Medicine, Faculty of
Medicine, Department of
DSpace
UBCV
Deegan, Emily Grace
Master of Science - MSc
University of British Columbia
Introduction and Objective: Near infrared spectroscopy (NIRS) is a noninvasive method of measuring oxygen recovery kinetics in skeletal muscle. NIRS detects changes in oxygenated (O₂Hb) and deoxygenated (HHb) hemoglobin in response to exercise, to provide interpretation of muscular capacity to restore incurred oxygen debt. Assessment of pelvic floor muscle (PFM) function is central to managing urinary incontinence (UI) and lower urinary tract symptoms (LUTS) but currently lacks oxygen kinetic parameters. This project aims to develop a NIRS probe that measures oxygen kinetics of bilateral PFM in females with UI/LUTS (cases) related to altered pelvic innervation compared to continent controls. Methods: A transvaginal NIRS prototype to detect bilateral PFM was developed. The vaginal NIRS probe monitored female volunteers during sustained PFM contraction (SMVC). O₂Hb, HHb and HbDiff (O₂Hb-HHb) allowed measurement of oxygen kinetics unique to bilateral PFM. Oxygen recovery kinetics determined by HbDiff half recovery time (½RT). PFM manometry assessed SMVC peak and average cmH₂O. Home-based 8-week PFM therapy (PFMT) intervention was performed by both participant groups and an exercise diary measured adherence, determined as total percentage of volume and frequency. Results: Observational NIRS findings demonstrated typical hemodynamic and ½RT responses in controls. Case group demonstrated atypical findings consistent with impaired muscle function. NIRS found quicker ½RT for controls (7.87 vs 38.03 seconds, p 0.01). Manometer detected greater PFM strength and endurance in controls (SMVC peak 35 vs 13 cmH2O, p <0.01, SMVC average 23 vs 10 cmH₂O, p 0.02). Intra-group improvements of PFM NIRS and manometer variables after PFMT were not determined. Post-PFMT ½RT in cases was highly correlated to SMVC peak and average cmH2O (r -0.83 and r -0.82, respectively). High adherence of PFMT frequency demonstrated in cases, 78%, which correlated to SMVC peak and average cmH₂O (rs 0.78 and rs 0.88, respectively), ½RT (rs -0.85) and reduced urgency (rs -0.85). Conclusions: This study shows the feasibility of NIRS to provide novel physiologic data regarding PFM function. PFM oxygen kinetics could provide more insight into PFM pathology and PFMT rehabilitation. Further refinement of the NIRS probe is required for use in larger studies with PFMT interventions incorporating adjunctive therapies.
BILATERAL MEASUREMENT OF PELVIC FLOOR MUSCLE DYSFUNCTION IN FEMALES WITH LOWER URINARY TRACT SYMPTOMS USING NEAR INFRARED SPECTROSCOPY by Emily Grace Deegan B.A., The University of Western Ontario, 2009 B.Sc.N., The University of Toronto, 2011 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) March 2019 © Emily Grace Deegan, 2019 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, a thesis/dissertation entitled: Bilateral measurement of pelvic floor muscle dysfunction in females with lower urinary tract symptoms using near infrared spectroscopy submitted by Emily Deegan in partial fulfilment of the requirements for the degree Master of Science in Experimental Medicine Examining Committee: Lynn Stothers, Urological Sciences Supervisor Andrew Macnab, Urological Sciences Supervisory Committee Member Supervisory Committee Member Gary Gray, Division of Urology Additional Examiner Additional Supervisory Committee Members: Tania Lam, School of Kinesiology Supervisory Committee Member iii Abstract Introduction and Objective: Near infrared spectroscopy (NIRS) is a noninvasive method of measuring oxygen recovery kinetics in skeletal muscle. NIRS detects changes in oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin in response to exercise, to provide interpretation of muscular capacity to restore incurred oxygen debt. Assessment of pelvic floor muscle (PFM) function is central to managing urinary incontinence (UI) and lower urinary tract symptoms (LUTS) but currently lacks oxygen kinetic parameters. This project aims to develop a NIRS probe that measures oxygen kinetics of bilateral PFM in females with UI/LUTS (cases) related to altered pelvic innervation compared to continent controls. Methods: A transvaginal NIRS prototype to detect bilateral PFM was developed. The vaginal NIRS probe monitored female volunteers during sustained PFM contraction (SMVC). O2Hb, HHb and HbDiff (O2Hb-HHb) allowed measurement of oxygen kinetics unique to bilateral PFM. Oxygen recovery kinetics determined by HbDiff half recovery time (½RT). PFM manometry assessed SMVC peak and average cmH2O. Home-based 8-week PFM therapy (PFMT) intervention was performed by both participant groups and an exercise diary measured adherence, determined as total percentage of volume and frequency. Results: Observational NIRS findings demonstrated typical hemodynamic and ½RT responses in controls. Case group demonstrated atypical findings consistent with impaired muscle function. NIRS found quicker ½RT for controls (7.87 vs 38.03 seconds, p 0.01). Manometer detected greater PFM strength and endurance in controls (SMVC peak 35 vs 13 cmH2O, p <0.01, SMVC iv average 23 vs 10 cmH2O, p 0.02). Intra-group improvements of PFM NIRS and manometer variables after PFMT were not determined. Post-PFMT ½RT in cases was highly correlated to SMVC peak and average cmH2O (r -0.83 and r -0.82, respectively). High adherence of PFMT frequency demonstrated in cases, 78%, which correlated to SMVC peak and average cmH2O (rs 0.78 and rs 0.88, respectively), ½RT (rs -0.85) and reduced urgency (rs -0.85). Conclusions: This study shows the feasibility of NIRS to provide novel physiologic data regarding PFM function. PFM oxygen kinetics could provide more insight into PFM pathology and PFMT rehabilitation. Further refinement of the NIRS probe is required for use in larger studies with PFMT interventions incorporating adjunctive therapies. v Lay Summary Many women experience involuntary urinary leakage related to pelvic floor nerve injury. Assessment of pelvic floor muscle is important aspect for managing this issue. This study developed a new method of assessment using near infrared light to measure pelvic floor muscle oxygen levels. The oxygen levels determine how well pelvic floor muscles perform during exercise. Two participant groups were in this study, females with urinary leakage related to nerve injury and females without urinary leakage or nerve injury. Participants had their pelvic floor muscles measured before and after 8-weeks of therapeutic exercise. This study found a difference in pelvic floor muscle function between the two groups and that urinary leakage symptoms were reduced after 8-weeks of therapeutic exercise. Further development of the near infrared light method to assess pelvic floor muscle oxygenation is needed to help manage urinary leakage. vi Preface This is an original thesis of independent efforts by the author, E.G. Deegan. All work was completed at the International Collaboration on Repair Discoveries (ICORD) located in the Blusson Spinal Cord Centre, affiliated with the University of British Columbia, Vancouver campus. E.G. Deegan was responsible for project coordination, participant recruitment, data collection procedures, statistical analysis and written thesis. Dr. Lynn Stothers, as acting supervisor, oversaw the grant proposal, study design, ethics proposal, participant recruitment and screening. Dr. Stothers provided her clinical and academic expertise and guidance through the span of this study, as well as assistance editing this thesis. Dr. Andrew Macnab and Dr. Tania Lam, as supervisory committee members helped to develop this project, contributed to the methods and provided feedback and edits for this thesis. Components from Chapter 1 section 1.1.3 Evaluation of PFM function, describing current methodologies of PFM assessment is part of a manuscript titled: “Quantification of pelvic floor muscle strength in female urinary incontinence: A systematic review and comparison of contemporary methodologies.” that has been published the in the journal, Neurology and Urodynamics. E.G. Deegan was responsible for the literature review, and primary manuscript composition. Dr. Alex Kavanagh and Dr. Andrew Macnab provided editorial assistance. Dr. Stothers oversaw the complete proceedings, provided guidance of literature selection and analysis, and edited the manuscript. All data obtained from this research project was approved by the UBC Clinical Research Ethics Board and Vancouver Coastal Health Research Institute under the respective Certificate numbers, H15-02040 and V15-02040. vii Table of Contents Abstract .................................................................................................................................... iii Lay Summary ........................................................................................................................... v Preface ...................................................................................................................................... vi Table of Contents .................................................................................................................... vii List of Tables.......................................................................................................................... xiv List of Figures ........................................................................................................................ xvi Abbreviations ....................................................................................................................... xviii Acknowledgements ................................................................................................................. xx Dedication .............................................................................................................................. xxi Chapter 1: Introduction ........................................................................................................... 1 1.1 Background and rationale ............................................................................................ 1 1.1.1 Urinary incontinence and pelvic floor muscle dysfunction ................................... 1 1.1.2 Pelvic floor muscle therapy.................................................................................. 3 1.1.3 Evaluation of PFM function ................................................................................. 5 1.1.4 Measurement of skeletal muscle oxygen kinetics ................................................. 7 1.2 Principles of Near Infrared Spectroscopy ..................................................................... 8 1.2.1 Development ....................................................................................................... 8 1.2.2 NIRS instrumentation .......................................................................................... 9 1.2.3 Principles of NIRS ............................................................................................. 10 1.2.3.1 Scatter ........................................................................................................... 11 1.2.3.2 Absorption ..................................................................................................... 11 viii 1.2.3.3 Pathlength ...................................................................................................... 12 1.2.4 Contribution of myoglobin and cytochrome-c-oxidase to light absorption .......... 13 1.2.5 Optical Density defined by the Beer Lambert Law ............................................. 14 1.2.6 NIRS adaptation to PFM.................................................................................... 15 1.3 Objectives and Hypotheses ........................................................................................ 17 1.3.1 Primary Aim ...................................................................................................... 17 1.3.2 Objectives ......................................................................................................... 17 1.3.3 Hypotheses ........................................................................................................ 18 Chapter 2: Methods ................................................................................................................ 19 2.1 Participants ............................................................................................................... 19 2.2 Protocol ..................................................................................................................... 20 2.3 Objective measures ................................................................................................... 23 2.3.1 Urinalysis and post void residual volume ........................................................... 23 2.3.2 Standing force plate ........................................................................................... 24 2.3.3 PFM manometry ................................................................................................ 25 2.3.4 NIRS ................................................................................................................. 27 2.4 Subjective measures .................................................................................................. 30 2.4.1 Bladder symptom questionnaires ....................................................................... 30 2.4.2 Waterloo footedness questionnaire..................................................................... 31 2.4.3 Bladder diaries................................................................................................... 31 2.5 Data analysis ............................................................................................................. 32 2.5.1 Standing force plate and WFQ ........................................................................... 32 2.5.2 SMVC focused analysis ..................................................................................... 32 ix 2.5.3 PFM manometry ................................................................................................ 33 2.5.4 NIRS ................................................................................................................. 35 2.5.4.1 Oxygen saturation patterns in response to exercise ......................................... 36 2.5.4.2 Unilateral PFM dominance based on contraction magnitude change .............. 38 2.5.4.3 Oxygen recovery kinetics in response to exercise (Half Recovery Time)........ 39 2.5.4.4 Original adaption of ½RT calculation analysis ............................................... 41 2.5.4.5 Unilateral PFM dominance based on ½RT ..................................................... 42 2.5.5 Bladder symptom questionnaires, bladder diaries and post void residual ............ 43 2.6 Statistical analysis ..................................................................................................... 44 Chapter 3: Results .................................................................................................................. 45 3.1 Participant demographics .......................................................................................... 45 3.2 Questionnaires, post void residual and bladder diary outcome measures .................... 47 3.2.1 Intra-group comparison...................................................................................... 47 3.2.2 Inter-group comparison of questionnaires and post void residual ....................... 49 3.3 Force plate, WFQ and NIRS dominance outcome measures ...................................... 50 3.3.1 Intra-group comparison...................................................................................... 50 3.3.2 Inter-group comparison...................................................................................... 52 3.4 NIRS observational outcome findings ....................................................................... 54 3.4.1 Observational NIRS findings ............................................................................. 54 3.4.1.1 Control group trends ...................................................................................... 54 3.4.1.2 Case group trends .......................................................................................... 58 3.4.1.2.1 High mobility clinical sub-group .............................................................. 59 3.4.1.2.2 Multiple Sclerosis clinical sub-group ....................................................... 63 x 3.4.1.2.3 SCI Clinical Sub-group ............................................................................ 67 3.5 NIRS objective outcome measures ............................................................................ 70 3.5.1 ½RT NIRS measurements ................................................................................. 70 3.5.1.1 Intra-group ½RT comparison ......................................................................... 70 3.5.1.2 Inter-group ½RT comparison ......................................................................... 70 3.5.2 DMag NIRS measurements ................................................................................ 74 3.5.2.1 Intra-group DMag comparison ....................................................................... 74 3.5.2.2 Inter-group DMag comparison ....................................................................... 75 3.5.3 Unilateral PFM ½RT and DMag NIRS Correlation ............................................ 79 3.5.3.1 Intra-group comparison .................................................................................. 79 3.6 Manometer objective outcome measures ................................................................... 81 3.6.1 Within assessment measurements ...................................................................... 81 3.6.1.1 Intra-group manometer comparison ............................................................... 81 3.6.2 Across assessment manometer measurements .................................................... 85 3.6.2.1 Intra-group manometer comparison ............................................................... 85 3.6.2.2 Inter-group PFM manometer comparison ....................................................... 87 3.6.3 Post-PFMT PFM manometer and NIRS dominance measures ............................ 90 3.6.4 Baseline unilateral PFM ½RT and PFM manometer measures ........................... 91 3.6.5 Post-PFMT ½RT and PFM manometer measures............................................... 92 3.7 Exercise adherence outcome measures ...................................................................... 94 3.7.1 Exercise adherence and post-PFMT PFM manometer measures ......................... 96 3.7.2 Exercise adherence correlation to questionnaire and PVR measures ................... 97 3.7.3 Exercise adherence and post-PFMT ½RT measures ........................................... 98 xi 3.7.4 Exercise adherence and post-PFMT DMag measures ....................................... 100 Chapter 4: Discussion ........................................................................................................... 102 4.1 Successful development of NIRS probe ................................................................... 102 4.2 Participant demographics ........................................................................................ 103 4.3 Observational NIRS findings ................................................................................... 105 4.3.1 Hemodynamic and oxygen kinetic response observed in heathy PFM .............. 105 4.3.2 Hemodynamic and oxygen kinetic response observed in PFM dysfunction ...... 109 4.3.2.1 High mobility clinical sub-group.................................................................. 109 4.3.2.2 MS and SCI clinical sub-groups ................................................................... 111 4.3.3 Explanations for atypical hemodynamic and oxygen kinetic response .............. 111 4.3.3.1 Innervation .................................................................................................. 111 4.3.3.1.1 Pudendal nerve innervation .................................................................... 111 4.3.3.1.2 Denervation related to pregnancy and labour .......................................... 112 4.3.3.1.3 Recruitment ........................................................................................... 112 4.3.3.1.4 Activation .............................................................................................. 113 4.3.3.2 Microvasculature ......................................................................................... 114 4.3.3.3 Contractile Intensity..................................................................................... 114 4.3.3.4 Cross Contamination ................................................................................... 115 4.3.3.5 Applicability of theoretical considerations to an individual case ................... 116 4.3.4 Objective outcome measures............................................................................ 118 4.3.4.1 Inter-group objective PFM function outcomes ............................................. 118 4.3.4.1.1 Half Recovery Time (½RT) outcomes .................................................... 119 4.3.4.1.2 Delta magnitude change (DMag) outcomes ............................................ 120 xii 4.3.4.1.3 PFM manometry outcomes .................................................................... 121 4.3.4.2 Intra-group objective PFM function outcomes ............................................. 121 4.3.4.2.1 ½RT outcomes ....................................................................................... 122 4.3.4.2.2 DMag outcomes ..................................................................................... 124 4.3.4.2.3 ½RT and DMag associated outcomes ..................................................... 125 4.3.4.2.4 PFM manometer outcomes ..................................................................... 125 4.3.4.2.5 ½RT and PFM manometer associated outcomes ..................................... 126 4.3.4.3 Lower limb and PFM dominance outcomes ................................................. 127 4.3.4.3.1 Fz and WFQ dominance outcomes ......................................................... 127 4.3.4.3.2 NIRS dominance outcomes .................................................................... 129 4.3.4.3.3 Degree of NIRS dominance and PFM manometer outcomes .................. 131 4.3.4.3.4 Degree of NIRS dominance and PFMT adherence outcomes .................. 131 4.3.4.4 QOL and clinical symptom outcomes .......................................................... 132 4.3.4.4.1 Inter-group QOL and clinical symptom outcomes .................................. 132 4.3.4.4.2 Intra-group QOL and clinical symptom outcomes .................................. 132 4.3.4.5 PFMT Adherence outcomes ......................................................................... 133 4.3.4.5.1 Adherence and reduced urgency symptoms ............................................ 135 4.3.4.5.2 Adherence and PFM function outcomes ................................................. 135 Chapter 5: Conclusion .......................................................................................................... 136 5.1 Main Findings ......................................................................................................... 136 5.2 Limitations .............................................................................................................. 138 5.3 Strengths and Future Directions ............................................................................... 142 5.4 Conclusion .............................................................................................................. 145 xiii Bibliography ......................................................................................................................... 147 Appendix A ........................................................................................................................... 169 Appendix A Methods .......................................................................................................... 169 A.1 PFMT Instruction Sheet ....................................................................................... 169 A.2 PFMT Recording Sheet ....................................................................................... 170 A.3 Bladder Diary ...................................................................................................... 171 A.4 Questionnaire for Urinary Incontinence Diagnosis (QUID).................................. 172 A.5 Urogenital Distress Inventory Short Form (UDI-6) .............................................. 173 A.6 Incontinence Impact Questionnaire Short Form (IIQ-7) ....................................... 174 A.7 Subjective Assessment of Improvement............................................................... 175 A.8 Waterloo Footedness Questionnaire-Revised ....................................................... 176 xiv List of Tables Table 2.1 SPAM stratification of oxygen patterns. .................................................................... 37 Table 3.1 Demographics of study sample by participant group. ................................................. 46 Table 3.2 Demographic details of case participants listed by participant ID. ............................. 46 Table 3.3 Demographic details of control participants listed by participant ID. ......................... 47 Table 3.4 Intra-group comparison of questionnaires and PVR. .................................................. 48 Table 3.5 Case group 3-day bladder diary variables. ................................................................. 49 Table 3.6 Inter-group SSI comparison. ...................................................................................... 50 Table 3.7 Intra-group Fz lower limb dominance comparison. .................................................... 51 Table 3.8 Intra-group Fz and WFQ lower limb dominance correlation. ..................................... 51 Table 3.9 Intra-group Fz, WFQ and NIRS dominance correlations. ........................................... 52 Table 3.10 Inter-group Fz, WFQ and NIRS dominance comparison. ......................................... 53 Table 3.11 Intra-group 1/2RT variables at baseline and post-PFMT. ......................................... 72 Table 3.12 Inter-group 1/2RT variables at baseline and post-PFMT. ......................................... 73 Table 3.13 Intra-group DMag variables at baseline and post-PFMT. ......................................... 76 Table 3.14 Inter-group DMag variables at baseline and post-PFMT. ......................................... 77 Table 3.15 Intra-group 1/2RT and DMag correlations at baseline and post-PFMT. .................... 80 Table 3.16 Within assessment control group PFM manometer variables. .................................. 83 Table 3.17 Within assessment case group PFM manometer variables. ....................................... 84 Table 3.18 Across assessment intra-group PFM manometer variables. ...................................... 86 Table 3.19 Inter-group PFM manometer variables at baseline and post-PFMT. ......................... 88 xv Table 3.20 Intra-group correlation of post-PFMT PFM manometer and NIRS dominance variables. .................................................................................................................................. 90 Table 3.21 Intra-group correlation of unilateral PFM 1/2RT and PFM manometer variables at baseline. ................................................................................................................................... 91 Table 3.22 Correlation of unilateral 1/2RT and PFM manometer variables at post-PFMT. ........ 93 Table 3.23 Inter-group exercise adherence. ............................................................................... 95 Table 3.24 Intra-group correlation of PFM manometer and exercise adherence variables. ......... 96 Table 3.25 Intra-group correlation of 1/2RT and exercise adherence variables. ......................... 99 Table 3.26 Intra-group correlation of DMag and exercise adherence variables......................... 101 xvi List of Figures Figure 2.1 Flow diagram for study procedures from baseline to post-PFMT assessment............ 22 Figure 2.2 Force plate configuration for lower limb dominance measures. ................................ 25 Figure 2.3 PFM manometer. .................................................................................................... 26 Figure 2.4 NIRS probe prototype design. ................................................................................. 28 Figure 2.5 NIRS probe prototype design details and equipment configuration. ......................... 30 Figure 2.6 SPAMD algorithm. .................................................................................................. 38 Figure 2.7 Example of 1/2RT calculation in control participant. ................................................ 41 Figure 2.8 Example of inverse 1/2RT calculation in a case participant. ..................................... 42 Figure 3.1 Case group QUID-UUI score reduction. ................................................................... 48 Figure 3.2 Intra-group DisFz and QFz association. ................................................................... 51 Figure 3.3 Inter-group DisFz and QFz comparison. ................................................................... 53 Figure 3.4 Control participant CS1 performing MVCs, SMVC and REP. .................................. 55 Figure 3.5 Control participant CS1 performing SMVC at baseline and post-PFMT. .................. 56 Figure 3.6 Control participant CS1 SMVC oxygenation patterns at baseline and post-PFMT. ... 56 Figure 3.7 Control participant CS7 performing SMVC at baseline and post-PFMT. .................. 57 Figure 3.8 Control participant CS7 SMVC oxygenation patterns at baseline and post-PFMT. ... 57 Figure 3.9 Case participant SS11 performing MVCs, SMVC and REP. .................................... 61 Figure 3.10 Case participant SS11 SMVC oxygenation patterns at baseline. ............................. 62 Figure 3.11 Case participant SS14 performing SMVC at baseline and post-PFMT. ................... 62 Figure 3.12 Case participant SS14 SMVC oxygenation patterns at baseline and post-PFMT. .... 63 Figure 3.13 Case participant SS12 performing MVCs, SMVC and REP.................................... 65 xvii Figure 3.14 Case participant SS12 performing SMVC at baseline and post-PFMT. ................... 66 Figure 3.15 Case participant SS12 SMVC oxygenation patterns at baseline and post-PFMT. .... 66 Figure 3.16 Case participant SS3 performing SMVC at baseline including full recovery time interval. .................................................................................................................................... 68 Figure 3.17 Case participant SS3 performing SMVC at baseline and post-PFMT. ..................... 68 Figure 3.18 Case participant SS3 SMVC oxygenation patterns at baseline and post-PFMT. ...... 69 Figure 3.19 Case participant SS4 SMVC at baseline. ................................................................ 69 Figure 3.20 Inter-group 1/2RT variables at baseline and post-PFMT. ........................................ 74 Figure 3.21 Inter-group DMag at baseline and post-PFMT. ....................................................... 78 Figure 3.22 Inter-group 1/2RT and DMag dominance at baseline and post-PFMT. .................... 79 Figure 3.23 Intra-group correlations for 1/2RT and DMag. ........................................................ 81 Figure 3.24 Across assessment correlation of PFM manometer measures. ................................. 87 Figure 3.25 Inter-group PFM manometer variables at baseline and post-PFMT......................... 89 Figure 3.26 Correlation of Right PFM 1/2RT and PFM manometer variables. .......................... 93 Figure 3.27 Correlation of Left PFM 1/2RT and PFM manometer variables. ............................. 94 Figure 3.28 Inter-group PFMT adherence mean values for Exercise Volume and Frequency..... 95 Figure 3.29 Intra-group exercise adherence percentage. ............................................................ 95 Figure 3.30 Case group correlation of PFM manometer and exercise adherence variables. ........ 