is held perpendicular to the ground, and the column of fluid within the syringe can be observed for any rise, which may represent detrusor hyperreflexia or decreased bladder compliance. Additionally, the bladder capacity can be determined with this study. If a patient has a large capacity with no rise in pressure (level of the fluid column) or no sensation of bladder fullness, this may indicate detrusor areflexia, particularly if the post-void residual is elevated.

Formal multichannel urodynamics adds detailed information regarding a patient's bladder function. Indications for multichannel urodynamics include hydronephrosis, renal insufficiency, urinary retention, recurrent urinary tract infections, and continued incontinence despite initial treat- ment. The bladder is filled through an 8-French urethral catheter, typically at a rate of 30-60 cc/min. The patient is observed for incontinence, which may be secondary to detrusor instability, hyperreflexia, or poor compliance. Additionally, the patient's bladder capacity, sensation, and degree of emptying are assessed.

Electromyography may be performed during the multichannel urodynamic study, although it is not routinely necessary. Blaivas and Barbalias demonstrated a subset of patients with hyperreflexia and detrusor-sphincter dyssynergia who were at a higher risk for complications despite treatment. It is unclear whether this was due to more advanced MS or to the patients' inability to perform regular clean intermittent catheterisation secondary to impaired hand function. Conversely, Sirls showed that no patient with detrusor hyperreflexia and detrusor-sphincter dyssynergia had hydronephrosis or an elevation in creatinine with medical management in his series.

Treatment Options

The goals of treatment are to restore continence, relieve urinary symptoms, reverse or stabilize upper urinary tract changes if they are present, and facilitate complete bladder emptying. To accomplish this, a common strategy is to create complete urinary retention and add clean intermittent catheterisation for emptying.

The course of MS is unpredictable, often involving exacerbations and remissions. Therefore, treatment should be as flexible and conservative as possible, with the option for modification based on repeat urodynamic studies if it becomes necessary. Additionally, the clinician should be aware that the lower urinary tract symptoms do not necessarily correlate with the pathophysiology of the bladder dysfunction. Therapeutic options for bladder dysfunction in MS patients are divided into non-surgical and surgical treatment.

Nonsurgical Treatment Options

Clean Intermittent Catheterisation

Indwelling Foley catheters should be avoided. The highest incidence of urologic complications in female MS patients with bladder dysfunction occurs in those patients with long-term indwelling Foley catheters (15). These complications include infection, sepsis, vesicoureteral reflux, vesical calculi, severe urethral damage, and hydronephrosis (16).

Clean intermittent catheterisation alone may be used when the patient does not empty the bladder completely and intravesical pressures are normal. However, it is usually used in conjunction with anticholinergic medications, which lower the intravesical pressure. One important limiting factor for the use of clean intermittent catheterisation is impaired manual dexterity, which may make the procedure difficult or impossible to perform. In this case, several options are available. When feasible, a partner may be taught to catheterise the patient. However, this approach can be difficult.

Various urinary diversion options are also available. These measures require surgery and are therefore less flexible treatment choices than the non-surgical options. (Please refer to the section on surgery for a detailed discussion.)

Anticholinergic and Antimuscarinic Medications

Anticholinergic medications are useful in the treatment of detrusor hyperreflexia and may also be used in conjunction with clean intermittent catheterisation if any degree of urinary retention is created. In most cases, anticholinergic medications and clean intermittent catheterisation are used together; the former can reduce intravesical pressures, whereas the latter can ensure complete bladder emptying.

In Sirls's series (3), only eight patients (7 percent) failed medical management and no patient who had aggressive management had upper urinary tract deterioration, including those with detrusor-sphincter dyssynergia. Twenty-five of 59 patients (42 percent) required the addition of a second anticholinergic agent to control persistent irritative symptoms. Alternative agents or intravesical oxybutynin were used in 18 patients who were unrelieved with standard medications (17). Urinary incontinence was reduced in 8 of 9 patients placed on intravesical oxybutynin.

