Alana M. Murphy, MD
BASICS
DESCRIPTION
• Multiple sclerosis (MS) is a neurologic disease causing focal demyelination of white matter in the brain and spinal cord that can impact urinary tract functioning.
• Plaques visible on magnetic resonance imaging (MRI) are inflammatory and often lead to scar tissue deposition. They interfere with conduction of electrical signals resulting in loss of central inhibition of reflex activity and dysfunctional conduction of sensory and motor signals.
• Neurologic impairment can vary from mild to severe.
• Urologic manifestations include urinary frequency, urgency incontinence, voiding symptoms, urinary retention, and sexual dysfunction.
• Detrusor sphincter dyssynergia (DSD) and detrusor overactivity (DO) are common dysfunctions noted on urodynamic studies (UDS).
EPIDEMIOLOGY
Incidence
• Most commonly presents between ages 20 and 50 yr old
• Females have 1.5–3 times greater incidence than males
Prevalence
• 1 in 750 lifetime risk of developing MS in USA
• Marked variations in worldwide prevalence
• More common in Caucasians and above 40° latitude
RISK FACTORS
• Caucasian ethnicity
• Primary relative with MS
• Live about 40° latitude
Genetics
• Increased risk if MS is present in a 1st-degree relative
• Primary relative with MS confers 20 times risk
• Identical twin: 300 times increased risk if other twin develops MS
• Unknown pattern of inheritance
PATHOPHYSIOLOGY (1)
• Autoimmune attack on the central nervous system (CNS) myelin:
– Focal demyelination with relative axon sparing
– Histopathology shows perivenular lymphocytic infiltrates, macrophages within the white matter, gliosis, and scarring
• Urologic pathophysiology:
– MS affects the cervical spinal cord in the pyramidal and reticulospinal tracts, affecting innervation of the bladder and external urethral sphincter, causing DO and DSD
– MS can affect the sacral cord and may lead to bladder areflexia and elevated post-void residual (PVR) volumes
ASSOCIATED CONDITIONS
• DSD leading to urinary retention, recurrent UTIs, and impairment in renal function
• Urolithiasis due to urinary stasis from incomplete bladder emptying and recurrent UTIs
GENERAL PREVENTION
No proven methods for prevention
DIAGNOSIS
HISTORY
• Presence of neurologic symptoms:
– Vision changes, balance problems, discoordination, numbness, or paresthesias
• Urologic history: All patients with MS should be screened for urologic problems
– Recurrent UTIs
– Urinary frequency
– Urgency incontinence
– Voiding symptoms
– Urinary retention
PHYSICAL EXAM
• Urologic exam:
– Testicular and prostate exam in males to rule out neoplasm or infection
– Pelvic exam in females to assess pelvic support and rule out urethral or vaginal pathology
• Focused neurologic exam:
– Bulbocavernosus reflex to assess function of sacral nerves (absent in up to 30%)
– Deep tendon reflexes, proprioception, Babinski reflex, and cranial nerve exam
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis: Concomitant infection or hematuria
• CSF for initial MS diagnosis (oligoclonal IgG bands)
Imaging (2,3)
• MRI:
– The most useful tool for diagnosing MS; diagnostic in 70–95% of cases
– Increased signal intensity on T2-weighted images in areas of demyelination
• Upper urinary tract imaging:
– Rule out presence of hydronephrosis
– Renal ultrasound (US) is a good screening test
– Important in patients with known DSD or in patients with indwelling catheters
• Lower tract imaging less commonly performed:
– Fluoroscopy during UDS can assess for bladder pathology (stones, trabeculation), vesicoureteral reflux, and DSD
Diagnostic Procedures/Surgery
• PVR
– Large (>275–300 cc) PVR on 2 separate occasions should initiate clean intermittent catheterization
• UDS done by urologic specialists to assess bladder capacity, compliance, detrusor function, continence, and detrusor–sphincter coordination:
– Routinely performed with fluoroscopy in MS patients
– Absolutely necessary to characterize voiding dysfunction in MS patients
– Assess risk for upper tract deterioration (elevated storage and voiding pressures)
– May suggest diagnosis of MS in patient with few other neurologic symptoms
– Need follow-up UDS with change in clinical symptoms
Pathologic Findings
Detrusor hypertrophy with trabeculation
DIFFERENTIAL DIAGNOSIS
• Idiopathic overactive bladder
• Dysfunctional voiding
• Detrusor underactivity or acontractile detrusor
TREATMENT
GENERAL MEASURES
• Remissions can occur spontaneously, making management difficult
• Physical therapy and exercise to help prevent muscle atrophy and loss of postural tone
• Avoid stressors
• Disease-modifying medications specific to MS can reduce relapses and control some symptoms: β interferons, glatiramer acetate, fingolimod, natalizumab, and teriflunomide
• Bladder emptying in cases of detrusor underactivity or DSD with urinary retention:
– Intermittent catheterization preferred over indwelling catheter
– Consider a suprapubic catheter if intermittent catheterization is not possible
– Patients on intermittent catheterization or with an indwelling catheter should not be treated with antibiotics for asymptomatic bacterial colonization of the urinary tract
• Urinary frequency and urgency incontinence treatment should include behavioral modification with avoidance of bladder irritants and management of fluid intake
MEDICATION
First Line
• Medical therapy is primarily aimed at urinary frequency and urgency incontinence
– Antimuscarinic medications: Most common side effects include dry mouth and constipation
Fesoterodine 4–8 mg QD
Hyoscyamine ER release 0.375 mg BID
Oxybutynin 5 mg BID-TID
Oxybutynin transdermal patch 3.9 mg/d
Oxybutynin XL 10–15 mg/d
Oxybutynin, topical gel 10% apply 1 sachet QD to dry skin
Solifenacin 5–10 mg/d
Tolterodine LA 1–2 mg BID
Tolterodine LA 2–4 mg/d
Trospium XR 60 mg/d
– β3-agonist: Most common side effects include an increase in blood pressure and palpitations
Mirabegron 25 mg/d increase to 50 mg/d after 8 wk PRN
Second Line (4)
• Botulinum toxin injection into the detrusor:
– Decreases the force and frequency of neurogenic DO
– Well-tolerated office-based therapy performed under local anesthesia
– Neurogenic DO treated with cystoscopic injection of 200–300 units botulinum toxin type A [onabotulinumtoxinA] into 10–25 sites within the bladder muscle
– Treatment effect lasts 3–9 mo
– Risk of temporary urinary retention requiring intermittent catheterization
SURGERY/OTHER PROCEDURES
• Suprapubic catheter placement:
– If unable to perform intermittent catheterization; avoids urethral erosion; reduces incidence of UTIs, epididymitis, and prostatitis
– Drawbacks include risk of bladder calculi and development of squamous cell carcinoma (usually in >10 yr).
