Proteomic insights into the pathophysiology of periodic limb movements and restless legs syndrome.

OBJECTIVES: We used a high-throughput assay of 5000 plasma proteins to identify biomarkers associated with periodic limb movements (PLM) and restless legs syndrome (RLS) in adults. METHODS: Participants (n = 1410) of the Stanford Technology Analytics and Genomics in Sleep (STAGES) study had blood collected, completed a sleep questionnaire, and underwent overnight polysomnography with the scoring of PLMs. An aptamer-based array (SomaScan) was used to quantify 5000 proteins in plasma. A second cohort (n = 697) that had serum assayed using a previous iteration of SomaScan (1300 proteins) was used for replication and in a combined analysis (n = 2107). A 5% false discovery rate was used to assess significance. RESULTS: Multivariate analyses in STAGES identified 68 proteins associated with the PLM index after correction for multiple testing (ie, base model). Most significantly decreased proteins were iron-related and included Hepcidin (LEAP-1), Ferritin, and Ferritin light chain. Most significantly increased proteins included RANTES, Cathepsin A, and SULT 1A3. Of 68 proteins significant in the base model, 17 were present in the 1300 panel, and 15 of 17 were replicated. The most significant proteins in the combined model were Hepcidin (LEAP-1), Cathepsin A, Ferritin, and RANTES. Exploration of proteins in RLS versus non-RLS identified Cathepsin Z, Heme oxygenase 2 (HO-2), Interleukin-17A (upregulated in the combined cohort), and Megalin (upregulated in STAGES only) although results were less significant than for proteins associated with PLM index. CONCLUSIONS: These results confirm the association of PLM with low iron status and suggest the involvement of catabolic enzymes in PLM/RLS.

Perceptions of exercise and restless legs syndrome: Results from a nationwide survey.

Restless legs syndrome is a prevalent, sensorimotor sleep disorder temporarily relieved by movement, with evidence of symptomatic improvement with regular exercise. The present study describes perceptions of the effects of exercise on symptoms of restless legs syndrome. Participants (N = 528) completed a mixed-methods (i.e. numerical and narrative), nationwide survey including items assessing personal experiences with exercise and restless legs syndrome (both positive and negative), as well as restless legs syndrome diagnosis, restless legs syndrome severity, and demographic and clinical characteristics. Responses varied widely on specific experiences with exercise, but a higher percentage of participants indicated positive experiences with exercise than those who reported negative experiences (72%-40%, respectively) with exercise. Further, 54% of respondents reported that exercise only improves restless legs syndrome, while 24% reported exercise only worsens symptoms. Participants described that any abrupt change in exercise routine would almost always elicit restless legs syndrome symptoms (e.g. hiking for a long time, stopping an exercise routine), and that a consistent pattern of exercise improved restless legs syndrome symptoms with an overall beneficial effect on the frequency of symptomatic bouts. Participants further described time of day as impactful for their exercise experience, with > 50% indicating morning exercise improves symptoms and evening exercise worsens symptoms. Participants described several questions that they wanted answered regarding the evidence for exercise in restless legs syndrome and specific exercise prescription recommendations. The present study describes information crucial to the creation of stakeholder-informed health promotion programs for individuals with restless legs syndrome to optimize personalized treatment plans that could prevent and manage symptoms.

Circadian protein expression patterns in healthy young adults.

