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Aliza Ben-Zacharia, DrNP, MSCN
Neurology Teaching Assistant
Mount Sinai Medical Center
New York, New York
MS Symptoms vs Relapses vs
Treatment Side Effects
MS symptoms
• Chronic or ongoing indicators of MS lesion damage
to certain areas of the brain or spinal cord
MS relapses
• Sudden worsening of any MS symptom or the
appearance of new symptom lasting at least 24
hours, separated from a previous exacerbation by at
least 1 month and occurring in absence of
environmental, metabolic, or infectious processes
MS treatment side effects
• Distinguishing treatment side effects from MS
symptoms/relapses
Managing Symptoms of MS
• Screening for symptoms
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Every follow-up visit
As needed
Questionnaire
History/neurologic exam
• Goal: symptom reduction
– Maintaining QOL despite symptoms
– Reduction of symptom progression through
adherence to disease-modifying treatments
– Prioritization of symptoms and individualization
of care
Common MS Symptoms
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Fatigue
Walking impairment
Spasticity
Cognitive impairment
Bladder dysfunction
Pain
Mood instability
Sexual dysfunction
MS Fatigue
• One of the most common (80%) symptoms
• One of the most disabling symptoms
– Primary reason to stop working
– More likely than other types of fatigue to interfere
with daily responsibilities
• Occurs daily, starts suddenly
– Can start early in the morning, even after restful
sleep
• Worsens as day progresses, and with heat
and humidity
• Cause unknown
National Multiple Sclerosis Society. http://www.nationalmssociety.org/about-multiple-sclerosis/what-weknow-about-ms/symptoms/fatigue/index.aspx.
Assessing MS Fatigue
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Modified Fatigue Impact Scale (MFIS)
Assessment of sleep pattern
History of exercise/activity level
Assessment of medications that may lead to
fatigue, ie, anti-spastic medications
• Other comorbidities, such as thyroid disease,
diabetes, depression
Managing MS Fatigue
Lifestyle Changes
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Physical therapy/exercise
Good nutrition
Weight management
Enough sleep
– Going to bed on time
– Management of other symptoms that interfere with sleep
• Rest breaks
• Prioritization of tasks; maintaining realistic
expectations
• Letting others help
• Avoid excessive caffeine, multitasking, overheating
Managing MS Fatigue
Pharmacologic Strategies (Off-Label Uses)
• Amantadine hydrochloride 100−200 mg/d early in day
(100 mg around noon)1
• Selective serotonin reuptake inhibitors (SSRIs)1
• Modafinil 100−200 mg/d early in day2
• Armodafinil: longer lasting isomer of modafinil–50, 150,
or 250 mg1
• Amphetamine-type therapies1
– Methylphenidate, can start at 5 mg PO in AM and titrate to
effect; 10 mg in AM and around noon or early afternoon is
common
– Can use long-acting formulations
• Possible contraindications
1. Personal communication: Aliza Ben-Zacharia; oral communication on 8/25/10.
2. National MS Society. http://nationalmssociety.org/about-multiple-Sclerosis/what-we-know-aboutmstreatments/medications/modafinil/index.aspx.
Walking Impairment
• Gait description
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Ataxic
Spastic
Paretic
Foot drop
• Disabling impact
– Negatively impacts work productivity,
employability, and income
– Impairs activities of daily living, ie, driving
– Significantly affects QOL
Factors Involved in Walking
Impairment
• Muscle weakness
– Results in toe drag, foot drop, vaulting
• Spasticity
• Loss of balance
• Sensory deficit
– Affects the ability to feel the floor, know where the
foot is
• Fatigue
– Increases walking impairment
National Multiple Sclerosis Society. http://www.nationalmssociety.org/about-multiplesclerosis/what-we-know-about-ms/symptoms.
Assessing Walking Impairment
• Timed 25-Foot Walk (T25FW)
• 500-meter walk (Extended Disabilities Status
Scale [EDSS])
• 6-minute walk (6MW)
• Assess posture
• Assess use of a device (ie, cane)
• Assess overuse of joint compensating
Fischer JS, et al. Multiple Sclerosis Functional Composite – Revised. National Multiple Sclerosis Society, 2001.
Managing Walking Impairment
• Dalfampridine—previously known as fampridine SR or 4aminopyridine SR
• FDA approved January 2010
• Indication: to improve walking speed in patients
with MS
– This is not a disease-modifying therapy
• Mechanism: K+ channel blockade
– Enhances conduction of action potentials in demyelinated axons
through inhibition of K+ channels
• Appropriate candidates
– Contraindicated in patients with history of seizures or moderate to
severe renal impairment
– Monitor patients with history of multiple urinary tract infections
Dalfampridine [PI]. Hawthorne, NY: Acorda Therapeutics; 2010.
Managing Walking Impairment
• Dalfampridine dose: 10 mg BID (12 hours apart)
with/without food
• Dose-dependent side effect: seizures
– Seizures at doses of 15 mg BID were >4 times higher
than rate at recommended maximum dose of 10 mg
BID
• Managing missed doses
– Patients should be advised not to take double or extra
doses if a dose is missed, as this may result in seizure
Dalfampridine [PI]. Hawthorne, NY: Acorda Therapeutics; 2010.
