© 2014 direct one communications, inc. all rights reserved. 1 symptomatic management of multiple...

© 2014 Direct One Communications, Inc. All rights reserved. 1

Symptomatic Management of Multiple Sclerosis

Ariel Antezana, MD

Multiple Sclerosis Comprehensive Care Center, NYU Langone Medical Center, New York, New York

A REPORT FROM THE 66TH ANNUAL MEETING OF THE AMERICAN ACADEMY OF NEUROLOGY (AAN 2014)


Gait Disturbance

Affects 40%–50% of multiple sclerosis (MS) patients

Nonpharmacologic treatment» Regular, tailored physical therapy addressing

specific patient needs

» Evaluation for orthotics and assistive devices (cane, etc)

» Occupational therapy

» Assessment of patient’s home for safety and recommend changes (grab bars, clearance of pathways, etc)

Pharmacologic therapy» Dalfampridine, 10 mg twice a day

» Main side effects: seizures (7%), insomnia (8%), nausea, and paresthesias

Weinshenker BG et al. Brain. 1989;112:133; LaRocca N. Patient. 2011;4:189; Cameron MH, Wagner JM. Curr Neurol Neurosci Rep. 2011;11:507; Jensen HB et al. Ther Adv Neurol Disord. 2014;7:97


Spasticity

Present in 70%–80% of MS patients» Contributes to worsening of pain, gait disturbances,

and falls

» Stretching and routine exercises crucial in treatment

Pharmacologic therapy» Baclofen, 10–80 mg orally in 2–3 divided doses

» Baclofen pump (requires familiarity with dosing, refilling, and programming the pump, as well as managing baclofen withdrawal in case of pump failure)

» Tizanidine, 4 mg orally q6–8h, up to 36 mg/d

» Botulinum toxin for small muscles of hands and legs

» Cannabis extracts or synthetic forms of THC (eg, dronabinol)

Hughes C, Howard IM. Phys Med Rehabil Clin North Am. 2013;24:593; Gold R, Oreja-Guevara. Expert Rev Neurother. 2013;13:55; Penn RD et al. N Engl J Med. 1989;320:1517; Yadav V et al. Neurology. 2014;82:1083


Fatigue

Reported by over 80% of MS patients Causes

» CNS inflammation, release of inflammatory cytokines (IL-1, IL-6, IL-10, TNF-a), demyelination, and axonal loss

» Secondary causes: sleep disorders, fragmented sleep, comorbidities, medications, neuroendrocrine dysfunction

Treatment» Energy conservation, physical therapy, yoga

» Amantadine, 100 mg orally twice a day

» Modafinil, 100–200 mg/d (evidence in MS is controversial)

» Aspirin, 500 mg/d (limited by risk of GI complications)

Indiruwa I, Constantinescu CS. J Neurol Sci. 2012;323:9; Blikman LJ et al. Arch Phys Med Rehabil. 2013;94:1360; Pucci E et al. Cochrane Database Syst Rev. 2007;(1):CD002818; Stankoff B et al. Neurology. 2005;64:1139; Wingerchuk DM et al. Neurology. 2005;64:1267; Shaygannejad V et al. Neurol Res. 2012;34:854; Krupp LB, in Cohen JA, Rudisk RA, eds. Multiple Sclerosis Therapeutics. London: Martin Dunitz; 2003:599


Sleep Disorders

Present in 24%–50% of MS patients Obstructive or central sleep apnea and

restless leg syndrome are the most common sleep disorders

Nocturia, pain, spasticity, and poor sleep hygiene may contribute to sleep disturbance

Treatment» Continuous positive airway pressure for obstructive

apnea

» Gabapentin, pregabalin, ropinirole, or pramipexole for restless leg syndrome

Veauthier C et al. Mult Scler. 2011;17:613; Braley TJ et al. Neurology. 2012;79:929; Allen RP et al. N Engl J Med. 2014;370:621


Pain

Neuropathic pain directly related to MS» Examples: painful paroxysmal symptoms (eg,

trigeminal or glossopharyngeal neuralgia); painful tonic spasms; painful paresthesias and dysesthesias

Pain indirectly related to MS as a consequence of other symptoms » Examples: spasticity; dyssynergic sphincter

MS treatment-related pain» Examples: injection-site pain and soreness

Pain unrelated to MS» Examples: headache; back pain; arthritis

Pöllmann W, Feneberg W. CNS Drugs. 2008;22:291; Foley PL et al. Pain. 2013;154:632


Pain Directly Related to MS

Trigeminal neuralgia» Treatment of choice: carbamazepine

» Alternatives: oxcarbazepine, gabapentin, pregabalin, or lamotrigine; surgery in refractory cases

Painful paroxysmal tonic spasms or dyskinesias» Treatment of choice: carbamazepine or gabapentin

» Alternatives: topiramate, lamotrigine, or valproate

Painful dysesthesias» Physical therapy, carbonated baths, or

electrotherapy

» Pharmacologic treatment: tricyclic antidepressants (eg, amitriptyline, nortriptyline), gabapentin, or lamotrigine

Pöllmann W, Feneberg W. CNS Drugs. 2008;22:291; Pöllmann W et al. Nervenarzt. 2004;75:135


Management of MS-Related Pain

Multidisciplinary approaches for treatment of pain in multiple sclerosis

Pöllmann W, Feneberg W. CNS Drugs. 2008;22:291


Pain Indirectly Related to MS

Pain may be caused by improper positioning, spasticity, or nerve compression.

Burning pain during micturition may be caused by pelvic floor muscle spasticity or external sphincter spasticity and may respond to treatment with tamsulosin, an a-adrenergic antagonist.

Pain associated with detrusor spasms may be treated with an antimuscarinic agent, such as oxybutynin or solifenacin, or with injection of botulinum toxin into the detrusor muscle.

