Transcript Dr. Antezana`s PowerPoint slides

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)
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1
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
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2
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
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3
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
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4
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
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5
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
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6
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
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7
Management of MS-Related Pain
Multidisciplinary approaches for treatment of pain in
multiple sclerosis
Pöllmann W, Feneberg W. CNS Drugs. 2008;22:291
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8
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
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9
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.
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10
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
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11
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
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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
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13
Bladder Dysfunction
Antimuscarinic drugs for overactive bladder
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14
Bladder Dysfunction
Non-antimuscarinic drugs for overactive bladder
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15
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
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16
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.
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17
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.
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18
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 MSrelated 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
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19
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
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