The Implications of Fatigue for Exercise in Patients with Neuromuscular Disease

1. The Implications of Fatigue for Exercise in Patients with Neuromuscular Disease Marc Magstadt, Beatrice Mireles, Patrick Smylie Bruce Baseflug Ricardo Morales Ryan Rhoads

2. Learning Objectives • At the end of this presentation the audience will be able to: • Define fatigue and differentiate fatigue from exhaustion • Describe exercise that is beneficial for post-polio patients and for patients that have TBI, as well as the effects of fatigue • Describe what effects constraint induced movement therapy has on fatigue and WMFT • Describe the benefits that exercise may have on patients with MS • Explain the implications of overworking MS patients • Discuss whether exercise is indicated for patients with NMD

3. Definitions • Fatigue - the inability to contract muscle repeatedly over time • Fatigue can also include a mental factor • Central - in CNS from mental/physiological • Peripheral - nerves/ NM junction/ muscle • Exhaustion • no further performance is possible • Fatigue and exhaustion exist on a continuum with fatigue progressing to exhaustion

4. Quantifying Fatigue • Fatigue can be quantified using a Fatigue Severity Scale (FSS) • Identifies fatigue in patients with MS and other NMDs. • Questionnaire consisting of 9 questions that requires the subject to rate his or her level of fatigue. • Numerical scores are averaged for the 9 questions: • Average score of 4 or greater indicates severe fatigue Multiple Sclerosis Encyclopedia, 2008

5. Quantifying Fatigue (cont’d) • Fatigue can also be identified using an RPE Scale. • Has been shown to be reliable for monitoring individuals with mild MS (2008 level 1b study at UC Irvine – Program in Geriatrics). • Either the 15-point Borg scale can be used, with a score of 6 meaning “no exertion at all,” and 20 meaning “maximal exertion,” • Or the 10-point Category Ratio Scale, with 0 meaning “nothing at all,” and 10 meaning “extremely strong.” Morrison, 2008

6. Post-polio Syndrome • Definition - Newly acquired weakness, fatigue, and joint pain after recovery from initial poliomyelitis • Decreased motor units/death of collateral sprouts • Some reports of muscle atrophy • Typically occurs 15 years after initial sickness • Interventions include educating patients on strategies for ADL’s

7. Exercise for post-polio patients • Individualized programs that minimize pain and fatigue (50-70% age predicted HRmax) 13-15 RPE (Borg Scale) • Benefits include: • Increase in activity level • Increase cardiovascular health • Weight loss • Activities included moderate exercise with rest periods • Aerobic exercise on treadmill • Flexibility exercises • Needs to be supervised J Oncu et al 2009

8. Strength Training for post-polio patients • Decreased motor units from cell body are not able to keep up with demand from enlarged motor units • Most recent research shows: • Strength training does not adversely affect motor unit survival • 3 sets of 8 isometric contractions • 3 times weekly for 12 weeks • Concluded that moderate intensity strength training was safe and effective for post-polio patients • Older research showed: • Strength training increases demand and further damages motor units? • No pain or soreness during training • 75% of 3 rep max • Fast eccentric to avoid muscle breakdown • Specificity of training • Resisted PNF with Gait Training • Muscle strengthening controlled by the therapist • Walking and balance strategies Chan, KM et al 2003 Spector et al 1996 Twist and Ma 1986

9. Aerobic and Neuromuscular Training: Effect on the Capacity, Efficiency, and fatigability of Patients with Traumatic Brain Injuries - Louis W. Jankowski, PhD, S. John Sullivan, PhD Purpose: To determine the feasibility and effects of exercise training in an unselected group of sedentary TBI volunteers.

10. Methods:14 adults(13M & 1F) with TBI were referred to the physical fitness program by their health professionals after completing formal physical and occupational therapy programs. Physical fitness program: Performed 3x per week, on alternate days, for 16 consecutive weeks. Concurrent with this investigation, six of the subjects continued working in a protected workshop vocational rehabilitation program.

11. Methods Continued Pre and post treatment measures: weight, BP, skin fold thickness, grip strength, abdominal muscular endurance, submax and peak VO2 were measured, and the index of physiological fatigue (IPF) was calculated. VO2 were measured during a modified Balke treadmill test protocol with an open circuit system Fatigability involves both physiologic efficiency and oxidative capacity. IPF was then calculated to integrate these causal elements and assess the effects of exercise training on the fatigability of TBI patients.

12. Index of Physiologic Fatigability (IPF) IPF= Normalized oxygen cots of locomotion Normalized aerobic capacity Example IPF= observed VO2 walking x Normal VO2max Normal VO2 walking x Observed VO2 Peak =15.4 x 49/ 10.5 x 32.8 =754.6/344.4= 2.19 Interpretation: Patient would be expected to fatigue 2.2x more rapidly than a nondisabled patient Note: Normal values for VO2 walking and VO2max are from the ACSM guidelines.

