How common are urinary symptoms in MS?
Up to 85% of people with MS report urinary symptoms related to neurogenic bladder dysfunction at some point during their disease course. Patients can experience a variety of symptoms. The specific symptoms and their severity vary between patients and can evolve over time.
What causes bladder dysfunction?
Storage of urine within the bladder involves bladder wall and detrusor relaxation and contraction of the bladder neck and internal sphincter. Conversely, bladder emptying involves contraction of the detrusor muscle and relaxation of the bladder neck and external urinary sphincter. The function of the bladder and sphincters is controlled by local reflexes mediated by the autonomic nervous system with central regulation from rostral micturition centers in the frontal lobe and brainstem. MS lesions in the brain and, particularly, in the spinal cord can damage the afferent and efferent pathways regulating these processes leading to the impairment of bladder function.
What types of bladder dysfunction occur in MS?
Bladder dysfunction can be broadly classified into three categories:
- Impaired storage
- Impaired emptying
- A combination of both impaired storage and emptying
What are the potential complications of bladder dysfunction?
Potential complications of bladder dysfunction include diminished quality-of-life, lower or upper urinary tract infections, decreased bladder wall compliance, kidney or bladder stones, bladder carcinoma, vesicoureteral reflux, hydronephrosis, and rarely kidney failure.
How do you differentiate between the different types of bladder dysfunction?
We screen all our MS patients for urinary symptoms using open-ended questions as part of a general review of symptoms. If a patient reports urinary symptoms, we then ask direct questions to try to differentiate between the different types of bladder dysfunction to guide further workup and treatment:
Symptoms suggesting difficulty with impaired storage:
- Increased frequency
- Frequent nocturia
- Incontinence with urgency, with Valsalva, or due to decreased mobility and inability to reach a bathroom in time
Symptoms suggesting impaired emptying:
- Sensation of incomplete emptying
- Urinary hesitancy or inability to void
- Slow or intermittent urinary stream
- Straining to void
- Incontinence without a sense of bladder fullness
Positive answers in both categories suggest a combined dysfunction.
It is important to note that urinary symptoms are sometimes an inaccurate reflection of the underlying pathophysiology because different types of bladder dysfunction can produce similar urinary symptoms. For example, patients suffering from an underlying difficulty with impaired storage, impaired emptying with overflow, or decreased bladder compliance may all complain of urinary frequency. Therefore, urinary symptoms should be interpreted as an indication of bladder dysfunction but not as definitive evidence for a specific type of pathology.
After the initial characterization of a patient’s urinary symptoms, we then evaluate for health behaviors, co-morbid conditions, and medications that may be contributing to bladder dysfunction.
When should a patient be referred to urology?
If the patient’s history suggests anything other than isolated difficulty with impaired storage, further evaluation is warranted. We sometimes initially evaluate patients suspected of having impaired bladder emptying by measuring a post-void residual by bladder ultrasound in the Mellen Center. Alternatively, some patients are directly referred to urology to confirm impaired emptying, determine the cause, and develop a treatment plan.
Other reasons for referral to urology include lack of benefit or inability to tolerate standard therapies for their symptoms or if they develop secondary complications including recurrent UTIs, renal impairment, hematuria, and kidney or bladder stones. Urologists may conduct further testing including upper and lower urinary tract imaging and urodynamic testing to further elucidate the cause of the patient’s symptoms. A referral to urology also is indicated for consideration of surgical interventions, e.g. augmentation cystoplasty, intravesicular Botox or capsaicin, sacral neuromodulator placement, or urinary diversion.
Are there non-pharmacological interventions for impaired storage?
Impaired storage due to detrusor hyperactivity should be treated with a combination of non-pharmacological and pharmacological interventions. There are several non-pharmacological interventions that can be trialed in patients reporting urinary symptoms suggestive of impaired storage. These interventions are not beneficial for patients reporting symptoms suggestive of impaired emptying.
|Scheduled voiding||Instruct patients to urinate at regular intervals (ex: every two hours) to control the timing of their urination|
|Pelvic floor (Kegel) exercises||Provide patients with a list of exercises that involve contracting and relaxing the muscles that support the urethra, bladder, uterus and rectum. Patients can also be referred to a physical therapist for training or for dedicated pelvic floor physical therapy|
|Avoid irritants and diuretics||Citrus, spicy foods, caffeinated beverages (coffee, tea, soft drinks) and alcohol can all exacerbate urinary frequency or urgency. Patients should be instructed to avoid or limit the intake of these items|
|Fluid management||Advise patients to restrict fluid intake approximately two hours before starting any activity where no bathroom will be available and avoid drinking fluids after dinner to prevent nocturia. They should not restrict fluids on a continuous basis as this can increase the risk of infection by decreasing the normal flushing of the urinary tract|
|Manage constipation||Screen for constipation and treat as needed to reduce intraabdominal pressure|
|Weight loss||Counsel patients on dietary and lifestyle modifications they can implement to achieve a healthy weight|
|Smoking cessation||Advise patients to stop smoking given that smoking irritates the bladder and worsens urinary symptoms|
What medications are used to treat impaired storage due to detrusor hyperactivity treated?