OBJECTIVES: To explore how the blood plasma proteome fluctuates across the 24-hour day and identify a subset of proteins that show endogenous circadian rhythmicity. METHODS: Plasma samples from 17 healthy adults were collected hourly under controlled conditions designed to unmask endogenous circadian rhythmicity; in a subset of 8 participants, we also collected samples across a day on a typical sleep-wake schedule. A total of 6916 proteins were analyzed from each sample using the SomaScan aptamer-based multiplexed platform. We used differential rhythmicity analysis based on a cosinor model with mixed effects to identify a subset of proteins that showed circadian rhythmicity in their abundance. RESULTS: One thousand and sixty-three (15%) proteins exhibited significant daily rhythmicity. Of those, 431 (6.2%) proteins displayed consistent endogenous circadian rhythms on both a sleep-wake schedule and under controlled conditions: it included both known and novel proteins. When models were fitted with two harmonics, an additional 259 (3.7%) proteins exhibited significant endogenous circadian rhythmicity, indicating that some rhythmic proteins cannot be solely captured by a simple sinusoidal model. Overall, we found that the largest number of proteins had their peak levels in the late afternoon/evening, with another smaller group peaking in the early morning. CONCLUSIONS: This study reveals that hundreds of plasma proteins exhibit endogenous circadian rhythmicity in humans. Future analyses will likely reveal novel physiological pathways regulated by circadian clocks and pave the way for improved diagnosis and treatment for patients with circadian disorders and other pathologies. It will also advance efforts to include knowledge about time-of-day, thereby incorporating circadian medicine into personalized medicine.

Stakeholder involvement in the optimization of a patient-centered exercise intervention for people with restless legs syndrome.

STUDY OBJECTIVES: Previous research supports exercise as a behavioral approach to manage symptoms of restless legs syndrome (RLS); however, completion rates in exercise studies are low. This study obtained key stakeholder feedback from people with RLS to modify and optimize a 12-week, evidence-based exercise program for RLS. METHODS: Participants with RLS (n = 513) completed a nationwide survey to provide feedback on the necessity, interest, feasibility, and efficacy of the program as well as perceived barriers and proposed modifications to improve the exercise program. RESULTS: Most respondents (67%) expressed the need for an exercise program designed specifically for people with RLS and 64% were interested in the program. Only 6% of participants thought the program would not be well tolerated and 6% responded that it would likely exacerbate symptoms. However, only 58% said they would be likely to participate in the program if it was available to them locally. Key barriers to participation were (1) accessibility, (2) personal factors, (3) trustworthiness, and (4) fear of injury, illness, or symptom exacerbations. Respondents highlighted modification considerations for the individualization of exercise features, adaptations for specific impairments/personal factors, inclusion of flexibility and balance exercises, and flexibility for more home-based activities. CONCLUSIONS: Interest in the program was driven by the desire to reduce medications and improve overall quality of life. Appropriately educated and trained exercise providers knowledgeable about RLS are integral to buy-in from stakeholders. This study provides an imperative step in clinical research that can increase the success of subsequent implementation efforts and may accelerate the adoption of exercise programs into practice. CITATION: Cederberg KLJ, Sikes EM, Mignot E. Stakeholder involvement in the optimization of a patient-centered exercise intervention for people with restless legs syndrome. J Clin Sleep Med. 2024;20(4):535-543.

Do fatigue and depression have a bivariate association with device-measured physical activity behavior in persons with multiple sclerosis?

PURPOSE: This study examined the bivariate association between fatigue and depression symptoms and physical activity behavior in persons with multiple sclerosis (MS). METHODS: The sample of adults with MS completed the Fatigue Severity Scale (FSS) and the Hospital Anxiety and Depression Scale (HADS) and wore a waist mounted accelerometer during waking hours for 7 days. We categorized participants as having elevated fatigue and depression based on cut-points for the FSS (i.e., 4+ as indicative of severe fatigue) and the HADS (i.e., 8+ as indicative of elevated depressive symptoms). We used a two-way multivariate analysis of variance (MANOVA) to examine the contribution of fatigue and depression to volume and pattern of sedentary, light (LPA) and moderate-to-vigorous physical activity (MVPA). RESULTS: Results indicated no bivariate association between fatigue and depression and measures of physical activity behavior. The MANOVA indicated there was a significant association between fatigue and MVPA (F = 2.30, p = 0.032) and steps/day (F = 13.6, p < 0.001), independent of depression symptoms. There was no association between depression symptoms and physical activity behavior. CONCLUSIONS: This study demonstrated an interrelation between fatigue symptoms and MVPA and steps/day in MS, independent of depression symptoms, and this should be considered in the future design and delivery of physical activity interventions in MS.IMPLICATIONS FOR REHABILIATIONFatigue and depression are prevalent and burdensome symptoms of multiple sclerosis (MS).These symptoms can collectively worsen psychological and functional outcomes in MS.Fatigue symptoms may impact ambulatory physical activity to a greater degree than depression symptom status in persons with MS.Fatigue is an important consideration when designing behavior change interventions targeted at promoting physical activity in persons with MS.