13. Training Training Session: included traditional warm up exercise, circuit training, a short game, and a cool down relaxation period. -Training intensity assigned to each subject was 70% of theoretical maximal value and target HR were prescribed accordingly. Exercise program involved both aerobic exercise and neuromuscular conditioning (10 stations total) -Aerobic training stations: stationary cycling, rope skipping, jogging, and stair climbing -Neuromuscular conditioning: basket shooting, ring tossing, three pin bowling, dribbling drills, weight lifting, and calisthenics. Patients performed the same amount of time at each station in rapid succession. Patients initially exercised for 20minutes (2min each station), but during the next 6 weeks, the exercise time at each station was gradually extended to 9min totaling 45min of aerobic exercise and 45min neuromuscular training in an exercise period which was approximately 2 hours.

14. Results: No significant change in body weight, composition, grip strength, or oxygen cost of walking were observed Significant changes were observed in abdominal muscular endurance(92%↑), peak VO2 (15.4% ↑), and IPF(17%↓; 2.62 to 2.18). IPF interpretation: Assuming that a normal person has an IPF of 1.0 manifests a normal degree of fatigue after having performed a standard 8hr workday, the average subject in this study theoretically increased their ability to work from 3.05hr to 3.67hr before manifesting normal fatigue.

15. Conclusion: A circuit aerobic training program of moderate intensity increases the average capacity of oxygen consumption of patients with TBI. The IPF is practical and may be used in the assessment, evaluation, and vocational placement of brain damaged individuals. Many patients with TBI have cognitive deficits, but they can perform unskilled manual labor. Aerobic training, which may increase oxidative capacity and reduce fatigability, seems essential to their successful vocational rehabilitation. TAKE HOME MESSAGE : TBI patients are capable of exercising for prolonged periods of time. It is up to the PT to monitor patient fatigue levels and ensure that patients maintain their motivational levels. Aerobic and neuromuscular exercises can improve function and decrease disability levels in TBI patients with moderate-intensity aerobic exercise..

16. Pain, fatigue, and intensity of practice in people with stroke who are receiving constraint-induced movement therapy (Underwood et al. 2006) Purpose: To determine if there was a relationship among pain, fatigue, intensity, and function in people receiving CI therapy. CI Therapy: Intensive task practice with multiple repetitions to achieve a challenging motor goal. Intensity: High 6hr 5x a week for 2 weeks Fatigue: measured on a scale of 1-10, 1indicating no fatigue and 10 indicating absolute exhaustion

17. Pain, Fatigue, and intensity cont. • Upper Extremity motor function: Function was measured with the Wolf Motor function test before and after CI Therapy. • WMFT consist of 15 timed performance items (max time=120s) and 2 strength items • Results: Upper extremity motor function improved. - No significant increase in fatigue levels during CI Therapy -Expected outcome average levels of fatigue were higher at the end of daily therapy as compared to average fatigue at the end of morning therapy

18. Pain, Fatigue, and intensity cont. • Clinical Implications: Patients are capable of participating in exercise training without aggravating their symptoms of fatigue. • Physical therapist must continually monitor patients levels of fatigue

19. Multiple Sclerosis • Definition – Multiple sclerosis is an autoimmune disease that affects the brain and spinal cord (central nervous system). MS demyelinates neurons. • One of the most prominent and perhaps worse symptoms is fatigue • No definitive pathogenesis factor behind fatigue • Primary Fatigue • CNS: influence unclear • Maybe due to demyelination, inflammation or axonal loss Kos et al, 2008

20. Exercise and fatigue in MS patients • One study showed that progressive cycling resistance training led to improved scores on the FSS in subjects with MS • Another study showed that aerobic training in patients with MS led to improvements in VO2max, increase in work rate, and activity level, but showed a tendency to less fatigue. • Frequency: 5 - 30 min sessions per week • This goes to show that just because MS patients have a high risk of fatigue, it does not mean they should not exercise. • But too much can be dangerous… Cakt BD, et al, 2010 S Mostertn, Multiple Sclerosis, 2002

21. Overwork Weakness - a real danger for MS patients • Definition - Prolonged decrease in absolute strength & endurance as a result of excessive activity of partially denervated muscle. • Many pts may not be able to get out of bed the next day & may have to spend a few days in bed following an exhaustive exercise session. DOMS is common in patients with overwork weakness peaking between 1-5 days post activity. • It is important for the PT to monitor and slowly progress the exercise program O’Sullivan, 2007

22. Recent RCT’s with defined exercise protocols & MS type • Effect of aerobic training on walking capacity & maximal exercise tolerance in Patients with MS (2007-Physical Therapy) • Study concluded that with aerobic training, subjects showed improved walking distances and speeds, maximum work rate, peak oxygen uptakes and oxygen pulse • More disabled individuals showed more improvement than healthier subjects. • Long-term benefits of exercising on quality of life and fatigue in MS patients with mild disability: a pilot study (2008-Clinical Rehabilitation) • Exercise participants showed improvements in exercise capacity as well as improvements in fatigue. Rampello et. al., 2007 McCullagh et. al., 2008

