THE RELATIONSHIP BETWEEN SELF-REPORTED FATIGUE, FATIGABILITY, AND SLEEP QUALITY IN INDIVIDUALS WITH MULTIPLE SCLEROSIS

The average lifetime cost of care for people with Multiple Sclerosis (PwMS) in the United States is approximately $2.2 million per person affected, and up to 80% of PwMS are unemployed within 10 years of disease onset. MS-related fatigue is a debilitating symptom experienced by around 90% of PwMS, it can significantly affect an individual’s functional quality of life by interfering with activities of daily living (ADLs), causing reduced work performance, and contributing to loss of employment. MS-related fatigue is an umbrella term that encompasses the individual’s perceptions of fatigue (perceived fatigue) and measurable deterioration in performance (fatigability). Perceived fatigue and fatigability interfere with the individual’s efficient performance of physical and cognitive tasks and both should be considered during the assessment and management of MS-related fatigue. What further makes MS-related fatigue complex is that not only the disease process itself can cause fatigue, but also other prevalent comorbidities likely contribute to fatigue in MS such as depression and sleep disturbances. Therefore, the approach undertaken in the current body of research was under the notion that a multidisciplinary approach would seem best to optimally assess fatigue in PwMS. Perceived fatigue in PwMS is measured using self-reported scales which are used extensively in the MS-related fatigue field of research. However, there have been recent concerns regarding the psychometric properties of commonly used perceived fatigue scales in PwMS. This is an issue as interpreting the findings of those previous studies is now somewhat difficult. The current study utilized a more psychometrically sound perceived fatigue scale that has been validated for use in PwMS, called the Neurological Fatigue Index (NFI-MS). What makes the NFI-MS a unique measure of perceived fatigue in PwMS is that to our knowledge, it is the only perceived fatigue scale that includes two sleep components acknowledging the importance of considering sleep quality during the assessment of fatigue. Chapter 2 attempted to explore the relationship between the NFI-MS and measures of physical and cognitive fatigability. Previous evidence showed conflicting results regarding the relationship between perceived fatigue and fatigability, as some showed associations while others did not. Fatigability is distinguished from perceived fatigue by the concept of change, i.e., a measurable difference in the performance of a task over a period of time. We initially hypothesized that there are certain items on the NFI-MS that objectify the performance ability of the individual and therefore can be associated with fatigability. A total of 52 ambulatory participants took part in this cross-sectional design study. Physical fatigability was measured using percent change in meters walked on the Six Minute Walk Test and percent change in force exerted on a repetitive maximal hand grip test. Cognitive fatigability was measured by Response Speed Variability on the Continuous Performance Test. The fatigability measures utilized in this study have been previously utilized before and where further modified in both administration and scoring in the current study to better capture fatigability in our study sample. Perceived physical and cognitive fatigue were measured using the NFI-MS. Current perceptions of fatigue were examined immediately before and after performing the fatigability measures using a 1-item Visual Analogue Fatigue Scale. The results of Chapter 2 showed that cognitive fatigability was significantly associated with the NFI-MS physical domain and NFI-MS cognitive domain. However, physical fatigability was not associated with the NFI-MS. All participants demonstrated significantly higher perceptions of current fatigue after performing the physical and cognitive fatigability measures. The findings suggest that the NFI-MS appears to capture the cognitive aspect of MS-related fatigue (meaning it captures both perceived cognitive fatigue and cognitive fatigability), but not the physical aspect (only captures perceived physical fatigue not physical fatigability), and the fatigability measures utilized were fatiguing to the participants which is a clinically important finding. We can conclude that both perceptions of fatigue and fatigability should be measured collectively for a comprehensive assessment of fatigue in PwMS. Next, because an extensive body of evidence demonstrated a strong relationship between perceived fatigue and self-reported sleep quality, but conflicting results regarding the association between perceived fatigue and objective sleep quality; we aimed in Chapter 3 to explore the relationship between the NFI-MS and self-reported and objective sleep quality measures which have never been explored before. All participants filled out the Pittsburgh Sleep Quality Index to asses sleep quality, and the Epworth Sleepiness Scale to assess daytime sleepiness. To objectively quantify sleep quality, the participants wore an actigraph device on their dominant wrist for one week after the assessment day. The results indicated that higher perceived fatigue is significantly associated with poorer self-reported sleep quality and excessive daytime sleepiness, but not with objective sleep quality. Our findings from Chapter 3 support previous research that showed higher perceived fatigue measured using other scales is associated with poorer self-reported sleep quality and daytime sleepiness. Regarding the lack of association between perceived fatigue and objective sleep quality, we argued that perhaps there is a limitation of actigraphy to accurately assess sleep in this sample, as evidence showed that the actigraph may overestimate sleep efficiency and total sleep time. Furthermore, actigraphy findings might be limited by wear time. Perhaps PwMS need to wear the actigraph for more than one week to accurately assess their sleep quality. A previous study that found significant associations between actigraphy and fatigue had the participants wear the actigraph for two weeks. Based on our findings we encourage a wider use of the NFI-MS in clinical and research settings to assess and manage the role sleep quality has on perceived fatigue in the MS population. The relationship between sleep quality and fatigability has never been explored before. Due to the involvement of central nervous system dysfunction mechanisms of both MS-related fatigue and sleep disturbances, and due to the evidence that shows a relationship between perceived fatigue and poor sleep quality, we hypothesized that there would be an association between higher physical and cognitive fatigability and poor sleep quality in our study sample. The results of Chapter 4 showed that several components of the Pittsburgh Sleep Quality Index and several actigraph parameters were significantly associated with physical fatigability and cognitive fatigability. We provide the first body of evidence showing the relationship between poor sleep quality and fatigability in PwMS. Fatigability is an important construct of MS-related fatigue that is a common debilitating symptom in the MS population, and more emphasis should be put on considering the role of sleep quality on exacerbating MS-related fatigue. In summary, the work presented in this dissertation expands on the body of evidence showing the relationship between perceived fatigue, fatigability, and sleep quality in PwMS. Our experiments and findings are novel and significant through the use of the NFI-MS as a measure of perceived fatigue and through the assessment of the association between sleep quality and fatigability in PwMS. For a comprehensive and multidimensional assessment of MS-related fatigue, the measures used in this study can be easily administered in clinical and research settings. In addition, more emphasis should be put on considering the role of sleep quality on exacerbating MS-related fatigue in those with the mild-disease forms of MS. Around 70% of PwMS report some sort of a sleep disturbance, and up to 50% have a diagnosable sleep disorder. Poor sleep quality in PwMS has been associated with a reduction in several quality of life indices, including physical function, psychological well-being, self-care, work ability, and interpersonal relationships. Clinicians and therapists may need to consider sleep assessment and treatment as part of the MS-related fatigue management plan