Vitamin D and Restless Legs Syndrome: A Review of Current Literature.

This review presents a detailed summary of the current literature regarding RLS and vitamin D deficiency. To our knowledge it is the first review of its kind. We review the prevalence of vitamin D deficiency in RLS as well as the evidence for the use of vitamin D supplementation in RLS management. We further examine the literature for proteomic and genetic evidence of a role for vitamin D in the pathogenesis of RLS. An alteration in vitamin D binding protein in RLS is one of the most consistent findings in the proteomic studies. Furthermore, we examine the interaction of vitamin D with calcium, phosphorus, and parathyroid hormone and the possible role of these connections in RLS. We also explore the possible nexus between RLS and vitamin D in renal disease, cardiovascular and cerebrovascular disease as well as inflammation. In addition, we review the potential interaction between vitamin D and RLS with iron, dopamine and other neurotransmitter systems including the endogenous opiate, serotoninergic, glutamatergic and adenosinergic systems. We also explore the role of vitamin D in RLS Augmentation (i.e., the paradoxical worsening of RLS symptoms when dopaminergic agents are used as a therapy for RLS). Although the literature is not entirely consistent in affirming vitamin D deficiency in RLS or the amelioration of RLS symptoms with vitamin D therapy, the collective studies overall indicate that vitamin D deficiency is common enough in RLS patients to suggest that RLS patients should have their vitamin D levels checked and any deficiency corrected as a standard of care. Highlights  Patients with Restless Legs Syndrome (RLS) may be deficient in vitamin D and therapy with vitamin D may ameliorate RLS. We present the first review dedicated solely to evaluating the relationship between RLS and vitamin D and present a case for the role of vitamin D in RLS pathogenesis.

The genetic etiology of periodic limb movement in sleep.

STUDY OBJECTIVES: Periodic limb movement in sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a genome-wide association study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e., discovery, replication, and joint meta-analysis) of four cohorts (MrOS, the Wisconsin Sleep Cohort Study, HypnoLaus, and MESA), comprised of 6843 total subjects. METHODS: The MrOS study and Wisconsin Sleep Cohort Study (N = 1745 cases) were used for discovery. Replication in the HypnoLaus and MESA cohorts (1002 cases) preceded joint meta-analysis. We also performed LD score regression, estimated heritability, and computed genetic correlations between potentially associated traits such as restless leg syndrome (RLS) and insomnia. The causality and direction of the relationships between PLMS and RLS was evaluated using Mendelian randomization. RESULTS: We found 2 independent loci were significantly associated with PLMS: rs113851554 (p = 3.51 × 10-12, ß = 0.486), an SNP located in a putative regulatory element of intron eight of MEIS1 (2p14); and rs9369062 (p = 3.06 × 10-22, ß = 0.2093), a SNP located in the intron region of BTBD9 (6p12); both of which were also lead signals in RLS GWAS. PLMS is genetically correlated with insomnia, risk of stroke, and RLS, but not with iron deficiency. Pleiotropy adjusted Mendelian randomization analysis identified a causal effect of RLS on PLMS. CONCLUSIONS: Because PLMS is more common than RLS, PLMS may have multiple causes and additional studies are needed to further validate these findings.

Does physical activity timing differentially correlate with symptoms of restless legs syndrome in adults with multiple sclerosis?