23. The Big Picture • Exercise can be beneficial for patients with NMD, and should be implemented • Progress and fatigue should be monitored and care should be taken to ensure the patient is not worked too hard • Studies have shown that resistance training can even improve fatigue in MS patients • Fatigue dropped 0.6 on the FSS after progressive resistance training • Improved function and decreased disability were manifested in patients with TBI after neuromuscular and aerobic training Dalgas U, 2010

24. General exercise recommendations for patients with NMDs • Intensity: 60-70% VO2max or a rating of 13 (“somewhat hard”) on the Borg RPE Scale is recommended • Any higher intensities are contraindicated • Frequency: 3 days/week while balancing exercise with rest • Emphasize energy conservation, activity pacing, and stress management O’Sullivan and Schmitz, 2007

25. Learning Objectives • At the end of this presentation the audience will be able to: • Define fatigue and differentiate fatigue from exhaustion • Describe exercise that is beneficial for post-polio patients and for patients that have TBI, as well as the effects of fatigue • Describe what effects constraint induced movement therapy has on fatigue and WMFT • Describe the benefits that exercise may have on patients with MS • Explain the implications of overworking MS patients • Discuss whether exercise is indicated for patients with NMD

26. References • Cakt BD, Nacir B, Genç H, Saraçoğlu M, Karagöz A, Erdem HR, Ergün U. (2010 March 3). Cycling Progressive Resistance Training for People with Multiple Sclerosis: A Randomized Controlled Study. Am J Phys Med Rehabil. • Chan KM, Amirjani N, Sumrain M, Clarke A, Strohschein FJ. (2003 March) Randomized controlled trial of strength training in post-polio patients. Muscle Nerve. 27(3):332-8 • Dalgas U, Stenager E, Jakobsen J, Petersen T, Hansen H, Knudsen C, Overgaard K, Ingemann-Hansen T.(2010) Fatigue, mood and quality of life improve in MS patients after progressive resistance training. Multiple sclerosis OnlineFirst. doi:10.1177/1352458509360040 • Fatigue Severity Scale. (2008, January). http://www.mult-sclerosis.org/fatigueseverityscale.html • Jankowski LW, & Sullivan SJ. (1990). Aerobic and neuromuscular training: effect on the capacity, efficiency, and fatigability of patients with traumatic brain injuries. Archives of Physical Medicine and Rehabilitation. 71(7), 500-4 • Kos, D, Kerckhofs, E, Nagels, G. D’hooghe, MB,Ilsbroukx, S.(2008) Origin of fatigue in multiple sclerosis:review of the literature. Neurorehabil Neural Repair 2008;22: 91–100. • McCullagh, R., Fitzgerald, A., Murphy, R., & Mater, G. (2008, March). Long-term benefits of exercising on quality of life and fatigue in multiple sclerosis patients with mild disability: a pilot study. Clinical Rehabilitation, 22(3), 206-214. • Morrison Morrison, E., Cooper, L., White, Larson, J., Leu,S., Zaldivar,F., Ng, A. (2008, Aug.) Ratings of perceived exertion during aerobic exercise in multiple sclerosis. Archives of Physical Medicine and Rehabilitation; 89 (8),1570-1574. • Mostert S, Kesselring J. (2002) Effects of a short-term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis. Multiple Sclerosis, Vol. 8, No. 2, 161-168

27. References • Oncu, J., Durmaz, B., & Karapolat, H. (2009, February). Short-term effects of aerobic exercise on functional capacity, fatigue, and quality of life in patients with post-polio syndrome. Clinical Rehabilitation, 23(2), 155-163. Retrieved April 30, 2009, from Academic Search Premier database. • O’Sullivan, S.B., Schmitz, T.J. (2007). Physical Rehabilitation. Philadelphia: F.A. Davis Company. • Pain, Fatigue, and Intensity of Practice in People With Stroke Who Are Receiving Constraint-Induced Movement Therapy. (2006, September). Physical Therapy, Retrieved April 30, 2009, from Academic Search Premier database • Rampello, A., Franceschini, M., Piepoli, M., Antenucci, R., Lenti, G., Olivieri, D., et al. (2007, May). Effect of aerobic training on walking capacity and maximal exercise tolerance in patients with multiple sclerosis: a randomized crossover controlled study. Physical Therapy, 87(5), 545-555. • Rietberg MB, Brooks D, Uitdehaag BMJ, Kwakkel G. Exercise therapy for multiple sclerosis. Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No.: CD003980.10.1002/14651858.CD003980.pub2. • Spector Sidney A., Gordon Patricia L., Feuerstein Irwin M., Sivakumar Kumaraswamy,. Hurley Ben F, Dalakas Marinos C.. (1996) Strength gains without muscle injury after strength training in patients with postpolio muscular atrophy, Muscle & Nerve, 19(10), 1282-1290 Retrieved April 30, 2009, from Pubmed • Twist, D.J., Ma, D.M. Physical therapy management of patients with post-polio syndrome. Physical Therapy 1986; 66: 1403-1406.