We most commonly prescribe an anticholinergic medication or mirabegron as our first-line agent and then shift to another medication or drug class if it is ineffective or not well-tolerated. If the patient has another indication that merits the prescription of a tricyclic antidepressant like neuropathy or depression, then we may prescribe a tricyclic antidepressant to treat this condition with the anticipation that the anticholinergic side effects will treat their detrusor hyperactivity.
|Anticholinergics||All anticholinergic medications can cause side effects of urinary retention, dry mouth, constipation, blurred vision, acute angle-closure glaucoma, and CNS alterations (sedation, hallucinations, memory impairment). These side effects often lead to drug discontinuation. The dose needs to be individualized and titrated every 1-2 weeks based on efficacy and side effects. Immediate-release formulations tend to have more potent efficacy but also more side effects. Extended-release formulations tend to be better tolerated but less potent. For some medications, the dose needs to be adjusted based on hepatic and/or renal function.|
|Oxybutynin (Oxytrol, Ditropan XL, Gelnique)||Immediate release: 5-10 mg two to three times daily
Extended release: 5-10 mg once daily
|Tolterodine (Detrol)||Immediate release: 1-2 mg twice daily
Extended release: 2-4 mg once daily
|Trospium (Trosec, MAR-Trospium)||Immediate release: 20 mg twice daily
Extended release: 60 mg once daily in the morning
*Adjust dosage based on renal function
|Darifenacin (Enablex)||7.5-15 mg once daily
*Adjust dosage based on hepatic function
|Solifenacine (Vesicare)||5-10 mg once daily
*Adjust dose based on renal and hepatic function
|Fesoterodine (Toviaz)||4-8 mg once daily|
|Beta-3 adrenergic agonist||Main adverse effects are hypertension, nasopharyngitis, headache, angioedema, urinary retention, UTI, and CYP2D6 inhibition|
|Mirabegron (Myrbetriq)||25-50 mg once daily|
|Desmopressin (DDAVP)||Exclusively for treatment of nocturia: 0.2 mg thirty minutes before sleep. May increase to 0.4 mg thirty minutes before sleep. Patients need to be carefully monitored for hyponatremia with regular BMPs, particularly when first starting DDAVP and when changing the dose|
What urological procedures can be used to treat detrusor hyperactivity?
For patients who fail oral therapy, there are other interventions that can be used to treat detrusor hyperactivity. We refer such patients to a urologist, ideally one with experience treating patients with neurogenic bladder, who will perform these interventions.
|Intravesical Botox||Injection of botox into the bladder to relax the detrusor muscle. Benefits typically last 10-12 months. Side effects include urinary retention, UTI, and rarely muscle weakness from systemic absorption|
|Intravesical capsaicin||Superficial nerve desensitization by instillation of capsaicin into the bladder. Side effects include suprapubic pain sensation, increased incontinence, macroscopic hematuria, or UTI|
|Sacral neuromodulation||An implantable programmable neurostimulator with electrodes that target sacral nerve III. Efficacy data from formal clinical studies are limited. The current implantable devices are MRI conditional and allow for brain and spinal MR imaging with 1.5 and 3 tesla MRIs, but some older models are not MRI compatible or are only MRI head conditional|
|Augmentation cystoplasty||Surgical enlargement of the bladder to increase bladder capacity and reduce detrusor pressure|
How is impaired emptying due to detrusor hypoactivity treated?
Impaired emptying can be caused by detrusor hypoactivity, outlet obstruction, or a combination. If the urological evaluation reveals impaired emptying due to underlying detrusor hypoactivity, we recommend intermittent catheterization or urinary diversion (described below). Bethanechol, a cholinergic agonist, can also be prescribed for patients with mild detrusor hypoactivity but, in our clinical experience, it is often ineffective and poorly tolerated.
