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PREDICTORS of POST-STROKE FATIGUE by Benjamin Yichen

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PREDICTORS of POST-STROKE FATIGUE by Benjamin Yichen PREDICTORS OF POST-STROKE FATIGUE BY Benjamin Yichen Tseng M.S. Wichita State University, Kinesiology and Sport Studies M.A. Wichita State University, Elliott School of Communication B.A. Wichita State University, Elliott School of Communication Submitted to the graduate degree program in Physical Therapy and Rehabilitation Science and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy __________________________________ Patricia Kluding, PT, Ph.D (Chairperson) __________________________________ Byron Gajewski, Ph.D __________________________________ Wen Liu, Ph.D __________________________________ Jeff Burns, MD. __________________________________ Jeff Radel, Ph.D __________________________________ Date of Dissertation Defense The Dissertation Committee for Benjamin Yichen Tseng certifies that this is the approved version of the following dissertation: PREDICTORS OF POST-STROKE FATIGUE Committee __________________________________ Patricia Kluding, PT, Ph.D (Chairperson) __________________________________ Byron Gajewski, Ph.D __________________________________ Wen Liu, Ph.D __________________________________ Jeff Burns, MD. __________________________________ Jeff Radel, Ph.D __________________________________ Date Approved ii Acknowledgements I dedicate this dissertation to my father, a brave, relentless fighter who snickered at all the adversities that unpredictably occurred in his life: Thank you, for being the most influential man in my life. You are a scholar, a philosopher, a poet, a visionary, an avid tennis player, an outstanding speaker, and also a very demanding math teacher with abundance of discipline. More importantly, you are a survivor. You survived the poverty of being born in a fisherman’s house with 8 children; you survived school teachers’ belittling of your family’s financial hardship; you survived Chiang Kai-Shek’s “white horror” and Kuomintang’s censorship in the name of national security; you survived cirrhosis; and you even survived a hemorrhagic stroke after a 10-day coma. You’ve worked hard your entire life to provide, but never had a day to enjoy life before stroke struck. After such life-changing event, you told me you decided to speak nothing but the truth, because you only have time for people who aren’t afraid to learn about themselves. Some might label you as eccentric, that’s because they can’t see what you see; and they will never benefit from what you have to offer – a invaluable lesson about life. It took me long time to understand you way; now I know how much I appreciate it. Thank you for all you’ve done. You are my Hero. Next, to my mother. Thank you for your unconditional love! The decision to send a pre-adolescent son away to a foreign continent for education had to be iii immensely difficult for a loving mother. I hope I’ve done something you can be proud of; my only regret would be the years we missed together. To my dear wife and moral compass, Debbie: Thank you for being there and putting up with me for the last 15 years (and my never-ending education and seemingly-effortless schedule). No one else in the world understands me like you do; and I’m a better person because of you. How much luck does a man need to be married to the love of his life, who also happens to be his best friend? To my mentor, Patty: I cannot be more grateful to have you as my mentor. Thank you for nurturing me with the perfect balance of flexibility and discipline, exactly what I needed, for the last few years. And thank you for all of your patience and support, and for providing me such exceptional learning environment. To my dissertation committee; thank you for your feedback and suggestions to make this dissertation project better. Also, thank you for challenging me to think critically. To Kiwi, who spent as much time napping under my desk as me writing at my desk: thank you for staying by my side through those lonely hours of writing after dark, I promise to take you to the park and walk you more often when I get my life back, if I get my life back. To the Kluding Krew: Sandy, Jason, Steve, Rupali, and Rachel. Thank you for your feedback; we have an incredible lab group. To Liliya, you made my summer a lot more productive. Thank you for all of your help with my project. iv To Eric, thank you for putting up with my disconnected sense of humor and language barrier. And certainly thank you for looking after that noobie who had no clues. How many pints of Guinness do I owe you anyway? To Kelli, Rose, Lindsay, Jodi, Judy, Joel, and the rest of the GCRC staff, thank you for making the exercise testing easy. This project could not be done without your incredible skill of taking blood pressure while subject is exercising and peddling at full throttle. v Table of Contents Acknowledgements iii Table of Contents vi List of Table and Figures ix Chapter 1 Introduction 1.1 Overview 2 1.2 Stroke 3 1.3 Fatigue 5 1.3.1 Historic View 5 1.3.2 Fatigue Redefined 5 1.3.3 Fatigue Models 7 1.3.4 