97 Figure 3.31 Case group correlation of QUID-UUI score and exercise adherence. ...................... 98 Figure 3.32 Control group correlation of 1/2RT and exercise adherence. .................................. 99 Figure 3.33 Case group correlation of 1/2RT and exercise adherence. ..................................... 100 Figure 3.34 Case group correlation of DMag and exercise adherence. ..................................... 101 xviii Abbreviations Abbreviated terms are in keeping with the International Urogynecological Association and the International Continence Society recommended terminology and definitions.1 DMag Magnitude change of hemoglobin concentration ½RT Half-Recovery Time 31P-MRS Phosphorus magnetic resonance spectroscopy CWS Continuous wave spectroscopy DisFz Distracted stance dominance measured by percentage difference of ground reaction force of bilateral lower limbs HbDiff Difference between oxygenated and deoxygenated hemoglobin HHb Deoxygenated hemoglobin IAP intra-abdominal pressure IIQ-7 Incontinence impact questionnaire short form, see Appendix A.6 LUTS Lower urinary tract symptoms MS Multiple sclerosis MUI Mixed urinary incontinence MVC maximal voluntary contraction NIRS Near infrared spectroscopy O2Hb Oxygenated hemoglobin PFM pelvic floor muscle PFMT pelvic floor muscle therapy PVR Post void residual xix QFz Quiet stance dominance measured by percentage difference of ground reaction force of bilateral lower limbs QUID-SUI Questionnaire for urinary incontinence diagnosis – stress urinary incontinence score, see Appendix A.4 QUID-UUI Questionnaire for urinary incontinence diagnosis – urgency urinary incontinence score, see Appendix A.4 REP Fast repeated contractions SB Spina bifida SCI Spinal cord injury SMVC Sustained maximal voluntary contraction SSI Subjective survey of improvement, see Appendix A.7 SUI Stress urinary incontinence tHb Total sum of oxygenated and deoxygenated hemoglobin UDI-6 Urogenital distress inventory short form, see Appendix A.5 UI urinary incontinence UUI Urgency urinary incontinence WFQ Waterloo footedness questionnaire, see Appendix A.8 xx Acknowledgements Foremost I would like to acknowledge my supervisory committee. I would like to thank Dr. Lynn Stothers, for believing in my capability, for encouraging my academic pursuit and for providing me with the support needed to complete this project. I would like to thank Dr. Andrew Macnab, for sharing his NIRS expertise, keen advise and patience. I would like to thank Dr. Tania Lam whose assistance on methodological components and support with statistical analysis is greatly appreciated. Also, a special thanks to the Lam Lab who graciously shared equipment and patiently guided me through Matlab. I would like to acknowledge the Rick Hansen Foundation and the Blusson Integrated Cures Partnership, whom without their appreciation for continued research and financial support this project would not have been made possible. I would also like to acknowledge the entire community at ICORD who not only facilitated the day to day activities of this project but also connected me to the SCI community at large. Special thanks are owed to the nurses and administrative staff of the Urology Clinic at the Brenda and David Mclean Integrated Spine Center, whose assistance, cooperation and patience made the data collection possible. A very sincere thanks is owed to the volunteers who participated in this study. Their gracious commitment is deeply appreciated and their contributions to this research is extremely valued. xxi Dedication I dedicate the completion of this thesis my supportive husband and parents. 1 Chapter 1: Introduction This chapter will introduce the research topic, providing background literature on urinary incontinence, pelvic floor muscle (PFM) dysfunction and lower urinary tract symptoms experienced in females. Specific attention will be given to how neurologic conditions and injuries contribute to these issues. To better appreciate the physiologic consequences of neurologic conditions and injuries on continence and PFM function, near infrared spectroscopy is introduced as a technology to address gaps in the current PFM literature surrounding oxygen kinetics and hemodynamics within the PFM, thus providing the rationale for this project. Subsequently objectives and hypotheses that guided the research are stated. 1.1 Background and rationale 1.1.1 Urinary incontinence and pelvic floor muscle dysfunction Urinary incontinence (UI) is a detrimental health condition that negatively impacts quality of life and generates a huge economic burden, totaling $2.3 billion in Canada alone.2-7 As many as 36.5 % of adult Canadian women are living with UI and this number increases to 55% among women older than 65 years of age.2 As determined by the International Urogynecological Association/International Continence Society (IUGA/ICS), there are three different types of urinary incontinence: stress incontinence, urgency incontinence and mixed incontinence.8 Stress incontinence is defined as involuntary urinary leakage due to physical exertion and urgency incontinence is defined involuntary urinary leakage due to strong urge to void that cannot be suppressed.8 Mixed urinary incontinence is defined as stress and urgency incontinence presenting in conjunction.8 UI, particularly urge incontinence, is even more pervasive among 2 individuals living with neurological conditions that cause interruption of innervation to the pelvic viscera, resulting in neurogenic bladder.9 Research from the U.S. reports frequency of neurogenic bladder to be 40-90% in those with multiple sclerosis (MS), 40-61% in those with spina bifida and 70-84% in those living with spinal cord injury (SCI).10 Neurogenic bladder leads to urinary incontinence due to overactivity or underactivity of the detrusor (contractile muscle of the bladder). Spinal injuries above the vertebral level of T12 results in overactive detrusor, resulting in urgency symptoms and incontinence and impaired bladder emptying as the external urethral sphincter muscles in the pelvic floor become uncoordinated with the detrusor contraction, resulting in detrusor sphincter dyssynergia which impedes urine flow when the bladder is attempting to empty.9,11 Underactive bladder, or loss of detrusor contractility, occurs in spinal injuries below the vertebral level of T12, resulting in over filling of the bladder, causing incontinence as the bladder volume exceeds the bladder’s capacity to retain increasing amounts of urine.10,11 On top of impaired detrusor activity, innervation to the pelvic floor muscle (PFM) is also interrupted. This further exacerbates the incontinence experienced in spinal cord injury as the somatic control of these skeletal muscles is inhibited. As the PFM is the only skeletal muscle in the lower urinary tract, it is the only mechanism that can be voluntarily controlled for maintaining continence. Not only is the motor control of the PFM inhibited in spinal cord injury but another detriment is the resulting consequence of PFM atrophy. This means that even in incomplete injuries with pudendal motor neuron sparing, the PFM will have weakened muscle function limiting the ability to produce contractions meaningful for maintaining continence. A wide variety of pathologies can result in disruption of innervation to the PFM, including: SCI, MS, spina bifida, Parkinson’s disease and even trauma induced by vaginal delivery.9,12,13 3 1.1.2 Pelvic floor muscle therapy Pelvic floor muscle therapy (PFMT) is defined by Bø et al. 2016 in the IUGA/ICS joint report as “exercise to improve PFM strength, endurance, power, relaxation or a combination of these parameters.”1 Prominent urological associations recommend PFMT as the first line therapy for management of UI.14-17 PFMT has been demonstrated to improve PFM function and strength by means of neuromuscular adaptations and muscle hypertrophy. 18,19 These beneficial responses to PFMT have been shown to improve or cure both stress and urge incontinence.20,21 Stress incontinence is improved by means of the strengthened PFMs increased capability to generate more force and at greater velocity.22,23 Such increased capability allows the external urethra to remain closed, by nature of compression exerted from PFM contraction, during situations of high intra-abdominal pressure (such as physical exertion, coughing or sneezing). During situations of high intra-abdominal pressure force is exerted on to the bladder, and when storage mechanisms are not competent, involuntary leakage of urine occurs. Thus, a strengthened PFM can maintain closure of the external urethral sphincter and prevent stress incontinence. Furthermore, strengthening the PFM also improves the structural integrity of the pelvic organs, including the urethra, bladder and uterus.19,22 The PFM supports optimal anatomical positioning of these pelvic organs, and improving PFM strength to maintain structural support prevents stress incontinence that can occur from pelvic organ prolapse. PFMT helps to improve urge incontinence by means of activating the “guarding reflex”. Contraction of the PFM, causes compression and contraction of the external urethral sphincter, this stimulates afferent nerves in the autonomic pathway of the sphincter to reduce parasympathetic excitation promoting detrusor contractions which generate urgency.19,24 PFM 4 contractions stimulate the afferent nerves in the somatic pathway of the lumbosacral spinal cord which also prevents activation of detrusor contractions.24 Most of the existing literature supports PFMT as a beneficial rehabilitation for females with stress incontinence. More recent literature supports the beneficial effects in females with urge and mixed incontinence. A current systematic review by Dumoulin et al. 2018, reports PFMT is beneficial for management of all UI.20 However, only limited investigations have examined the benefits of PFMT in females with UI and neurologic conditions. Investigations have demonstrated that PFMT with and without adjunctive EMG biofeedback and electrical stimulation was effective in reducing lower urinary tract symptoms (LUTS) in females with MS.25-27 Voorham et al. 2017 and Fitz et al. 2017, both examined the effectiveness of PFMT (which included biofeedback or supervised PFMT sessions) on a female population with overactive bladder symptoms and demonstrated improvements in PFM function with EMG, reduced symptoms and improved quality of life (QOL).28,29 Described by IUGA/ICS, common overactive bladder symptoms include urgency, frequency and nocturia with or without urgency continence,8 which makes this study relevant to a neurologic population, as these are also common symptoms experienced by individuals with neuronal impairments in the PFM.9 Vasquez et al. 2015, examined the effectiveness of home-based PFMT in a case-based study of 2 males with incomplete SCI and found improvements in voluntary PFM control which helped to reduce detrusor overactivity and incontinence.30 Based on this literature it seems reasonable to evaluate PFM function in individuals with neurological impairment to the PFM and to further assess the physiologic parameters contributing to the effectiveness of PFMT in this population. 5 1.1.3 Evaluation of PFM function The positive therapeutic effects of PFMT for UI were first discovered by Dr. Arnold Kegel in 1948, at this time he developed the first vaginal manometer to measure PFM strength and evaluate outcomes of PFMT.31,32 Although research has progressed the understanding of the PFM and furthered development of evaluative instruments, there still remains no current gold standard methodology for quantifying PFM function.33-38 Evaluation of skeletal muscle function and strength involves consideration of both slow and fast twitch muscle fibers (type I and type IIA, IIX). Slow type I fibers are dependent upon oxygen and reflect the aerobic capacity of muscles. This fiber type is of particular importance when evaluating PFM as this muscle group is comprised of approximately 70% slow twitch fibers.39 Fast type IIA and type IIX fibers are recruited under high muscle force demands, metabolize anaerobically and reach peak tension two times faster than type I fiber.40 Although type II fibers are responsible for producing quick and forceful muscular contractions, slow twitch fibers are important for muscular endurance, as they help sustain repeated muscular contractions at certain intensity levels over time. Active engagement from both fiber types in the PFM are integral for maintaining continence. The fatigue resistance of type I is crucial for supporting continued demands placed on the PFM as it contributes to pelvic stability during everyday physical activities, such as walking, and counteracting intra-abdominal pressure (IAP) occurring with postural changes that exert downward on the pelvic floor, to prevent stress incontinence.22,41-43 The type II fibers are necessary for providing quick, strong contractions and are responsible for facilitating urethral closure during intensive brief changes in IAP, like coughing or sneezing, and to suppress urgency until voluntary micturition.22,44 As such, both fiber types of the PFM are assessed by 6 measuring strength and endurance, and these are important outcome measures when evaluating PFM function after PFMT interventions. When assessing PFM strength in females, a maximal voluntary contraction (MVC) is performed, produced by voluntarily squeezing the pelvic floor while pulling upward and inward to generate as much force as possible. The measurement of strength can be determined by digital palpation, manometry or dynamometry.1 Endurance is determined by the duration of the PFM to sustain a percentage of MVC or by the number of repeated contractions at percentage of MVC.1 Although these parameters are reported by the IUGA/ICS, they do not identify a gold standard methodology for quantifying PFM strength and endurance. This lack of standardization is not only problematic for proper assessment of PFM function within the general female population experiencing UI, but also complicates the difficult assessment of PFM function among females with neurological conditions. Their impaired motor function often only allows generation of weak contractions, if any, that can be indiscernible by an examiner or undetected by current assessment devices, thus preventing appropriate application and progression of PFMT therapy for these individuals. The metabolic properties of muscle fiber type dictate their functional roles in muscular function. Type II fibers rapidly generate force through the breakdown of phosphocreatine and glycogen stores within the tissue. However, the energy derived from these metabolic processes is only capable of maintaining high intensity contractions for short periods of time as the phosphocreatine and glycogen quickly depletes.40,45 Once these energy fuel sources are depleted muscular function is sustained by aerobic glycolysis, utilizing oxygen from the vascular system to generate energy.40,45 Measuring these metabolic pathways within the PFM would provide insight on the different fiber type contributions to PFM function during exercise and help explain 7 the interplay between the demands placed on the metabolic processes of PFM during functional situations that require both strength and endurance. Further understanding of the metabolic processes specific to the PFM will provide more insight to how the PFM performs in both healthy and pathologic conditions. Such information could be utilized to best direct PFMT methods for management of LUTS. A common way of assessing skeletal muscle metabolic processes is by measuring oxygen kinetics. This is routinely performed in sports medicine to better facilitate athletic training regimes and in medicine to better understand pathophysiology of disease, as oxygen kinetics provides valuable information about the workload capacity of muscle (oxygen extraction) and fatigue resistance (oxygen recovery). Methods utilized to measure oxygen kinetics will be addressed in the following section. 1.1.4 Measurement of skeletal muscle oxygen kinetics In the fields of sport medicine and physiology skeletal muscle fitness is quantified by examining the oxygen kinetics of muscle tissue during exercise conditions, and the gold standard measurement for this is performing muscle biopsies.46,47 Due to this severely invasive and often impractical method, new approaches for assessing in vivo skeletal muscle oxygen kinetics have been developed. Phosphorus magnetic resonance spectroscopy (31P-MRS) is currently accepted as the gold standard for measuring in vivo skeletal muscle oxygen kinetics, which, although it is not a direct measure like muscle biopsy, has the advantage of allowing for in vivo assessment of skeletal muscle oxygen kinetics as changes occur in real time with response to exercise.48,49 Although this method is definitely less invasive than sampling of tissue from muscle biopsy, 31P-MRS is an expensive methodology to employ and requires the use of a magnetic coil that limits 8 the ability of this measurement to be utilized during various exercise modalities.49 Near infrared spectroscopy (NIRS) is another method of in vivo assessment of skeletal muscle oxygen kinetics, which, similar to 31P-MRS, allows for real time measurement of skeletal muscle oxygen kinetics in response to exercise. However, unlike 31P-MRS, NIRS equipment does not require the limb of muscle under investigation to be confined to a magnetic coil. NIRS devices are applied superficially over the muscle area of interest, and being relatively small in size can be easily secured with tape and wraps, allowing the limbs to move freely with movement naturally occurring with various exercise modalities.50 This particular advantage of NIRS makes it more suitable to clinical investigations of skeletal muscle oxygen kinetics and as a result it is rapidly becoming a ubiquitous and valuable research modality to evaluate skeletal muscle oxidative metabolism in both states of health and disease.50-52 More recently, NIRS has been utilized to investigate hemodynamic pathophysiology occurring in the presence of neurological conditions and muscular disorders.53-56 Validation studies performed by Ryan et al. 2014, have demonstrated that NIRS methodology is considered to provide reliable and sensitive measures when compared to the gold standard of muscle biopsy and the currently accepted 31P-MRS measures.46 1.2 Principles of Near Infrared Spectroscopy 1.2.1 Development NIRS is an emerging scientific tool being used to advance the understanding of hemodynamic properties in human tissue. Since the 1970’s NIRS technology has progressed and become adopted by a broad range of research communities to study hemodynamic characteristics 9 of cerebral, skeletal muscle and visceral organ tissue as a means to better understand human health and disease.50,51,57-59 NIRS was utilized for hemodynamic studies in animal models by Jöbsis et al. 1977,60 which demonstrated that NIRS could noninvasively detect concentration changes of oxygen in cerebral tissue. Wray et al. 1988, further progressed this finding by defining separate near infrared light spectra for specific chromophores that indicated oxygenation status.61 NIRS was applied to human skeletal muscle by De Blasi et al. 1991, demonstrating oxygen desaturation in the forearm8 Efforts from Mancini et al. 1994 validated the use of NIRS in human skeletal muscle, determining its detection of oxygenation changes to be more sensitive than that of traditional plethysmography measurements.62 NIRS is now a commonly used technology, particularly in exercise physiology due to its sensitivity and specificity in detecting skeletal muscle oxygenation patterns.50 1.2.2 NIRS instrumentation There are three main types of NIRS instrumentation used to detect chromophore concentration in biological tissue and they are defined by the means with which they measure optical properties. They consist of time-resolved, frequency-modulated and continuous wave spectroscopy. Time-resolved spectroscopy uses rapid pulses of light and examines the shape of the light pulses as they propagate through tissue to derive chromophore concentrations, allowing the exact flight time of light travel to be quantified.63-66 Frequency-modulated spectroscopy compares different frequency of light intensity at distinct points within the light cycle, along with the rate of the light cycle shift to derive chromophore concentrations.50,64,66 Both time-resolved and frequency-modulated spectroscopy have the benefits of deeper tissue penetration and 10 provide absolute chromophore concentrations by their ability to derive precise pathlength variables.50,64,66 The third type is continuous wave spectroscopy (CWS), which continuously emits light and detects chromophore concentration changes based on the amount of light attenuation that occurs.51,57,64,66,67 Unlike time-resolved and frequency-modulated spectroscopy, CWS provides only relative chromophore concentration changes, as it utilizes the Beer Lambert Law equation with estimated coefficient values to calculate light attenuation. Newer CWS instruments have incorporated spatially-resolved spectroscopy (SRS), which emits continuous light at multiple distances within a tissue. SRS provides absolute chromophore concentrations to be quantified by summing the values measured across all the distances of light emission.50,51 1.2.3 Principles of NIRS In order to apply NIRS to any field of hemodynamic investigation, the principles of NIR light must be considered. It is established that NIR light, which propagates between 700 to 1000 wavelengths (nm) within the light spectrum, can penetrate through biological tissue to reach small vessels with the microvasculature.60,61,64 Within these small vessels, NIR light is absorbed by three biological chromophores: hemoglobin, myoglobin and cytochrome-c-oxidase. 57,67,68 The amount of absorption that occurs provides an indication of the oxygenation status, as the ability of hemoglobin and myoglobin to absorb NIR light is directly influenced by whether or not oxygen is bound to these molecules.60,61,64,66 There are several factors that influence the transmission of NIR light as it travels from its source through biological tissue to reach its targeted absorption site. 11 1.2.3.1 Scatter Light scatter refers to how much light is lost along its full trajectory path originating from its source to targeted end point. As NIR light does not travel is one direct straight line, it is subject to light loss from scattering in divergent directions through multiple planes and from coming into contact with tissue that can either reflect or absorb it. Thus, this scattering property of light can result in a reduction in the strength of the light signal when it has reached its targeted end point.60,66 The amount of scattering that occurs is also dependent on the wavelength the light is transmitted at. At higher wavelengths, such as in the NIR spectrum (700-1000nm), there is less light scatter than in the visible light spectrum, which facilitates NIR light being able to penetrate through biological tissue.60,69 Based on studies that defined the amount of NIR light scattering at different wavelengths and through multiple types of biological tissue, scattering coefficients have been established for use in mathematical equations to derive NIRS values on hemodynamic patterns.66,70 This scattering coefficient also incorporates the light scattering that is caused from NIR light travelling through skin, adipose and fibrous tissue before it reaches its final point of absorption. 1.2.3.2 Absorption The ultimate absorption of light is also dependent upon the wavelength that the light is transmitted at and of the molecular characteristics of the tissue the light is being transmitted through.60,61,66 As previously mentioned the chromophores of hemoglobin, myoglobin and cytochrome-c-oxidase absorb light differently depending on the presence of a molecular bond with oxygen. It has been determined that hemoglobin has an isobestic point at the wavelength of 800nm, meaning both deoxygenated hemoglobin and oxygenated hemoglobin absorb light 12 equally at this wavelength.61 However, below this wavelength at approximately 750-770 nm deoxygenated hemoglobin highly absorbs light, whereas above the isobestic point at approximately 830-850nm oxygenated hemoglobin has higher light absorbency.61,62 The comparison of the amount of light absorption occurring at these different wavelengths allows NIRS to convert the amount of detected absorption into deoxygenated or oxygenated chromophore concentrations values. Therefore, there must always be at least two light wavelengths emitted from the light source.64,66 The concentration values that NIRS provides are then used to infer the oxygenation patterns of the tissue under investigation. Similar to scattering coefficient values required to derive chromophore concentrations, established absorption extinction coefficient values for the three chromophores (hemoglobin, myoglobin and cytochrome) at all the light wavelengths employed during a NIRS measurement are also required.66 1.2.3.3 Pathlength When establishing the absorption extinction coefficient, the total distance the light has travelled is of great importance and is defined as the pathlength. As described by Jacques 2013, an increasing pathlength will result in an exponential decrease in light absorption. Standard pathlength values have been defined specific to the type of tissue under investigation, which will influence the absorption coefficient value used.66 Studies from Deply et al. 1988, were among the first to establish a known pathlength value for cerebral tissue within a rat model.69 Several investigations were the completed by, Ferarri et al. 1992, Van der Zee et al. 1992, Essenpreis et al. 1993, and Duncan et al. 1995, which quantified pathlength for human skeletal muscle tissues.65,71-73 Derived from these studies, standard pathlength values for skeletal muscle have 13 been established. It is important to note that the pathlength value is also specific to inter-optode distance. The inter-optode distance is to be determined prior to any measurement and is the distance between the optode transmitting the light source (light entry point) and the optode receiving the transmitted light (light exit point). In CWS, which utilizes the Beer Lambert Law to calculate the chromophore concentration values, the pathlength value is assumed to remain constant throughout the duration of the NIRS measurement.70,74,75 However, it should be noted that specific pathlengths for each individual muscle have not been determined and that each muscle has a different composition of fiber types and varying tissues that result in unique pathlength parameters.50,62,70 Saitoh et al. 2010, also report that scatter coefficient and pathlength can change in a given muscle as a direct result of exercise and that more accurate, absolute values in oxygenation of the muscle should be measured with time-resolved spectroscopy to account for this.76 1.2.4 Contribution of myoglobin and cytochrome-c-oxidase to light absorption Although NIR light absorption of reduced cytochrome-c-oxidase was measured in the founding work of Jöbsis et al. 1977, there remains controversy over this value as it is difficult to isolate the light absorption occurring solely due to cytochrome-c-oxidase reduction from that of the much stronger hemoglobin signal. The consensus opinion is that the influence of cytochrome-c-oxidase only contributes to approximately 10-15% of the light absorbency signal, and is therefore dismissed by some researchers as an insignificant contributing factor in the measured values of light absorbency.61,68 Similarly, it has been determined that myoglobin accounts for approximately 10-20% of the measured hemoglobin light absorbency signals, which 14 at this point cannot be separated from the hemoglobin signal and therefore myoglobin oxygenation status is inferred from the hemoglobin measures.50,57,62,68 1.2.5 Optical Density defined by the Beer Lambert Law When collecting NIRS measurements it is essential to consider the type of biological tissue the NIR light will be transmitted through and the type of tissue at the terminal site of light transmission, as this determines the specific parameters used for the scatter and absorption extinction coefficients. With standard estimated values for the absorption extinction coefficient, scatter coefficient and pathlength, along with a defined inter-optode distance specific to the measurement, the Beer Lambert Law can then be utilized to derive the oxygenation status of biological tissue by quantifying optical density.57,61,68,77,78 The Beer Lambert Law defines the optical density of a medium, and the modified equation utilized in continuous wave instruments is expressed as: A = e[c]LB+G In this equation, A represents optical density, e represents the absorption extinction coefficient, [c] represents the chromophore concentration, L represents the distance from the light source to terminal end point, B represents the pathlength and G represents scatter coefficients for other parameters that can interfere with light transmission, such as skin and adipose tissue.51,57,77 This equation only works for one chromophore, so in order to examine multiple chromophores simultaneously there needs to be the same number of light wavelengths emitted for the corresponding number of chromophores under investigation. NIRS systems then employ algorithms to solve the equations for each chromophore at the varying wavelengths, ultimately 15 providing the relative concentration values of the chromophores to allow for the interpretation of oxygenation status of the tissue.51,57,77 It is also important to note that only standard values or estimates for these coefficients are used and that variation in light scatter and absorption occurs across subjects, tissue site and measurement times.66 This is why relative trends in oxygenation patterns are derived from NIRS studies using continuous wave spectroscopy, as opposed to absolute oxygenation values measured with time-resolved or frequency-modulated spectroscopy.51,66,77 1.2.6 NIRS adaptation to PFM Similar to the use of NIRS in sports medicine and physiology, the adaptation of NIRS for investigations in urology is appealing due to its sensitive and non-invasive measurements. Traditional urological measurements of bladder function require insertion of multiple catheters, causing discomfort and risk for infection. NIRS allows transcutaneous measurement of the bladder, as it resides rather superficially in the lower abdomen just proximal to the symphysis pubis. Due to its accessibility, the detrusor (visceral muscle of the bladder) has been investigated with NIRS techniques similar to that of skeletal muscle investigations. Adapting NIRS to monitor the bladder was first established by Macnab et al. 2005, and through this research NIRS has demonstrated its ability to be used as an effective clinical tool for monitoring and diagnosing urological pathologies.59,79 More recently, this group of UBC based researchers have been adapting NIRS technologies to examine the skeletal muscle of the female pelvic floor in attempt to address clinical issues related to LUTS, PFM dysfunction and pelvic organ prolapse.59 Shadgan et al. 2008 developed the first probe for assessment of the PFM in relation to urinary incontinence.74 16 This design utilized CWS NIRS to provide simultaneous tracings of the detrusor and the mid-urethral sphincter for the purposes of monitoring bladder function in females with stress incontinence.74 The data collected from the NIRS probe was reported to be reproducible and consistent with NIRS oxygenation trends captured by their transcutaneous bladder measurements. Furthermore, they were also able to demonstrate NIRS measurements of voluntary PFM contractions were consistent with physiologic responses of typical voluntary skeletal muscle contractions measured with NIRS.74 This prior prototype, although capable of measuring multiple structures of the lower urinary tract, required repositioning for each targeted site (bladder, urethra, right and left PFM). Utilizing the same CWS NIRS technology, a new transvaginal NIRS probe will be designed, allowing simultaneous measurement of bilateral PFM with maintained positioning, in order to assess the hemodynamic and oxygen kinetic response of the PFM during exercise. Current devices used to objectively assess this muscle group assess the muscle as one functioning unit, and do not always account for asymmetry that might occur from weakness to a specific side of the muscle. This is of particular importance for the female population with LUTS and underlying nerve impairment, as asymmetrical muscular function of the PFM might occur due to neurological impairment causing differential motor and sensory function on contralateral sides of the body.80-82 With this instrument it was planned to compare the hemodynamic trends and oxygen recovery kinetics of the PFM in response to exercise. These parameters will be assessed in females with continence (controls) and in females experiencing LUTS due to neurologic conditions and injury (cases). Both groups will be exposed to a PFMT regime to evaluate whether a training response in the PFM can be captured by NIRS measures of hemodynamics and oxygen recovery kinetics. 