Pöllmann W, Feneberg W. CNS Drugs. 2008;22:291; Pöllmann W et al. Nervenarzt. 2004;75:135


Depression

Affects 20%–50% of MS patients » Risk factors include female gender, age < 35 years,

and family history of depression.

» MS symptoms and depressive symptoms may overlap.

Treatment is similar to that of non-MS patients» Duloxetine is helpful in treating depression and

pain.

» Bupropion is helpful for depression and smoking cessation.

» Citalopram can prolong the QT interval; use with caution in MS patients being treated with fingolimod.

» Tricyclic antidepressants increase the risk of suicide during the first few days of treatment; their anticholinergic effect helps with bladder symptoms.


Cognitive Impairment

Experienced by 30%–50% of MS patients Commonly affected areas of cognition in MS:

speed of processing, memory, complex attention, and executive function

A neuropsychologic evaluation and cognitive rehabilitation should be considered when activities of daily living are affected.

Occupational therapy providing targeted interventions for specific cognitive deficits may be helpful.

Drug therapy has no benefit in MS-related cognitive impairment and is not routinely recommended. Benson C, Kerr BJ. Curr Top Behav Neurosci. 2014; He D et al. Cochrane Database Syst Rev. 2013;12:CD008876


Bladder Dysfunction

Present in up to 75% of MS patients Failure to store urine due to detrusor

overactivity» Manifested by urgency, frequency, nocturia, and/or

urge incontinence; urodynamic studies may show detrusor overactivity.

Detrusor sphincter dyssynergia » Manifested by hesitancy, straining, and urinary

retention; urodynamic studies show disrupted coordination of sphincter relaxation and detrusor contraction.

Hypoactive bladder» Manifested by urinary retention or overflow

incontinence; often associated with urinary tract infection or renal injury.

Betts CD et al. J Neurol Neurosurg Psychiatry. 1993;56:245


Bladder Dysfunction

Treatment» Behavioral modifications: controlling comorbidities;

avoiding common bladder irritants; avoiding consumption of water and other fluids by mouth 2–3 hours before bedtime; scheduled voiding; bladder retraining; and strengthening of the pelvic muscles with Kegel exercises

» Overactive bladder: antimuscarinic agents; mirabegron; tricyclic antidepressants; desmopressin; in refractory cases, intradetrusor injections of botulinum toxin or sacral nerve stimulation or intermittent tibial nerve stimulation

» Urinary retention: early urologic referral is recommended; treatment includes intermittent self-catheterization, suprapubic catheterization, and urinary diversion.

Stoffel JT. Urol Clin North Am. 2010;37:547; Gras J. Drugs Today (Barc). 2012;48:25; Knuepfer S, Juenemann KP. Ther Adv Urol. 2014;6:34


Bladder Dysfunction

Antimuscarinic drugs for overactive bladder


Bladder Dysfunction

Non-antimuscarinic drugs for overactive bladder


Bowel Dysfunction

Neurogenic bowel, usually spastic bowel, produces constipation and/or fecal incontinence.

Experienced by more than 50% of MS patients

Nonpharmacologic treatment of constipation» Behavioral modifications: advise patient to avoid

bowel irritants such as caffeine and alcohol, candy or gum artificially sweetened with sorbitol or xylitol; drugs that can cause or worsen constipation, such as opioids, tricyclic antidepressants, and sedatives.

» Also useful: maintaining good fluid/fiber intake; having regular morning bowel movements; exercising regularly; digital rectal stimulation to activate the anorectal reflex; abdominal massage; and biofeedback


Bowel Dysfunction

Pharmacologic treatment of constipation» Generally, bulk-forming agents and stool softeners

are recommended.

» Laxative or colonic and rectal stimulants should be used with caution.

» Enemas can cause loss of rectal reflexes and are not indicated routinely except for cases of fecal impaction.

» In more severe and intractable cases, a determination of colonic transit time and anorectal manometry by a gastroenterologist will help to determine the correct treatment.


Bowel Dysfunction

Management of fecal incontinence» Advise patients to avoid bowel irritants, such as

caffeine or alcohol, and attempt to have regular morning bowel movements.

» Bulk-forming agents produce more consistent stools, and anticholinergic agents can reduce bowel transit.

» Referral to a gastroenterologist should be sought in refractory cases.


Sexual Dysfunction

Reported by up to 60% of MS patients Categories

» Primary sexual dysfunction is caused directly by MS; symptoms include erectile dysfunction, ejaculatory dysfunction and/or orgasmic dysfunction, reduced libido, and anorgasmia in men; sensory genital dysfunction, difficulty achieving orgasm, decreased vaginal lubrication, and reduced libido in women.

» Secondary sexual dysfunction is a result of other MS-related symptoms (eg, fatigue, pain) and drug therapy.

» Tertiary sexual dysfunction results from psychologic factors, such as mood dysregulation, negative self-image, fear of rejection, and communication problems.

Celik DB et al. J Neurol Sci. 2013;324:17; Fletcher SG et al. Nat Clin Pract Urol. 2009;6:96


Sexual Dysfunction

Management» Check testosterone levels and, if low, correct with

hormonal supplementation

» For erectile dysfunction, prescribe sildenafil, vardenafil or tadalafil.

» In more severe cases, intracavernosal injections of alprostadil (prostaglandin E1) or using vacuum erection devices can achieve satisfactory erections and improvement in sexual and reproductive function.

Fletcher SG et al. Nat Clin Pract Urol. 2009;6:96; Fowler CJ et al. J Neurol Neurosurg Psychiatry. 2005;76:700

© 2014 direct one communications, inc. all rights reserved. 1 symptomatic management of multiple...

Documents