Self-report sleep quality combined with sleep time variability distinguishes differences in fatigue, anxiety, and depression in individuals with multiple sclerosis: A secondary analysis

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background: Nearly 70% of individuals with multiple sclerosis report sleep disturbances or poor sleep quality. Sleep disturbances may exacerbate or complicate the management of multiple sclerosis-related symptoms. While sleep variability has been associated with several health outcomes, it is unclear how sleep variability is associated with multiple sclerosis-related symptoms. Objective: The purpose of this study was to determine how total sleep time variability combined with self-reported sleep quality is associated with fatigue, depression, and anxiety in individuals with multiple sclerosis. Methods: This study involved a secondary analysis of actigraphy data and questionnaires to assess sleep quality, fatigue, anxiety, and depression. Results: There were significant differences between the Good Sleepers (good sleep quality/low sleep time variability; n¼14) and Bad Sleepers (poor sleep quality/high sleep time variability; n¼23) in overall fatigue (p¼0.003), cognitive (p¼0.002) and psychosocial fatigue (p¼0.01) subscales, and in trait anxiety (p¼0.007). There were significant differences in state (p¼0.004) and trait (p¼0.001) anxiety and depression (p¼0.002) between the Good Sleepers and Poor Reported Sleepers (poor sleep quality/low sleep time variability; n¼24). Conclusion: These results indicate different factors are associated with poor sleep quality in individuals with low versus high total sleep time variability. Considering the factors that are associated with sleep quality and variability may allow for better tailoring of interventions aimed at improving sleep issues or comorbid conditions.National Multiple Sclerosis Society Pilot Grant (PP2068)National Institutes of Health Clinical and Translational Science Award Grant (UL1TR000001 formerly UL1RR033179)

Translation, cultural adaptation and validation of the Arabic version of the king’s Parkinson’s disease pain scale

Purpose: Pain in Parkinson’s disease (PD) is a highly prevalent non-motor symptom occurring in this population. The King’s PD Pain Scale (KPPS) was developed to assess pain in people with PD. This study aimed to provide a cross-cultural adaptation and translation of the KPPS into the Arabic language (A-KPPS), and to investigate the construct and convergent validity, internal consistency, and reliability of the translated scale. Materials and Methods: The English KPPS was translated into Arabic and back-translated into English by an independent translation team. The Arabic version was tested in 103 native Arabic speaking PD patients. We assessed construct validity, convergent validity, and test-retest reliability of the A-KPPS using factor analysis method, comparison with other valid and reliable measures, and using intra-class correlations, respectively. Results: The A-KPPS had three main factors “somatic pain”, “visceral and burning pain” and “orofacial pain”, rather than the original four factors scale. The A-KPPS correlated with measures of disease motor severity, depression, anxiety, quality of life and pain (p < 0.05). Furthermore, the A-KPPS total score had high test-retest reliability (ICC = 0.9). Conclusions: The A-KPPS demonstrated moderate to good validity and reliability. The A-KPPS can facilitate the assessment and treatment of pain in Arabic-speaking people with PD worldwide.Jordan University of Science and Technology - grant No. [HK-20170012/HK-20170158