|Intermittent catheterization||Considered the preferred treatment in MS patients with chronic urinary retention. This treatment may be infeasible in patients with significant upper extremity weakness, poor dexterity, or cognitive dysfunction. Interested patients should be trained on how to perform catheterization safely. The frequency of intermittent catheterization will depend on the severity of the patient’s detrusor hypoactivity. For patients who are completely unable to void, catheterization should be performed 4-6 times daily or every 4 to 6 hours. Patients who retain a partial ability to void should start intermittent catheterization every 4 to 6 hours and monitor the volume of urine produced. They should target a volume of 300-500 ml with each catheterization. If they are finding low or minimal volumes (<100 ml) then they should catheterize less frequently. If patients are frequently getting high volumes (>500 ml) then they should catheterize more frequently. The most common side effect of intermittent catheterization is UTI which can be prevented by avoidance of bladder overfilling and hygienic techniques.|
|Urinary diversion||Placement of a suprapubic catheter or urostomy. Usually reserved for severe urinary retention or in patients in whom intermittent catheterization is indicated but infeasible. We avoid long-term indwelling Foley catheters due to the high risk of infection and other complications|
How is impaired emptying due to outlet obstruction treated?
Impaired emptying due to outlet obstruction can be caused by either a structural abnormality, like prolapse, urethral stricture, or benign prostate hyperplasia, or by detrusor-sphincter dyssynergia. Detrusor-sphincter dyssynergia is a condition in which damage to the neuronal connection between the pontine micturition center and the brain and spinal cord results in simultaneous contraction of the detrusor and urethral sphincter causing a functional outlet obstruction. If urological testing demonstrates the presence of a structural abnormality, then surgery to treat the structural abnormality should be pursued. If the impaired emptying is caused by detrusor-sphincter dyssynergia, potential interventions include:
|Intermittent catheterization||As described above|
|Terazosin (HytrinHyt)||1 mg once daily. Adjust dose as needed based on response and tolerability in weekly intervals of 1 mg to a max dose of 20 mg daily. Side effects include dizziness/lightheadedness, leg swelling, increased or irregular heart rate, and chest pain. Rarely effective as a monotherapy|
|Tamsulosin (Flomax)||0.4-0.8 mg once daily. Indicated for patients with benign prostate hyperplasia. Side effects include dizziness and orthostatic hypotension|
What urological procedures can be used to treat outlet obstruction caused by detrusor-sphincter dyssynergia?
If a patient fails pharmacological treatment for detrusor-sphincter dyssynergia and is unable to perform or tolerate intermittent catheterization, the following procedures can be performed:
|Urinary sphincter dilatation, sphincterotomy, or artificial sphincter placement||A variety of operative procedures can be performed to increase the patency of the urinary sphincter. These procedures have a risk of causing urinary incontinence|
|Sacral neuromodulation||As described above|
|Urinary diversion||As described above|
How is combined storage and emptying due to detrusor hyperactivity and detrusor-sphincter dyssynergia treated?
With combined bladder dysfunction involving co-occurring detrusor hyperactivity and detrusor-sphincter dyssynergia, the patient should be treated for both disorders simultaneously using a combination of the interventions described above. For example, in a patient experiencing both detrusor hyperactivity and detrusor-sphincter dyssynergia, they may be started on an anticholinergic medication to treat their detrusor hyperactivity while also performing intermittent self-catheterization for detrusor-sphincter dyssynergia.
When is intermittent catheterization indicated?
Intermittent catheterization is considered a preferred treatment in patients experiencing symptoms of impaired emptying caused by detrusor hypoactivity or detrusor-sphincter dyssynergia. This treatment may be infeasible in patients with significant upper extremity weakness, poor dexterity, or cognitive dysfunction. Interested patients should be trained on how to perform catheterization safely and hygienically.
When are urinary diversion procedures indicated?
Urinary diversion procedures should be considered in patients in whom intermittent catheterization is indicated but infeasible. For example, an MS patient with quadriplegia and symptoms of urinary retention caused by detrusor hypoactivity may be unable to perform intermittent catheterization due to their disability and therefore should be referred for urinary diversion. Specific diversion approaches include the placement of a suprapubic catheter or urostomy.
How are patients with recurrent UTIs treated?
Urinary tract infections are the most frequent acute comorbidity recorded after the diagnosis of MS, occurring in approximately 80% of patients. Bladder dysfunction can increase the risk for a urinary tract infection through several mechanisms, including urinary stasis, bladder lithiasis, and the use of an intermittent catheter (when technique is suboptimal). Chronic urinary symptoms make it challenging to diagnose UTIs in MS patients. Patients who complain of acute changes in their urinary symptoms should be evaluated for possible UTI via urinalysis and urine culture.
Patients with recurrent UTIs may benefit from a referral to urology to determine if bladder dysfunction is a contributing factor. If urine culture identifies antibiotic-resistant bacteria, referral to infectious disease is indicated. We recommend against chronic antibiotic prophylaxis given the lack of efficacy for this approach and the risk of antibiotic resistance.
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