OBJECTIVE/BACKGROUND: The present study examined the associations among physical activity during different times of the day(i.e., morning, midday,evening) and days of the week(i.e., weekdays, weekend days) with restless legs syndrome(RLS) severity and sleep quality in adults with multiple sclerosis(MS). PATIENTS/METHODS: Participants(N = 39) completed the International Restless Legs Syndrome Study Group Scale and the Pittsburgh Sleep Quality Index as measures of RLS severity and global sleep quality, respectively, and wore an ActiGraph GT3X + on the non-dominant hip for seven days for measuring physical activity(i.e., light physical activity[LPA], moderate-to-vigorous physical activity[MVPA], and steps). RESULTS: There was a significant effect of time of day wherein participants had more midday activity compared with morning or evening for LPA, MVPA, and steps; there was no effect of day of the week. Spearman's rho correlations across the week indicated higher evening LPA, evening steps, and overall daily steps (ρ = -0.42,ρ = -0.51,ρ = -0.40,respectively) were associated with lower RLS severity. Similar associations were demonstrated for weekdays(ρ = -0.39,ρ = -0.50,ρ = -0.41,respectively) and weekend days(ρ = -0.44,ρ = -0.51,ρ = -0.39,respectively). Higher evening MVPA on weekend days(ρ = -0.42) was associated with lower RLS severity. Higher morning and overall daily LPA(ρ = 0.34,ρ = 0.33,respecitvely) were associated with worse sleep quality. Similar associations were demonstrated on weekdays(ρ = 0.33,ρ = 0.37,respectively) and more evening MVPA(ρ = 0.32) was associated with worse sleep quality. On weekend days, more morning MVPA(ρ = 0.42) was associated with worse sleep quality. CONCLUSIONS: Our results suggest that undertaking physical activity, particularly LPA and steps, in evenings may be important for managing symptoms of RLS without worsening sleep quality.

Proteomic Biomarkers of the Apnea Hypopnea Index and Obstructive Sleep Apnea: Insights into the Pathophysiology of Presence, Severity, and Treatment Response.

Obstructive sleep apnea (OSA), a disease associated with excessive sleepiness and increased cardiovascular risk, affects an estimated 1 billion people worldwide. The present study examined proteomic biomarkers indicative of presence, severity, and treatment response in OSA. Participants (n = 1391) of the Stanford Technology Analytics and Genomics in Sleep study had blood collected and completed an overnight polysomnography for scoring the apnea−hypopnea index (AHI). A highly multiplexed aptamer-based array (SomaScan) was used to quantify 5000 proteins in all plasma samples. Two separate intervention-based cohorts with sleep apnea (n = 41) provided samples pre- and post-continuous/positive airway pressure (CPAP/PAP). Multivariate analyses identified 84 proteins (47 positively, 37 negatively) associated with AHI after correction for multiple testing. Of the top 15 features from a machine learning classifier for AHI ≥ 15 vs. AHI < 15 (Area Under the Curve (AUC) = 0.74), 8 were significant markers of both AHI and OSA from multivariate analyses. Exploration of pre- and post-intervention analysis identified 5 of the 84 proteins to be significantly decreased following CPAP/PAP treatment, with pathways involving endothelial function, blood coagulation, and inflammatory response. The present study identified PAI-1, tPA, and sE-Selectin as key biomarkers and suggests that endothelial dysfunction and increased coagulopathy are important consequences of OSA, which may explain the association with cardiovascular disease and stroke.

Restless Legs Syndrome Severity and Cognitive Function in Adults With Multiple Sclerosis: An Exploratory Pilot Study.

