NEGOTIATING A PROGRESS PARADOX: THE VALUE OF EXERCISE FOR PEOPLE LIVING WITH AMYOTROPHIC LATERAL SCLEROSIS by Laura Jane Sawula A thesis submitted to the School of Kinesiology & Health Studies In conformity with the requirements for the degree of Master of Science Queen’s University Kingston, Ontario, Canada (August, 2017) Copyright © Laura Jane Sawula, 2017 Abstract Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease that leads to the paralysis of voluntary muscles used for walking, talking, eating and breathing. There is no cure for ALS and current treatments, including exercise therapies, are extremely limited (Kiernan et al., 2011). The first of two studies presented herein aimed to examine the tolerance and training effects of modified sprint interval training (SIT) for people with ALS. Despite an available population and persistent efforts, one participant completed the training study over eighteen months. For this individual, SIT was well tolerated acutely and chronically, and functional capacity and aerobic fitness were unchanged following six weeks of home-based SIT training. The inability to recruit sufficient participants for this intervention trial called into question how individuals living with ALS negotiate exercise and barriers to participation. A second study guided by interpretive phenomenology used in-depth interviews to better understand how everyday experiences of living with ALS impact the ways individuals with ALS engaged with physical activity and exercise. From the subjective accounts of seven men and women living with ALS in Southeastern Ontario, three major themes were identified: 1) living in a changing body, 2) environmental access and 3) the (f)utility of exercise, which speak to the complex process of negotiating the value of exercise for a body that is progressively and incurably deteriorating. Findings suggest there is immense variability and individuality amongst people with ALS and their experiences and attitudes towards physical activity and exercise. Numerous physical, psychological and environmental barriers were also found to be common to people with ALS and may serve as targets to be addressed by future customized exercise interventions. ii Dedication I have endless gratitude for the eight individuals who shared their time, stories and experiences that contributed to this thesis. My understanding of ALS has been forever changed by each of you. iii Acknowledgements I would like to extend my sincerest gratitude to Dr. Brendon Gurd, Dr. Matti Allen and Dr. Sean Taylor, it was a privilege to benefit from your mentorship. Brendon, thank you for your sound advice, feedback and willingness to support an endeavor outside your area of expertise. I appreciate your humour, guidance and reassurance when I had my doubts. Thank you, Matti, for your thoughtful check-ins, diligent revisions and genuine support over the last two years. I admire your positivity, approachability and work ethic. Sean, thank you for graciously tolerating a human shadow, connecting me with participants and allowing me to gain valuable insight to the clinical treatment of ALS. To Dr. Scott Carey and my colleagues in qualitative research methods, thank you for making me feel welcome and opening my mind to new ideas. Week after week I developed a better understanding and appreciation of different approaches to knowledge production. This experience was instrumental in the way I came to see the value of my thesis work. To Brittany, Jacob, Hashim and Mike, thank you for being the most fun and fit lab in the SKHS. I can always count on the Gurd Lab for a good laugh, spontaneous workout or baseball story that I don’t understand. The passion and dedication you each have for your work is truly inspiring and I wish each of you the absolute best in the future. To my support system outside of the lab, I thank the people and pups of CrossFit Queen Street for my daily dose of gratitude and joy. Nothing keeps me grounded like playing with dogs and sweating with friends. Finally, to the real MVPs, the chicken soup for my soul- my parents, siblings, boyfriend and close friends who continuously meet my moments of weakness with sympathetic ears, words of encouragement and all the heartwarming animal videos on the internet: I am incredibly grateful for each of you. Thank you for always helping me see the positive in life. iv Table of Contents Abstract ......................................................................................................................................................... ii Dedication .................................................................................................................................................... iii Acknowledgements ...................................................................................................................................... iv List of Figures ............................................................................................................................................ viii List of Tables ............................................................................................................................................... ix List of Abbreviations .....................................................................................................................................x Chapter 1 Introduction ...................................................................................................................................1 1.1 General Introduction ............................................................................................................................1 1.2 Thesis Organization .............................................................................................................................2 1.3 References ............................................................................................................................................2 Chapter 2 Literature Review ..........................................................................................................................4 2.1 Introduction ..........................................................................................................................................4 2.2 Neuromuscular Physiology ..................................................................................................................5 2.3 Mechanisms of Disease ........................................................................................................................9 2.4 Clinical Phenotypes and Functional Decline .....................................................................................11 2.5 Current Treatment and Therapeutic Strategies ..................................................................................14 2.6 Exercise and ALS ..............................................................................................................................15 2.6.1 Exercise Therapy and Animal Models of ALS ...........................................................................16 