A New Tool for Safety Evaluation and a Combination of Measures for Efficacy Assessment of Cotransplanting Human Allogenic Neuronal Stem Cells and Mesenchymal Stem Cells for the Treatment of Parkinson Disease: Protocol for an Interventional Study

BackgroundParkinson disease (PD) is a neurodegenerative disorder associated with a broad spectrum of motor and nonmotor symptoms. Any proposed cure needs to address the many aspects of the disease. Stem cell therapy may have potential in this regard as indicated in recent preclinical and clinical studies. ObjectiveThis protocol aims to examine the safety and therapeutic benefit of human Wharton jelly-derived mesenchymal stem cells (WJ-MScs) and their derivatives, neuronal stem cells (NSCs) in PD. MethodsThis clinical trial is a double-arm, single-blinded, phase I-II interventional study. Participants have been allocated to 1 of 2 groups: one receiving allogeneic WJ-MSCs alone, the other receiving NSCs and WJ-MScs. Participants are being followed-up and assessed over a period of 6 months. To assess safety, an incidence of treatment-emergent adverse events (TEAEs) tool tailored for PD is being used immediately and up to 6 months after treatment. For efficacy assessment, a number of factors are being used, including the gold standard severity test and the Unified Parkinson Disease Rating Scale. In addition, the following standardized assessments for different common symptoms in PD are being included: motor (both subjectively and objectively assessed with wearable sensors), sensory, quality of life and psychological well-being, cognition, and sleep quality. Furthermore, immune-modulatory cytokines and neuronal damage versus regeneration markers in PD, including the neuronal protein linked to PD, α-synuclein, are being monitored. ResultsTen patients have been enrolled in this study and thus participant recruitment has been completed. The study status is active and beyond the recruiting stage. Study chart implementation, data collection, and analysis are ongoing. ConclusionsThe combination of NSCs and MSCs in PD may be useful for harnessing the best of the immunomodulation and neural repair characteristics of these cell types. The tailored comprehensive and scaled TEAEs and the variety of evaluation tools used enables a comprehensive assessment of this cellular therapy treatment protocol. A consideration of this expanded tool set is important in the design of future clinical studies for PD. Trial RegistrationClinicalTrials.gov NCT03684122; https://clinicaltrials.gov/ct2/show/NCT03684122 International Registered Report Identifier (IRRID)DERR1-10.2196/2969

Knowledge and attitudes of physiotherapists toward sleep: A survey study.

Sleep has been considered as a critical brain state that affects various body functions relevant to physiotherapy (PTs) practice such as motor learning and relearning, pain management, and cognitive function. Despite the importance of sleep for successful rehabilitation outcomes, sleep is often overlooked by PTs. The purpose of this study was to assess the attitude and perception of PTs on the need to assess sleep and provide education about sleep for their patients, as well as the perceived need for PTs to be educated on sleep topics. A survey questionnaire to assess physical therapist's perceptions and attitudes about sleep was utilized in this study. 90 PTs fill out the survey. All respondents agreed that poor sleep is important to people's health, 93% agreed that PTs should assess patients' sleep habits and sleep quality and 88% agreed that addressing sleep issues may impact PTs outcomes. The majority did not receive education about sleep during PT education (75%) or following graduation (86%). Most respondents (95%) think PTs should receive education about sleep. our findings indicated that PTs recognize that sleep impacts their outcomes and patients' sleep should be assessed, as well as the need to receive education about sleep. Therefore, PT education programs may consider incorporating education about sleep, and the development of continuing education courses is also needed

Validation of the Arabic Version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale

Background: The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has become the gold standard for evaluating different domains in Parkinson's disease (PD), and it is commonly used in clinical practice, research, and clinical trials. Objectives: The objectives are to validate the Arabic-translated version of the MDS-UPDRS and to assess its factor structure compared with the English version. Methods: The study was carried out in three phases: first, the English version of the MDS-UPDRS was translated into Arabic and subsequently back-translated into English by independent translation team; second, cognitive pretesting of selected items was performed; third, the Arabic version was tested in over 400 native Arabic-speaking PD patients. The psychometric properties of the translated version were analyzed using confirmatory factor analysis (CFA) as well as exploratory factor analysis (EFA). Results: The factor structure of the Arabic version was consistent with that of the English version based on the high CFIs for all four parts of the MDS-UPDRS in the CFA (CFI ≥0.90), confirming its suitability for use in Arabic. Conclusions: The Arabic version of the MDS-UPDRS has good construct validity in Arabic-speaking patients with PD and has been thereby designated as an official MDS-UPDRS version. The data collection methodology among Arabic-speaking countries across two continents of Asia and Africa provides a roadmap for validating additional MDS rating scale initiatives and is strong evidence that underserved regions can be energically mobilized to promote efforts that apply to better clinical care, education, and research for PD. © 2022 International Parkinson and Movement Disorder Society