17 1.3 Objectives and Hypotheses 1.3.1 Primary Aim The primary aim of this project is to develop a transvaginal NIRS probe capable of isolating bilateral PFM oxygenation and to determine the feasibility of utilizing NIRS derived parameters obtained with this probe. Furthermore, this project aims to objectively measure NIRS parameters of hemodynamics and oxygen recovery kinetics in females with LUTS due to impaired pelvic innervation (cases) and in continent controls (controls) to determine if beneficial PFMT training effects can be captured with NIRS instrumentation. 1.3.2 Objectives The secondary objectives supporting this primary aim are to: 1. Compare oxygen kinetic responsiveness of bilateral PFM as detected by NIRS. 2. Compare NIRS derived parameters to currently used objective parameters of PFM function derived by manometry. 3. Determine if lower limb dominance contributes to bilateral PFM function. 4. Evaluate the effectiveness of PFMT on NIRS and manometry parameters of PFM function. 5. Evaluate the impact of PFMT to reduce clinical symptom of LUTS and PFM dysfunction and improve QOL. 6. Determine how PFMT adherence influence effectiveness of PFM function improvement and symptom reduction in the cases group. 18 1.3.3 Hypotheses 1. Oxygen kinetic responses of bilateral PFM detected by NIRS will present differences contralaterally in the case group and similarities contralaterally in the control group. 2. NIRS derived parameters will demonstrate a relation to manometer parameters of PFM function. 3. Lower limb dominance will be related to bilateral imbalances of PFM. 4. PFMT will improve the proficiency of oxygen kinetics as measured by NIRS and PFM strength and endurance as measured by manometry. 5. PFMT will reduce clinical symptoms and improve QOL, as measured by validated questionnaires. 6. Higher PFMT adherence rates will demonstrate greater effectiveness of PFM function improvement (as measured by NIRS and manometer variables) and demonstrate greater reduction in clinical symptoms (as measured by validated questionnaires), within the case group. 19 Chapter 2: Methods This chapter will provide a detailed description of the methodology of the entire research project. The eligibility and protocol for participant involvement is described. The objective and subjective outcome measures are identified, along with the utilized equipment and the means to which measurements were conducted. A thorough description of the technical development of the prototype for the NIRS probe is provided. Careful consideration is given in addressing how outcome measures were analyzed and the rationale for how analysis was conducted. 2.1 Participants Inclusion criteria for study participants included females 19 years of age or older who experience urinary leakage, have a history of neurological condition for > 6 months and able to communicate in English. Inclusion criteria for control participants included females 19 years of age or older who do not currently experience urinary leakage or bladder symptoms, no history of a neurological condition and able to communicate in English. Exclusion criteria for all participants included the following: pregnancy or planned pregnancy, post-partum < 2months, pelvic radiotherapy, pelvic pain symptoms, use of indwelling catheter, pelvic organ prolapse beyond introitus, atrophic vaginitis, hypertonic pelvic floor muscles, skin break down of perineum, orthopedic or cognitive impairment that does not allow for physical exercise. A total of 45 individuals were screened for eligibility for the case group following referral from physician or poster recruitment advertisement. Of these individuals 6 did not meet the criteria. Of the 39 individuals that did meet the criteria for inclusion in the study group after initial screening 25 individuals decided not to proceed with participation. The remaining 14 individuals were enrolled in the study and all had a baseline assessment. However, one 20 participant began menstruation during baseline assessment, therefore assessment ceased at this time and the participant subsequently withdrew from further participation. Two participants experienced falls (unrelated to study procedures) during the home-based PFMT intervention and were unable to complete follow-up assessment. Two participants reported vaginal discomfort with attempted manometer insertion at baseline and were therefore excluded from further participation in the study. One participant completed the study to post assessment but reported vaginal discomfort on attempted final manometer insertion, and therefore this final measure was not collected for this participant. Upon baseline assessment one participant was unable to stand safely on the force plates, and therefore this measure was not collected for this participant. Of these 14 enrolled participants, 10 participants completed the entire baseline assessment and 8 participants completed their post-PFMT assessments. Of 31 control participants screened, 4 individuals did not meet the criteria as they reported bladder symptoms and 12 individuals decided not to proceed participation. The remaining 15 individuals were enrolled in the study and had a baseline assessment. 2.2 Protocol This pilot study utilized a prospective, non-randomized study design with pre and post comparisons. All of the testing took place at the Blusson Spinal Cord Centre, located in Vancouver, British Columbia, Canada during the time period of November 2016 to April 2018. Complete protocol of the study was approved by the University of British Columbia’s Research Ethics Board and by the Vancouver Coastal Health Research Institute Ethics Board. All participants provided written informed consent prior to participation. All assessments were scheduled around participants menstruation cycles to avoid active menstruation during 21 assessment appointments. At baseline assessment demographics and health history reviewed, including parity and delivery type, neurological history, surgical history, urinary incontinence symptoms and treatments, and current medications. A physical activity Life Style Index score was given based on participant’s subjective report of being: “Sedentary” (no physical exercise during the week, score of 0), “Moderate” (20 minutes of vigorous intensity physical activity 3 days a week, score of 1) or “Active” (30 minutes of moderate intensity physical activity 5 days a week, score of 2). PFM function was assessed at baseline and after 8-weeks of home-based PFMT intervention (post-PFMT). Standardized PFMT instruction was provided to participants at the completion of the baseline assessment. The PFMT was based on previous work by Bø et al. 1990,18 who conducted a study that compared two types of home-based PFMT to address SUI. Their first PFMT intervention consisted of 8-12 strong contractions repeated 3 times throughout the day.18 Their second PFMT intervention included this first regime along with weekly 45minute instructor-based sessions that consisted of supervised contractions in lying, sitting and standing positions.18 Based on their results women with SUI in both the assigned intervention groups showed significant improvement in PFM strength as measurement by manometer after 1-month of PFMT.18 These improvements were maintained at 6-months follow-up in the first regime group and continued to improve at 6-months with the second regime group.18 The PFMT regime for this current study incorporated the lying, sitting and standing contractions from Bø et al.’s 1990 supervised sessions which participants were required to perform daily at maximum effort.18 As each contraction was to be repeated 6-8 times, participants would be performing at minimum, the same amount of contractions as Bø et al.’s 1990 home-based PFMT.18 In combining these two exercise regimes into one it was intended to elicit and improvement in PFM 22 strength and fitness within our constructed time span of 2-months. Participants were given instruction on how to perform all PFMT exercises and given the opportunity to seek clarification, demonstration and practice. A written instruction sheet of each exercise was given to participants along with an exercise recording sheet (example in Appendix). Participants were required to perform the standardized PFMT daily for the duration of 8-weeks. Case group participants were also instructed on how to perform 3-day bladder diaries and materials required to complete bladder diary were supplied to participant (example in Appendix). Participants completed bladder diaries 3-days prior to initiating PFMT and 3-days after completion of 8-week PFMT. Figure 2.1 Flow diagram for study procedures from baseline to post-PFMT assessment. 23 2.3 Objective measures 2.3.1 Urinalysis and post void residual volume Upon each visit the participant was requested to arrive with a comfortably full bladder in order to collect a urine sample and measure post void residual volume. The participant was instructed on how to properly collect a clean catch midstream urine sample in a sterile urine container. The participant was also instructed to ensure they voided to perceived complete emptying, to ensure urine collection did not interfere with complete voiding. The void was performed in a bathroom just outside the examination room and once the participant returned to examination room urinalysis was performed on their sample to rule out presence of urinary tract infection. Siemens Multistixâ 5 reagent strips were used for urinalysis, which tested for leukocytes, nitrites, protein, red blood cells and glucose. Based on negative findings the assessment proceeded, positive findings would prompt follow-up with physician and result in rescheduling until urinary tract infection resolved. Following urinalysis, the post void residual volume (PVR) was assessed. For this measure participants were positioned supine on an examination table, scanner settings were selected as appropriate (depending whether the female had a hysterectomy or not), a water-soluble lubricant was applied to the pubis, the symphysis pubis was used as a landmark and the handheld ultrasound was placed 1 inch above the landmark in a downward direction towards the bladder. Only scans that indicated accurate placement were used to report the PVR volume measured using a bladder scanner (BladderScanâ BVI 9400, Verathon). 24 2.3.2 Standing force plate Following PVR assessment participants performed a standing force plate measurement under two different conditions to quantify percentage of total body weight distributed across the bilateral lower limbs as determined by ground reaction force (Fz). Force plate equipment used was that of Bertec; Columbus, Ohio, United States. The participants were positioned in an upright standing position on the center of two individual side-by-side force plates so that the left foot was in the center of force plate 1 and the right foot was in the center of force plate 2. Under the first standing condition participants were not instructed on how to stand, only to not move their feet, and they were distracted with a video on a screen centred directly in front of them. The participants were instructed to watch the video which reviewed concepts of pelvic floor muscle function and contraction. Participants were instructed not to attempt any of the contractions mentioned in the video while in the standing position. During the duration of this video 3 separate force plate measures were collected for 60-seconds each. After completion of the video the participant was informed that force plate data had been collected at this time to determine if altered body weight distribution occurred during distracted standing. This condition was determined as distracted stance (DisFz). Following this the participant was instructed to stand as straight, still and centered as possible, while maintaining their feet in the aforementioned positions, for the duration of 60-seconds. This was considered as quiet stance (QFz). All force plate data was collected at a sample rate of 100Hz and a low pass filter of 5. Data was subsequently analyzed in Matlab. 25 Figure 2.2 Force plate configuration for lower limb dominance measures. Force plates within the floor, “X” marked indicators for left and right foot placement during both distracted and quiet stance. During distracted stance video played in front of participant on supported video screen. 2.3.3 PFM manometry Prior to starting PFM assessment, the participant was given verbal overview of basic PFM anatomy, function and contraction. Participants were then allowed to practice contractions and examiner monitored to make sure no accessory muscles were being used. Once participant felt comfortable performing a contraction examiner confirmed ability of subject to contract PFM with visual inspection of perineal elevation.1,8 Participants were positioned in the supine position, knees bent and hips flexed with external rotation so that soles of feet were touching, in order to minimize accessory muscle contraction.83 The PFM manometer used in this study was the Peritronâ by Laborie. Individual single use vaginal sensors were used for each participant and infection control procedures were followed as per manufacturer guidelines and institution standards. A water-soluble lubricant was applied to manometer prior to insertion and following a resting time of 60-seconds to allow PFM to relax after response to insertion, a series of standardized PFM contractions were conducted. Participants completed a set of 3 maximal voluntary contractions (MVC) where they were instructed to contract the PFM as strong as 26 possible and to relax once they felt they reached their strongest effort. Each MVC was separated by a 10-second recovery. After the final MVC there was a 5-minute recovery period prior to the next contraction which was 1 sustained MVC (SMVC), where they were instructed to contract their PFM as strong as possible and to hold the strong contraction for as long as possible before allowing their PFM to relax. Another 5-minute recovery period followed the SMVC prior to conducting a set of fast repeated contractions (REP) to point of perceived exertion. For the REP participants were instructed to perform quick PFM contractions as strong as possible and quickly relax, and to continue repeating this until they feel they can no longer perform a strong contraction (feeling of perceived exertion). Following the REP set there was a 10-minute recovery period prior to conducting the same set of PFM contractions with the NIRS probe. Upon completion of PFM contractions with the NIRS probe there was another 10-minute recovery before the manometry measures were repeated. The purpose of repeating the manometer measures after the NIRS was to allow for assessment of learner effect and effort consistency/muscular fatigue since the manometer and NIRS measurements were not occurring simultaneously. Figure 2.3 PFM manometer. (Peritronâ by Laborie) used for objective pressure measurements in cmH2O of PFM strength and endurance. Individual single-use vaginal sensors used for each participant. 27 2.3.4 NIRS The NIRS probe that was used for assessment of PFM for this study was of original design. This design was structured from a previous NIRS probe prototype created by Shadgan et al. 2008, which utilized continuous wave NIRS and provided simultaneous tracings of the detrusor and the mid-urethral sphincter for the purposes of monitoring bladder function and related incontinence.74 They reported reproducible data with consistent NIRS oxygenation trends when compared to the NIRS data during transcutaneous measurements of the bladder.74 With this first prototype they were also able to demonstrate that NIRS measurements of voluntary PFM contractions were consistent with the physiologic response of typical voluntary skeletal muscle contractions measured with NIRS.74 When testing the feasibility of this prototype they also determined that movement artifact did not appear to compromise the NIRS tracings as positioning was well maintained with the probe handle.74 Based on this prototype and using the same continuous wave NIRS equipment, (OXYMON MK III, Artinis Medical Systems BV, The Netherlands), a dual channel (2x1) set up consisting of one emitter and one receiver fiber optic cable were secured on parallel sides of a transparent disposable speculum. Due to size constrictions of the speculum, miniature fiber optic cables were attached to standard fiber optic cables which were secured together via an attachment block. Both the standard and miniature fiber optic cables were screwed into to the attachment block and the block itself is completely opaque and black in colour to prevent any external light contamination at the attachment point. During tracings this attachment block was also covered with an opaque black cloth to further prevent against environmental light contamination. The ends of the miniature fiber optic cables where actual NIR light transmission and detection occurs are referred to as the optodes. These optodes were secured to a base foam 28 inlay to ensure consistent position of optodes within the speculums across all measurements. Placement of the foam inlay was positioned such that optodes were a 2 cm distance from the end of the probe. This was done with the intention that with transvaginal insertion the optodes would be emitting/receiving light into the PFM tissue at the same location where the manometer pressure sensor would be detecting pressure changes from the PFM. The interoptode of each emitter and receiver was set at 20 mm to yield a tissue penetration depth of 10 mm directly into the PFM microvasculature. Figure 2.4 provides image of NIRS probe design and Figure 2.5 provides detailed images for NIRS probe configuration and equipment configuration. Figure 2.4 NIRS probe prototype design. Dual channel (2x1) set up consisting of one emitter and one detector fiber optic cable secured within foam inlay on parallel sides of transparent disposable speculum. Individual single-use speculum for each participant, image without condom cover. NIR was light transmitted at 766nm, 861nm, 906nm and 971nm. Data captured at 10Hz included raw optical data from O2Hb, HHb, and calculated values were derived from this raw data. The first being the sum total hemoglobin (tHb) where tHb= O2Hb + HHb, and the second being the difference in hemoglobin (Hdiff) where Hdiff= O2Hb – HHb. All raw and calculated variables produced simultaneous, real time tracings of right and left musculature during NIRS measurements. A fixed DPF of 4 was used based on previous studies employing the same NIRS equipment investigating skeletal muscle tissue.70,84,85 Two important factors for maintaining the trace quality are the laser output setting and the receiver gain. For this study the “Brain” laser 29 output setting was used instead of the “Muscle” setting as the “Brain” setting yields a higher intensity of light and results in a better signal to noise ratio. The receiver gain level determines the degree of amplification of the received signal and must be set at a level to optimize the saturation of received light. Saturation percentages allow you to monitor the quality of trace by indicating levels that are too low or too high. Levels that are too low indicate that all transmitted light is being absorbed by the tissue and not enough light is being detected by the receiver to produce a reasonable signal.57 Levels that are too high indicate over saturation of the received light signal which indicates contamination from environmental light, resulting in reduction of received signal and lower detected concentration values.57 Gain settings were adjusted at the beginning of each measurement to prevent over saturation and maintain acceptable signal strength within the range of 1-20%.57 In order to collect NIRS probe measurements with participants a new speculum was fitted with the NIRS configuration as previously described for individual measurement and the NIRS probe was covered with a latex free condom. The participant was positioned supine with legs in the “butterfly” position, similar to that of the manometer measurement condition. The probe was then inserted transvaginally to indicated insertion point. The NIRS laser output was then turned on and once acceptable signal percentages were confirmed, the trace was biased to arbitrary zero. Resting baseline values were then recorded prior to initiating the same protocol for PFM contractions as described above in the manometer section (3 MVCs, 1 SMVC, REP). 30 Figure 2.5 NIRS probe prototype design details and equipment configuration. Both vaginal sensor for manometer and NIRS probe were individual single-use, NIRS probe shown without condom cover. 2.4 Subjective measures 2.4.1 Bladder symptom questionnaires Participants in the case group were asked complete the Incontinence Impact Questionnaire (IIQ-7),7,86,87 and the Urogenital Distress Inventory (UDI-6),86,87 at baseline and post-PFMT assessments. All participants completed the Questionnaire for Urinary Incontinence Diagnosis (QUID),88 at baseline and post-PFMT assessment. All participants were also asked to complete a subjective assessment of bladder symptom improvement after completion of the home-based PFMT. This subjective survey of improvement (which will be referred to as SSI in this document), was developed by Bø et al. 1990, and it utilizes a Likert scale of 5 to assess for 31 self-identified changes categorized as worsened: (1), unchanged (2), improved (3), almost continent (4) or continent (5).18 2.4.2 Waterloo footedness questionnaire Following the force plate measurements at baseline all participants were asked to complete the Waterloo Footedness Questionnaire-Revised version (WFQ).89 This is a validated questionnaire to determine footedness preference. It asks a series of 10 imagined scenario questions were participants must answer: Left always, Left usually, Equal, Right usually, Right always. These answers are assigned with corresponding values from -2 to 2 to provide a footedness preference score. Therefore, the minimum score of -20 would indicate the greatest left footedness preference and the maximum of 20 would indicate the greatest right footedness preference. 2.4.3 Bladder diaries Participants in the case group were required to complete bladder diaries. At baseline participants were instructed on how to complete a 24-hour 3-day bladder diary and were given a urinary hat in order to measure all urinary output. The 3-day bladder diary has been validated in previous literature.90 Participants were instructed to complete a baseline 3-day bladder diary immediately prior to initiating home-based PFMT. Participants were also instructed to complete an additional 24-hour 3-day bladder diary immediately after completing the 8-week home-based PFMT, prior to post-PFMT assessment. An example of how to record fluid intake, urinary output and urinary events in the diary was also provided to the participants.8 (Example of bladder diary provided in Appendix). 32 2.5 Data analysis 2.5.1 Standing force plate and WFQ Matlab was used to calculate the percentage of total ground reaction force (Fz) distributed to both the right and left lower limbs. The 3 trials of distracted stance were averaged. A calculation was then performed in SPSS to both the averaged distracted stance condition and to the quiet stance condition to determine Fz Ground Limb Dominance: Fz Limb Dominance = RFz-LFz This calculated Fz Limb Dominance value difference between ground reaction force measured from right limb (RFz) and left limb (LFz). A positive value indicates right limb dominance and a negative value indicates left limb dominance. The Wilcoxin Signed Rank test was performed to compare Fz Limb Dominance between Distracted and Quiet stance conditions. A Paired-T Test was performed to compare Fz Limb Dominance between Distracted and Quiet stance conditions for the study group. Spearman’s Rank Correlation was performed to test association between the absolute WFQ scores and the Fz Limb Dominance in Distracted and Quiet stance conditions separately within each the control and case groups. 2.5.2 SMVC focused analysis PFM assessment was carried out in the nature of performing MVCs, SMVCs and REPs as described and recommended by Laycock and Jerwood 2001 and Devreese et al. 2004.1,91,92 NIRS tracings from this full assessment were used in consideration of the functionality of the 33 tool itself and for the consideration of observational trends which will be further characterized in the results section. Although a full PFM assessment was performed, the objective NIRS analysis centred on the SMVC only. This was done in order to focus the results of the investigation on the ability of NIRS to detect oxygen recovery kinetics of the PFM. Rationale to do so is supported by the previous literature of Muthalib et al. 2010, who reported SMVCs are more likely than other contractions to demonstrate the O2 demand of the muscle tissue under investigation, as it requires more continued force production than MVCs and does not allow for the amount of resaturation which occurs during fast repeated contractions.93 The resaturation that occurs during fast repeated contractions allows for measure of the balance between O2 demand and O2 supply, as the tissue attempts to maintain equilibrium during a repeated task. As we were mostly interested in the O2 demand experienced by the PFM, we focused our analysis and objective outcome measures with values obtained from SMVC only. The SMVC in other PFM literature is also considered a good measure of both strength and endurance, compared to that of MVC which is considered to assess strength alone.1,30,94 2.5.3 PFM manometry The peak pressure of each contraction and the average pressure achieved during each contraction was evaluated for change from baseline to post-PFMT assessment. These pressure values were directly recorded from the manometer output. Prior to each contraction the manometer was set to zero while it remined in situation transvaginally to give absolute pressure change during the contraction. The peak and average pressures, along with the duration of each SMVC were used for analysis. 34 Due to participant follow-up attrition the sample size between baseline and post-PFMT assessments is variable both among the control and case groups. For analysis of manometer measures among the case group at baseline assessment N = 11 (SS1, SS3, SS4, SS5, SS7, SS9, SS10, SS11, SS12, SS13, SS14). For analysis at post-PFMT assessment N = 7 (SS1, SS3, SS9, SS10, SS12, SS13, SS14), SS7 did not complete post-NIRS manometer measurements due to reporting discomfort. As only the pre-NIRS manometer measurements ended up being used in analysis as will be described further in this section, analysis for manometer outcomes between baseline and post-PFMT assessment N=8 (SS1, SS3, SS7, SS9, SS10, SS12, SS13, SS14). For analysis of within assessment manometer measures among the control group at baseline assessment N = 14 (CS2 excluded as data missing from post-NIRS manometer measurement). For analysis within post-PFMT assessment and between baseline and post-PFMT assessment N = 13 (CS3 and CS5 withdrew after baseline assessment). Paired sample statistical testing was performed for SMVC Peak cmH2O, SMVC Average cmH2O and SMVC Timesec for the within session (both at baseline and post-PFMT assessment individually) pre and post NIRS manometer measurements to assess for evidence of muscular fatigue and learner effect. Since there was no significant difference found, except in one variable, post-PFMT assessment Average cmH2O, which still was highly positively correlated, the pre-NIRS manometer measurements were used for analysis for paired sample statistical testing of manometer measurements across sessions, comparison to NIRS measurement outcomes and to interventional exercise adherence. 35 2.5.4 NIRS Prior to all NIRS analysis a filter was applied to smooth the data. This filter was the Moving Gaussian Average which is a generic smoothing filter to reduce high frequency noise. This filters at a width of 1second and calculates the average within that 1second time point.57 This filter is a function inherent to the Oxysoft software. Similar filters have been utilized in other NIRS investigations.55,56,95 Also prior to analysis of each contraction (MVCs, SMVC and REPs) the NIRS tracing was set to arbitrary value of zero and the averaged 30seconds prior to the onset of each type of contraction was used as the baseline and calculated within the Oxysoft software.85,93,95-97 Although four NIRS variables were collected during the measurements (O2Hb, HHb, tHb, HbDiff) only HbDiff was selected for analysis. tHb is representative of blood volume and shifts in volume are indicative of blood flow changes, therefore it is a value used to assess hemodynamic changes within the muscle.97 HHb was not assessed independently as a NIRS variable as it has been determined by previous literature to be an unreliable means of measurement when employing occlusion free ½RT analysis (which was used in this study and will be explained further in this section).85 Whereas O2Hb and HbDiff represent relative oxygen saturation, HbDiff (in occlusion free ½RT analysis) is considered to be more indicative of metabolic changes within the muscle tissue, and less susceptible to blood flow changes than O2Hb.67,85,93,98-101 The responsiveness of HbDiff during exercise is a measure of coupled oxygen demand and supply, and when in recovery from exercise it reflects an index of oxygen delivery.99 Due to participant follow-up attrition the sample size between baseline and post-PFMT assessments is variable both among the controls and case participant groups for NIRS measurements. Also, four earlier NIRS measurements (CS2, CS3, CS4, SS1) had to be excluded 36 from analysis due to inaccurate signal transmission, which was later corrected with adjusted foam inlay as described previously in this section. For analysis of NIRS measures among the case group at baseline assessment only N = 10 (SS3, SS4, SS5, SS7, SS9, SS10, SS11, SS12, SS13, SS14). For analysis at post-PFMT assessment and across baseline and post-PFMT assessment N = 7 (SS3, SS7, SS9, SS10, SS12, SS13, SS14). For analysis of NIRS measures among the control group at baseline assessment N = 12 (CS1, CS5, CS6, CS7, CS8, CS9, CS10, CS11, CS12, CS13, CS14, CS15). For analysis at post-PFMT assessment and across baseline and post-PFMT assessment N = 11 (CS1, CS6, CS7, CS8, CS9, CS10, CS11, CS12, CS13, CS14, CS15). 2.5.4.1 Oxygen saturation patterns in response to exercise Peak magnitude change of the HbDiff NIRS variable was determined by the following means. The maximum magnitude change of each NIRS variable reached during every contraction was subtracted from its corresponding baseline value. Magnitude values were based on oxygen saturation patterns. The oxygen saturation pattern observed during PFM contraction and corresponding recovery interval is important to take into consideration, as saturation trends during exercise are an indicator of oxygen stress experienced by the muscle during exercise, while the oxygen saturation pattern in recovery indicates an oxygen deficit induced by exercise.102 Chance et al. 1992 describe how the observation of oxygen desaturation occurring with exercise represents an oxygen demand exceeding the ability of oxygen delivery mechanisms to maintain consistent oxygenation to the muscular capillaries, implying increased rate of oxygen consumption.93,102 Inversely, an increased oxygen concentration, or restaturation, pattern 37 indicates that oxygen delivery is greater than that of the muscular oxygen demand, implying reduced oxygen consumption and return to hemostatic balance within the tissue.93 Therefore, magnitude changes occurring during contractions were assessed based on their oxygen saturation pattern. In contractions where desaturation was identified the greatest minimum value reached during contraction was subtracted from the baseline. For contractions where increased saturation occurred the greatest maximum value reached during contraction had the baseline subtracted from it. The calculated peak magnitude change during contraction is referred to in this study as DMag. Pattern Contraction Recovery 1 Desaturation Resaturation 2 Desaturation Desaturation 3 Increased saturation Resaturation 4 Increased saturation Desaturation (to baseline) 5 No response No response 6 No response Increased saturation 7 No response Desaturation 8 Increased saturation Desaturation 9 Desaturation Resaturation (to baseline) Table 2.1 SPAM stratification of oxygen patterns. Stratification of oxygen saturation patterns observed during PFM contraction and corresponding 90-sedond recovery interval. The peak magnitude changes of the Right and Left PFM at baseline assessment were compared with paired sample statistical testing. Likewise, the peak magnitude changes of Right and Left PFM at post-PFMT assessment were compared with paired sample statistical testing. Also, the peak magnitude changes of Right PFM at baseline and post-PFMT assessment and Left PFM at baseline and post-PFMT assessment were compared with paired sample statistical testing. 