BACKGROUND: Restless legs syndrome (RLS) is a sleep disorder present in as many as 26% of persons with multiple sclerosis (MS) and can be associated with cognitive function. The present study examined the relationships between RLS symptoms (severity, frequency, occurrence) and cognitive function in adults with MS who have RLS. METHODS: Twenty-two participants attended 1 laboratory session and completed the International Restless Legs Syndrome Study Group Rating Scale (IRLS), the Restless Legs Syndrome-6 Scale, and then the Brief International Cognitive Assessment for Multiple Sclerosis battery consisting of the Symbol Digit Modalities Test; California Verbal Learning Test, Second Edition; and Brief Visuospatial Memory Test-Revised. RESULTS: Nonparametric bivariate correlations indicated that worse IRLS total severity was associated with slower processing speed (ρ = -0.42), worse verbal memory (ρ = -0.63), and worse visual memory (ρ = -0.61); worse RLS severity at falling asleep was associated with worse verbal memory (ρ = -0.45) and worse visual memory (ρ = -0.55); and worse RLS severity during the day while active was associated with slower processing speed (ρ = -0.58), worse verbal memory (ρ = -0.52), and worse visual memory (ρ = -0.60). CONCLUSIONS: These results suggest that those with more severe RLS, including worse symptoms at falling asleep and during the day while active, might experience worse cognitive function, particularly processing speed and memory. Future research should evaluate whether treatment of RLS symptoms can offer new opportunities for managing cognitive dysfunction in adults with MS.

Restless legs syndrome severity associated with reduced physical function in adults with multiple sclerosis.

BACKGROUND: Restless legs syndrome (RLS) is a sleep disorder that occurs in approximately 26 % of adults with multiple sclerosis (MS) and may be associated with reduced physical function. RESEARCH QUESTION: The present study examined the relationship between RLS symptomology (i.e., overall severity, frequency, and occurrence) and physical function outcomes in adults with MS who had RLS. METHODS: Participants (N = 22) with MS who had RLS came into the laboratory for a single session wherein a rater performed a brief neurological examination for scoring the Expanded Disability Status Scale (EDSS) and completed a demographics questionnaire, the International Restless Legs Syndrome Study Group Scale (IRLS), and the Restless Legs Syndrome Scale-6 (RLS-6) followed by the Short Physical Performance Battery (SPPB) and the Six-minute Walk Test (6 MW). RESULTS: Bivariate Spearman's rho correlation analyses indicated total IRLS had a strong, negative association with total distance traveled during the 6 MW (ρ = -0.50) and a moderate association with SPPB scores (ρ = -0.43), but not EDSS scores (ρ = 0.28). RLS severity during the day while active had strong, negative associations with total distance traveled during the 6 MW (ρ = -0.61) and SPPB scores (ρ = -0.52), but not EDSS scores (ρ = 0.13). SIGNIFICANCE: We observed associations between worse overall RLS severity and RLS severity during the day while active with reduced performance during the 6 MW and lower SPPB scores. The management of RLS may offer an opportunity for mitigating reductions in physical function in adults with MS who have RLS.

Proteomic biomarkers of Kleine-Levin syndrome.

STUDY OBJECTIVES: Kleine-Levin syndrome (KLS) is characterized by relapsing-remitting episodes of hypersomnia, cognitive impairment, and behavioral disturbances. We quantified cerebrospinal fluid (CSF) and serum proteins in KLS cases and controls. METHODS: SomaScan was used to profile 1133 CSF proteins in 30 KLS cases and 134 controls, while 1109 serum proteins were profiled in serum from 26 cases and 65 controls. CSF and serum proteins were both measured in seven cases. Univariate and multivariate analyses were used to find differentially expressed proteins (DEPs). Pathway and tissue enrichment analyses (TEAs) were performed on DEPs. RESULTS: Univariate analyses found 28 and 141 proteins differentially expressed in CSF and serum, respectively (false discovery rate <0.1%). Upregulated CSF proteins included IL-34, IL-27, TGF-b, IGF-1, and osteonectin, while DKK4 and vWF were downregulated. Pathway analyses revealed microglial alterations and disrupted blood-brain barrier permeability. Serum profiles show upregulation of Src-family kinases (SFKs), proteins implicated in cellular growth, motility, and activation. TEA analysis of up- and downregulated proteins revealed changes in brain proteins (p < 6 × 10-5), notably from the pons, medulla, and midbrain. A multivariate machine-learning classifier performed robustly, achieving a receiver operating curve area under the curve of 0.90 (95% confidence interval [CI] = 0.78-1.0, p = 0.0006) in CSF and 1.0 (95% CI = 1.0-1.0, p = 0.0002) in serum in validation cohorts, with some commonality across tissues, as the model trained on serum sample also discriminated CSF samples of controls versus KLS cases. CONCLUSIONS: Our study identifies proteomic KLS biomarkers with diagnostic potential and provides insight into biological mechanisms that will guide future research in KLS.