2.6.2 Exercise Therapy in Human Patients with ALS .........................................................................18 2.7 Barriers and challenges for the use of exercise as therapy ................................................................21 2.8 Thesis Hypotheses .............................................................................................................................22 2.9 References ..........................................................................................................................................22 Chapter 3 The Effect of Modified Sprint Interval Training in ALS ............................................................29 3.1 Introduction ........................................................................................................................................29 3.2 Methods..............................................................................................................................................30 3.2.1 Participants ..................................................................................................................................30 3.2.2 Experimental Design ...................................................................................................................31 3.2.2.1 Phase I: Acute exercise tolerance and fatigue. .....................................................................31 3.2.2.2 Phase II: Six-week sprint interval stair climbing .................................................................32 3.2.2.3 Home-based Training ...........................................................................................................33 3.3 Results ................................................................................................................................................33 3.3.1 Participant Characteristics ..........................................................................................................33 v 3.3.2 Acute Tolerance and Fatigue ......................................................................................................34 3.3.3 Home-based Training ..................................................................................................................35 3.4 Discussion ..........................................................................................................................................36 3.4.1 Acute exercise tolerance .............................................................................................................36 3.4.2 Rating of Perceived Exertion ......................................................................................................37 3.4.3 Six weeks of home-based training ..............................................................................................38 3.4.4 Recruitment Limitations .............................................................................................................39 3.4.4 Barriers to exercise for individuals with ALS ............................................................................40 3.5 Conclusion .........................................................................................................................................40 3.6 References ..........................................................................................................................................41 Chapter 4 Revising the Research Question ..................................................................................................44 4.1 Introduction ........................................................................................................................................44 4.2 Personal Reflection ............................................................................................................................44 4.2 From Physiology to Phenomenology .................................................................................................45 4.4 Interactions, self-identity and choice .................................................................................................48 4.5 The Study of Chronic Illness .............................................................................................................49 4.6 ALS: Chronic and Terminal ...............................................................................................................50 4.7 Conclusion .........................................................................................................................................52 4.8 References ..........................................................................................................................................54 Chapter 5 Living and Exercising with ALS: Exploring a Progress Paradox ...............................................56 5.1 Introduction ........................................................................................................................................56 5.2 Methods..............................................................................................................................................57 5.2.1 Research Design and Methodology ............................................................................................57 5.2.2 Ethical Considerations ................................................................................................................57 5.2.3 Recruitment .................................................................................................................................58 5.2.4 Data Gathering and Analysis ......................................................................................................58 5.3 Findings .............................................................................................................................................59 5.3.1 Living in a changing body ..........................................................................................................60 5.3.1.1 Bodily Uncertainty ...............................................................................................................60 5.3.1.2 Protecting Self ......................................................................................................................61 5.3.1.3 Self as Expert .......................................................................................................................63 5.3.2 Environmental Access ................................................................................................................65 5.3.3 (F)utility of Exercise ...................................................................................................................67 5.4 Discussion ..........................................................................................................................................69 vi 5.4.1 The Erratic Body .........................................................................................................................69 