38 2.5.4.2 Unilateral PFM dominance based on contraction magnitude change Once the Peak DMag were calculated based, all values were converted to absolute values, in order to determine unilateral PFM dominance. Dominance was determined based an algorithm accounting for saturation patterns, (Saturation Pattern Algorithm for PFM Dominance-SPAMD), which is shown below in Figure 2.5. Ultimately this algorithm calculated dominance by subtracting the absolute Peak DMag of the Left PFM from the absolute Peak DMag of the Right PFM. This yielded positive values indicative of Right DMag dominance and negative values indicative of Left DMag dominance. These values were then correlated to Fz scores in Distracted and Quiet stance conditions, as well as to WFQ scores. Figure 2.6 SPAMD algorithm. SPAMD algorithm for using saturation patterns to calculate unilateral PFM dominance. 39 2.5.4.3 Oxygen recovery kinetics in response to exercise (Half Recovery Time) The ability of skeletal muscle to recover from the oxygen deficit induced by exercise represents the oxidative metabolism of the muscle and implies muscular fitness, or aerobic capacity in that a muscle tissue has greater aerobic capacity when it is quickly able to restore depleted oxygen saturation levels after exercise.102,103 Early investigations with NIRS determined that the time of oxygen recovery following exercise can be used as a means to assess oxygen delivery deficits in relation to oxygen consumption.98,101,102 The specific NIRS variable of HbDiff (HbDiff = O2Hb-HHb), a calculation is an inherent function of the Oxysoft software and occurs in real time with the recorded measurements, is thought to represent deoxygenation102 and provide a stronger signal for analysis.104 Modern NIRS CWS-SRS equipment is able to provide a more accurate and absolute value of deoxygenation, the tissue saturation index (TSI). When measured in conjunction with transient occlusions to control for blood volume, TSI provides a validated and reliable means of noninvasively assessing respiratory capacity in skeletal muscle.46,97,105 These current TSI and occlusion method measurements evolved from the early investigations of Chance et al. 1992 and McCully et al. 1994, who both developed means of assessing the kinetics of muscle tissue recovery from exercise by calculating the half recovery time (½RT) from the cessation point of exercise to the point of maximum resaturation in recovery.98,102 As the NIRS equipment employed in this investigation is that of the CWS era, methods of measurement and analysis were used based on the initial literature derived from Chance et al. 1992 and McCully et al. 1994.102,98 McCully et al. 1994 further validated this method by fitting the HbDiff recovery to a mono-exponential curve, which gave similar results to the gold standard measurement of muscle oxidative metabolism with PCr under conditions of submaximal exercise.98 McCully et al. 1997 then applied this HbDiff curve fitting in a study 40 investigating peripheral vascular disease in an elderly population. However, they found that mono-exponential curve did not fit the majority of the HbDiff resaturation response following cessation of exercise in this clinical population. In order to analyze their data, they employed the ½RT of HbDiff, defined as half the time duration from the HbDiff difference at the end of exercise to near baseline and either did not change or showed overshoot for at least 30seconds.99 With this method they were able to determine that the ½RT of individuals with peripheral vascular disease were significantly slower than controls. Utilizing the ½RT methods, Ichimura et al. 2006 used the O2Hb variable to measure half recovery time and determined that it was inversely correlated with Peak VO2, meaning that lower systemic oxygenation capacity is related to having slower ½RT.101 Buchheit et al. 2010 compared ½RT calculations to ½RT mono-exponential curve fitting of O2Hb, HbDiff and HHb and found that O2Hb and HbDiff were moderately reliable (in occlusion free methods) but not HHb, and further suggested the ½RT calculation over mono-exponential curve fitting as it can be applied to more complex data sets.85,95,103 Based on this literature the ½RT calculation (for both HbDiff and O2Hb) method was used in this analysis in order to assess the muscle oxidative metabolism of PFM. All of these previous studies had varying recovery time intervals defining their ending points, based on Muthalib et al. 2010. As they had the most similar exercise protocol, we utilized their recovery time interval as 90-seonds following cessation of exercise, which was also used by DeLorey et al. 2002.97,106 41 Figure 2.7 Example of 1/2RT calculation in control participant. NIRS trace of Right SMVC in control participant and ½RT calculation. Vertical green bars denote the onset and cessation of SMVC contraction. 2.5.4.4 Original adaption of ½RT calculation analysis As we were investigating a population with impaired motor function due to neurologic conditions, the typically oxygen saturation response expected to be observed did not always occur in the study subjects. Rather, with some attempted contractions the inverse of the expected was observed, in that there would be an increase of oxygenation during the active contraction phase and desaturation (either returning to baseline or continued desaturation) during the recovery phase. As it is known that increased saturation means the oxygen supply is greater than oxygen demand,102 in cases where this atypical saturation pattern was observed it suggests a hemodynamic response, almost a priming response, to supply the muscle with extra oxygen to support anticipated oxygen consumption. However, no oxygen consumption occurs (lack of desaturation during contraction) meaning the PFM are not actively engaging or have a weak contraction with small oxygen demand, which the oxygen delivery exceeds, then returning to baseline with the relaxation in recovery phase. The presence of continued desaturation beyond the baseline levels would suggest an inability to fully relax the PFM after attempted contraction. 42 In cases where saturation patterns did not present with desaturation during contraction but rather an increase of oxygen saturation with desaturation return to baseline or continued desaturation in 90 second recovery period an Inverse ½RT calculation was used. Inverse ½RT determined as half the time to reach the difference value between the highest saturation point in HbDiff at end of contraction and the lowest point of desaturation in the recovery period. Figure 2.8 Example of inverse 1/2RT calculation in a case participant. NIRS trace of Right SMVC in case participant and Inverse ½RT due to an oxygen saturation pattern, Pattern 8 as per stratification Table 2.1. Vertical green bars denote the onset and cessation of SMVC contraction. The ½RT of the Right and Left PFM at baseline assessment were compared with paired sample statistical testing. Likewise, the ½RT of Right and Left PFM at post-PFMT assessment were compared with paired sample statistical testing. Also, the ½RT of Right PFM at baseline and post-PFMT assessments and Left PFM at baseline and post-PFMT assessments were compared with paired sample statistical testing. 2.5.4.5 Unilateral PFM dominance based on ½RT Unilateral dominance of PFM based on ½RT was calculated to provide a means of comparison to force plate measurements, WFQ scores and NIRS derived magnitude changes. 43 The calculation was completed by subtracting Left PFM from Right side to give a (+) value for a quicker Right Sided ½RT and (-) value for a quicker Left Sided ½RT. This was done so that (+) values for Right sided dominance would correspond with (+) Right sided values for the Fz Dominance values and WFQ scores. Careful consideration was paid to contraction and recovery saturation patterns to determine dominance when the patterns did not match, as non-matching oxygenation patterns could indicate unilateral dominance within itself. For instance, a Right sided SMVC with oxygen saturation pattern 1 with a concurrent Left sided SMVC with oxygen saturation pattern 8, would imply a more responsive PFM on the right, regardless if the recovery time is longer, as it is actually demonstrating oxygen consumption with contraction when the left side is not. Therefore, the same algorithm, SPAMD (as shown in Figure 2.5), was used to define unilateral DMag Dominance was also utilized for ½RT Dominance. ½RT Dominance was then correlated to DisFz, QFz, WFQ and DMag Dominance. 2.5.5 Bladder symptom questionnaires, bladder diaries and post void residual Intra-group pairwise comparison was performed for questionnaire scores, bladder diary variables and PVR measures recorded at baseline and post-PFMT. For the bladder diary comparison n=7 as SS9 did not complete bladder diaries. Inter-group independent parametric and non-parametric comparisons were performed for QUID (SUI and UUI) and PVR. Inter-group SSI responses of bladder symptoms improvement were reported as frequency and percentage of individual group total. 44 2.6 Statistical analysis Statistical analysis was performed using SPSS version 20. Data sets were analyzed with shapiro wilk test of normality to determined when parametric or non-parametric statistical testing should be employed. When performing independent samples testing the levene’s test was also performed, secondary to the shapiro wilk test to determine if parametric or non-parametric statistical testing should be employed. For all statistical testing a p-value of a <0.05 was utilized to determine significance. As outlined by Mukaka 2012, the following parameters were used to interpret the size of correlation coefficients: Very high correlation = +0.90 to +1.00, High correlation = +0.7 to +0.9, Moderate correlation = +0.5 to +0.70, Low correlation +0.30 to +0.50, Negligible correlation +0.00 to +0.30.107 45 Chapter 3: Results This chapter will provide a detailed account of the data collected and analyzed in this research project. Participant demographics and subjective outcome measures will be presented first. Observational findings regarding oxygen saturation patterns captured by the NIRS probe will be presented in terms of trends found among controls and among clinical sub-groups within the case group. Lastly, objective outcome measures derived from the NIRS probe and the PFM manometer are presented, along with their relation to PFMT adherence. 3.1 Participant demographics Demographic variables for both participant groups are demonstrated in Table 3.1. The mean age of controls and the case group was not shown to be statistically significant (p-value 0.05), although the controls on average were younger (mean 42 years compared to mean 51 years). Statistical significance was demonstrated between the parity of the two groups, the case group having a greater proportion of participants with parity >1 (90.9% compared to 46.7%, p-value 0.04). No significant differences were found between groups among the rest of the demographic variables including: BMI, menopause status, life style index of physical activity and smoking. Full summaries of demographic variables for each group at individual participant level are provided in Table 3.2 and Table 3.3. 46 DEMOGRAPHICS STUDY SAMPLE n=26 CONTROLS n=15 CASES n=11 P-VALUE AGE mean +SD range 46 +14 (24 to 72) 42 +15 (24 to 71) 51 +11 (35 to 72) .05 BMI mean +SD range 24.6 +5.2 (19.2 to 41.5) 23.5 +3.7 (19.2 to 33.7) 26.0 +6.8 (41.5 to 19.8) .37 PARITY 0 >1 9 (34.6%) 17 (65.4%) 8 (53.3%) 7 (46.7%) 1 (9.1%) 10 (90.9%) .04 MENOPAUSE Pre Post 17(65.4%) 9 (34.6%) 10 (66.7%) 5 (33.3%) 7(63.6%) 4 (36.3%) 1.00 LIFE STYLE INDEX Sedentary Moderate Active 3 (11.5%) 9 (34.6%) 14 (53.8%) 1 (0.07%) 5 (33.3%) 9 (60.0%) 2 (18.2%) 4 (36.4%) 5 (45.5%) .41 SMOKING Non-Smoker Smoker 24 (92.3%) 2 (0.08%) 14 (93.3%) 1 (0.07%) 10 (90.9%) 1 (0.09%) 1.00 Table 3.1 Demographics of study sample by participant group. Mann-Whitney U-test with (2-tailed) performed for the variables: age, BMI (kg/m2) and life style index. Fischer’s Exact test (2-tailed) was performed for the variables: parity, menopause and smoking. Grouped menopause peri status into pre (only one peri-menopause status in case group). Parity grouped as nulliparous and parity>1, (parity range 0-3 for both groups). PARTICIPANT AGE BMI PARITY MENOPAUSE ETIOLOGY of PFM DYSFUNCTION LIFE STYLE INDEX SMOKER SS1 72 25.5 3 POST Post-Polio Syndrome MODERATE NO SS3 42 22 1 PRE Non-Traumatic SCI (benign tumor in spine hemorrhage, persisting arachnoiditis) ASIA-B ACTIVE NO SS4 53 25.4 1 PRE Traumatic SCI (T8 incomplete paraplegia ASIA-D) MODERATE NO SS5 63 24.5 2 POST Multiple Sclerosis (secondary progressive) MODERATE NO SS7 59 20.2 1 POST Traumatic SCI (L4-L5 incomplete) & Subsequent TBI SEDENTARY NO SS9 48 22.3 1 PRE Labour Trauma ACTIVE YES SS10 45 25.3 1 PRE Labour Trauma ACTIVE NO SS11 42 23.7 2 PRE Labour Trauma & Congenital Right Hip Dysplasia ACTIVE NO SS12 35 36.3 0 PRE Multiple Sclerosis (relapse-remitting) MODERATE NO SS13 57 41.5 3 POST Spinal Stenosis (L4) & Congenital bilateral hip dysplasia (multiple surgical interventions) SEDENTARY NO SS14 45 19.8 2 PERI Traumatic SCI (C2-C4 incomplete) & Concurrent TBI ACTIVE NO Table 3.2 Demographic details of case participants listed by participant ID. 47 PARTICIPANT AGE BMI PARITY MENOPAUSE LIFE STYLE INDEX SMOKER CS1 30 20.7 0 PRE ACTIVE NO CS2 32 26.8 0 PRE MODERATE NO CS3 32 33.7 0 PRE SEDENTARY NO CS4 71 23.1 3 POST ACTIVE NO CS5 56 19.2 3 POST MODERATE NO CS6 24 26.9 0 PRE MODERATE NO CS7 60 24 1 POST MODERATE NO CS8 34 20.2 2 PRE MODERATE NO CS9 30 22.6 0 PRE ACTIVE YES CS10 31 22.4 0 PRE ACTIVE NO CS11 62 22.1 2 POST ACTIVE NO CS12 38 23.7 1 PRE ACTIVE NO CS13 58 19.5 2 POST ACTIVE NO CS14 32 24.7 0 PRE ACTIVE NO CS15 33 22.5 0 PRE ACTIVE NO Table 3.3 Demographic details of control participants listed by participant ID. 3.2 Questionnaires, post void residual and bladder diary outcome measures 3.2.1 Intra-group comparison A reduction in mean values for both control and case groups is demonstrated from baseline to post-PFMT for all questionnaires and PVR, (Table 3.4). These reductions only demonstrated to be statistically significant for one questionnaire variable among the case group, and this was the QUID-UUI score (Figure 3.1). Although the case group demonstrated less urgency symptoms as per reduction in the QUID-UUI score, there were no statistical differences found for all variables measured in the 3-day bladder diaries completed at baseline and post-PFMT. Results shown in Table 3.5. 48 Participant Group Variable Baseline Post-PFMT P-value Controls n=13 QUID-SUI mean +SD range 1.46 +1.56 (0 to 5) 0.85 +0.80 (0 to 2) .25 NP QUID-UUI mean +SD range 1.92 +2.66 (0 to 8) 1.23 +1.48 (0 to 4) .55 NP PVR (ml) mean +SD range 48.23 +41.38 (0 to 138) 47.69 +55.55 (0 to 200) .96 Cases n=8 UDI-6 mean +SD range 33.85 +9.82 (16.67 to 45.83) 30.73 +12.19 (12.50 to 50.00) .31 NP IIQ-7 mean +SD range 35.08 +27.14 (0.00 to 66.60) 26.87 +24.98 (0.00 to 61.84) .20 QUID-SUI mean +SD range 4.75 +3.37 (0 to 11) 2.75 +2.25 (0 to 6) .08 QUID-UUI mean +SD range 7.5 +3.89 (1 to 14) 5.0 +2.33 (1 to 7) .03 PVR (ml) mean +SD range 51.00 +55.54 (13 to 175) 16.50 +13.40 (0 to 40) .44 NP Table 3.4 Intra-group comparison of questionnaires and PVR. Intra-group comparison of questionnaires and PVR measures at baseline and post-PFMT assessments. Parametric and non-parametric paired sample tests performed. NP denotes when non-parametric performed with Wilcoxin Signed Rank test (2-tailed). Figure 3.1 Case group QUID-UUI score reduction. Case group demonstrated statistically significant (p-value 0.03) reduction in QUID-UUI score at post-PFMT compared to baseline score. * indicates statistical significance. 0246810121416Baseline Post-PFMTQUID-UUI ScoreSS1SS3SS7SS9SS10SS12SS13SS14* 49 Variable Baseline Post-PFMT P-value Frequency (mean count) mean +SD range 6.74 +1.66 (4.5 to 9.00) 7.29 +1.68 (4.67 to 9.67) .22 DVVmax (ml) mean +SD range 416.67 +179.83 (200.00 to 733.33) 408.33 +166.18 (150.00 to 66.67) .88 Nocturia (mean count) mean +SD range 0.74 +0.88 (0.00 to 2.00) 0.26 +0.27 (0.00 to 0.67) .37NP Incontinence (mean count) mean +SD range 0.67 +0.67 (0.00 to 2.00) 0.60 +1.29 (0.00 to 3.50) .82 Table 3.5 Case group 3-day bladder diary variables. Comparison of recorded measures from 3-day bladder diaries completed by case group at baseline and post-PFMT. N=7 (SS9 did not complete bladder diaries). Parametric and non-parametric Paired Sample tests performed. NP denotes when non-parametric performed with Wilcoxin Signed Rank test (2-tailed). DVVmax indicates the maximum volume of one void per day. 3.2.2 Inter-group comparison of questionnaires and post void residual Inter-group comparisons for QUID (SUI and UUI) and PVR did not demonstrate a statistically significant difference in measured improvement from baseline to post-PFMT assessment. Results demonstrated in Table 3.6. Results of the SSI inter-group comparison also did not demonstrate statistical difference in how both groups subjectively rated their bladder symptoms post-PFMT. Among the control group 6 out 13 (46.15%) reported feeling “continent”, 1 out of 13 (7.69%) reported feeling “almost continent”, 2 out of 13 (15.38%) reported feeling “improved” and 4 out of 13 (30.77%) reported feeling “unchanged” on the SSI at post-PFMT assessment. Among the case group 1 out of 8 (12.5%) reported feeling “continent”, 4 out of 8 (50.00%) reported feeling “improved” and 3 out of 8 (37.50%) reported feeling “unchanged” on the SSI at post-PFMT assessment. 50 Variable Controls n=13 Cases n=8 P-value QUID-SUI mean +SD range -0.61 +1.56 (-4 to 2) -2.00 +2.73 (-7 to 2) .15 QUID-UUI mean +SD range -0.69 +2.53 (-6 to 3) -2.50 +2.56 (-7 to 1) .13 SSI mean +SD range 3.69 +1.38 (2 to 5) 3.06 +0.90 (2 to 5) .22NP PVR (ml) mean +SD range -0.54 +37.08 (-58 to 78) -34.5 +64.33 (-175 to 13) .14 Table 3.6 Inter-group SSI comparison. Inter-group comparison for QUID (SUI and UUI), SSI and PVR. PVR values represented are that of the change in score calculated by subtracting post-PFMT score from baseline score. Independent T-Tests (2-tailed) performed. NP denotes when Mann-Whitney U-test (2-tailed) performed. 3.3 Force plate, WFQ and NIRS dominance outcome measures 3.3.1 Intra-group comparison During intra-group comparison the controls demonstrated a statistically significant highly positive correlation between DisFz and QFz lower limb dominance, (rs= 0.83, p-value <0.001), with no demonstrated difference between the values measured during either standing condition, data shown in Table 3.7-3.8 and Figure 3.2. No positive correlation was demonstrated between lower limb dominance and NIRS PFM dominance measures for controls, but a moderate inverse association was demonstrated between QFz and baseline DMag Dom, refer to Table 3.9. Although the case group suggested a moderately positive correlation between DisFz and QFz lower limb dominance it was not statistically significant (rs= 0.61, p-value 0.06), suggesting more variability in standing posture between the two conditions even though the pairwise comparison did not demonstrate show any difference. Findings shown in Table 3.7-3.8 and Figure 3.2. Similar to controls the case group did not demonstrate any correlation between lower 51 limb dominance and NIRS PFM dominance measures, refer to Table 3.9, suggesting lower limb dominance measures did not translate to unilateral PFM dominance. Also, no correlation was demonstrated between lower limb dominance and NIRS dominance variables at post-PFMT. Participant Group n Variables Mean +SD P-value Controls 14 DisFz QFz 0.11 +0.20 0.09 +0.17 0.17 Cases 10 DisFz QFz -0.07 +0.09 -0.05 +0.08 0.85NP Table 3.7 Intra-group Fz lower limb dominance comparison. Intra-group comparison of DisFz and QFz measures of lower limb dominance. Parametric and non-parametric Paired Sample tests performed. NP denotes when non-parametric performed with Wilcoxin Signed Rank test (2-tailed). Participant Group n Variables Correlation Coefficient P-value Controls 14 DisFz vs QFz rs = 0.83 <0.001 14 DisFz vs WFQ rs = -0.38 0.18 14 QFz vs WFQ rs = -0.45 0.10 Cases 10 DisFz vs QFz rs = 0.61 0.06 10 DisFz vs WFQ rs = 0.08 0.82 10 QFz vs WFQ rs = 0.21 0.57 Table 3.8 Intra-group Fz and WFQ lower limb dominance correlation. Intra-group correlation between Fz and WFQ measures of lower limb dominance. Non-parametric Spearman Rank correlation performed for all variables. Figure 3.2 Intra-group DisFz and QFz association. Intra-group association between Distracted stance ground reaction force lower limb dominance (DisFz) and Quiet stance ground reaction force lower limb dominance (QFz). Positive value indicates right lower limb dominance and negative value indicates left lower limb dominance. Blue represents controls (rs= 0.83, p-value = <0.001). Orange represents case group (rs= 0.61, p-value = 0.06). * indicates statistical significance. 52 Participant Group n Variables Correlation Coefficient P-value Controls 12 DisFz vs Baseline ½RT Dom rs = 0.00 1.00 12 DisFz vs Baseline DMag Dom rs = -0.36 0.25 12 QFz vs Baseline ½RT Dom rs = -0.15 0.63 12 QFz vs Baseline DMag Dom rs = -0.64 0.03 12 WFQ vs Baseline ½RT Dom rs = 0.29 0.37 12 WFQ vs Baseline DMag Dom rs = 0.18 0.57 Cases 9 DisFz vs Baseline ½RT Dom rs = 0.40 0.29 9 DisFz vs Baseline DMag Dom rs = -1.00 0.80 9 QFz vs Baseline ½RT Dom rs = 0.48 0.19 9 QFz vs Baseline DMag Dom rs = -0.07 0.87 9 WFQ vs Baseline ½RT Dom rs = 0.12 0.76 9 WFQ vs Baseline DMag Dom rs = -0.48 0.19 Table 3.9 Intra-group Fz, WFQ and NIRS dominance correlations. Intra-group correlation between Fz, WFQ lower limb dominance measures and NIRS PFM dominance measures. Non-parametric Spearman Rank correlation performed for all variables. 3.3.2 Inter-group comparison When performing inter-group comparisons there was a statistically significant difference in the lower limb dominance in both DisFz and QFz conditions. On average the controls demonstrated predominant Right lower limb dominance and the case group demonstrated predominant Left lower limb dominance, which remained consistent for both DisFz and QFz conditions (0.11 compared to -0.07, and 0.09 compared to -0.05, respectively). Findings shown in Table 3.10 and Figure 3.3. However, it should be noted that there were 2 significant outliers in the control group (CS6 and CS7), who demonstrated a large degree of dominance, which remained consistent across both standing conditions. 53 Variable Controls n=14 Cases n=10 P-value DisFz mean +SD range 0.11 +0.20 (-0.05 to 0.58) -0.07 +0.09 (-0.25 to 0.06) <.01 QFz mean +SD range 0.09 +0.17 (-0.07 to 0.48) -0.05 +0.08 (-0.22 to 0.06) <.01 WFQ mean +SD range 9.5 +6.36 (-3.00 to 20.00) 7.30 +9.88 (-16.00 to 17.00) .69 Controls n=12 Cases n=10 Baseline ½RT Dominance mean +SD range 4.96 +12.21 -0.80 to 43.40 -3.39 +25.10 -57.00 to 33.90 0.47 Baseline DMag Dominance mean +SD range 1.12 +6.03 -6.04 to 11.03 -2.10 +4.39 -12.51 to 2.80 0.46 Controls n=11 Cases n=7 Post-PFMT ½RT Dominance mean +SD range 1.67 +23.66 -42.80 to 61.40 -7.56 +26.92 -60.80 to 28.00 0.47 Post-PFMT DMag Dominance mean +SD range 1.85 +7.02 -9.27 to 15.81 -6.69 +13.00 -34.23 to 3.58 0.18 Table 3.10 Inter-group Fz, WFQ and NIRS dominance comparison. Inter-group comparison of lower limb dominance and PFM dominance measures. Non-parametric Mann-Whiney U T-tests (2-tailed) performed. Figure 3.3 Inter-group DisFz and QFz comparison. Inter-group comparison between Fz measures of lower limb dominance. Error bars represent + 1 SD. * indincates statistical significance. Distracted stance ground reaction force lower limb dominance (DisFz) and Quiet stance ground reaction force lower limb dominance (QFz). Positive value indicates right lower limb dominance and negative value indicates left lower limb dominance. Statistically significant difference between groups for both DisFz and QFz variables (p-value < 0.01). 54 3.4 NIRS observational outcome findings 3.4.1 Observational NIRS findings Based on the inter-group observational trends the case group demonstrated more complex NIRS tracings during measurements, reflected by atypical muscle tissue contraction and recovery hemodynamic patterns, resulting in slower ½RT and decreased DMag changes on average. (Please refer to Table 3.12 and 3.14, and Figures 3.20-3.21). Similarly, the exploratory findings of Ryan et al. 2014, also suggested that individuals with a neurologic condition (amyotrophic lateral sclerosis), tended to have slower ½RT than controls.53 It should be noted that this research group used ½RT calculations based on occlusion NIRS methods and TSI%. To demonstrate the observational trends found between the control and case groups during PFM assessment an example of control participant NIRS tracings are provided, evidencing typical hemodynamic response of muscle contraction and recovery patterns. Following these typical hemodynamic tracings found among the control group a series of case participant NIRS tracings are presented. Due to large heterogeneity the case group tracings were further categorized into relevant clinical sub-groups based on NIRS tracing trends characterized by etiology of PFM dysfunction and mobility status. 3.4.1.1 Control group trends With each attempted contraction desaturation is demonstrated with resaturation occurring in recovery, consistent with skeletal muscle oxygenation patterns in response to exercise as described in previous literature.93,95,99 The following Figures: 3.4 to 3.8, demonstrate the typical PFM response during the NIRS assessment. 55 Figure 3.4.A. Control participant CS1 performing MVCs. NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Figure 3.4.B. Control participant CS1 performing SMVC. NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Black dotted lines denote contraction onset and cessation. Figure 3.4.C. Control participant CS1 performing REP. NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Black dotted lines denote contraction onset and cessation. Figure 3.4 Control participant CS1 performing MVCs, SMVC and REP. 56 Figure 3.5 Control participant CS1 performing SMVC at baseline and post-PFMT. NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Black dotted lines denote contraction onset and cessation. Figure 3.6.A Control participant CS1 SMVC oxygenation patterns at baseline. Bilateral PFM HbDiff oxygenation patterns during SMVC at baseline. Starting at contraction onset and inclusive of last 10 deciseconds following end of contraction. Figure 3.6.B Control participant CS1 SMVC oxygenation patterns at post-PFMT. Bilateral PFM HbDiff oxygenation patterns during SMVC at baseline. Starting at contraction onset and inclusive of last 10 deciseconds following end of contraction. Figure 3.6 Control participant CS1 SMVC oxygenation patterns at baseline and post-PFMT. -9-8-7-6-5-4-3-2-104536 4736 4936HbDiff Concentration umolTime in DecisecondsSMVC BaselineRight PFM Left PFM-14-12-10-8-6-4-204872 4922 4972 5022 5072HbDiff Concentration umolTime in DecisecondsSMVC Post-PFMTRight PFM Left PFM57 Figure 3.7 Control participant CS7 performing SMVC at baseline and post-PFMT. NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Black dotted lines denote contraction onset and cessation. Figure 3.8.A Control participant CS7 SMVC oxygenation patterns at baseline. Bilateral PFM HbDiff oxygenation patterns during SMVC at baseline. Starting at contraction onset and inclusive of last 10 deciseconds following end of contraction. Figure 3.8.B Control participant CS7 SMVC oxygenation patterns at post-PFMT. Bilateral PFM HbDiff oxygenation patterns during SMVC at baseline. Starting at contraction onset and inclusive of last 10 deciseconds following end of contraction. Figure 3.8 Control participant CS7 SMVC oxygenation patterns at baseline and post-PFMT. -15-13-11-9-7-5-3-115607 5807 6007 6207 6407HbDiff Concentration umolTime in DecisecondsSMVC BaselineRight PFM Left PFM-25-20-15-10-509104 9604 10104 10604 11104HbDiff Concentration umolTime in DecisecondsSMVC Post-PFMTRight PFM Left PFM58 3.4.1.2 Case group trends There was large heterogeneity among sampled population in their underlying etiology for PFM dysfunction (as described in Table 3.2). This heterogeneity resulted in observation of diverse PFM oxygenation patterns in response to exercise during NIRS assessments. Observational trends of the oxygenation patterns were categorized according to clinical sub-groups. Clinical sub-groups were categorized based on consideration of underlying etiology of PFM dysfunction and mobility status. Mobility status was categorized in the following manner: high mobility (not dependent on mobility aid), assisted mobility (dependent on mobility aid with limited ability of independent ambulation), wheelchair user (wheelchair used for primary mode of mobility). The high mobility group included four case participants (SS9, SS10, SS11, SS13, SS14) and had the following underlying etiology for PFM dysfunction: labour trauma, congenital hip dysplasia, traumatic SCI. The specific etiology of PFM dysfunction of each participant within the high mobility group can be referred to in Table 3.2. Despite participant SS12 having high mobility status, the oxygenation trends presented more similarly to other participant, SS5, both presenting with the immune mediated neurologic condition of multiple sclerosis (MS). Although both had MS, this neurologic condition results in varying clinical presentations and diagnoses. SS12 had relapse-remitting MS with high mobility and SS5 had secondary progressive MS and was as a wheelchair user. Both presented with similar atypical characteristics, but also presented with similarity trends overlapping with the SCI clinical sub-group. However, due to their underlying etiology of an immune mediated neurological condition, they were categorized independently for initial observational characterization of oxygenation pattern trends. 59 The final clinical sub-group were participants with SCI who had either assisted mobility or were wheelchair users, which included SS3, SS4, SS7, (refer to Table 3.2 for specific etiology). Specific to mobility status, SS3 was a wheelchair user, whereas SS4 and SS7 were considered to have assisted mobility status. 3.4.1.2.1 High mobility clinical sub-group Those participants in the high mobility group tended to demonstrate PFM oxygenation patterns similar to that of the control group, generating desaturation with contraction and resaturation during recovery phase, and exhibited on bilateral PFM. Figures 3.9-3.10 demonstrate the oxygenation patterns observed in a participant with labour trauma, congenital dysplasia of the right hip and LUTS, with unimpaired mobility (SS11). The NIRS assessment with this participant demonstrated typical saturation patterns, as compared to controls. Similar tracings were also demonstrated by SS13, who had underlying spinal stenosis, congenital hip dysplasia and multiple bilateral hip replacement surgeries, with minimal cane assisted mobility. Similar tracings were also demonstrated by SS14. This participant has a history incomplete traumatic C2-C4 SCI (no current ASIA score), but independent unassisted mobility, decreased sensation to pelvis with self-reported hypersensitivity and hyper-reflexes of bilateral lower limbs. As shown in Figure 3.11-3.12, SS14, demonstrates typical desaturation during contraction with resaturation in recovery, similar to control group. At post-PFMT assessment greater desaturation evidenced during contraction and resaturation in recovery is observed. Furthermore, despite a discrepancy in magnitude change, the contraction patterns evidence similar curve characteristics bilaterally, see Figure 3.12. 