Invisible Symptoms in Multiple Sclerosis:

Fatigue, Cognitive Dysfunction and Pain

MS Symptom Overview

Fatigue (most common)

Pain

Emotional disturbances – Depression or Anxiety

Cognitive difficulties

Halper J, Harris C. Nursing Practice in Multiple Sclerosis: A Core Curriculum. 3rd ed. New York:

Springer Publishing Company, 2012.

Crayton, H. et al. Neurology 2004;63:S12-S18

Multiple sclerosis symptoms can be interrelated

Symptoms may be primary, secondary or tertiary symptoms

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Management of MS Symptoms

FATIGUE

Fatigue

Multiple Sclerosis Council for Clinical Practice Guidelines, Paralyzed Veterans of America. Fatigue

and Multiple Sclerosis. Evidence-Based Management Strategies for Fatigue in Multiple Sclerosis.

Washington, DC: Paralyzed Veterans of America; 1998.

Fatigue

1. Schapiro. Managing the Symptoms of Multiple Sclerosis. (6th ed). New York: Demos Medical

Publishing, 2014.

2. Amato, Portaccio. Expert Opin Pharmacother. 2012 Feb;13(2):207-216.

3. Halper, Harris. Nursing Practice in MS: A Core Curriculum. 3rd ed. NY: Springer Publishing, 2012.

Clinical Characteristics of Fatigue

Comi G, Leocani L. Expert Rev Neurother. 2002;2:867-876.

Krupp LB. CNS Drugs. 2003;17:225-234.

Multiple Sclerosis Council for Clinical Practice Guidelines. Fatigue and MS: Evidence-Based

Management Strategies for Fatigue in Multiple Sclerosis. 1998.

Potential Causes and Effects

Fatigue

Multiple sclerosis Primary MS symptom

Psychologic Health Depression

Anxiety Stress

Medications Anti-spasmodics,

analgesics, sedative-hypnotics, anticonvulsants,

interferons

Physical Health Other health issues:

anemia, thyroid disease, anemia,

infections

Environment Heat sensitivity Physical activity

Multiple sclerosis Secondary symptom:

depression, sleep disturbance, pain

Frohman, et al. TANDS 2011; 4(2): 83-89.

Fatigue management.

Crayton H et al. Neurology 2004;63:S12-S18

Fatigue Management

Amato, Portaccio. Expert Opin.Pharmachother. 2012;13(2):207-216.

Bennett et al. Int J MS Care. 2014; 16(Suppl 1):25-32.

Non-pharmacologic treatments

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Fatigue: Pharmacologic Treatments

Frohman, et al. Ther Adv Neurol Disord 2011;4(2):83-98.

Pharmacologic Treatment

Drug Dose Adverse Effect

Amantadine 100-200 mg/d

Hallucinations Livido reticularis Nausea Lightheadedness Insomnia Constipation

Modafinil Up to 400 mg/d

Headache Nausea Rhinitis Insomnia

Frohman, et al. Ther Adv Neurol Disord 2011;4(2):83-98.

Pharmacologic Treatment

Drug Dose Adverse Effect

Acetyl L-carnitine Up to 4,000 mg/d

Loose stools Abdominal discomfort

Dalfampridine 10mg BID

Seizures UTIs

Frohman, et al. Ther Adv Neurol Disord 2011;4(2):83-98.

Pharmacologic Treatment (cont.)

Drug Dose Adverse Effect

Methylphenidate

10-60 mg/d

Nausea Lightheadedness Insomnia Constipation Hypertension Tachycardia

Dextroamphetamine

5-40 mg/d Nausea

Feeling faint Insomnia Constipation Hypertension Tachycardia

Krupp, Christodoulou. Curr Neuro Neurosci Rep. 2001;1(3):294-298. Olson, et al. Psychosomatics.

2003;44(1):38-43. Medline Plus Drug Information: Methylphenidate:

http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682188.html.

Medline Plus Drug Information: Dextroamphetamine

http://www.nlm.nih.gov/medlineplus/druginfo/meds/a605027.html.

Patient Resources

http://www.msfocus.org/article-details.aspx?articleID=48.

http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Brochure-Fatigue-What-You-Should-Know.pdf

COGNITIVE DYSFUNCTION

Cognitive dysfunction in MS

Amato, et al. Neurol Sci 2010;31(Suppl 2):S211-S214.