Fatigue Classifications 10 1.4 Fatigue Scales 12 1.4.1 Previous Fatigue Scales 12 1.4.2 Measuring Chronic Fatigue 14 1.4.3 Measuring Exertion Fatigue 16 1.5 Post-Stroke Fatigue 18 1.6 Contributing Factors to PSF 21 1.6.1 Overview of Potential Factors 21 1.6.2 Aerobic Fitness 22 1.6.3 Physical Impairment 23 1.6.4 Depression 26 vi 1.6.5 Lesion Characteristics 28 1.6.6 Sleep Disorders 30 1.6.7 Medication Side Effects 31 1.7 Distinction of Experimental Design 32 1.7.1 Visual Analog Fatigue Scale 32 1.7.2 Real-Time Fatigue Assessment 33 1.8 Significance of the Presented Work 34 1.9 Specific Aims and Statement of Hypotheses 35 Tables and Figures 38 Chapter 2 Preface 42 Reliability, Responsiveness and Validity of the Visual Analog Fatigue Scale to Measure Exertion Fatigue in People with Chronic Stroke 2.1 Abstract 44 2.2 Introduction 46 2.3 Methods 49 2.4 Results 54 2.5 Discussion 55 2.6 Conclusion 58 Tables and Figures 59 Chapter 3 Preface 67 Predictors of Exertion Fatigue in People Post-Stroke vii 3.1 Abstract 69 3.2 Introduction 71 3.3 Methods 75 3.4 Results 81 3.5 Discussion 81 3.6 Conclusion 86 Tables and Figures 88 Chapter 4 Preface 94 Predictors of Chronic Fatigue in People Post-Stroke 4.1 Abstract 96 4.2 Introduction 97 4.3 Methods 101 4.4 Results 106 4.5 Discussion 107 4.6 Conclusion 113 Tables and Figures 114 Chapter 5 Discussion and Conclusions 5.1 Summary of Findings 122 5.2 Possible Mechanisms for Post-Stroke Fatigue 124 5.3 Limitations 128 5.4 Clinical Implications 133 5.5 Future Directions 136 viii 5.6 Conclusions 140 Table and Figures 141 References 142 Appendix I 153 Appendix II 154 Appendix III 155 List of Tables and Figures Chapter 1 Figure 1.1 Piper’s Original Fatigue Model 38 Figure 1.2 Portenoy’s Integrated Fatigue Model 39 Figure 1.3 Piper’s Dichotomy Fatigue Model 40 Figure 1.4 Factors Contributing to Post-Stroke Fatigue 41 Chapter 2 Figure 2.1 Visual Analog Scale and the VAFS 60 Figure 2.2 VAFS Measures from Visit 1 & 2 61 Figure 2.3 Bland-Altman Plot of the VAFS Scores 62 Figure 2.4 Relationship between Exertion Fatigue and Heart Rate 63 igure 2.5 Relationship between Exertion Fatigue and Blood Pressure 64 Table 2.1 Participant Characteristics 65 Table 2.2 Intraclass Correlation Coefficient of the VAFS 66 Chapter 3 Figure 3.1 Relationship between Recovery Rate and Exertion Fatigue 88 ix Figure 3.2 Relationship between Recovery Rate and VO2peak 89 Table 3.1 Participant Characteristics 90 Table 3.2 Outcome Measure Values 91 Table 3.3 Relationship between Variables 92 Table 3.4 Regression Model for EF 93 Chapter 4 Figure 4.1 Relationship between Chronic Fatigue and Depression 114 Figure 4.2 Relationship between Real-Time Chronic Fatigue and Depression 115 Table 4.1 Participant Characteristics 116 Table 4.2 Outcome Measure Values 117 Table 4.3 Relationship between Variables 118 Table 4.4 Regression Model for CF 119 Table 4.5 Difference in Fatigue and Depression between Genders 120 Chapter 5 Figure 5.1 Exertion and Chronic Fatigue Models 141 x Chapter 1 Introduction 1 1.1 Overview In 2005, stroke was the cause for 5.7 million deaths worldwide and was identified as the second leading cause of death by the World Health Organization (WHO).1 In the United States, stroke is considered as the most life-threatening neurological disorder and accounts for one of every fifteen deaths.2 It has also been identified as the third leading cause of death and the first leading cause of disability in order adults.3 Reports indicate that more than 780,000 new strokes occur each year in the United States.4 Many survivors of stroke require extensive care,5 and the health consequences of stroke have a substantial economic impact on not only the individual and family, but also on the society.6 Stroke can lead to loss of function both physically and cognitively,7 and the severity of stroke dictates the severity of disablement. Depending on the lesion size and location, the injury to the brain can affect multiple systems.8 These include motor and sensory impairments and language, perception, affective, and cognitive dysfunction.9 Physical symptoms of stroke usually include weakness or paralysis. Most survivors of stroke show some residual loss of function on either the right or left side of the body, referred to as hemiplegia or hemiparesis.10 Secondary conditions in people post-stroke include a higher incidence of injury from falls, spasticity, memory loss, aphasia, sleep apnea, back pain, stress, and social isolation,9, 11 while some of the common co-morbidities may include coronary heart disease, obesity, hypertension, type 2 diabetes, and hyperlipidemia.12 In addition, it has been shown that up to 60% of people post-stroke can develop 2 depression;13 and there has been reported a high incidence rate of fatigue in people post-stroke as well.11, 14-16 Only recently, researchers have acknowledged the negative impact of post- stroke fatigue (PSF);11, 17-19 and the causes of PSF appear multi-factorial.20 However, PSF remains under-recognized and under-treated due to limited comprehensive investigation, although PSF is potentially a major public health concern.
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