60 SS9 and SS10 were also considered to have high mobility, and both had an underlying etiology of labour trauma. Interestingly, their NIRS tracings had boarder line trends between the high mobility and assisted mobility clinical sub-groups. Although both displayed typical patterning at post-PFMT, the characteristics of the patterning was less similar across bilateral PFM, a characteristic trend found among the SCI assisted mobility group, as demonstrated in Figure 3.19. 61 Figure 3.9.A. Case participant SS11 performing MVCs NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Figure 3.9.B. Case participant SS11 performing SMVC NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Black dotted lines denote contraction onset and cessation. Figure 3.9.C. Case participant SS11 performing REP NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Black dotted lines denote contraction onset and cessation. Figure 3.9 Case participant SS11 performing MVCs, SMVC and REP. 62 Figure 3.10 Case participant SS11 SMVC oxygenation patterns at baseline. Bilateral PFM HbDiff oxygenation patterns during SMVC at baseline. Starting at contraction onset and inclusive of last 10 deciseconds following end of contraction. Figure 3.11 Case participant SS14 performing SMVC at baseline and post-PFMT. Case participant SS14 with traumatic SCI, SS14, performing SMVC at baseline and post-PFMT assessment. NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Black dotted lines denote contraction onset and cessation. -5-4-3-2-1014699 4719 4739 4759 4779HbDiff Concentration umolTime in DecisecondsSMVC BaselineRight PFM Left PFM63 Figure 3.12.A. Case participant SS14 SMVC oxygenation patterns at baseline. Bilateral PFM HbDiff oxygenation patterns during SMVC at baseline. Starting at contraction onset and inclusive of last 10 deciseconds following end of contraction. Figure 3.12.B. Case participant SS14 SMVC oxygenation patterns at post-PFMT. Bilateral PFM HbDiff oxygenation patterns during SMVC at baseline. Starting at contraction onset and inclusive of last 10 deciseconds following end of contraction. Figure 3.12 Case participant SS14 SMVC oxygenation patterns at baseline and post-PFMT. 3.4.1.2.2 Multiple Sclerosis clinical sub-group MS is a very complex auto-immune mediated disease attacking the central nervous system. This progressive disease causes cell death as chronic inflammation of immune cell infiltrates form plaques in the central nervous system, resulting in demyelination and axonal transection.108,109 Due to this pathology the neurological deficits incurred present in a heterogeneous manner across MS subtypes and across individuals, but often include: autonomic and sensorimotor defects, ataxia, lower urinary tract symptoms, fatigue, visual disturbances and cognitive difficulties.109-113 Exercise training is a common therapy used in the MS population to help manage symptoms and promote quality of life.114,115 Ataxia and sensorimotor defects typically cause unilateral asymmetries in muscular function,110,116 which result in dominant muscles taking on more of the workload during functional tasks and exercise.111 Therefore, -5-4-3-2-1014466 4516 4566 4616HbDiff Concentration umolTime in DecisecondsSMVC BaselineRight PFM Left PFM-50-40-30-20-1005475 5495 5515 5535HbDiff Concentration umolTime in DecisecondsSMVC Post-PFMTRight PFM Left PFM64 exercise therapy in the MS population not only aims to improve muscular strength and endurance but also targets discoordination and muscular imbalances found with unilateral asymmetries.111,112,116,117 As such it was expected that NIRS would capture muscular discoordination and asymmetry in the bilateral PFM during exercise. Figures 3.13-3.15 demonstrate oxygenation patterns observed in a participant with relapse-remitting MS (SS12). At the time of NIRS assessments participant was not experiencing relapse symptoms, although they did occur during the intervention phase and subsequently remitted. Such symptoms reported by participant were impaired sensation to perineum, abdomen, and bilateral lower limbs. Participant did not present with mobility issues and did not use any mobility aids. SS5 had secondary progressive MS and a wheelchair user, with inability to support sustained weight bearing on lower limbs. For both MS participants atypical pattern presentation during SMVC was noted with increase in oxygenation during contraction, although SS12 demonstrated a return to baseline or increased oxygenation in recovery and SS5 demonstrated increase during contraction with return to baseline or continued desaturation in recovery. However, both demonstrated typical patterning with REP contractions. Although both MS participants shared these similarities in patterning, individually they shared characteristics similar to the SCI clinical sub-group. SS5 demonstrated trends similar to SS4 and SS7, SCI assisted mobility sub-group, in that atypical patterning was consistent across different contractions with unilateral discrepancy, as shown in Figure 3.19. In contrast, SS12, demonstrated patterning characteristics similar to SS3, SCI assisted mobility sub-group, in that they both demonstrate an apparent lack of response unilateral PFM during attempted contraction, as shown in Figure 3.14 and 3.17. 65 Figure 3.13.A. Case participant SS12 performing MVCs at baseline. SS12 in MS clinical sub-group. NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Figure 3.13.B. Case participant SS12 performing SMVC at baseline. SS12 in MS clinical sub-group. NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Black dotted lines denote contraction onset and cessation. Figure 3.13.C. Case participant SS12 performing REP at baseline. SS12 in MS clinical sub-group. NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Black dotted lines denote contraction onset and cessation. Figure 3.13 Case participant SS12 performing MVCs, SMVC and REP. 66 Figure 3.14 Case participant SS12 performing SMVC at baseline and post-PFMT. SS12 in MS clinical sub-group. NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Black dotted lines denote contraction onset and cessation. Figure 3.15.A. Case participant SS12 SMVC oxygenation patterns at baseline. SS12 in MS clinical sub-group. Bilateral PFM HbDiff oxygenation patterns during SMVC at baseline. Starting at contraction onset and inclusive of last 10 deciseconds following end of contraction. Figure 3.15.B. Case participant SS12 SMVC oxygenation patterns at post-PFMT. SS12 in MS clinical sub-group. Bilateral PFM HbDiff oxygenation patterns during SMVC at baseline. Starting at contraction onset and inclusive of last 10 deciseconds following end of contraction. Figure 3.15 Case participant SS12 SMVC oxygenation patterns at baseline and post-PFMT. -1012345674541 4561 4581 4601HbDiff Concentration umolTime in DecisecondsSMVC BaselineRight PFM Left PFM00.20.40.60.811.24928 4948 4968 4988HbDiff Concentration umolTime in DecisecondsSMVC Post-PFMTRight PFM Left PFM67 3.4.1.2.3 SCI Clinical Sub-group The NIRS observations in this clinical sub-group varied based on mobility status, in that those with assisted mobility tended to generate more responsive NIRS tracings than the wheelchair user, SS3, who presented with history of incomplete non-traumatic SCI at T10-12 ASIA-B, and self-reported increased sensation to left side. At both baseline and post-PFMT assessments SS3 patterning is characterized by an apparent lack of response in unilateral Right PFM with atypical patterning in the Left PFM, as shown in Figures 3.16-3.18. SS4 presented with incomplete traumatic SCI at T8-T12 ASIA-D, self-reported increased sensation in left lower limb compared to right and assisted mobility status. SS4 demonstrates some apparent typical saturation pattern in contraction, although it is complex. As it is slower to present on one side compared to the other and at low magnitude. Refer to Figure 3.19. There is almost a biphasic contraction response (initial increase wit transition to decrease during contraction), which is also suggested in SS3 left PFM at baseline. However, the larger degree of magnitude change, in SS4 compared to SS3, with desaturation occurring in contraction, suggests pattern characteristics more similar to the high mobility than the SCI wheelchair user. However, the atypical and bilateral variability in oxygen patterns presenting during recovery period, along with less stable resting periods prior to contractions is observed to be similar of those trends seen in MS participants. SS7 demonstrated similar trends as observed in SS4. 68 Figure 3.16 Case participant SS3 performing SMVC at baseline including full recovery time interval. Case participant in SCI clinical sub-group. Black boxes indicate beginning and end of SMVC contraction. Figure 3.17 Case participant SS3 performing SMVC at baseline and post-PFMT. Case participant in SCI clinical sub-group. NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Black dotted lines denote contraction onset and cessation. 69 Figure 3.18.A. Case participant SS3 SMVC oxygenation patterns at baseline. Case participant in SCI clinical sub-group. Bilateral PFM HbDiff oxygenation patterns during SMVC at baseline. Starting at contraction onset and inclusive of last 10 deciseconds following end of contraction. Figure 3.18.B. Case participant SS3 SMVC oxygenation patterns at post-PFMT. Case participant in SCI clinical sub-group. Bilateral PFM HbDiff oxygenation patterns during SMVC at baseline. Starting at contraction onset and inclusive of last 10 deciseconds following end of contraction. Figure 3.18 Case participant SS3 SMVC oxygenation patterns at baseline and post-PFMT. Figure 3.19.A. Case participant SS4 SMVC at baseline. Case participant in SCI clinical sub-group. NIRS traces include 10 seconds prior to contraction and 10 seconds after contraction. Black dotted lines denote contraction onset and cessation. Figure 3.19.B. SS4 SMVC oxygenation patterns at baseline. Case participant in SCI clinical sub-group. Bilateral PFM HbDiff oxygenation patterns during SMVC at baseline. Starting at contraction onset and inclusive of last 10 deciseconds following end of contraction. Figure 3.19 Case participant SS4 SMVC at baseline. -2.5-2-1.5-1-0.500.511.525396 5446 5496HbDiff Concentration umolTime in DecisecondsSMVC BaselineRight PFM Left PFM-0.500.511.525929 5949 5969 5989HbDiff Concentration umolTime in DecisecondsSMVC Post-PFMTRight PFM Left PFM-6-4-20246810124664 4764 4864 4964HbDiff Concentration umolTime in DecisecondsSMVC BaselineRight PFM Left PFM70 3.5 NIRS objective outcome measures 3.5.1 ½RT NIRS measurements 3.5.1.1 Intra-group ½RT comparison When comparing intra-group ½RT at baseline only the control group demonstrated a statistically significant difference bilaterally (p-value 0.02). On average the control group had faster ½RT in the Right PFM compared to the Left PFM, (6.30seconds and 11.39seconds, respectively). Despite having quicker ½RT in the Right PFM, Right and Left PFM ½RT had high positive correlation (rs=0.76) at baseline. The control group did not demonstrate any significant difference or association in bilateral PFM ½RT at post-PFMT. Nor was any significant difference or association found in unilateral PFM ½RT or in ½RT Dominance across baseline and post-PFMT assessments. Refer to Table 3.11. Intra-group comparison for the case group demonstrated a moderate positive correlation of bilateral PFM ½RT at baseline (rs= 0.68). The case group also demonstrated high positive correlation between baseline and post-PFMT ½RT Dominance (r= 0.91). No other significant findings were demonstrated among the case group when analyzing bilateral PFM ½RT at baseline and post-PFMT, unilateral PFM ½RT across baseline and post-PFMT, or in ½RT Dominance across baseline and post-PFMT. Refer to Table 3.11. 3.5.1.2 Inter-group ½RT comparison Statistically significant differences were found among the ½RT of the Right PFM at baseline, where the control group demonstrated on average faster recovery times than the case group (mean ½RT 6.30seconds and 18.90seconds, p-value <0.01), as shown in Table 3.12 and 71 Figure 3.20. Although the control group also on average demonstrated faster ½RT in the Left PFM as well, the difference between the two groups was not statistically significant. Furthermore, the control group demonstrated significantly less unilateral ½RT Dominance at baseline than the case group, (5.16 compared to 17.41, p-value < 0.01) At post-PFMT statistical significance was demonstrated between control and case groups for Right PFM ½RT, providing evidence that the case group had slower ½RT unilateral in Right PFM compared to the control group, (7.87seconds compared to 38.03seconds, p-value 0.01). Results shown in Table 3.12. Similar to the baseline inter-group comparison, there was no statistical difference found between groups for the ½RT among the unilateral Left PFM. Although a statistically significant difference was not determined, the case group on average did demonstrate slower ½RT in the Left PFM (18.54seconds compared to 9.55seconds). Interestingly, the significant difference in degree of ½RT Dominance demonstrated at baseline between the two groups was not maintained at post-PFMT. 72 Participant Group n Variable Mean +SD Variable Mean +SD Pairwise P-value Correlation Coefficient Correlation P-value Controls 12 Baseline Right ½RT Baseline Left ½RT 6.30 +9.75 (Lg10)0.59 +0.36 11.39 +21.83 (Lg10)0.76 +0.12 (Lg10) .02 rs= .76 <.01 11 Post-PFMT Right ½RT Post-PFMT Left ½RT 7.87 +13.34 9.55 +18.11 .72NP rs= .44 .17 11 Baseline Right ½RT Post-PFMT Right ½RT 3.66 +1.51 7.87 +13.34 .79NP rs= .18 .59 11 Baseline Left ½RT Post-PFMT Left ½RT 5.33 +2.51 (Lg10)0.66 +0.23 9.55 +18.11 (Lg10)0.69 +0.44 (Lg10) .82 rs= .06 .87 11 Baseline ½RT Dominance Post-PFMT ½RT Dominance 1.46 +1.65 1.67 +23.66 .13NP rs= .11 .76 Cases 10 Baseline Right ½RT Baseline Left ½RT 18.90 +11.35 19.36 +19.82 .92 rs= .68 .03 7 Post-PFMT Right ½RT Post-PFMT Left ½RT 38.03 +26.93 18.54 +23.09 .12 (Sqrt)r= .45 .31 7 Baseline Right ½RT Post-PFMT Right ½RT 18.59 +10.38 38.03 +26.93 .15 r= -.23 .62 7 Baseline Left ½RT Post-PFMT Left ½RT 18.71 +20.05 18.54 +23.09 .98 (Sqrt)r= .19 .69 7 Baseline ½RT Dominance Post-PFMT ½RT Dominance -8.20 +25.77 -7.56 +26.92 .89 r= .91 <.01 Table 3.11 Intra-group 1/2RT variables at baseline and post-PFMT. Intra-group comparison of ½RT measurements at baseline and post-PFMT assessments. Parametric and non-parametric Paired Sample tests performed. NP denotes when non-parametric performed with Wilcoxin Signed Rank test (2-tailed). (Lg10) denotes that log base-10 transformation was performed. (Sqrt) denotes that square root transformation was performed.73 NIRS Variable Controls n=12 Cases n=10 P-value Baseline Right ½RT mean +SD range 6.30 + 9.75 1.10 – 36.90 18.90 +11.35 2.40 – 33.90 <.01NP Baseline Left ½RT mean +SD range 11.39 + 21.83 1.70 – 80.30 19.36 + 19.82 1.60 – 57.00 .34NP Baseline ½RT Dominance mean +SD range 5.16 + 12.12 0.00 – 43.40 17.41 + 17.50 2.50 – 57.00 <.01NP NIRS Variable Controls n=11 Cases n=7 P-value Post-PFMT Right ½RT mean +SD range 7.87 + 13.34 2.20 – 47.80 38.03 + 26.93 3.00 – 68.60 .01NP Post-PFMT Left ½RT mean +SD range 9.55 + 18.11 1.80 – 63.80 18.54 + 23.09 0.90 – 60.80 .47NP Post-PFMT ½RT Dominance mean +SD range 10.38 + 21.08 0.00 – 61.40 15.64 + 22.49 0.20 – 60.80 .39NP Table 3.12 Inter-group 1/2RT variables at baseline and post-PFMT. Inter-group comparison of unilateral PFM NIRS ½RT at baseline and post-PFMT assessments. Parametric and non-parametric Independent Samples T-tests performed. NP demotes when non-parametric Mann-Whitney U-test with (2-tailed) was performed. Absolute values used for dominance variables as comparing the degree of dominance rather than the side of presenting dominance. 74 Figure 3.20 Inter-group 1/2RT variables at baseline and post-PFMT. Inter-group comparison of unilateral PFM NIRS variable ½RT at baseline (top row) and post-PFMT (bottom row). Error bars represent + 1 SD. * indicates statistical significance. For both baseline and post-PFMT Right ½RT significantly reduced in controls (p <0.01 and 0.01, respectively). 3.5.2 DMag NIRS measurements 3.5.2.1 Intra-group DMag comparison Intra-group association between bilateral PFM of DMag at baseline demonstrated moderate positive correlation (r= 0.63) among the control group, suggesting that the desaturation tended to occur similarly in bilateral PFM. However, this association was not statistically maintained at post-PFMT assessment. 75 Conversely, the case group demonstrated a high positive correlation in association of unilateral Left PFM DMag across baseline and post-PFMT, as well as for DMag Dominance across baseline and post-PFMT, (rs= 0.79 and rs= 0.75, respectively). Neither the control or casegroups demonstrated a statistically significant pairwise difference for all DMag NIRS variables, for within and across assessment measurements. Refer to Table 3.13. 3.5.2.2 Inter-group DMag comparison At baseline assessment the control group demonstrated on average greater for Right and Left DMag during SMVC contractions, (-7.31 µmol and -1.53 µmol, -5.04 µmol and -2.21µmol, respectively), however, the difference was not found to be statistically significant. At post-PFMT statistical significance was demonstrated between control and case groups for unilateral Right DMag (-10.34 µmol compared to -2.19 µmol, p-value < 0.01). Suggesting the case group had reduced oxygenation desaturation in unilateral PFM compared to the control group, results shown in Table 3.14. and Figure 3.21-3.22. Whereas the average DMag of the Left PFM appeared comparable between both groups. 76 Participant Group n Variables Mean +SD Paired Samples P-value Correlation Coefficient Correlation P-value Controls 12 Baseline Right DMag Baseline Left DMag -7.30 +7.00 -5.04 +6.98 .22 r= .63 .03 11 Post-PFMT Right DMag Post-PFMT Left DMag -10.34 +6.17 -8.49 +6.17 .40 rs= .36 .29 11 Baseline Right DMag Post-PFMT Right DMag -8.38 +6.23 -10.34 +6.17 .30 r= .54 .09 11 Baseline Left DMag Post-PFMT Left DMag -6.22 +5.92 -8.49 +6.17 .29 rs= .30 .37 11 Baseline DMag Dominance Post-PFMT DMag Dominance 1.54 +6.13 1.85 +7.02 .91 r= .08 .82 Cases 10 Baseline Right DMag Baseline Left DMag -1.53 +2.19 -2.21 +6.02 .71 r= .36 .31 7 Post-PFMT Right DMag Post-PFMT Left DMag -2.19 +5.48 -8.06 +18.23 .33 rs= .00 1.00 7 Baseline Right DMag Post-PFMT Right DMag -0.79 +2.21 -2.19 +5.48 .57 r= -.13 .78 7 Baseline Left DMag Post-PFMT Left DMag -2.98 +6.45 -8.06 +18.23 .87NP rs= .79 .04 7 Baseline DMag Dominance Post-PFMT DMag Dominance -3.23 +4.57 -6.69 +13.00 .87 NP rs= .75 .05 Table 3.13 Intra-group DMag variables at baseline and post-PFMT. Summary of intra-group comparison DMag at baseline and post-PFMT. Parametric and non-parametric Paired Sample tests performed. NP denotes when non-parametric performed with Wilcoxin Signed Rank test (2-tailed). Parametric and non-parametric correlation coefficients performed. rs denotes non-parametric Spearman Rank correlation coefficient.77 NIRS Variable Controls n=12 Cases n=10 P-value Baseline Right DMag mean +SD range -7.31 +7.00 -15.89 – 4.47 -1.53 +2.19 -4.57 – 1.70 .13NP Baseline Left DMag mean +SD range -5.04 +6.98 -13.97 – 8.01 -2.21 +6.02 -14.78 – 6.02 .33 Baseline DMag Dominance mean +SD range 4.98 +3.54 0.00 – 11.03 3.25 + 3.52 0.88 – 12.51 .25 NP NIRS Variable Controls n=11 Cases n=7 P-value Post-PFMT Right DMag mean +SD range -10.34 +6.17 -19.63 – -1.05 -2.19 +5.48 -13.10 – 2.55 .01 Post-PFMT Left DMag mean +SD range -8.49 +6.17 -23.25 – -2.70 -8.06 +18.23 -47.33 – 7.51 .24NP Post-PFMT DMag Dominance (Lg10) mean +SD range 5.38 + 4.61 (Lg10)0.54 + 0.49 0.49 – 15.81 (Lg10) -0.31 – 1.20 8.15 +11.99 (Lg10) 0.53 + 0.66 0.35 – 34.23 (Lg10) -0.46 – 1.53 .97 Table 3.14 Inter-group DMag variables at baseline and post-PFMT. Inter-group comparison of unilateral PFM NIRS DMag at baseline and post-PFMT assessments. Parametric and non-parametric Independent Samples T-tests performed. NP demotes when non-parametric Mann-Whitney U-test with (2-tailed) was performed. Absolute values used for dominance variables as comparing the degree of dominance rather than the side of presenting dominance. Lg10 denotes that log base-10 transformation was performed on baseline and post-PFMT data. 78 Figure 3.21 Inter-group DMag at baseline and post-PFMT. Inter-group comparison of unilateral PFM NIRS variable DMag at baseline (top row) and post-PFMT (bottom row). Error bars represent + 1 SD. * indicates statistical significance. For post-PFMT Right DMag significantly greater in controls (p 0.01). 79 Figure 3.22 Inter-group 1/2RT and DMag dominance at baseline and post-PFMT. Inter-group comparison of unilateral PFM NIRS variables of ½RT and DMag dominance (absolute difference) at baseline (top row) and post-PFMT (bottom row). Error bars represent + 1 SD. 3.5.3 Unilateral PFM ½RT and DMag NIRS Correlation 3.5.3.1 Intra-group comparison The control group demonstrated a moderately positive correlation (rs= 0.65) at baseline in the unilateral Left PFM between ½RT and DMag measures, suggesting that quicker ½RT accompanied greater desaturation changes during SMVC contractions. No other correlation was determined among ½RT and DMag NIRS variables for unilateral PFM at baseline or post-PFMT assessments for the control group. Refer to Table 3.15 and Figure 3.23. 80 The case group demonstrated a highly positive correlation (rs= 0.93) at baseline in the unilateral Right PFM between ½RT and DMag measures, suggesting that quicker ½RT accompanied greater desaturation changes during SMVC contractions. No other correlation was determined among ½ RT and DMag NIRS variables for unilateral PFM at baseline or post-PFMT assessments for the case group. Refer to Table 3.15. and Figures 3.23. Participant Group n Variables Mean +SD Correlation Coefficient Correlation P-value Controls 12 Baseline Right ½RT Baseline Right DMag 6.30 +9.75 -7.30 +7.00 rs= .46 .14 12 Baseline Left ½RT Baseline Left DMag 11. 39 +21.83 -5.04 +6.98 rs= .65 .02 11 Post-PFMT Right ½RT Post-PFMT Right DMag 7.87 +13.34 -10.34 +6.17 rs= .20 .55 11 Post-PFMT Left ½RT Post-PFMT Left DMag 9.55 +18.11 -8.49 +6.17 rs= .31 .36 Cases 10 Baseline Right ½RT Baseline Right DMag 18.90 +11.35 -1.53 +2.19 rs= .37 .30 10 Baseline Left ½RT Baseline Left DMag 19.36 +19.82 -2.21 +6.02 r= .37 .29 7 Post-PFMT Right ½RT Post-PFMT Right DMag 38.03 +26.93 -2.19 +5.48 rs= .93 <.01 7 Post-PFMT Left ½RT Post-PFMT Left DMag 18.54 +23.09 -8.06 +18.23 rs= .00 1.00 Table 3.15 Intra-group 1/2RT and DMag correlations at baseline and post-PFMT. Intra-group association between ½RT and DMag NIRS variables for unilateral PFM at baseline and post-PFMT assessments. Parametric and non-parametric correlation coefficients (2-tailed) performed. rs denotes non-parametric Spearman Rank correlation coefficient. 81 Figure 3.23.A. Control group Left 1/2RT and DMag correlation at baseline. Spearman rank correlation coefficient rs= 0.65 p-value 0.02, for ½RT and DMag of unilateral left PFM at baseline for control group, n=12. Figure 3.23.B. Case group Right 1/2RT and DMag correlation at post-PFMT. Spearman rank correlation coefficient rs= 0.93 p-value <0.01, for ½RT and DMag of unilateral right PFM at post-PFMT for case group, n=7. Figure 3.23 Intra-group correlations for 1/2RT and DMag. 3.6 Manometer objective outcome measures 3.6.1 Within assessment measurements 3.6.1.1 Intra-group manometer comparison The control group demonstrated positive correlation for all manometer variables for within assessment measurements. No pairwise difference was found among all manometer variables for within assessment measurements. Refer to Table 3.16. These findings suggest reliability of the manometer, which has also been shown in previous literature.83,118-120 The case group demonstrated positive correlation at baseline assessment for manometer Timesec and at post-PFMT assessment for both Peak cmH2O and Average cmH2O. Refer to Table 3.17. This suggests variability in manometer measurements among the case group. However, similar to the control and case groups, no pairwise difference was demonstrated for within -20-15-10-50510150 20 40 60 80 100Left DMag µmolLeft ½RT in seconds*-14-12-10-8-6-4-20240 20 40 60 80Right DMag µmolRight ½RT in Seconds*82 assessment testing of all manometer variables during SMV contractions. Due to these results only the Pre-NIRS manometer values were used for subsequent statistical analysis. 83 Participant Group n Variables Mean +SD Pairwise P-value Correlation Coefficient Correlation P-value Controls 14 Baseline Peak cmH2O Pre-NIRS Baseline Peak cmH2O Post-NIRS 31.83 +17.29 32.61 +16.79 .66 r= .93 <.001 14 Baseline Average cmH2O Pre-NIRS Baseline Average cmH2O Post-NIRS 22.59 +14.69 20.91 +12.72 .23 r= .94 <.001 14 Baseline Timesec Pre-NIRS Baseline Timesec Post-NIRS 23.09 +15.38 26.39 +25.41 .98NP rs= .58 .03 13 Post-PFMT Peak cmH2O Pre-NIRS Post-PFMT Peak cmH2O Post-NIRS 35.68 +18.40 37.52 +18.16 .49 r= .87 <.001 13 Post-PFMT Average cmH2O Pre-NIRS Post-PFMT Average cmH2O Post-NIRS 23.68 +14.11 22.95 +13.68 .62 r= .93 <.001 13 Post-PFMT Timesec Pre-NIRS Post-PFMT Timesec Post-NIRS 33.52 +50.22 38.28 +58.75 .17 (Lg10) r= .93 <.001 Table 3.16 Within assessment control group PFM manometer variables. Within assessment, control group manometer comparison and association. Parametric and non-parametric Paired Sample tests (2-tailed) performed. NP denotes when non-parametric performed with Wilcoxin Signed Rank test (2-tailed). Parametric and non-parametric correlation coefficients performed. rs denotes non-parametric Spearman Rank correlation coefficient (2-tailed). (Lg10) denotes that log base-10 transformation was performed. (Sqrt) denotes that square root transformation was performed. 84 Participant Group n Variables Mean +SD Pairwise P-value Correlation Coefficient Correlation P-value Cases 11 Baseline Peak cmH2O Pre-NIRS Baseline Peak cmH2O Post-NIRS 13.12 +9.80 (Sqrt) 3.21 +1.76 10.35 +5.34 (Sqrt) 3.02 +1.17 (Sqrt) .66 rs= .29 .39 11 Baseline Average cmH2O Pre-NIRS Baseline Average cmH2O Post-NIRS 8.13 +4.04 (Sqrt) 2.68 +1.01 9.49 +6.94 (Sqrt) 2.73 +1.49 (Sqrt) .83 rs= .19 .58 11 Baseline Timesec Pre-NIRS Baseline Timesec Post-NIRS 13.12 +5.71 19.45 +21.99 .42NP rs= .87 <.001 7 Post-PFMT Peak cmH2O Pre-NIRS Post-PFMT Peak cmH2O Post-NIRS 12.94 +10.61 13.57 +8.08 .67 r= .96 <.01 7 Post-PFMT Average cmH2O Pre-NIRS Post-PFMT Average cmH2O Post-NIRS 9.39 +7.19 8.65 +5.86 .50 r= .93 <.01 7 Post-PFMT Timesec Pre-NIRS Post-PFMT Timesec Post-NIRS 11.89 +7.30 9.53 +5.24 .39 r= .51 0.24 Table 3.17 Within assessment case group PFM manometer variables. Within assessment, case group PFM manometer comparison and association. Parametric and non-parametric Paired Sample tests (2-tailed) performed. NP denotes when non-parametric performed with Wilcoxin Signed Rank test (2-tailed). Parametric and non-parametric correlation coefficients performed. rs denotes non-parametric Spearman Rank correlation coefficient (2-tailed). (Lg10) denotes that log base-10 transformation was performed. (Sqrt) denotes that square root transformation was performed. 85 3.6.2 Across assessment manometer measurements 3.6.2.1 Intra-group manometer comparison When assessing for PFM strength (as measured by manometer pressure) after the 8-week PFMT no statistical difference was found in both control and case groups for all manometer variables. Although there was no significant difference, both groups demonstrated positive correlation for all manometer variables across session testing, suggesting that all participants were likely to have comparable performances at baseline and post-PFMT assessments. The case group only demonstrated a moderate positive correlation for average manometer pressure across baseline and post-PFMT assessment, which was also not found to be significant. Refer to Table 3.18 and Figure 3.24. 86 Participant Group n Variables Mean +SD Paired Difference P-value Correlation Coefficient Correlation P-value Controls 13 Baseline Peak cmH20 Post-PFMT Peak cmH20 32.31 +18.03 35.73 +19.22 .31 r= .83 <.01 13 Baseline Average cmH20 Post-PFMT Average cmH20 21.08 +11.93 23.27 +14.66 .42 r= .79 <.01 13 Baseline Timesec Post-PFMT Timesec 23.66 +16.64 (Lg10 1.29+0.28) 35.13 +52.10 (Lg10 1.30 +0.44) (Lg10) .92 (Lg10) r= .79 <.01 Cases 8 Baseline Peak cmH20 Post-PFMT Peak cmH20 14.66 +10.48 (Sqrt) 3.49 +1.68 13.91 +10.20 (Sqrt) 3.37 +1.72 .73 (Sqrt) r= .89 <.01 8 Baseline Average cmH20 Post-PFMT Average cmH20 10.71 +7.37 10.30 +7.14 .79 rs= .55 .16 8 Baseline Timesec Post-PFMT Timesec 18.38 +25.58 (Lg10) 1.06 +0.38 13.15 +7.64 (Lg10) 1.06 +0.26 (Lg10) .94 rs= .76 .03 Table 3.18 Across assessment intra-group PFM manometer variables. Across assessment, intra-group PFM manometer comparison and association. Parametric Paired Sample tests (2-tailed) performed. Parametric and non-parametric correlation coefficients performed. rs denotes non-parametric Spearman Rank correlation coefficient (2-tailed). (Lg10) denotes that log base-10 transformation was performed. (Sqrt) denotes that square root transformation was performed.87 Figure 3.24 Across assessment correlation of PFM manometer measures. Association of across assessment PFM manometer measurements. Blue= controls. Orange= cases.* indicates statistically significant correlation coefficient. 3.6.2.2 Inter-group PFM manometer comparison At baseline assessment the control group had statistically significant greater peak (32.09cmH2O compared to 13.12cmH2O, p-value < 0.01), and average (20.54cmH2O compared to 8.13cmH2O, p-value < 0.01) manometer pressures than the case group when performing SMVCs. At baseline assessment the control group also demonstrated on average greater duration of SMVC than the case group (24.43 seconds compared to 13.12 seconds, p-value 0.04). Refer to Table 3.19 and Figure 3.25. At post-PFMT assessment the control group maintained greater peak (35.68cmH2O compared to 13.91cmH2O, p-value < 0.01), and average (23.68cmH2O compared to 10.30cmH2O, p-value 0.02) PFM manometer pressures than the case group. However, at post-88 PFMT assessment there was no statistically significant difference in the duration of SMVC between the two groups. Refer to Table 3.19. and Figure 3.25. PFM Manometer Variable Controls n=15 Cases n=11 P-value Baseline Peak cmH20 mean +SD range 32.09 +16.69 11.00 – 59.00 13.12 +9.80 0.00 – 37.40 <.01NP Baseline Average cmH2O mean +SD range 20.54 +11.12 7.10 – 42.00 8.13 +4.04 0.00 – 15.80 <.01NP Baseline Timesec (Lg10) mean +SD range 24.43 +17.33 (Lg10) 1.30 +0.29 7.25 – 65.04 (Lg10) 0.86 – 1.81 13.12 +5.71 (Lg10) 1.08 +0.21 4.29 – 25.42 (Lg10) 0.63 – 1.41 .04 PFM Manometer Variable Controls n=13 Cases n=8 P-value Post-PFMT Peak cmH20 mean +SD range 35.68 +18.40 12.60 – 72.30 13.91 +10.20 0.00 – 32.70 <.01 Post-PFMT Average cmH2O mean +SD range 23.68 +14.11 7.10 – 51.40 10.30 +7.14 0.00 – 22.70 .02 Post-PFMT Timesec (Lg10) mean +SD range 33.52 +50.22 (Lg10) 1.29 +0.42 5.30 – 193.11 (Lg10) 0.72 – 2.29 13.15 +7.64 (Lg10) 1.05 +0.26 4.25 – 26.51 (Lg10) 0.63 – 1.42 .18 Table 3.19 Inter-group PFM manometer variables at baseline and post-PFMT. Inter-group comparison of PFM manometer measurements at baseline and post-PFMT assessments. Parametric and non-parametric Independent Samples T-tests performed. NP demotes when non-parametric Mann-Whitney U-test with (2-tailed) was performed. Lg10 denotes that log base-10 transformation was performed on baseline and post-PFMT data. 89 Figure 3.25 Inter-group PFM manometer variables at baseline and post-PFMT. Inter-group PFM manometer measurements at baseline and post-PFMT. Log10 denotes that log base-10 transformation was performed on baseline and post-PFMT data. Error bars represent + 1 SD. * indicates statistical significance. 