Tolterodine (Detrol®) is a competitive muscarinic antagonist that was released for use in the United States in mid-1998. It is administered at 2 mg twice a day. Because of its higher specificity for bladder muscarinic receptors, its systemic and central side effects are significantly decreased and it is far better tolerated than is Ditropan® (18-20).

Behavioural Therapy

Some patients may benefit from timed voiding, fluid restriction, and dietary modification to avoid stimulants such as caffeine. Behavioural therapy should be used in combination with anticholinergic medications and clean intermittent catheterisation and can provide excellent preservation of renal function and quality of life.

Surgical Treatment Options

Patients who fail anticholinergic therapy with or without self-catheterisation may require surgery to create a low-pressure storage reservoir to prevent renal damage and/or to provide easier access to the bladder to facilitate clean intermittent catheterisation. Surgery may be necessary in 10 percent of MS patients.

Surgical options include augmentation cystoplasty and various types of urinary diversion. Augmentation cystoplasty involves the enlargement of the bladder with a segment of bowel and usually lowers the intravesical pressure by increasing the bladder capacity and compliance. Patients with bladder augmentation need to perform clean intermittent catheterisation following surgery in order to empty the bladder and keep it free of mucus, but intravesical pressures are maintained at low enough levels to avoid incontinence and/ or upper tract damage.

Augmentation cystoplasty with a continent stoma or complete urinary diversion (see below) is a surgical option in patients who are unable to perform intermittent urethral catheterisation secondary to either impaired manual dexterity or difficult access to the urethra. Closure of the bladder neck may be necessary in patients with urinary incontinence secondary to intrinsic sphincter deficiency in addition to detrusor hyperreflexia or low bladder compliance, in whom augmentation cystoplasty alone would not prevent the incontinence. Creation of a catheterizable stoma is preferred over suprapubic tube placement when it is feasible, because suprapubic catheters may potentially result in many of the complications seen in patients with long-term indwelling Foley catheters. In rare cases such as in patients with a small fibrosed bladder secondary to long-term Foley catheter drainage or recurrent urinary tract infections, severe urethral damage, or pyocystis, the bladder and/ or urethra are not available for augmentation.

Urinary diversion, which includes conduits and continent diversions using bowel segments, is an excellent option for patients in whom bladder augmentation is not feasible. A catheterizable abdominal stoma may provide the necessary accessibility to the bladder. In cases in which catheterisation is an impossibility or when renal function is not adequate to overcome the metabolic abnormalities that may be created by extended exposure of urine to the bowel mucosa, diversion to a conduit may be necessary. Conduits drain continuously into an external collection device that must be emptied periodically. No catheterisation is necessary.

Conclusion

Patients with MS and bladder dysfunction often present with a broad range of voiding symptoms. Once the diagnosis of MS is confirmed, a patient's urine should be sent for culture. If the culture is positive, the patient should be treated with appropriate antibiotics based on the sensitivity of the organism(s). Once the urine is free of infection, or if the initial urine culture is negative, all MS patients should have a post-void residual (PVR) checked either by in-and-out catheterisation or ultrasound of the bladder (bladder scan). Referral to a urologist is indicated if the urinary tract infection cannot be cleared or there is no relief of the initial symptoms despite a clean urine culture.

When the PVR is greater than 100 cc and the patient's manual dexterity is satisfactory, he or she may be taught to perform clean intermittent catheterisation and baseline studies are obtained. Referral to an urologist is indicated if either the renal ultrasound or serum creatinine value is abnormal at any time. A urologic referral should be made if urinary tract infections, incontinence, or urgency continues despite clean intermittent catheterisation. In cases in which the PVR is less than 100 cc, empiric anticholinergic medication may be tried, with careful monitoring of the PVRs. If the PVR is ever greater than 100 cc, the above pathway should be followed. When anticholinergic medications provide adequate relief of symptoms, the medications are continued and baseline studies are obtained. However, if the patient continues to have symptoms, he or she should be referred to a urologist.

All MS patients with bladder dysfunction should have a baseline renal ultrasound and serum creatinine. An annual creatinine check is adequate to follow these patients when the baseline renal ultrasound and creatinine are normal. Follow-up renal ultrasound is only necessary if the patient's symptoms or renal function change.