• Augmentation cystoplasty: To address significantly impaired bladder compliance or when conservative management of incontinence from DO has failed
• Urinary diversion: Ileal conduit, ileovesicostomy, or catheterizable stoma
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
N/A
Complementary & Alternative Therapies
Stress reduction therapies and acupuncture have been associated with symptom reduction
ONGOING CARE
PROGNOSIS
With proper urologic follow-up, renal function can be preserved in most patients
COMPLICATIONS
• Hydronephrosis and impairment in renal function due to elevated bladder storage or voiding pressure
• Urolithiasis due to urinary stasis, indwelling catheters and infection
• Recurrent UTIs
• Urethral erosion from indwelling catheters
FOLLOW-UP
Patient Monitoring
• Upper urinary tract screening is especially important in men, since men with MS often develop high bladder storage pressure and urinary stasis without developing overt urologic symptoms such as incontinence.
• Incontinence, especially in women, can become problematic as the severity of MS progresses.
• Patients with bladder dysfunction secondary to MS can be stratified into low- and high-risk:
– High-risk patients: Incontinence, recurrent infections, DSD, elevated storage pressures >40 cm H2O, indwelling catheters
Follow closely for upper tract deterioration, development of squamous cell carcinoma of the bladder, and other problems associated with long-term indwelling catheters.
– Low-risk patients: Those with normal continence, no UTIs, and complete bladder emptying. These patients do not require frequent upper tract imaging.
• All patients should undergo periodic urodynamic testing, especially if there is a change in symptoms, an increase in infections, or an overall worsening of their MS.
Patient Resources
• http://www.nationalmssociety.org
• http://www.msfocus.org
REFERENCES
1. Carr LK. Lower urinary tract dysfunction due to multiple sclerosis.Can J Urol. 2006;Suppl1:2–4.
3. Lemack GE, Hawker K, Frohman E. Incidence of upper tract abnormalities in patients with neurovesical dysfunction secondary to multiple sclerosis: Analysis of risk factors at initial urologic evaluation. Urology. 2005;65(5):854–857.
4. Ukkonen M, Elovaara I, Dastidar P, et al. Urodynamic findings in primary progressive multiple sclerosis are associated with increased volumes of plaques and atrophy in the central nervous system. Acta Neurologica Scand. 2004;109(2):100–105.
5. Ginsberg D, Gousse A, Keppenne V, et al. Phase 3 efficacy and tolerability study of onabotuli-numtoxinA for urinary incontinence from neurogenic detrusor overactivity. J Urol. 2012;187(6):2131–2139.
ADDITIONAL READING
• Tremlett H, Zhao Y, Rieckmann P, et al. New perspectives in the natural history of multiple sclerosis. Neurology. 2010;74:2004–2015.
• Provider’s Approach to Bladder Management in Multiple Sclerosis. http://www.va.gov/MS/articles/Provider_s_Approach_to_Bladder_Management_in_Multiple_Sclerosis.asp (Accessed February 13, 2014)
See Also (Topic, Algorithm, Media)
• Detrusor Overactivity
• Detrusor Sphincter Dyssynergia
• Neurogenic Bladder, General Considerations
CODES
ICD9
• 340 Multiple sclerosis
• 788.31 Urge incontinence
• 788.41 Urinary frequency
ICD10
• G35 Multiple sclerosis
• N39.41 Urge incontinence
• R35.0 Frequency of micturition
CLINICAL/SURGICAL PEARLS
• Medical therapy and behavioral modification remain the 1st-line treatment for urinary frequency and urgency incontinence.
• Cystoscopic injection of botulinum toxin should be used for refractory neurogenic detrusor overactivity.
• Adequate management of lower urinary tract function will lead to preservation of renal function.