90 3.6.3 Post-PFMT PFM manometer and NIRS dominance measures Absolute values of ½RT and DMag Dominance were used as measure of degree of PFM dominance which were correlated to post-PFMT to assess whether more synergistic PFM contraction (reduced degree of dominance) were associated with large manometer pressures (PFM strength). The control group did not demonstrate any correlation between post-PFMT manometer variables and NIRS dominance variables. The case group showed a suggestion of association between ½RT dominance and both Peak and Average cmH2O, however this was only a moderate negative correlation with which did not prove to be statistically significant. Refer to Table 3.20. Participant Group n Variables Correlation Coefficient Correlation P-value Controls 11 ½RT Dominance v Peak cmH2O rs= .16 .63 ½RT Dominance v Average cmH2O rs= .18 .59 ½RT Dominance v Timesec rs= .08 .81 DMag Dominance v Peak cmH2O rs= .09 .79 DMag Dominance v Average cmH2O rs= .14 .69 DMag Dominance v Timesec rs= .18 .59 Cases 7 ½RT Dominance v Peak cmH2O (Sqrt) r= -.69 .09 ½RT Dominance v Average cmH2O (Sqrt) r= -.67 .10 ½RT Dominance v Timesec rs= -.50 .25 DMag Dominance v Peak cmH2O rs= .04 .94 DMag Dominance v Average cmH2O rs= -.14 .76 DMag Dominance v Timesec rs= .14 .76 Table 3.20 Intra-group correlation of post-PFMT PFM manometer and NIRS dominance variables. Summary of correlation between post-PFMT PFM manometer variables and post-PFMT NIRS dominance (absolute values) variables. Parametric and non-parametric correlation coefficients performed. rs denotes non-parametric Spearman Rank correlation coefficient (2-tailed). Sqrt denotes square root transformation performed. 91 3.6.4 Baseline unilateral PFM ½RT and PFM manometer measures The control group demonstrated moderate negative correlation between unilateral Right PFM ½RT and both Peak cmH2O and Average cmH2O (rs = -0.63 and rs= -0.67, respectively). The control group did not demonstrate any other associations between unilateral PFM ½RT and manometer variables at baseline assessment. Refer to Table 3.21. The control group did not demonstrate any correlation between unilateral PFM DMag and manometer variables. The case group demonstrated a moderate negative correlation between unilateral Right PFM ½RT and Average cmH2O (rs= -0.67). The case group did not demonstrate any other associations between unilateral PFM ½RT and manometer variables at baseline assessment. Refer to Table 3.21 and Figures 3.26-3.27. The case group did not demonstrate any significant correlation between unilateral PFM DMag and manometer variables at baseline. Participant Group n Variables Correlation Coefficient Correlation P-value Controls 12 Right ½RT v Peak cmH2O rs= -.63 .03 12 Right ½RT v Average cmH2O rs= -.67 .02 12 Right ½RT v Timesec rs= .52 .08 12 Left ½RT v Peak cmH2O rs= -.32 .32 12 Left ½RT v Average cmH2O rs= -.35 .26 12 Left ½RT v Timesec rs= .21 .51 Cases 10 Right ½RT v Peak cmH2O rs= -.38 .28 10 Right ½RT v Average cmH2O rs= -.67 .04 10 Right ½RT v Timesec r= -.07 .85 10 Left ½RT v Peak cmH2O rs= -.40 .25 10 Left ½RT v Average cmH2O rs= -.35 .32 10 Left ½RT v Timesec rs= .56 .09 Table 3.21 Intra-group correlation of unilateral PFM 1/2RT and PFM manometer variables at baseline. Summary of association between unilateral PFM NIRS ½RT and PFM manometer variables at baseline. Parametric and non-parametric correlation coefficients performed. rs denotes non-parametric Spearman Rank correlation coefficient. 92 3.6.5 Post-PFMT ½RT and PFM manometer measures The control group did not demonstrate any associations between unilateral PFM ½RT and manometer variables at post-PFMT assessment. Refer to Table 3.22. Similar to baseline findings the control group did not demonstrate any correlation between unilateral PFM DMag and manometer variables at post-PFMT. Conversely, the case group demonstrated highly negative correlations between both unilateral PFM ½RT and all manometer variables, suggesting that reduced ½RT was associated with greater manometers pressures and duration of pressure at post-PFMT assessment. This was not demonstrated by the case group at baseline. It should be noted that although the case group suggested a highly positive correlation (r= -0.73) for unilateral Right PFM ½RT and Timesec, this correlation was not considered to be statistically significant. Refer to Table 3.22. and Figures 3.26-3.27. Similar to controls, the case group did not demonstrate any significant correlation between unilateral PFM DMag and manometer variables at post-PFMT. 93 Participant Group n Variables Correlation Coefficient Correlation P-value Controls 11 Right ½RT v Peak cmH2O rs= .19 .58 11 Right ½RT v Average cmH2O rs= .21 .54 11 Right ½RT v Timesec rs= .22 .53 11 Left ½RT v Peak cmH2O rs= .00 1.00 11 Left ½RT v Average cmH2O rs= .00 1.00 11 Left ½RT v Timesec rs= .11 .75 Cases 7 Right ½RT v Peak cmH2O r= -.83 .02 7 Right ½RT v Average cmH2O r= -.82 .02 7 Right ½RT v Timesec r= -.73 .06 7 Left ½RT v Peak cmH2O (Sqrt) r= -.84 .02 7 Left ½RT v Average cmH2O (Sqrt) r= -.84 .02 7 Left ½RT v Timesec (Sqrt) r= -.84 .02 Table 3.22 Correlation of unilateral 1/2RT and PFM manometer variables at post-PFMT. Summary of association between unilateral PFM NIRS ½RT and PFM manometer variables at post-PFMT. Parametric and non-parametric correlation coefficients performed. rs denotes non-parametric Spearman Rank correlation coefficient. Figure 3.26 Correlation of Right PFM 1/2RT and PFM manometer variables. SMVC unilateral Right PFM ½RT correlation with PFM manometer variables at baseline (top row) and post-PFMT (bottom row) assessments. * indicates statistically significant correlation coefficient. 94 Figure 3.27 Correlation of Left PFM 1/2RT and PFM manometer variables. SMVC unilateral Left PFM ½RTcorrelation with PFM manometer variables at baseline (top row) and post-PFMT (bottom row) assessments. * indicates statistically significant correlation coefficient. 3.7 Exercise adherence outcome measures Exercise adherence to the PFMT intervention was accounted for with self-recording sheet which allowed for two adherence variables to be measured, exercise volume and frequency. Exercise Volume is defined as amount of completed exercises per day. Exercise Frequency is defined as the number of days any exercises were completed during the 8-week PFMT intervention. Table 3.23 shows no statistical difference among comparison of exercise adherence between control and case groups, although the case group did demonstrate a higher average for percentage for Exercise Frequency. On average the control group and case group only performed 51.10% and 52.23% of required amount of exercises, Table 3.23 and Figure 3.29. Both groups performed better with regards to frequency, completing 62.91% and 78.57% of required exercise days (control and case group respectively). 95 Exercise Adherence Variable Controls n=13 Cases n=8 P-value Exercise Volume mean +SD range 51.10 +28.28 0.00-92.86% 52.23 +26.37 0.00-84.82% .93 Exercise Frequency mean +SD range 62.91 +29.52 0.00-100.00% 78.57 +33.81 0.00-100.00% .10NP Table 3.23 Inter-group exercise adherence. Inter-group comparison of exercise adherence as measured by percentage of completed amount of exercises completed per day (Exercise Volume) and percentage of days any exercises completed (Exercise Frequency). Parametric and non-parametric Independent T-test performed (2-tailed). NP demotes when non-parametric Mann-Whitney U-test with (2-tailed) was performed. Figure 3.28 Inter-group PFMT adherence mean values for Exercise Volume and Frequency. Error bars represent + 1 SD. Figure 3.29 Intra-group exercise adherence percentage. Exercise adherence to 8-week PFMT for controls (blue) and case (orange) groups. Dark blue & orange bars = Exercise Volume (total amount of PFMT exercises completed). Light blue & orange bars = Exercise Frequency (number of days PFMT completed). 96 3.7.1 Exercise adherence and post-PFMT PFM manometer measures For the control group no significant correlation between PFM manometer variables and exercise adherence variables. Refer to Table 3.24. Similarly, among the case group, there was no correlation found between Exercise Volume and manometry values. However, the case group did demonstrate a significant positive correlation between Exercise Frequency and all the PFM manometry variables. This suggests that for the case group, the number of days that any PFMT is attempted, rather than the amount of PFMT completed each day, is more likely to help improve PFM function as measured by manometry. Refer to Table 3.24 and Figure 3.30. Participant Group n Variables Correlation Coefficient Correlation P-value Controls 13 Peak cmH2O v Exercise Volume r= -.45 .12 13 Peak cmH2O v Exercise Frequency r= -.33 .27 13 Average cmH2O v Exercise Volume r= -.50 .08 13 Average cmH2O v Exercise Frequency r= -.38 .20 13 Timesec v Exercise Volume rs= .22 .47 13 Timesec v Exercise Frequency rs= .14 .66 Cases 8 Peak cmH2O v Exercise Volume r= .04 .93 8 Peak cmH2O v Exercise Frequency rs= .78 .02 8 Average cmH2O v Exercise Volume r= .11 .80 8 Average cmH2O v Exercise Frequency rs= .88 <.01 8 Timesec v Exercise Volume r= .13 .76 8 Timesec v Exercise Frequency rs= .76 .03 Table 3.24 Intra-group correlation of PFM manometer and exercise adherence variables. Association between post-PFMT manometer variables and exercise adherence. Parametric and non-parametric correlation coefficients performed. rs denotes non-parametric Spearman Rank correlation coefficient (2-tailed). 97 Figure 3.30 Case group correlation of PFM manometer and exercise adherence variables. Case group association between SMVC post-PFMT manometer variables with percentage of adherence to PFMT measured by Exercise Volume and Frequency. * indicates statistically significant correlation coefficient. 3.7.2 Exercise adherence correlation to questionnaire and PVR measures As the case group demonstrated a significant reduction in the QUID-UUI, this outcome measure DQUID-UUI (change in score from baseline to post-PFMT) was correlated with exercise adherence. There was a highly negative correlation (rs= -.85, p-value <0.01) between DQUID-UUI and Exercise Frequency. This association suggests that QUID-UUI scores were more likely to be reduced in participants with higher percentage of completed exercise days. Data in Figure 3.31 suggests that Exercise Frequency of at least 80% was required in this sample to demonstrate a reduction in urgency symptoms. There was no correlation demonstrated between Exercise Frequency and the remaining questionnaire score changes (QUID-SUI, UDI-6, IIQ-7, SSI) or PVR changes. Nor was any correlation found among Exercise Volume and all 98 questionnaire score changes or PVR changes. The control group did not demonstrate any correlation between exercise adherence and questionnaire or PVR variables. Figure 3.31 Case group correlation of QUID-UUI score and exercise adherence. Association between subjective change in QUID-UUI score from baseline to post-PFMT and exercise adherence based on Exercise Frequency.* indicates statistically significant correlation. Spearman Rank correlation coefficient (rs= -0.85). 3.7.3 Exercise adherence and post-PFMT ½RT measures As conducted in post-PFMT PFM manometer and NIRS Dominance analysis, the absolute ½RT Dominance value was used as measure of degree of PFM dominance was correlated to exercise adherence variables to assess whether more synergistic PFM contraction (reduced degree of dominance) were associated with exercise adherence rates. No correlation found among individual unilateral sides of PFM and both exercise adherence measures for the control group. However, the controls did demonstrate a moderately negative correlation between ½RT Dominance and both Exercise Volume and Frequency, (rs= -0.69 and rs= -0.61, respectively). Results shown in Table 3.25 and Figure 3.32. The case group demonstrated a highly negative correlation between unilateral Right PFM ½RT and Exercise Frequency, (rs= -0.85). Suggesting that the PFMT intervention only had a 99 training effect on the PFM unilaterally, as no other correlations were found. Refer to Table 3.25 and Figure 3.33. Participant Group n Variables Correlation Coefficient Correlation P-value Controls 11 Right ½RT v Exercise Volume rs= -.12 .73 Right ½RT v Exercise Frequency rs= -.14 .68 Left ½RT v Exercise Volume rs= -.35 .30 Left ½RT v Exercise Frequency rs= -.35 .29 ½RT Dominance v Volume rs= -.69 .02 ½RT Dominance v Frequency rs= -.61 .05 Cases 7 Right ½RT v Exercise Volume r= -.35 .44 Right ½RT v Exercise Frequency rs= -.85 .02 Left ½RT v Exercise Volume rs= .13 .79 Left ½RT v Exercise Frequency rs= -.52 .23 ½RT Dominance v Volume rs = -.38 .40 ½RT Dominance v Frequency rs = -.48 .27 Table 3.25 Intra-group correlation of 1/2RT and exercise adherence variables. Association between post-PFMT ½RT (Dominance absolute) variables and exercise adherence. Parametric and non-parametric correlation coefficients performed. rs denotes non-parametric Spearman Rank correlation coefficient (2-tailed). Figure 3.32 Control group correlation of 1/2RT and exercise adherence. Association between 1/2RT Dominance (absolute) and exercise adherence among controls. ½RT Dominance and Exercise Volume rs= -0.69. ½RT Dominance and Exercise Frequency rs= -0.61. * indicates statistically significant correlation coefficient. 100 Figure 3.33 Case group correlation of 1/2RT and exercise adherence. Association between unilateral Right PFM ½RT and Exercise Frequency among the case group, rs= -0.85.* indicates statistically significant correlation coefficient. 3.7.4 Exercise adherence and post-PFMT DMag measures As conducted in post-PFMT PFM manometer and NIRS Dominance analysis, the absolute DMag Dominance value was used as measure of degree of PFM dominance which was correlated to exercise adherence variables to assess whether more synergistic PFM contraction (reduced degree of dominance) were associated with exercise adherence rates. The control group did not demonstrate any significant findings when associating post-PFMT DMag NIRS variables with exercise adherence, as shown in Table 3.26. The case group did demonstrate a significant highly negative correlation when associating post-PFMT unilateral Right PFM DMag and Exercise Frequency variables, (rs= -0.78). This suggests that case participants were more likely to have greater magnitude of desaturation in the Right PFM with increase in exercise adherence. Refer to Table 3.26 and Figure 3.34. 101 Participant Group n Variables Correlation Coefficient Correlation P-value Controls 11 Right DMag v Exercise Volume r= -.45 .17 Right DMag v Exercise Frequency rs= -.30 .37 Left DMag v Exercise Volume rs= -.02 .96 Left DMag v Exercise Frequency rs= .03 .94 DMag Dominance v Exercise Volume r= .37 .28 DMag Dominance v Exercise Frequency r= .28 .40 Cases 7 Right DMag v Exercise Volume r= -.43 .34 Right DMag v Exercise Frequency rs = -.78 .04 Left DMag v Exercise Volume rs= -.34 .45 Left DMag v Exercise Frequency rs= .11 .81 DMag Dominance v Exercise Volume rs= .18 .70 DMag Dominance v Exercise Frequency rs= -.11 .81 Table 3.26 Intra-group correlation of DMag and exercise adherence variables. Association between post-PFMT DMag (Dominance absolute) variables and exercise adherence. Parametric and non-parametric correlation coefficients performed. rs denotes non-parametric Spearman Rank correlation coefficient (2-tailed). Figure 3.34 Case group correlation of DMag and exercise adherence. Association between post-PFMT unilateral Right PFM DMag and Exercise Frequency among the case group, (rs = -0.78).* indicates statistically significant correlation coefficient. -14-12-10-8-6-4-202460 20 40 60 80 100DMag umolExercise Frequency*102 Chapter 4: Discussion This chapter will provide interpretation of the research findings within the perspective of physiological theories and academic literature pertaining to skeletal muscle, NIRS and PFM dysfunction. The major research findings will be discussed in detail with mention of relevance for clinical applicability. 4.1 Successful development of NIRS probe Findings shown in Results section 3.4 demonstrate that the technical design of the NIRS probe has the capacity to capture hemodynamic and oxygen kinetic response of bilateral PFM independently and simultaneously. This capability was also demonstrated in both a continent female control sample and in a sample of females with LUTS. The probe was tolerated well by participants when used in the manner described in Methods section 2.3.4. However, it should be noted that two case participants were excluded from the study due to reported discomfort with manometer insertion and therefore were not exposed to the NIRS probe. The presence of pelvic pain presents as a limitation for the use of the NIRS probe, along with other PFM assessment devices that must be used transvaginally. With this in consideration all other participants (controls n=15 and cases n=11) who did not report any discomfort with the manometer also did not report any discomfort with the NIRS probe. This suggests that the NIRS probe has similar tolerability to current transvaginal PFM assessment devices. Findings shown in Results section 3.4 demonstrate that the NIRS probe prototype design has the capacity to capture differential hemodynamic and oxygen kinetic response of bilateral PFM. PFM assessment was carried out in the nature of performing MVCs, SMVCs and REPs as 103 described and recommended by Laycock and Jerwood 2001 and Devreese et al. 2004.1,91,92 NIRS tracings from this full assessment were used in consideration of the functionality of the tool itself and for the consideration of observational trends to characterize hemodynamic and oxygen kinetic responses of the PFM. Based on the inter-group observational trends the case group demonstrated more complex NIRS tracings during measurements, atypical muscle tissue contraction and recovery hemodynamic patterns, resulting in longer ½RT and decreased DMag changes on average. Please refer to Table 3.12, Table 3.14, and Figures 3.9-3.19 in NIRS objective outcome measures section 3.5. Similarly, the exploratory findings of Ryan et al. 2014, also suggested that individuals with a neurologic condition (amyotrophic lateral sclerosis), tended to have slower ½RT than controls.53 It should be noted that this research group used ½RT calculations based on occlusion NIRS methods and TSI%. The NIRS parameters also demonstrated similar outcomes to that of manometry, which also found greater PFM strength and endurance in the control group compared to the case group. Interestingly, both devices did not detect a significant change in PFM function within groups after the 8-week PFMT intervention. 4.2 Participant demographics There was a difference in the mean age of each group, the control group on average being younger than the case group (mean 42 years compared to mean 51 years, respectively). Although not reaching statistical significance, it should be noted that the difference between the two was just shy of reaching the significance cut off (p-value <0.05). Refer to Table 3.1. 104 Increasing age is associated with muscle atrophy and mass reduction, causing decreased strength and power.121,122 Reduction in the contractile properties of skeletal muscle tissue, particularly that of contractile velocity, also decreases fatigue resistance in aging muscle.121,122 More specific PFM literature also reports aging as a contributor to loss of pelvic floor function.12 These considerations of age-related factors influencing muscle should be considered, even though statistical significance was not demonstrated between the two groups. Since the case group was older on average, age could be a contributing factor in the slower ½RT, reduced DMag and manometer pressure results. An age matched study design would have helped control for this confounding variable and should be considered for future studies. There was also statistically significance found in the parity between groups, with the case group demonstrating a higher proportion of participants with parity >1 than the controls, (90% compared to 46.7%, respectively). This is important for consideration as parity status is an influential factor contributing to structural integrity of the PFM. A recent review article by Van Geelen et al. 2018, determined that parity is associated with decreased PFM contractility, pelvic organ prolapse, UI, bladder descent and hypermobility, as well as pudendal denervation.12 Injury to the pudendal nerve is thought to be influenced by many factors during pregnancy and labour, although evidence in the literature varies on which factors are most significant, they include: vaginal delivery, prolonged second stage labour, multiparity, forceps and vacuum assisted labour, perineal lacerations, infant birth weight and head circumference.12 Van Geelen et al. 2018, conclude that the first vaginal delivery poses the greatest risk for PFM dysfunction including levator ani trauma and neurogenic injury. Although these complications are likely to occur, Van Geelen et al. 2018, state they typically resolve within the year post-delivery, however, 5-20% experience irreversible pelvic floor changes due to PFM trauma and neurogenic 105 injury.12 More specifically neurogenic injury has been reported to occur in 25-30% of primiparous women acutely postpartum with denervation of PFM continuing up to 6-months postpartum,13,123 which can result in permanent pudendal nerve damage contributing to long term PFM dysfunction.12 The negative influences that parity, and most specifically vaginal delivery trauma can have on the PFM, provides rationale for including women who have experienced labour trauma resulting in bladder symptoms to be included in our study sample population of interest. Furthermore, the findings of this study further support the negative impact of delivery trauma on the PFM, as participants with this etiology presented with atypical contraction patterns observed by NIRS. Such findings will be discussed in further detail in section 4.3.2. 4.3 Observational NIRS findings 4.3.1 Hemodynamic and oxygen kinetic response observed in heathy PFM The observational NIRS trends observed in the control group, Figures 3.4-3.8, were consistent with skeletal muscle oxygenation patterns in response to exercise as described in previous literature.85,93,99 With each PFM contraction, desaturation of the muscle tissue occurred, as evidenced by drop in both HbDiff and O2Hb. With this desaturation there was also observable drop in tHb, suggesting that the blood volume of the muscle tissue also decreased during contraction. At the cessation of contraction all three of these NIRS variables then returned to baseline levels or increased above baseline levels during the 90-second recovery time interval before returning to baseline levels. Such physiologic responses of skeletal musculature are well documented in NIRS research.50,70,97,99 The decline of HbDiff and O2Hb reflect the oxidative 106 capacity of the musculature, in that greater desaturation occurs as an actively contracting muscle uptakes oxygen to meet its oxygen demand and maintain the workload required of it. The decline in the tHb infers a decrease in blood volume within the musculature, as the muscle contracts the blood volume immediately available with the muscle tissue is decreased as the contraction causes mechanical constriction of the vasculature, limiting incoming blood flow.124 Furthermore, after the initial decrease at onset of contraction, HHb levels increase, although not to the same magnitude as O2Hb desaturation, demonstrated in Figure 3.5. This reflects continued oxygen consumption with sustained contraction, as HHb levels within the given blood volume of the musculature rises as a direct result of O2 uptake by the PFM. This observation was more evident during SMVC contractions. The longer duration compared to the MVCs created a larger demand on the muscle causing more desaturation of oxygen levels within the muscle. Also, as the SMVC was sustained, compared to REP contractions, there was limited capability for the microvasculature to restore oxygen supply to facilitate continued muscular effort. In REP contractions the brief relaxation between each contraction allows more opportunity to increase blood flow and oxygenation levels within the musculature. Were this study to have employed an occlusive NIRS methodology, the amount of blood volume during contraction would be controlled, constant blood volume then allows for accurate calculation of muscle oxygen consumption (rate of HbDiff recovery to baseline during occlusion measured after bout of exercise).47 Furthermore, had the occlusion method been employed it is suspected that the observation of an inverse response from O2Hb (decreasing) and HHb (increasing) would be more pronounced. Nonetheless, the fact that in the control group all four NIRS variables responded in typical pattern reported in NIRS literature demonstrates that 107 the NIRS probe is capable of assessing the PFM function in healthy tissue, while providing the added benefit of isolating bilateral PFM response. The continued downward slope of HbDiff, with inverse relationship between O2Hb (downward slope) and HHb (upward slope) during the post-PFMT SMVC’s is demonstrated particularly well in Figure 3.5. The observations from Figure 3.5 suggest that although the SMVC contraction was not held as long as during baseline, the O2 consumption of the PFM was greater during post-PFMT, demonstrating that the oxygen consumption exceeds oxygen delivery during this contraction as tHb also declines. During arterial occlusion when ischemia is induced, a similar inverse pattern of O2Hb and HHb occurs, which represents rapid O2 consumption occurring as a result of impeded blood flow (O2 delivery). In Figure 3.6 (post-PFMT Right PFM), this contraction appears strong enough to induce such an oxygenation pattern. As described by Muthalib et al. 2010, isometric contractions sustained at high intensity of MVC results in intramuscular pressure high enough to impeded O2 supply of the muscle’s microvasculature.97 This means that oxygenation patterns observed at SMVC’s of high intensity reflect the O2 consumption related to the force generated by that muscle.97 Furthermore, this trace of interest appears to demonstrate a quicker ½RT in post-PFMT, (½RT Right, 4.1 vs 3.9seconds and Left 8.5 vs 2.0seconds, at baseline and post-PFMT respectively), despite having achieved greater O2 consumption during the contraction. Since it has been determined that there is a direct and proportional relationship between blood flow and O2 consumption, the quicker ½RT corresponding with the greater HbDiff desaturation, suggests that supply is proportionally and more efficiently meeting the demand in order to restore homeostasis and facilitate recovery.97,125 108 Furthermore, Figure 3.7 (baseline and post-PFMT SMVC), demonstrate similar results. In baseline SMVC the magnitude of desaturation remains fairly constant throughout the duration of the contraction, with a less obvious inverse relationship between O2Hb and HHb. Particularly on the Left PFM, which produces greater desaturation (as per DMag), a hyperemic-like response is seen in the recovery which is consistent with recovery response when occlusion methods are used.50,67 The hyperemic response again demonstrates a vasodilatory response proportional to the oxygen consumption of the active musculature. When comparing bilateral tracings from baseline to post-PFMT the contraction was approximately twofold at post-assessment. Although contraction was maintained throughout, some resaturation is occurring as noted by progressive increase in tHb, O2Hb and HbDiff before the cessation of contraction, although the restoration still remains well below baseline values. This resaturation, or continued O2 delivery with incoming blood flow will partially explain the lack of obvious inverse relationship of O2Hb and HHb, and it could also explain the absence of a hyperemic response in post-PFMT Left compared to baseline. However, it could also be argued that the ability of the PFM to sustain such a long contraction with obvious desaturation (without a complete restoration of O2 delivery or resaturation to baseline), suggests an adapted metabolic training response of the PFM. The absence of the hyperemia in recovery would further support this, in that the microvasculature can more efficiently restore oxygen deficits incurred by energy expenditure with exercise. These two control participants are representative of the tracings obtained from control participants as a whole and as previously discussed their observational findings are suggestive of improvement in PFM function in response to the intervention, despite no determined statistical significance of improved ½RT, DMag or manometer variables. It should also be noted that the 109 varying duration of these contractions could skew the interpretation of these baseline and post-PFMT comparison oxygenation trends. 4.3.2 Hemodynamic and oxygen kinetic response observed in PFM dysfunction As detailed in the Chapter 3: Results section 3.4.1.2, heterogeneity among the case group tracings were categorized into to relevant clinical sub-groups. The categorization of observational trends was conducted according to underlying etiology and mobility status. It should be noted that mobility status was not determined by a clinical tool but rather by how the participant presented at time of assessment and based on the degree to which they used a mobility aid or wheelchair, as described in section 3.4.1.2 4.3.2.1 High mobility clinical sub-group Participants in the high mobility group tended to demonstrate PFM oxygenation patterns similar to that of the control group, generating desaturation with contraction and oxygen restoration during recovery phase. This typical oxygen pattern was also exhibited on bilateral PFM, with general synchronicity of unilateral oxygen patterns, regardless of the degree of magnitude of changes occurring during contraction. Figures 3.9-3.10 demonstrate the oxygenation patterns observed in a participant with delivery trauma, congenital dysplasia of the right hip and LUTS, with no impaired mobility (SS11). The NIRS assessment with this participant demonstrated typical saturation patterns, as compared to observations from controls. Similar tracings were also demonstrated by SS13, with underlying spinal stenosis, congenital hip dysplasia and multiple bilateral hip surgeries, with minimal cane assisted mobility. Similar tracings were also demonstrated by SS14. This participant has a history incomplete traumatic 110 C2-C4 SCI no current ASIA score, but independent unassisted mobility, decreased sensation to pelvis with self- reported hypersensitivity and hyper-reflexes of bilateral lower limbs. As demonstrated in Figure 3.11-3.12, SS14 demonstrated typical desaturation during contraction with restoration in recovery, similar to control group. At post-PFMT assessment greater bilateral desaturation is evidenced during contraction. These observational findings, particularly in Figure 3.12, draw parallels to control findings shown in Figure 3.6. Both illustrate a shorter contraction at post-PFMT than at baseline, with the greater oxygen consumption, suggestive of greater force generation.97 Likewise, this trace also demonstrates reduced ½RT in post-PFMT, despite having achieved greater oxygen consumption during the contraction, (½RT Right, 26.5 vs 5.6seconds and Left 29.0 vs 5.9seconds, at baseline and post-PFMT respectively). As mentioned previously, this suggests that oxygen supply is proportionally and more efficiently meeting the demand in order to maintain workload and facilitate recovery.97,125 Furthermore, despite a discrepancy in magnitude change, the contraction patterns evidenced similar curve characteristics bilaterally, which is also a trend found among the control groups, refer to Figures 3.6 and 3.8 and Figures 3.10 and 3.12. That the bilateral musculature is responding in a synchronized manner suggests coordinated bilateral motor unit activation and microvascular unit perfusion. Furthermore, the fact that there is a magnitude discrepancy bilaterally despite their being symmetric in their desaturation pattern might suggest that the unilateral PFM with the greater magnitude change is activating larger motor pools (when considering the size principle of motor neuron recruitment), in turn generating a larger contraction within that muscle.126 In turn with larger contraction a greater metabolic demand would be generated, producing larger oxygen extraction from the microvasculature, resulting in the lower oxygenation saturation levels.127 111 4.3.2.2 MS and SCI clinical sub-groups NIRS observations from these two clinical sub-groups demonstrated atypical hemodynamic and oxygen kinetic patterns during PFM contractions. An increase in oxygenation during contraction with either restoration to resting levels or continued oxygenation increase in recovery phase was observed, as shown in Figures 3.13-3.19. There was also less symmetry observed in the response between the bilateral PFM, as seen in differing curve characteristics in Figures 3.15, 3.18, 3.19. The atypical NIRS patterns observed in these sub-groups are suggestive of muscle impairment. A study by Azevedo et al. 2015 investigated oxygen recovery kinetics of the vastus lateralis with NIRS in COPD patients, not only did they find slower recovery times in COPD patients, they also observed an increase in oxygenation during both exercise and recovery intervals, similar to the atypical tracings presented in this study.128 They report that this implies muscular impairment. The following paragraphs will provide an interpretation attempting to explain these atypical observations related to muscular impairments. 