5.4.2 Environmental Considerations ....................................................................................................70 5.4.3 Evaluating the Usefulness of Exercise ........................................................................................72 5.4.4 Implications for Exercise in ALS ...............................................................................................73 5.4.5 Limitations ..................................................................................................................................75 5.5 Conclusion .........................................................................................................................................76 5.6 References ..........................................................................................................................................76 Chapter 6 General Discussion ......................................................................................................................80 6.1 Summary of Key Findings .................................................................................................................80 6.2 Responding to the Call for Further Randomised Trials .....................................................................80 6.3 Strengths ............................................................................................................................................82 6.4 Limitations .........................................................................................................................................83 6.5 Future Directions ...............................................................................................................................83 6.6 MSc. Research Experience ................................................................................................................84 6.7 Conclusion .........................................................................................................................................85 6.8 References ..........................................................................................................................................85 Appendix A : Research Ethics Board- Letter of Informed Consent ...........................................................87 Appendix B : Research Ethics Board- Letter of Approval .........................................................................97 Appendix C : Research Ethics Board- Amendment Approval ...................................................................99 Appendix D : ALSFRS-R .........................................................................................................................100 Appendix E : Fatigue Severity Scale ........................................................................................................104 Appendix F : Interview Guide ..................................................................................................................105 Appendix G : Recruitment Hand-out ........................................................................................................107 vii List of Figures Chapter 2 Figure 1. Labelled segments of a lower motor neuron ..................................................................................5 Figure 2. Schematic of upper motor neuron (purple) synpasing on lower motor neuron (blue) ...................5 Figure 3. Schematic illustrations of A; small, B; medium and C; large motor units. Cell body and number of fibers increasing with size .........................................................................................................................6 Figure 4. Schematic cross-section of a bicep muscle belly. A: fibers from small MUs B: fast-oxidative fibers from medium Mus, C: fast-glycolytic fibers of large MUs .................................................................6 Figure 5. Schematic illustrating motor unit action potential (MUP) under normal conditions, spontaneous activity of fibrillations during early denervation and a polyphasic MUP resulting from collateral reinnervation. (Taylor, 2016) .........................................................................................................................8 Figure 6. Muscle atrophy consistent with ALS A: deltoid wasting B: Loss of supraspinatus, infraspinatus and deltoid C: Wasting of the thenar muscles between the thumb and first finger D: wasting of the tongue, difficulty with mouth-opening (Kiernan et al., 2011) ..................................................................................12 Figure 7. Depicting the somatotopic organization of the spinal motor neurons (Purves et al., 2001) .........12 Figure 8. Depicting the somatotopic organization of the motor cortex (Purves et al., 2001) ......................13 Chapter 4 Figure 9. Simplified model of how constructs may influence one another in the negotiation of lived experience ....................................................................................................................................................48 Figure 10. Model of ‘ongoing change and adaptation’ developed by King et al (2009). ............................53 viii List of Tables Chapter 2 Table 2.1 Exercise and ALS trials in animal models ...................................................................................17 Table 2.2 Exercise intervention studies in human ALS ...............................................................................20 Chapter 3 Table 3.1 Participant Characteristics ...........................................................................................................34 Table 3.2 Acute Tolerance to Exercise Bouts ..............................................................................................34 Table 3.3 Daily activity by intensity level ...................................................................................................35 Table 3.4 Percentage of daily activity by intensity level .............................................................................35 Chapter 4 Table 4.1 Descriptive and Interpretive Phenomenology ..............................................................................46 Table 4.2 Summary of select studies investigating the experience of ALS .................................................51 ix List of Abbreviations ALS- Amyotrophic Lateral Sclerosis ALSFRS-R- Revised Amyotrophic Lateral Sclerosis Functional Rating System EMG- Electromyography END- Endurance FSS- Fatigue Severity Scale HCP- Healthcare Professional HR- Heart Rate HRR- Heart Rate Reserve LMN- Lower Motor Neuron MN- Motor Neuron MND- Motor Neuron Disease PSW- Personal Support Worker QoL- Quality of Life RCT- Randomized Controlled Trial RPE- Rating of Perceived Exertion RPM- Revolutions Per Minute SIT- Sprint Interval Training SMEP- Strictly Monitored Exercise Program UCP- Usual Care Program UMN- Upper Motor Neuron VAFS- Visual analogue fatigue scale VO2 peak- Peak Volume of Oxygen 8UG- 8-foot Up and Go Test x