Potential problems in the diagnosis and treatment of bladder dysfunction in multiple sclerosis patients

The clinical picture of patients with MS is unpredictable, and the disease course is variable. Voiding symptoms may change over time. Potential misdiagnoses are occasionally encountered that may not be related to MS. Additionally, there are factors that must be considered in the treatment of bladder dysfunction in MS patients that every primary care physician who encounters this patient population should consider.

Bladder Outlet Obstruction Secondary to Benign Prostatic Hyperplasia Versus Impaired Detrusor Contractility

Men with MS often describe voiding symptoms similar to those of benign prostatic hyperplasia. Patients with this condition often complain of obstructive voiding symptoms, such as hesitancy, decreased force of stream, sensation of incomplete bladder emptying, pushing or straining to void, and urinary retention (21) and/or irritative symptoms such as frequency, urgency, nocturia, and urge incontinence. The obstructive symptoms are most commonly due to the bladder outlet obstruction or are occasionally secondary to impaired detrusor contractility. The irritative symptoms are due to detrusor instability in response to the bladder outlet obstruction. Frequency may also be a result of incomplete bladder emptying, which results in a decreased functional capacity of the bladder. In order to differentiate whether a patient's symptoms are due to bladder outlet obstruction or bladder dysfunction, a pressure-flow study is performed (see preceding). "Classic" outlet obstruction is characterized by a poor flow rate concomitant with a strong detrusor contraction and incomplete bladder emptying. Obstructive voiding symptoms in a male MS patient should not be attributed to benign prostatic hyperplasia without evaluating bladder function.

Treatment of Urinary Tract Infections Without a Complete Workup

Urinary tract infections are common in MS patients. They should be treat- ed with appropriate urologic studies such as post-void residual, urodynamics, renal ultrasound, and serum creatinine. Bladder acontractility often results in retention of a variable volume of urine, which may result in recurrent urinary tract infections. Symptoms of irritative voiding may be caused by a urinary tract infection, detrusor hyperreflexia, bladder outlet obstruction, or other lower urinary tract pathology.

Treatment of Urinary Retention with a Long-Term Indwelling Foley Catheter

Long-term indwelling Foley catheters should be avoided in MS patients. Foley catheters are not a benign method of treatment when left in place indefinitely. They can result in severe urethral damage, stones, recurrent infections, urosepsis, hydronephrosis, and in some cases, malignancy (3). Numerous alternative options are available (see "Treatment Options").

Treatment of Detrusor Hyperreflexia with Single Agent Therapy and Misdiagnosis of Overflow Incontinence as Detrusor Hyperreflexia

Finally, patients with detrusor hyperreflexia who do not respond to single agent therapy may be tried on multiple anticholinergic agents or a combination of medications. Treatment with only one anticholinergic is often not adequate to control the patient's symptoms or elevated intravesical pressures. Multiple oral anticholinergic agents [oxybutynin (Ditropan®) , propantheline (Pro-Banthine®) , tolterodine (Detrol®) , imipramine (Tolfranil®) ] are available in addition to intravesical oxybutyinin. One must be aware of the use of these medications in combination before concluding that anticholinergic therapy is unsuccessful. Additionally, one should not automatically attribute urinary incontinence to detrusor hyperreflexia. Incontinence can also be a result of overflow in the case of an acontractile bladder either as a primary problem or as an iatrogenic problem secondary to anticholinergic therapy.

Summary

The goal of urologic treatment of MS patients is to restore continence, protect renal function, and improve the patient's quality of life (22). Assessment of the clinical symptoms, physical examination, post-void residual, and basic urodynamics are often adequate to form an effective treatment plan. Electromyography is important in the diagnosis of patients suspected of having MS, but not in the bladder management of patients with an established diagnosis. A baseline upper urinary tract evaluation is important, but annual radiologic follow-up is only necessary if the initial studies are abnormal or in patients with normal baseline studies only if the patient develops renal insufficiency, hydronephrosis, or progressive or new voiding symptoms.

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