4.3.3 Explanations for atypical hemodynamic and oxygen kinetic response 4.3.3.1 Innervation 4.3.3.1.1 Pudendal nerve innervation As Ryan et al. 2014 describes, the oxygenation detected by NIRS is the result of exercise activating muscle fibers.53 With the atypical patterning characterization similar to clinical sub-groups with neurological deficits it might possible suggest that certain patterning characteristics allow inference to motor neuron innervation to the PFM, in that demonstrated atypical patterning 112 (either unilaterally or bilaterally), infers impaired motor neuron innervation preventing normal muscle function and in turn normal oxygenation patterns in response to exercise. With this possibility of innervation inference, perhaps it could then also be speculated that in the case group when typical patterning characterization presents in conjunction with urinary symptoms (as in the high-mobility sub-group), their symptoms might be more related to sensory innervation rather than motor neuron innervation. This could provide an explanation for why they experience symptoms but still have similar hemodynamic and oxygen kinetic responses as controls (suggestive of intact motor innervation). 4.3.3.1.2 Denervation related to pregnancy and labour SS9 and SS10 were also considered to have high mobility, both had underlying etiology of vaginal delivery trauma, interestingly, their NIRS tracings had trends boarder lining between the high mobility and assisted mobility clinical sub-groups. Although both displayed typical patterning at post-PFMT, the characteristics of the patterning displayed less synchronicity contralaterally, a characteristic trend found among the assisted mobility group, as demonstrated in Figure 3.17-3.19. This lack of synchronicity in the musculature response to contraction could be the result of the delivery trauma (forceps, tears, prolonged 2nd stage labour) causing muscular defect or pudendal nerve injury, preventing optimal and coordinated muscular contraction.13,123,129 4.3.3.1.3 Recruitment Also, when considering motor neuron recruitment, the catch principle may provide some insight. If impulses to motor units occurring simultaneously generate more force, it may be 113 speculated that the control group, with intact innervation was capable of firing impulses simultaneously or at quicker intervals since they were able to generate higher PFM manometer pressures. But in the case of interrupted innervation among the case group, impulse conduction could be less synchronous and have longer time intervals between impulses, resulting in weaker contractions. This might help to explain the weaker contractions among the case group as measured by manometer but also the atypical oxygenation patterning observed during contractions. 4.3.3.1.4 Activation Weidner et al. 2006 reported that neuropathic injury of the PFM not only caused fewer action potentials of low amplitude but that they also occurred spontaneously and in fibrillation.13 The abnormal action potential activity might explain the abnormal increases in oxygen saturation patterns observed in NIRS. The impulses that are being generated in neuropathic injury occur at low amplitude and at varying intervals, which could be influencing the weak, delayed, uncoordinated or absent contractions as observed by NIRS. For example, Figure 3.19, demonstrates delayed and uncoordinated contraction. At the start contraction, only unilateral desaturation occurs (and in low magnitude) within the Left PFM, which also begins to resaturate before cessation of contraction. On the contralateral side, increase in oxygenation occurs at onset of contraction, with desaturation occurring several seconds after onset of contraction, also occurring at low magnitude. 114 4.3.3.2 Microvasculature Increased muscle pressure during contraction can cause vascular compression, based on previous literature demonstrating NIRS response of contracting muscle.50,52,67,100,106,130 As such the initial sharp downward spike observed at onset of contraction in controls, reflects vascular compression and the continued desaturation during sustained contraction generates oxygen demand exceeding that of oxygen supply. Thus, allowing the observation of inverse in O2Hb and HHb, with HbDiff decrease to reflect oxygen consumption. The slow upward trend of oxygenation during SMVC before cessation of contraction, can be attributed to the vasodilatory response of the microvasculature as it attempts to meet oxygen demands. It is probable that atypical responses in the case group were due to low intensity contraction, not resulting in vascular compression but through stimulus of attempted contractions a vasodilatory response might still be occurring. As described by Delorey et al. 2002, exercise causes an increase in blood volume by means of vasodilation, increased hemoconcentration, and capillary recruitment.106,127 Vasomotor properties of the vasculature are regulated by the sympathetic system, which may be responding to cause vasodilation even though there is not enough muscle activity requiring increased oxygen supply provided from vasodilation. 4.3.3.3 Contractile Intensity A third explanation for the atypical NIRS responses seen in the case group is the variability of exercise intensity achieved. Since the high mobility group demonstrated similar tracings to the control group it can be speculated that they were able to achieve similar contraction intensities. In the MS group and the SCI sub-groups the atypical pattern presentation could be a result of low contraction intensity, which is plausible as on inter-group comparison of manometer pressure 115 variables were significantly lower for the case group (Baseline: 32.09 vs 13.12 Peak cmH2O, 20.54 vs. 8.13 Average cmH2O and post-PFMT: 35.68 vs 13.91 Peak cmH2O, 23.68 vs 10.30 Average cmH2O; for controls and cases respectively, Refer to Table 3.19 and Figure 3.25). Boushel et al. 2001, reports that when exercise intensity is not great enough, arterial inflow can be greater that uptake which causes increased O2 saturation detected by NIRS or no change in saturation is demonstrated.51 Segal et al. 2005, further describes this physiological occurrence by the fact that microvasculature supply supports multiple motor units, which allows for increased blood flow to quiescent muscle fibers as the blood flow is also supporting an active motor unit.126,131 The increased blood flow to quiescent fibers can be detected by NIRS as unchanged or increased oxygenation patterns.51 This is also supported by the findings of Ryan et al. 2014, who reported that even with electrical stimulation they were not always able to achieve desaturation of the denervated muscle tissue in ALS participants.53 Furthermore, initial response of muscle microvasculature to contraction is to increase perfusion, which can proceed the activation of muscle fibers, essentially providing a feed forward mechanism, in that oxygen is made readily available to support the oncoming muscular contraction.127 This feed forward mechanism could be what is observed in these NIRS tracings, as increase in oxygenation and blood volume occurs with attempted contraction, which ultimately occurs at lower intensity not adequate to produce desaturation or no contraction as result of innervation impairment. 4.3.3.4 Cross Contamination Another explanation for the atypical changes observed in NIRS oxygenation patterns among the clinical groups is cross contamination from Valsalva maneuver or accessory muscle use (obliques, transverse abdominus, hip adductors and flexors, gluteus muscles). Performing a 116 correct PFM contraction is difficult even for women without LUTS and intact musculature.132 Although methods, as described in Methods section 2.3.3, attempted to control for this, it could still be occurring. This cross contamination could be a possibility when the atypical response occurs with synchronicity across bilateral PFM. Valsalva maneuver and accessory muscle use result in increased intraabdominal pressure, resulting increased manometer pressures.133 As such cross contamination may then also increase the oxygenation of the PFM detected by NIRS due to blood volume distribution from the contraction of adjacent muscle groups, although it may also be speculated that cross contamination may result in desaturation of PFM due to increased abdominal pressure causing compression to the microvasculature. This may provide a basis for lack of cross contamination influence as increased oxygenation was demonstrated. Moreover, when the atypical response is occurring without synchronicity bilaterally, in that unilateral PFM produce different responses, such presentation may be more in align with altered innervation, microvasculature and contractile intensity discussed previously. 4.3.3.5 Applicability of theoretical considerations to an individual case Altered physiology including innervation, microvasculature, and contractile intensity may provide insight to the oxygenation responsiveness in isolated unilateral PFM for the case participants SS12 and SS3, Figures 3.13-3.18. With particular interest in SS3, who demonstrated oxygenation change detected by NIRS but no measurable pressure with attempted contraction by manometer. (To reiterate, NIRS and manometer measurements were not performed simultaneously). Across all three types of contractions: MVC, SMVC and REPS, the manometer detected no change in pressure. With NIRS the MVCs demonstrated increased O2Hb, tHb, and 117 HbDiff to the left PFM. Interestingly, this participant self-reported more sensation below injury level to their left side. As has been determined by the concept of central pattern generation, peripheral afferent input can generate neuronal activation to produce a motor task, without any supraspinal input.126,134-136 Research has concluded that, in the lumbosacral region central pattern generation is crucial for regulating posture and locomotion.126,134,135 As PFM nerves project from the sacral region, it may be plausible to consider some degree of central pattern generation regulating PFM, especially since this muscle group is so closely connected to those of locomotion and posture.41,42,137-139 It may then be considered that mechanoreceptors in the PFM can send lengthening sensory information to the lumbosacral spinal cord which in preparation of a motor response, microvasculature is recruited and increases perfusion to the musculature. Since the motor innervation is impaired, no contraction occurs and the oxygenation of the PFM remains elevated due to continued afferent stimuli. The PFM is 70% type I fiber,39 which has a high concentration of mechanoreceptors sensitive to lengthening.126 Afferent stimuli could be coming from the mechanoreceptors of the PFM, detecting changes in length due to presence of the probe. Observations from SMVC of SS3 at baseline, Figure 3.16, are suggestive of NIRS capturing oxygenation patterns of PFM due to central pattern generation as a result of free nerve ending excitation. Free nerve ending excitation can be provoked by mechanical and metabolic stimuli,126 and is given particular attention in SCI as a contributor to spasticity.134 It is plausible that in the case of SS3, excitation of free nerve endings results from PFM mechanoreceptors detecting change in muscle length induced by the presence of the NIRS probe. Which results in an oscillatory motor output causing the PFM to contract. As evidenced in Figure 3.16, desaturation is apparent after an initial increase in HbDiff and O2Hb, within the time frame that the 118 participant is actively attempting a contraction. However, once “voluntary” contraction is over (denoted by the black ox), several more desaturation patterns occur in repetition. This is suggestive that the unilateral Left PFM at baseline assessment, actually demonstrated a spasm rather than a voluntary contraction. This would be further supported by that desaturation does not occur in opposite unilateral PFM, during any other attempted voluntary contraction, no detected manometer pressures during attempted contractions, along with the clinical history of the participant, non-traumatic SCI T8 AIS-B. 4.3.4 Objective outcome measures 4.3.4.1 Inter-group objective PFM function outcomes The control group demonstrated better PFM function than the case group at both baseline and post-PFMT, with regard to objective measures, including: Peak cmH2O and Average cmH2O manometer variables (Table 3.19), as well as ½RT (Table 3.12) and DMag (Table 3.14) NIRS variables. Although, values for these outcome variables were better for the control group compared to the case group, they did not always achieve statistical significance. With this in mind, the findings still suggest that the case group has weakened contractile strength1,22,140 and reduced oxidative performance.49 That the ½RT was slower for the case group also demonstrates that the oxidative kinetics of the PFM has reduced capacity to restore homeostasis proceeding muscular contraction, indicating more fatigability than the control group, as would be expected with assumed PFM atrophy among the case group.126 Furthermore, the reduction in DMag achieved during contraction suggests reduced oxygen demand generated during contraction, which supports (1) the manometer evidence of reduced contractile strength, 119 in that lower contraction intensity would also create lower oxygen demand, and (2) limited oxygen uptake capability of the PFM. Which be explained by the physiological consequences experienced by the case group, such as impaired innervation, muscle atrophy, diminished microvasculature, transition of muscle isoform composition to type II fibers. These findings are also supported by previous literature reporting diminished PFM strength in incontinent females compared to continent controls.92,140-142 Also, NIRS investigations of oxygen kinetics in individuals with neurologic conditions determined these sample populations to have slower oxygen recovery kinetics than able-bodied counterparts.53,130,143 In addition, Jürgensen et al. 2017, reported that in continent females, PFM strength (measured by manometry) is correlated to whole body aerobic capacity (measured by oxygen consumption and ventilatory anaerobic threshold), however, the correlation reported only had moderately positive significance (r= 0.55).137 4.3.4.1.1 Half Recovery Time (½RT) outcomes At baseline the control group demonstrated faster ½RT than the case group, for both Right and Left PFM (6.30 vs 18.90 seconds and 11.39 vs 19.36 seconds, respectively, refer to Table 3.12) with the difference being statistically significant for the unilateral Right PFM (p-value <0.01). Interestingly, the control group also demonstrated Right PFM dominance based on Fz, ½RT and DMag measures of dominance (refer to Tables 3.7, 3.10), suggesting that the controls not only had better bilateral oxygenation recovery kinetics of PFM, but this appeared to be specific to their dominant side. Furthermore, the case group appeared to demonstrate Left PFM dominance based on Fz, ½RT and DMag measures of dominance (refer to Tables 3.7, 3.9, 3.10). This suggests that the lack of statistically significant findings on ½RT of unilateral Left 120 PFM is due to the fact that the controls generally had worse ½RT in their dominant PFM and the case group demonstrated greater ½RT in their dominant PFM, making the unilateral left PFM more comparable to each other. This is in contrast to the contralateral Right PFM, in which the control was more dominant and the case group less dominant, pronouncing the difference of PFM oxygen recovery kinetics between the two groups. At post-PFMT faster ½RT values for the control compared to the case group in both Right and Left PFM were maintained, (7.87 vs 38.03 seconds, and 9.55 vs 18.54 seconds, respectively, refer to Table 3.12). Again, statistical difference was only demonstrated among the unilateral Right PFM (p-value 0.01). Further supporting dominant derived differences among the two groups. 4.3.4.1.2 Delta magnitude change (DMag) outcomes At baseline the control group demonstrated greater DMag (oxygen consumption) than the case group, for both Right and Left PFM, however these differences did not yield statistical significance (-7.31 vs -1.53 µmol and -5.04 vs -2.21 µmol, respectively, refer to Table 3.12). At post-PFMT the control maintained greater DMag desaturation values compared to the case group for both Right and Left PFM, (-10.34 vs -2.19 µmol, and -8.49 vs -8.06 µmol, respectively, refer to Table 3.14), however, in this instance the difference among unilateral Right PFM yielded statistical significance (p-value 0.01). Interestingly, this supports the findings of ½RT in relation to PFM dominance, as the case group demonstrated comparable desaturation values with their dominant side of the Left PFM and the pronounced difference in desaturation in the Right PFM between groups due to Right dominance of control group. 121 4.3.4.1.3 PFM manometry outcomes At baseline the controls performed better compared to the case group across all three variables with statistical significance achieved for: Peak cmH2O, Average cmH2O and Timesec (32.09 vs 13.12 cmH2O p-value <0.01, 20.54 vs 8.13 cmH2O p-value <0.01, 1.30 vs 1.08 seconds Lg10 p-value 0.04). At post-PFMT the controls maintained better performance than the case group across all three variables, with statistical significance achieved for peak and average cmH2O but not for Timesec (35.68 vs 13.91 cmH20 p-value <0.01, 23.68 vs 10.30 cmH20 p-value 0.02, 1.29 vs 1.05 seconds Lg10 p-value 0.18). This supports the findings of the NIRS variables demonstrating better oxygen kinetics among the control group, allowing for more functional strength and endurance of the PFM as measured by manometry. Although, there was no difference in Timesec between the two groups, the fact that the Peak and Average cmH2O achieved are lower, implies that the cases do not have comparable levels of muscular endurance needed to sustain higher levels of contractile intensity. 4.3.4.2 Intra-group objective PFM function outcomes Neither the control group or the case group demonstrated an improvement of objectively measured PFM function from baseline to post-PFMT assessment, for the following variables: Peak cmH2O and Average cmH2O (Table 3.18), as well as ½RT (Table 3.11) and DMag (Table 3.13). This was surprising as previous literature has reported improvement in PFM strength and symptom scores after PFMT intervention, and PFMT is considered first line therapy for urinary incontinence (regardless of type).20,21 122 A possible contributing factor for this lack of improvement is the fact that the PFMT utilized was a home-based therapy only; should supervised sessions have occurred throughout the intervention more pronounced improvements may have been observed, as reported in studies which have employed such means of supervised PFMT.141,144,145 Also, the duration of PFMT may not have been long enough to result in improved performance, varying lengths of PFMT have been used in research and no standardized time frame has been documented. Duration range for effective therapies reviewed in the literature spanned from 2 to 6 months of training, with various dosing of exercise intensities and modalities.20,21,146 Impaired innervation within in the case group may have resulted in insufficient activation of the PFM to produce meaningful contractions at intensities required to elicit a training effect. For the more severe cases of neurologic conditions, where only a flicker response was seen at baseline, it is likely that neuromuscular stimulation may be the best approach to induce beneficial neuronal and muscular adaptations.25 Overall adherence to PFMT was also low, which has a direct negative impact the improvement outcome measures. Specific to the control group, it is possible that the PFMT intensity was not demanding enough promote muscular hypertrophy and oxygen kinetic improvements, as these adaptations are specific to intensity of exercise regimes, as explained by the overload principle of strength training.147,148 4.3.4.2.1 ½RT outcomes Neither group demonstrated an improvement of ½RT from baseline to post-PFMT. In addition to general explaining factors for this lack of anticipated finding, another consideration specific to the ½RT should be considered. The PFMT utilized was meant to target both strength and endurance of PFM, and therefore should be activating both fiber types, although the PFM is 123 70% type 1 fibers. With regards to specific endurance training, slow fibers tend to have small changes in mitochondrial enzymes promoting oxidative phosphorylation, whereas their neuroelectrical properties tend to demonstrate larger changes.126 This could perhaps be a contributing factor to lack of improvement in ½RT from baseline to post-PFMT. Furthermore, as recovery kinetics are most likely to be influenced by increased number of mitochondria within the muscle tissue, and this adaptation requires consistent progressive training to a point which exceeds the initial PFM endurance capacity, that which was measured at baseline.149 The control group demonstrated a significant difference between Right and Left PFM ½RT at baseline (6.30 vs 11.39 seconds p-value 0.02 (Lg10), respectively, refer to Table 3.11). Again, this supports the controls demonstrated greater oxygen recovery kinetics within their dominant side based on Fz scores. Interestingly, this significant difference disappeared at post-PFMT (7.87 vs 9.55 seconds p-value 0.72, refer to Table 3.11), although this was initially thought to suggests improved synergistic recovery response of the bilateral PFM at post-PFMT, the degree of dominance for controls increased at post-PFMT, contradicting this initial interpretation (5.16 compared to 10.38 at post-FMT, refer to Table 3.12) Also, interesting to note is that the ½RT dominance of controls from baseline to post-PFMT was not significantly different but neither was it correlated (1.46 vs 1.67 p-value 0.13, rs 0.11, refer to Table 3.11) suggesting some degree of variability, even though dominance was maintained on the Right PFM. Whereas the case group also did not demonstrate any difference in the ½RT dominance from baseline to post-PFMT, these variables were highly positively correlated (-8.20 vs -7.56 p-value 0.89, r -0.91 p-value <0.01, refer to Table 3.11). This suggests that ½RT dominance was not altered among the case group after PFMT, meaning improved coordination between bilateral PFM did not occur. 124 4.3.4.2.2 DMag outcomes In general, the DMag of desaturation increased for all variables from baseline to post-PFMT in both groups, although no statistical significance was determined. This may infer some improvement in oxygen consumption of the PFM, suggesting the muscle tissue may have responded to certain aspect of the training, but was not enough to elicit a demonstrable difference or to influence the recovery kinetics. As the PFMT was only for 8-weeks, this duration would not be long enough to induce muscle hypertrophy, therefore the suggestion of reduced desaturation after PFMT would likely be due to neuronal adaptations.18,25 Such adaptations could include increased firing rates and increased motor unit recruitment that can cause increased muscle contractile properties, which in turn would result in greater desaturation as more muscle fibers are active and at higher intensity. Furthermore, both groups maintained the DMag dominant side, similar to the ½RT dominance variables. The DMag dominance of controls from baseline to post-PFMT was not significantly different but neither was it correlated (1.54 vs 1.85 p-value 0.91, r 0.08, refer to Table 3.13) suggesting some degree of variability, even though dominance was maintained on the Right PFM within the controls. Whereas the case group also did not demonstrate any difference in the DMag dominance from baseline to post-PFMT, these variables were highly positively correlated (-3.23 vs -6.69 p-value 0.87, r 0.75 p-value 0.05, refer to Table 3.13). This further supports the suggestion that PFM dominance, as measured by NIRS variables, was not altered among the case group after PFMT, meaning improved coordination between bilateral PFM did not occur. 125 4.3.4.2.3 ½RT and DMag associated outcomes Interestingly the only correlations demonstrated in either group were in the non-dominant PFM (according to Fz and NIRS variables of dominance). The control group demonstrated a moderately positive correlation between ½RT and DMag in the Left PFM at baseline (rs 0.65 p-value 0.02, refer to Table 3.15). This suggests that as the ½RT lengthened, less DMag desaturation occurred, implying limited oxygen consumption occurred with reduced recovery kinetics (limited oxygen uptake and limited oxygen supply). However, at post-PFMT correlation was not demonstrated in the non-dominant PFM of the controls. This does not imply that oxygen uptake and delivery mechanisms improved but it may support the suggestion of a change in one of these variables, further supporting the idea of some improved uptake mechanism due to PFMT, but in this case specific to the non-dominant PFM. Although the case group demonstrated a correlation between NIRS variables, this did not occur at baseline as it did in the controls. Rather at post-PFMT data shows a highly positive correlation between ½RT and DMag (rs 0.93 p-value <0.01, refer to Table 3.13 and Figure 3.23). That this correlation presented at post-PFMT suggests greater oxygen uptake occurred with reduced ½RT, suggesting some training effect may have taken effect in the non-dominant PFM. 4.3.4.2.4 PFM manometer outcomes No statistical significance was determined in both groups in manometry variables from baseline to post-PFMT. Despite lack of statistically significant findings, the control group demonstrated slight improvements in all variables whereas the case group actually demonstrated slight worsening at post-PFMT. The lack of improvement was not anticipated as it has been well 126 documented in the literature that PFMT can be effective. It is possible that the standardized PFMT methods used in this study were not at appropriate dose for individual participants and therefore the therapeutic effect was not achieved. Furthermore, overall adherence to PFMT was low which will influence these results. The slight reduction also observed in the case group could also be due to the fact that one participant had 0% adherence to PFMT, another participant experienced symptomatic episode of relapse-remitting MS and a third participant reported a week of hospitalization (cause of which was unrelated to study). Although there was a lack of difference for both groups between baseline and post-PFMT, correlation of most variables between assessments were highly positive, suggesting that participants who performed well at baseline also performed well at post-PFMT. 4.3.4.2.5 ½RT and PFM manometer associated outcomes When intra-group ½RT and manometer variables were correlated, interestingly only the case group demonstrated a significant correlation at post-PFMT. Furthermore, the correlation that was demonstrated for bilateral PFM ½RT and all manometer variables was highly negatively correlated, as presented in Table 3.22 and Figure 3.26-3.27, (Right ½RT and Timesec had highly negative correlation although this did not reach significance, r -0.73, p-value 0.06). This suggests those participants that demonstrated greater PFM strength at post-PFMT, as per higher pressure measures and increased contraction duration, or endurance, also demonstrated quicker recovery times, or greater oxidative performance. This infers that among the case group, greater PFM strength corresponds with oxygen recovery kinetics of the musculature. As this relation was not observed at baseline, it suggests that perhaps some training effect occurred for the case group, since in response to exercise, 127 corresponding adaptations occur in motor neurons and metabolic properties in order to increase muscle activation and oxidative capacity.126 Although, if changes in muscle volume and its consequent adaptations occurred, improvements in manometer and NIRS variables from baseline to post-PFMT would also be expected, which was not observed in this study, with reasoning for this lack of finding discussed previously. 4.3.4.3 Lower limb and PFM dominance outcomes 4.3.4.3.1 Fz and WFQ dominance outcomes Isolating bilateral PFM response to exercise was examined in this study in attempt to see whether contralateral muscular function might help explain PFM dysfunction and LUTS. It was also hypothesized that PFM dominance would be more pronounced in the case group due to the nature of innervation impairment. Furthermore, since the PFM plays an integral role in posture and lumbosacral support, 41-43 it was thought that measure of lower limb dominance would be associated with PFM unilateral dominance. For this reason, the relationship between Fz, WFQ and NIRS dominance variables was assessed. Inter-group comparisons of both DisFz and QFz demonstrated significance difference between the two groups, controls demonstrating greater dominance in Right lower limb (as indicated by positive value) and case group demonstrating greater dominance in the Left dominant (as indicated by negative value). (DisFz 0.11 and -0.07, p-value <0.01, QFz 0.09 and -0.05, p-value <0.01, refer to Table 3.10). As demonstrated in Table 3.10, no other differences were found between groups for the remaining dominance variables. 128 Intra-group comparison of DisFz and QFz for both groups did not demonstrate significant difference, indicating that lower limb dominance during stabilization tasks is maintained during a distractive cognitive stimulus. This is further evidenced by the high positive correlation between DisFz and QFz among the control group (rs 0.83, p-value <0.001, refer to Table 3.8 and Figure 3.2). Despite the objective measure of lower limb dominance during both distracted and quiet stance, the WFQ measure of self-reported lower limb dominance as described by “footedness” did not demonstrate a difference between the two groups as both groups reported greater preference for their Right foot. This WFQ measure indicating Right foot preference among the controls appears reasonable, since as a group across all measures of dominance (including NIRS) they demonstrated positive average values, indicating greater responsiveness on their Right side. However, the WFQ measure indicating Right foot preference among the case groups is curious, since as a group across all measures of dominance they demonstrated negative average values, indicating greater responsiveness from their Left side. It was initially expected that WFQ scores would be associated with Fz scores of dominance, however, this was not demonstrated. The lack of correlation between these variables could be due to the fact that the WFQ poses questions that pertain to two type of motor tasks, stabilization and active movement,89 although both types of questions are equal in number the responder may be more likely to choose their motor task foot for both types of questions with the perception that the preferred foot indicates greater strength of that lower limb, making it the best choice for all tasks. Research by Hart et al. 1997 and Grouios et al. 2009, determined that the WFQ is not a good indicator of motor task dominance, as they found that participants commonly switched limbs when actually performing a motor tasks, contradicting what they reported on the 129 WFQ.150,151 This could explain why none of the of the lower limb dominance measures correlated with the PFM NIRS dominance measures, (refer to Table 3.9), as Fz scores measured lower limb dominance during a stabilization task and the NIRS dominance measures were assessing PFM dominance during an active movement motor task. 4.3.4.3.2 NIRS dominance outcomes With implementation of PFMT it was thought that PFM dominance as determined by NIRS would decrease, as PFMT is thought to promote coordination within the whole muscle group.28,92,132,152 Also, it has been determined that training can cause neuromotor adaptations in response to exercise training can result in contralateral limb improvements.148 It was thought that this might translate to the PFM, in that the weaker or non-dominant side would experience benefits directly from engagement in the PFMT, and further promoted by this contralateral phenomenon as the dominant PFM may be producing the majority of the work performed by the PFM during the training regime. Among both the control and case groups no difference was demonstrated between baseline and post-PFMT for ½RT Dominance (refer to Table 3.11) or DMag Dominance (refer to Table 3.13). Interestingly, the case group demonstrated high positive correlation between baseline and post-PFMT for ½RT (r 0.91, p-value <0.01) and for DMag Dominance (r 0.75 p-value 0.05). Although DMag Dominance did not reach statistical significance, these correlations both suggest that PFM dominance was more consistent within the case group and tended to remain within the unilateral Left PFM, as values indicated by negative values, refer to Tables 3.11 and 3.13. 