Invisible Symptoms in Multiple Sclerosis: Fatigue, Cognitive Dysfunction and Pain

MS Symptom Overview  Fatigue (most common)

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 Pain

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  Emotional disturbances – Depression or Anxiety  Cognitive difficulties

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Halper J, Harris C. Nursing Practice in Multiple Sclerosis: A Core Curriculum. 3rd ed. New York: Springer Publishing Company, 2012.

Multiple sclerosis symptoms can be interrelated

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

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  

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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 Multiple sclerosis Primary MS symptom

Secondary symptom: depression, sleep disturbance, pain

Psychologic Health Depression Anxiety Stress

Medications

Fatigue Physical Health

Anti-spasmodics, analgesics, sedativehypnotics, anticonvulsants, interferons

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

Multiple sclerosis

Other health issues: anemia, thyroid disease, anemia, infections

Environment Heat sensitivity Physical activity

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

Fatigue management.

Fatigue Management   

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 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

Amantadine

100-200 mg/d

Modafinil

Up to 400 mg/d

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

Adverse Effect Hallucinations Livido reticularis Nausea Lightheadedness Insomnia Constipation Headache Nausea Rhinitis Insomnia

Pharmacologic Treatment Drug

Dose

Acetyl L-carnitine

Up to 4,000 mg/d

Dalfampridine

10mg BID

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

Adverse Effect Loose stools Abdominal discomfort

Seizures UTIs

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/me dia/MSNationalFiles/Brochures/Brochure-Fatigue-WhatYou-Should-Know.pdf

COGNITIVE DYSFUNCTION

Cognitive dysfunction in MS 

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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 

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Areas of cognition affected Cognitive Domains Affected by MS

Domains typically impaired in MS Memory Short term - working memory Attention

Domains typically not affected in MS Long-term memory Semantic memory (ie, general fund of knowledge) Procedural memory

Complex attention tasks - selective, divided or alternating attention Language Multitasking Processing speed Executive Function Organizing, prioritizing, problem solving, decision making Visual spatial tasks

IQ

Assessment of Cognitive Impairment 

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Neuropsychological testing  

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(SDMT) • •

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Managing Cognitive Impairment: Non-pharmacologic Treatment 

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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 

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Managing Cognitive Impairment: Pharmacologic Treatment  

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

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

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

 • • 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/articledetails.aspx?articleID=46.  http://www.nationalmssociety.org/NationalMSSociety/ media/MSNationalFiles/Brochures/Brochure-SolvingCognitive-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

Avoid Triggers

Interventional approach

Medications

Surgical

Medications    

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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 

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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-TheBasic-Facts.pdf

CONCLUSION

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QUESTIONS?