Dalfampridine Phase III Studies
P <.001
Responders (%)
• Dalfampridine 10 mg BID
(n = 229) or placebo
(n = 72) x 14 weeks
• Response = consistent
improvement on
timed 25-foot walk
• Walking speed improved
by 25% among
dalfampridine
responders vs 5% with
placebo (Trial 1)1
1. Goodman AD, et al. Lancet. 2009;373:732-738. 2. Goodman AD, et al. Mult Scler. 2008;14:S2989 (abstr P909).
3. Dalfampridine [PI]. Hawthorne, NY: Acorda Therapeutics; 2010.
Amy Perrin Ross, MSN
Neurosciences Program Coordinator
Loyola University, Chicago
Maywood, Illinois
Spasticity
• Results from demyelination in the descending
corticospinal, vestibulospinal, and
reticulospinal CNS pathways
• Can be manifested in a variety of muscle
groups depending on the lesion location
• Spasticity may increase over time without
new CNS lesions
• Very cold temperatures may aggravate
spasticity
Crayton H, et al. Neurology. 2004;63(suppl 5):S12-S18.
Modified Ashworth Scale
Score Criteria
0
No increased tone
1
Slight increased tone (catch and release at end of ROM)
1+
Slight increase in tone manifested by a catch followed by
minimal resistance throughout the remainder of the ROM (less
than half the ROM)
2
Marked increase in tone through most of ROM but affected
part(s) move easily
3
Considerable increased tone, passive movement difficult
4
Affected part(s) rigid in flexion or extension
Abbreviation: ROM, range of movement.
Bohannon RW, Smith MB. Phys Ther. 1987;67:206-207.
Spasticity Management
• Rehabilitation
– Stretching exercises
– Physical therapy
– Casting
• Oral medications
– Baclofen
– Tizanidine
– Gabapentin
• Intrathecal baclofen
Botulinum Toxin (BTX) for
Spasticity
• Wrist and finger spasticity1
– Randomized controlled trial (RCT) in 126 patients with increased
flexor tone after a stroke
– One-time injection: BTX 200−240 units vs placebo
– BTX-treated patients had greater improvement in personal
hygiene, dressing, pain, and limb position than placebo patients
through week 12 (P <.001)
• Upper limb spasticity2
– RCT in 91 patients with excessive muscle tone in elbow, wrist, and
fingers after a stroke
– Up to 2 treatments of BTX 90,180, or 360 U vs placebo
– Greater decrease in muscle tone in BTX-treated patients
in wrist (P ≤.026), elbow flexors (P ≤.033), and fingers
(P <.031), compared with placebo group
1. Brashear A, et al. N Engl J Med. 2002; 347:395-400.
2. Childers MK, et al. Arch Phys Med Rehabil. 2004;85:1063-1069.
Botulinum Toxin for MS
Spasticity
New 2010 FDA Indication
• Treatment of distal arm spasticity in adults
• Select dosage on muscles affected, severity
of muscle activity, prior response to
treatment, and adverse event history
OnabotulinumtoxinA [PI]. Irvine, CA: Allergan, Inc; March 2010.
Spasticity Treatment Options
Rehabilitation
Oral
Medications
Surgical
Procedures
Patient
Intrathecal
Baclofen
Slide courtesy of Aliza Ben-Zacharia, DrNP, MSCN.
Injections,
ie,
Botulinum
Toxin
Cognition − The Mind’s Ability
to Store, Organize, and
Recall Information
• Each person’s experience is unique and
evolving
• Most symptoms are mild
• Affects up to two thirds of patients with MS
• MS can affect cognition indirectly
• Widespread impact affecting
– Employment
– Social relationships
– Activities of daily living
Burks JS, Johnson KD, eds. Multiple Sclerosis: Diagnosis, Medical Management, and Rehabilitation. Demos Medical
Publishing; 2000.
Assessing Cognitive Impairment
• Simple processing efficiency
– Symbol Digit Modalities Test (SDMT) – Oral Version1
• Complex information processing efficiency
– Paced Auditory Serial Addition Test (PASAT)2
• Verbal learning and verbal memory
– Logical Memory subtests (LM-I and LM-II) of the Wechsler
Memory Scale – Revised3
• Verbal learning: LM-I
• Verbal memory: LM-II
• Cognitive questionnaire4
1.Benedict R, et al. Clin Neuropsychologist. 2002;16:381-397. 2. Cutter GR, et al. Brain.1999;122:871-882. 3. Wechsler D. The
Psychological Corporation, San Antonio, Texas, 1987. 4. Benedict RHB, et al. Mult Scler. 2003;9:95-101.
Managing Cognitive Impairment
• Nonpharmaceutical interventions
– Cognitive rehabilitation and psychotherapy
– Memory aids (ie, recordings, lists, mnemonics,
etc)
– Assistive technologies (computers, electronic
calendars)
– Minimization of distractions
– Addressing possible contributors to cognitive
impairment (ie, medication side effects, sleep
disorders, infections, thyroid conditions, etc)
Managing Cognitive Impairment
• Pharmaceutical interventions
– Interventions slowing further impairment: reinforce
use of disease-modifying agents to minimize
atrophy and burden of MRI disease
– Reduce the use of other medications that may be
sedating and contribute to cognitive impairment
– No effective pharmaceutical agent currently
available
Patient Education
• Provide the information needed to promote
active participation in care and symptom
management
• Promote maximum health potential towards
wellness
• Promote coping and adaptation
• Promote empowerment towards improved
QOL and hope
Role of the Nurse
• Empower patients to live with their disease
and adjust as much as possible
• Teach and educate patients and their families
• Counsel and support patients and families
• Advocate for patients and families
Managing Symptoms of MS
Conclusions
• Continuing treatment to minimize risk of relapses,
new lesions, and disease progression that result
in increased MS symptoms
• Address MS symptoms that interfere with QOL
• Symptoms need to be recognized in order to treat
• Address 1 or 2 symptoms per visit—prioritize
• Through counseling and treatment, most
symptoms can be managed
• Refer to specialists as needed for optimized
symptom control