130 Furthermore, absolute values for both ½RT and DMag NIRS dominance were utilized to examine the degree of dominance. The absolute ½RT and DMag NIRS dominance (degree of dominance) provides a parameter representing how pronounced the difference is between unilateral Right and Left PFM in their oxygen kinetic performance. A smaller absolute value of degree of dominance indicates the Right and Left PFM were more similar, meaning the dominant side was less pronounced, suggestive of a more coordinated bilateral PFM oxygen kinetic performance. A larger absolute value of degree of dominance indicates the Right and Left PFM were less similar, meaning there was more prominent unilateral dominance in the PFM, suggestive of less coordination between of the bilateral PFM oxygen kinetic performance. Thus, allowing for a means of assessing of improved coordination within the bilateral PFM in response to PFMT. At baseline inter-group comparison demonstrated a significant difference between the degree of ½RT Dominance, that of controls being much less than the case group (5.16 and 17.41, respectively, p-value <0.01, refer to Table 3.12). However, at post-PFMT the degree of ½RT Dominance between the two groups was comparable (10.38 and 15.64, respectively, p-value 0.39, refer to Table 3.12). The fact that the control group demonstrated an increase in the degree of ½RT Dominance suggests that there might be reduced coordination during PFM after the PFMT. This could imply that only the dominant PFM responded to the PFMT, thus causing the increased dominance, however this is not supported by the comparison between Right and Left ½RT post-PFMT which did not demonstrate a significant difference bilaterally. Neither did the Right of Left ½RT improvement at post-PFMT, refer to Table 3.11. Interestingly, both groups did not demonstrate any difference between the degree of DMag Dominance at baseline or post-PFMT (refer to Table 3.14), suggesting that the difference between desaturation of unilateral PFM within groups at each assessment was comparable. 131 4.3.4.3.3 Degree of NIRS dominance and PFM manometer outcomes Intra-group correlations between degree of ½RT Dominance and Mag Dominance did not demonstrate any significant findings within the control group. The case group showed some suggestion of a moderate negative correlation between degree of ½RT Dominance and manometer Peak and Average cmH2O, however this did not reach statistical significance (r -0.69, p-value 0.09 and r -0.67, p-value 0.10, respectively, refer to Table 3.20). This implies that less difference between the ½RT of unilateral PFM, or a more coordinated response from the PFM, could be related to better PFM strength (higher Peak and Average cmH20 pressures). Since the correlations were only moderate and not statistically significant this implication is only suggested and not confirmed. 4.3.4.3.4 Degree of NIRS dominance and PFMT adherence outcomes The control group demonstrated a moderate negative correlation between degree of ½RT Dominance and both Exercise Volume and Frequency (r -0.69, p-value 0.02 and r -0.61, p-value 0.05, respectively, refer to Table 3.25 and Figure 3.55), although only the correlation to Exercise Volume had statistical significance. This provides a possible implication that greater adherence to PFMT was associated with greater similarity of the bilateral PFM recovery response from contraction, suggesting more consistent exercise could improve coordinated muscular effort in health tissue. 132 4.3.4.4 QOL and clinical symptom outcomes 4.3.4.4.1 Inter-group QOL and clinical symptom outcomes According to Dumoulin et al. 2018, general improvements of LUTS are experienced by females with pelvic floor dysfunction and incontinence who have undergone PFMT.20 These reported improvements are measured by the same validated questionnaires utilized in this study. As such it was expected that symptom scores would reduce at post-PFMT for the case group and demonstrate a larger degree of reduction from the control group. However, inter-group comparison of both QUID, and PVR score changes did not demonstrate statistically significant differences of change incurred between groups. Although not statistically significant, these variables did demonstrate larger reductions among the case group, refer to Table 3.6. 4.3.4.4.2 Intra-group QOL and clinical symptom outcomes Intra-group reductions in symptom scores were expected at post-PFMT. This hypothesis was directed towards to the cases group, however, as some controls did report symptoms on the QUID, diminishment of symptoms would also be expected. Although not significant, controls on average did show a reduction in all measured questionnaire variables and for PVR. Similar findings were demonstrated among the cases, however, only a statistically significant reduction in the QUID-UUI score at post-PFMT was demonstrated (7.5 and 5.0, p-value 0.03, refer to Table 3.4). As this is an indication of LUTS specific to urgency symptoms, it appears that PMFT had more of an impact on urge related incontinence rather than stress related incontinence. This could be due to the fact that urgency and UUI are symptoms related to detrusor overactivity, which is a common characteristic of neurogenic bladder.8-10,30 PFMT can effectively reduce 133 symptoms of urgency, as PFM contractions can inhibit detrusor activity by means of afferent stimulation eliciting the guarding reflex to suppress parasympathetic excitation in the sacral nerves innervating the bladder.24,28 In addition to suppression of the parasympathetic excitation, PFM contraction also promotes sympathetic excitation of the sacral nerves. This results in internal sphincter closure and inhibition of detrusor activity.24,28 Even though the case participants reported a reduction in urgency symptoms it is interesting that the average frequency recorded on the 3-bladder diary increased (6.74 to 7.29 voids/day, refer to Table 3.5), typically a measure associated with urgency.8 However, this increase from baseline was not significant and nor were any of the other bladder diary variables. Similar findings in lack of significant improvement of bladder diary measures are reported by McClurg et al. 2006.25 McClurg et al. 2006, also found that when females with MS received PFMT without biofeedback or NMES, there was no statistical improvements found on QOL scores measured by the IIQ and UDI (full length versions).25 This was also demonstrated in this study, as the results from the IIQ-7 and UDI-6 both reduced, refer to Table 3.4, but not significantly. 4.3.4.5 PFMT Adherence outcomes Adherence to is the most important indicator for successful rehabilitative PFMT.25,153,154 An ICS consensus report identified six key barriers to PFMT adherence: knowledge regarding PFM function and reasoning for PFMT, competence regarding physical skill of correct PFM contraction, emotional perceptions surrounding PFMT, cognitive engagement, prioritization, accessibility of service provider.155 In addition to addressing these barriers, Dumoulin et al. 2014 emphasize the importance of instructing proper PFM contraction, education of pelvic floor 134 function and benefits of PFMT.153 This was performed both at baseline and post-PFMT, where PFM anatomy and function were reviewed, along with instruction and practice of corrected PFM contraction. Although adherence is considered an integral part of PFMT there is no standard method of measuring it and in turn no set parameters to distinguish acceptable levels of adherence.153,156 Adherence in this study was measured by percentage of total amount of required exercises completed per day (Exercise Volume) and the percentage of days any amount of the exercises were completed over the course of 8-weeks (Exercise Frequency). McClurg et al. 2006 reported high adherence rates, considered to be >75%, among their participant population,25 and Borello-France et al. 2010, reported initial high adherence rates of 81% and 90% for both exercise frequency and volume measures.157 According to the reported rates from these studies, it can be inferred that both the control and case groups demonstrated low levels of adherence when considering the Exercise Volume adherence was 51.10% and 52.23%, respectively (refer to Table 3.23). Similar low adherence rates were reported by Porta Roda et al. 2016, who had 50% adherence rate among women with UI performing home-based PFMT.156 Although adherence was better for Exercise Frequency among both groups, 62.91% and 78.57%, (refer to Table 3.23), with the case group demonstrating greater frequency. If considering the interpretation by Fitz et al. 2017 and McClurg et al. 2006, of high adherence as 75-81%, the case group met this criterion for the Exercise Frequency measure of adherence.25,29 135 4.3.4.5.1 Adherence and reduced urgency symptoms As shown in Table 3.24 and Figure 3.30, a highly positive correlation was determined between all PFM manometer variables and percentage of Exercise Frequency among the case group. This provides evidence that participants who performed excises more consistently throughout the 8-week intervention had better PFM function as measured by PFM manometer variables of strength and endurance. Furthermore, the significant reduction in QUID-UUI score from baseline to post-PFMT found among the case group was also highly negatively correlated to Exercise Frequency (rs -0.85, refer to Figure 3.31). Data presented in Figure 3.31, seems to suggest that adherence rates of >80% of Exercise Frequency over an 8-week intervention period is required to reduce urgency symptoms. This finding is supported by Fitz et al. 2017,29 who found that high adherence of 80% to home exercise routine reduced overactive bladder symptoms and improved PFM function. 4.3.4.5.2 Adherence and PFM function outcomes In addition, among the case group, the DMag and ½RT variables of the non-dominant PFM also demonstrated a high negative correlation to Exercise Frequency (rs -0.78 and rs -0.85, respectively, refer to Tables 3.25-3.26 and Figures 3.33-3.34), suggesting improved oxygenation and recovery kinetics with greater frequency of daily exercise. High adherence rates (specific to Exercise Frequency) among cases was also positively associated with PFM manometer measures, (Table 3.24 and Figure 3.30). This agrees with literature concerning the importance of adherence for promoting beneficial PFMT effects.20,28,154-156 Interestingly, the controls on average did not exceed an adherence rate >75% for both variables (Table 3.21-3.24), which did not demonstrate correlation to PFM manometer, DMag or unilateral ½RT variables. 136 Chapter 5: Conclusion This chapter will highlight the main findings of the research and address how they align with the objectives and hypotheses of this project. The strengths and limitations pertaining to this project will be discussed while also providing suggestions for future directions for continued research in this area. This chapter will finalize the thesis with concluding statements specific to the findings within this project while providing relevance for clinical applicability. 5.1 Main Findings The primary aim of this project was achieved through the successful development of an original transvaginal NIRS probe capable of isolating bilateral PFM function. This was the first study to our knowledge that incorporated NIRS technology to investigate the bilateral PFM physiological response to exercise. Based on the findings of this research we conclude that the NIRS probe designed in this project is capable of detecting differential oxygen kinetics of the PFM bilaterally, thus meeting the primary objective. Observational NIRS findings agree with the hypothesis that contralateral differences would be detected in unilateral PFM responsiveness, although this finding was specific to underlying etiology and mobility status. The NIRS variables demonstrated similar results to that of manometry, in that greater PFM function was established in controls compared to the case group at both assessment points. In addition, neither device was capable of detecting intra-group differences in PFM function after implementation of PFMT. Whether this is due to the inherent capabilities of the devices or other factors such as PFMT dose and adherence remains unanswered and warrants further investigation. Nevertheless, the comparable findings support the second hypothesis that NIRS parameters of PFM function will relate to those of manometer parameters. The case group 137 demonstrated high correlation among oxygen recovery kinetics and PFM strength and endurance at post-PFMT, demonstrating a relationship indicative of greater oxygen recovery capacity corresponding with greater muscular strength and endurance. However, the second hypothesis would have been more strongly supported had all NIRS and manometer parameters demonstrated correlation at both assessment time points for both groups, which was not evidenced in this study. In contrast to the original hypothesis, lower limb dominance did not demonstrate a strong relationship to PFM dominance. It was also thought that lower limb dominance as measured by percentage of ground reaction force exerted by each limb, might differ during different standing conditions. In both groups no difference was detected between lower limb dominance in distracted (DisFz) or quiet stance (QFz). Furthermore, the WFQ did not demonstrate association with either Fz dominance variables or NIRS dominance variables, suggesting it is not a good predictor lower limb dominance during stabilizing motor tasks or PFM dominance during active motor movement tasks. Inconclusive statements can be made regarding PFM dominance based on the findings in this study, however the suggestion among the case group data of degree of ½RT dominance reducing with higher manometer pressures at post-PFMT and the control group demonstrating reduced degree of ½RT dominance with increasing exercise adherence, suggest that this parameter warrants further investigation. It was hypothesized that PFMT would improve PFM strength, endurance and oxygen kinetics. This was not demonstrated in either group, likely due to the factors regarding PFMT dose and adherence. A PFMT with regular supervised sessions, longer duration and adjunctive therapies such as NMES should be considered in futures studies of this population. 138 Clinical symptoms of urgency were significantly reduced among the case group after PFMT intervention, but this did not translate into significant improvements of QOL. Finally, as hypothesized, adherence to PFMT was a strong determinant in promoting beneficial effects of PFMT, observed in its relation to improved NIRS, manometer variables and urgency symptoms among females with LUTS due to impaired pelvic innervation. For this sample population a daily adherence rate of 80% appeared crucial for reducing urgency symptoms. From the results of this study it appears that daily consistency of PFM exercise is important to promote therapeutic effects and is positively associated with better PFM strength and endurance. PFMT adherence did not demonstrate a strong association to oxygen kinetics of healthy PFM in controls, which was not expected and should be further investigated in future studies. 5.2 Limitations With respect to the actual construction of the probe there are some considerations around light emission and detection. The transparent plastic encasing of the probe adds an extra physical barrier that the NIR light must travel through, which can alter the path of emitted light directed towards the musculature. As was experienced with the first probe design a degree NIR light was being refracted by the plastic encasing, preventing adequate emission of NIR light to the musculature to get an appropriate signal. With adjustment of the opaque foam inlay, the scatter of NIR light was reduced to prevent refraction from interfering with the emission and detection of light attenuation, allowing for sufficient signal strength. (Additional details regarding NIR light properties and technical probe design, refer to Introduction section 1.2.3 and Methods 139 section 2.3.4, Figure 2.5). However, some degree of light scatter and refraction could still be occurring due to the inherent nature of light have to pass through this physical barrier. Although an advantage of NIRS is its specificity in targeting muscular tissue area of interest, this can also pose a limitation. As the NIRS probe targets only a small cross- sectional area of the PFM,49 it must be assumed that all the PFM behaves in the same manner as the target site. Since it is known that microvasculature can supply more than one motor pool, and that not all motor pools supplied by the same microvasculature may be activated simultaneously, the NIRS could be detecting hemodynamic changes in quiescent motor pools due to neighbouring active motor pools. Although this would likely only be in the case when NIRS detected no change or an unexpected increasing in oxygenation in response with contraction, and since these atypical NIRS tracings were seen among the case group, it would still be a relevant finding in that implies that not all motor pools of the PFM are activated when exercise conditions warrant full activation. Another technical limitation with the NIRS probe is the consistency of placement during assessment both at within and across assessments. As described in the Methods section 2.3.4, the design of the NIRS probe was such have same detection area as the PFM manometer with a marker to indicate similar insertions depth among the two devices. Although placement during any PFM assessment method (digital palpation, manometer, dynamometer, EMG, ultrasonography), is likely to vary to some degree, and all these methods are still employed with acceptable levels of reliability and validity.1,83,91,159-161 As mentioned in the Methods section this probe design was modelled after that of Shadgan et al. 2008, which determined that movement artifact during contraction did not compromise the NIRS tracings as positioning was well maintained with the probe handle.74 140 Furthermore, to maintain consistency of targeted PFM, the optodes were positioned in alignment with the PFM manometer sensor, as described in more detail with illustrations in Methods section 2.3.4 and Figure 2.5. However, although we attempted to control for consistency of placement across the two devices, the NIRS configuration we utilized only had two detection sites, and should the device move in a clockwise or counter clockwise direction once in situation, it could alter the target area of investigation. A constraint in using NIRS to study the PFM is that the specific path length differential of this muscle has not been identified and therefore the DPF of 4 was used based on previous NIRS methodology and literature reporting skeletal muscle DPF values. Furthermore, a definitive DPF cannot be obtained with CW-NIRS modality. Therefore, the fixed value of DPF 4 was used, even though it is known that the pathlength factor will have variability within the muscle from one subject to the next and due to the cellular environment changes induced by exercise.66,67,76 An issue posed with any PFM assessment is the influence of activated accessory muscles during contraction or the inappropriate response of Valsalva and/or straining. Efforts to minimize accessory muscle contraction are described in Methods section 2.3.3. Although precautions were taken, it is possible that undetected accessory muscle contributed to some degree with PFM contractions. This is particularly true in the case group, where participants with very weak contractions demonstrated only a perineal flicker during contraction. There were many recruiting challenges for this study that lead to a small sample size and heterogeneity among the case group of interest. To begin with the population of interest, females with incomplete spinal cord injury and specific bladder symptoms of urinary incontinence is a limited population. Interested females also had to be willing to undergo pelvic floor exam which 141 hindered some individual interest. Also, the fact that altered motor and sensory innervation due to spinal cord injury or neurological condition present with great variation, even when underlying injury level is the same or neurological condition is similar, further resulting in large heterogeneity. Although this is a limitation of the study and presents challenges for statistical comparison, we are still able to draw some meaningful insight from the observational trends within the study population. Also, the fact that is a heterogeneous population may make the findings more clinically relevant as it would be more similar to the clinical population presenting to health care providers in real life situations. Challenges with recruitment for small clinical populations of study interest with the use of NIRS has been discussed by Ryan et al. 2014, who also attest to the value of discussing observational trends of the data in conjunction with the statistical findings.53 The findings from this pilot study also help to lay the groundwork for development of a larger scale study with more a targeted population. Exercise adherence was low among participants as whole and is a warranted factor for the lack of statistical significance in comparison of outcome variables from baseline to post-PFMT. Adherence rates for both Exercise Volume and Frequency might have been improved had the PFMT intervention included supervised sessions or biofeedback during exercise at home, as these factors have been reported to promote motivation and self-efficacy.28,154 However, 75% the case participants completed at least 82% of required days (Exercise Frequency), during PFMT intervention, (refer to Figure 3.29). Given that transportation is an accessibility barrier limiting exercise participation among individuals with SCI,147 the use of a home-based PFMT could be well suited for some individuals. Perhaps longer-term follow-up (4, 6, or 12months) of home-based PFMT that also includes a supervision component, weekly or monthly visits, would 142 better facilitate and capture PFM improvements.20,162,163 Research from Sran et al. 2016 demonstrated that PFMT with weekly supervision in combination with home-based routine for 3-months was beneficial for women with osteoporosis and UI.144 Bø et al. 1990,18 demonstrated that with PFMT adherence of 100%, both unsupervised home exercise and supervised home exercise groups had significant improvements at 1-month but that the supervised group continued to greatly increase strength at 6-months. 18 Lastly, the average age between groups was determined to be significantly different, with the case group being older. This introduces a limitation to comparison between groups. Since it is known that with increasing age skeletal muscle function diminishes.12,121 Utilizing an age matched cohort design should be considered for future investigations of this nature. 5.3 Strengths and Future Directions The strengths of this study are the success of the technical development of the NIRS probe in isolating the physiological response of bilateral PFM and in its capability of detecting PFM performance under exercise conditions. The fact that the captured NIRS tracings were different between controls and case groups provides evidence that this NIRS probe can provide insight to the altered physiological state of impaired PFM function due to neurological conditions in females. Furthermore, the fact that the NIRS traces of the control group were typical of that expected of healthy skeletal muscle tissue supports this claim. An additional strength of this study is that it utilized a clinically relevant objective method of measuring PFM function with a manometer. The use of this objective tool help to clarify the interpretation of NIRS findings with meaningful applicability to field of study regarding PFM dysfunction and LUTS in females. 143 In light of these strengths, further development of the technical construction of the vaginal NIRS probe to monitor bilateral PFM oxygenation is warranted. In attempt to eliminate NIR light refraction and scatter, a probe made of medical grade silicone housing the optodes would be ideal. To increase the cross-sectional area of the PFM targeted by NIRS a complete circumferential optode configuration, both at the proximal and distal end of the probe would allow greater inference to the PFM function as a whole muscle group. This would incorporate the anterior/posterior components as typically isolated with dynamometric force measures,133,164 the lateral aspects as isolated in this study and the deep and superficial muscular tissue as described by Devreese et al. 2004, considered to be important for coordination.92 Having a circumferential optode configuration would also negate the issue of rotational displacement during assessment. Furthermore, using NIRS technology that employed time-resolved or spatially-resolved spectroscopy to provide absolute hemoglobin concentration values and a measure of tissue oxygen percentage, thus allowing more accurate analysis of the hemodynamic and oxygen kinetic variables. Conducting NIRS investigations concurrently with other modalities would be greatly beneficial. The use of simultaneous perineal EMG during NIRS assessment would help to clarify how impaired innervation from neurologic conditions or injury affects motor unit activation and corresponding oxygen patterns with the PFM. As well as use of superficial EMG over accessory muscles in order to rule out their contribution to PFM contraction and/or consider how their contribution may be beneficial to function PFM contractions and LUTS symptom management. Some researchers consider the lower abdomen involvement to be beneficial and necessary for proper PFM contraction.165 144 Future studies should employ supervised progressive PFMT training to maximize the effects of intervention as described by previous literature, this appears to be more beneficial not only for improvements in PFM strength but also for reduction in reported symptoms.20,28,144,162,163 Particularly for the complicated neurologic population the use of adjunctive therapy may be beneficial for more effective PFM improvements, such as the use of neuromuscular stimulation and biofeedback.25,28,29,166 More involved PFMT for a longer duration with a longer follow-up period would provide better insight on how to translate this research findings into clinical management strategies. Using PFMT that employed more supervision and adjunctive therapies might also help to improve participant adherence to exercise intervention, as it appears studies that employed supervision had demonstrated effectiveness and high adherence rates.25,28,29,144,157,162,163,165 Further research is required to determine the applicability of NIRS to investigate the theoretical concepts regarding the physiological properties of innervation, microvasculature, contractile intensity that were previously discussed. This is needed to validate methods of characterizing oxygenation trends and dominance (SPAM stratification and SPAMD algorithm) used in this study, which may be beneficial for continued investigations of altered PFM physiology in women with LUTS and for physiological adaptations that might occur in response to PFMT. This would need to include studies of NIRS technology capable of measuring TSI%, methods controlling for blood flow, simultaneous measures with EMG, manometry or dynamometry, and morphological imaging. As this research is exploratory in nature, a more refined study, with better controlled parameters for objective measurements would need to be conducted before these speculations can be given weighted consideration. If further advanced, NIRS would add the benefit of oxygen kinetic and hemodynamic response of the PFM, 145 physiological measures which are not currently utilized in research or clinical settings with the field of pelvic floor medicine. Oxygen kinetics and hemodynamics are commonly used as to assess physiologic alterations that occur in pathologic conditions and as parameters to guide management of these conditions and as training parameters for athletes.51,52 Therefore, refinement of NIRS applicability to the PFM could provide new insight to the physiological alterations of the musculature in PFM dysfunction and could be utilized as in other fields to help manage PFMT to improve dysfunction and LUTS. Such implications may be that ½RT and desaturation magnitude levels could be used to guide clinical decisions to determine the appropriateness of home-based PFMT, supervised PFMT or NMES intervention. 5.4 Conclusion With the use of NIRS in this study we were able to determine that this technology can be utilized to detect differential bilateral PFM response to exercise. NIRS is capable of detecting differences in oxygen kinetics in controls and females with LUTS due to altered pelvic innervation. This NIRS methodology provided comparable objective outcomes as PFM manometry, in that both were capable of detecting functional differences between controls and cases, without determining within group differences in function from baseline to post-PFMT. While providing comparable PFM assessment as comparable to PFM manometry, NIRS provides additional information of PFM function through its ability to discriminate between the bilateral musculature. Females with LUTS and altered pelvic innervation demonstrated a relationship between oxygen recovery kinetics and strength and endurance of PFM. Adherence to PFMT is critical for facilitation of beneficial training effects with regards to both muscular adaptations 146 and symptom management. Furthermore, the findings of adherence among the case group corroborate existing PFM literature in that PFMT provides benefits of strengthening PFM while also helping to reduce clinical symptoms. Our findings add to the existing literature by showing that these benefits can also be obtained by females with neurological conditions and injury impacting the pelvic floor, however, due to the small sample size and heterogeneity of the study sample, the extent to which benefits of PFMT may be experienced females with specific neurological conditions (with regard to severity of neurological impairment, chronicity and underlying etiology) still warrants meaningful analysis. This research also contributes to the field of pelvic floor medicine by demonstrating NIRS as means to provide physiological assessment of PFM oxygen kinetics, as is commonly practiced in other fields to investigate pathology and direct management. As such, NIRS demonstrates promise as an investigational method capable of providing additional understanding of the pathophysiology occurring in PFM dysfunction, thus contributing to PFMT rehabilitation. 147 Bibliography 1. Bø K, Frawley HC, Haylen BT, et al. 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Biofeedback and pelvic floor exercises for the rehabilitation of urinary stress incontinence. Gynecol Obstet Invest. 2003;56(1):23-27. 169 Appendix A Appendix A Methods A.1 PFMT Instruction Sheet 170 A.2 PFMT Recording Sheet 171 A.3 Bladder Diary 172 A.4 Questionnaire for Urinary Incontinence Diagnosis (QUID) 173 A.5 Urogenital Distress Inventory Short Form (UDI-6) 174 A.6 Incontinence Impact Questionnaire Short Form (IIQ-7) 175 A.7 Subjective Assessment of Improvement 176 A.8 Waterloo Footedness Questionnaire-Revised
Thesis/Dissertation
eng
Experimental Medicine
Vancouver : University of British Columbia Library
Attribution-NonCommercial-NoDerivatives 4.0 International
Graduate
Bilateral measurement of pelvic floor muscle dysfunction in females with lower urinary tract symptoms using near infrared spectroscopy
Text