Characteristics of MS-related Cognitive Dysfunction

Crayton et al. Neurology. 2004;63(11 Suppl 5):S12-S18.

Foley et al. Int J MS Care. 2014; 16(Suppl 1):33-36.

Risk Factors

1. Benedict, Zivadinov. Nat Rev Neurol 2011;7:332-342.

Areas of cognition affected

Cognitive Domains Affected by MS

Domains typically impaired in MS Domains typically not affected in MS

Memory Long-term memory

Short term - working memory Semantic memory (ie, general fund of knowledge)

Attention Procedural memory

Complex attention tasks - selective, divided or alternating attention Language

Multitasking IQ

Processing speed

Executive Function

Organizing, prioritizing, problem solving, decision making

Visual spatial tasks

Assessment of Cognitive Impairment

Neuropsychological testing

(SDMT) •

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Managing Cognitive Impairment: Non-pharmacologic Treatment

Foley et al. Int J MS Care. 2014; 16(Suppl 1):33-36.

Managing Cognitive Impairment: Non-pharmacologic Treatment

Managing Cognitive Impairment: Non-pharmacologic Treatment

Managing Cognitive Impairment: Pharmacologic Treatment

Foley et al. Int J MS Care. 2014; 16(Suppl 1):33-36.

Pharmacologic

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• Krupp, et al. Neurology 2004;63:1579-1585

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• Krupp, et al. Neurology 2011;76(17):1500-1507.

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• Shaygannejab, et al. Canadian Journal of Neurological Sciences 2007;35:476-481.

Pharmacologic

• Villoslada, et al. Neuro 2009;72:1630-1633.

• Lovera, et al. Mult Scl 2010; 16 (6):715-723.

Pharmacologic treatments

Patti, et al. Neurol Sci 2010; 31 (Suppl 2): S265-S269.

L-Amphetamine sulfate

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Morrow, et al. J Neurol 2009:256:1095-1102.

Patient Resources

http://www.msfocus.org/article-details.aspx?articleID=46.

http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Brochure-Solving-Cognitive-Problems.pdf

PAIN

Pain and Multiple Sclerosis

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Neuropathic pain

Treatment of Neuropathic Pain

Drug Dose Adverse Effect

Gabapentin 100-3600 mg/d Fatigue Somnolence Dizziness Ataxia

Carbamazepine

400-1000 mg/d

Dizziness Drowsiness Nausea Unsteadiness

Pregabalin

150-600 mg/d Dry mouth Constipation Unsteadiness Somnolence

Schapiro. Neurorehabil Neural Repair. 2002;16(3):223-231.

Solaro, Uccelli. Nat Rev Neurol. 2011; 7(9): 519–527.

Pharmacologic Treatment (cont.)

Drug Dose Adverse Effect

Topiramate

25-400 mg/d

Fatigue Somnolence Cognitive dysfunction Weight loss

Amitriptyline

10-150 mg/d

Drowsiness Dry mouth Fatigue Constipation

Duloxetine

60-120 mg/d

Upset stomach Vomiting Constipation Dizziness

Schapiro. Neurorehabil Neural Repair. 2002;16(3):223-231.

Kline et al. South Med J. 2003;96:602-605.

Pharmacologic Treatment (cont.)

Drug Dose Adverse Effect

Citalopram

20-60mg/day

Gi symptoms Dizziness Dry mouth Somnolence

Milnacipran

100-200 mg/d

GI symptoms Headache Dizziness Palpitations

Musculoskeletal Pain

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Functional approach

Surgical Interventional

approach

Medications Avoid Triggers

Medications

Treatment of Spasticity

Drug Dose Adverse Effect

Balcofen

10-80mg/day

Fatigue Constipation Nausea

Tizanidine

2-36mg/day

Drowsiness Orthostatic hypotension Dry mouth Dizziness

Clonazepam

0.25-3mg/day

Drowsiness Sedation Gait imbalance May build tolerance

Schapiro. Neurorehabil Neural Repair. 2002;16(3):223-231.

Kline et al. South Med J. 2003;96:602-605.

Botox

Intrathecal Baclofen pump

Non-pharmacologic Treatment Measures

Archibald CJ, et al. Pain. 1994;58(1):89-93.

Bashir K, Whitaker JN. Handbook of Multiple Sclerosis. 2002

Patient Resources

http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Brochure-Pain-The-Basic-Facts.pdf

CONCLUSION

QUESTIONS?