Social Cognitive Theory variables as correlates of physical activity in fatigued persons with multiple sclerosis.

BACKGROUND: There is interest in the application of behavioral interventions based on theory for increasing physical activity among adults with multiple sclerosis (MS). To date, researchers have applied theory such as Social Cognitive Theory (SCT) for identifying correlates of physical activity that can then inform the design and delivery of behavioral interventions. Such research often has been conducted in heterogeneous samples of persons with MS without a focus on those with a specific symptom, such as fatigue, that may be targeted by physical activity behavioral interventions. To that end, this study examined SCT variables (i.e., self-efficacy, barriers, outcome expectations, goal-setting, planning, social support, and functional limitations) as correlates of physical activity in persons with MS who self-reported elevated fatigue. METHODS: Persons with MS (N=210; aged 49.6[13.2] years) who ambulated with or without assistance participated in the study. Participants completed self-report measures of fatigue, physical activity, and SCT variables and wore an ActiGraph GT3X+ accelerometer on a belt around the waist for 7 days. The accelerometer data were processed and delineated into time spent in light and moderate-to-vigorous physical activity (MVPA) based on MS-specific cut-points. We generated groups of fatigued (n=134) and non-fatigued (n=76) persons with MS based on the cut-off score of 4 for the Fatigue Severity Scale. RESULTS: There were differences in physical activity and SCT variables between fatigued and non-fatigued persons with MS. Among those with fatigue, functional limitations (ρ=0.52), self-efficacy (ρ=0.31), and goal-setting (ρ=0.25) were associated with device-measured MVPA, and all SCT variables except outcome expectations were associated with self-reported physical activity. The regression analyses indicated self-efficacy, functional limitations, and goal-setting as significant correlates of MVPA in those with fatigue. CONCLUSION: Self-efficacy, goal-setting, and social support may be important targets of SCT-based behavioral interventions for increasing physical activity among persons with MS who have fatigue.

Physical Activity and Sedentary Behavior Timing in Fatigued and Nonfatigued Adults With Multiple Sclerosis.

OBJECTIVE: To examine device-measured physical activity levels and sedentary behavior participation during different times of the day (ie, morning, midday, and evening) in adults with multiple sclerosis (MS) who differed in fatigue status. DESIGN: Cross-sectional survey. SETTING: Remote survey study managed by a university-based research laboratory. PARTICIPANTS: A population-based sample of 1000 participants with MS were sent recruitment materials by the North American Research Committee on Multiple Sclerosis and 218 participants completed all relevant outcomes (N=218). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants (N=218) completed the Fatigue Severity Scale (FSS) as a measure of fatigue severity and were divided into subgroups of fatigued (FSS score ≥4) and nonfatigued (FSS score <4). Participants wore an ActiGraph GT3X+ on the nondominant hip for 7 days to measure physical activity (ie, light physical activity [LPA], moderate-to-vigorous physical activity [MVPA], steps) and sedentary behavior. RESULTS: Fatigued participants engaged in less MVPA (F[1216]=18.5, P<.001), fewer steps (F[1216]=27.8, P<.001), and more sedentary time (F[1216]=8.2, P=.005) than nonfatigued participants. Regardless of group, the highest levels of LPA (F[1.7355.7]=72.9, P<.001) and MVPA (F[1.8395.3]=23.0,P<.001) occurred in the morning and middle of the day, with the lowest levels in the evening. Regardless of group, the highest levels of sedentary behavior occurred in the evening, with similar levels in the morning and evening (F[1.6354.5]=84.3,P<.001). Regardless of group, participants had more steps in the middle of the day, followed by morning and then evening (F[1.8383.9]=84.7,P<.001). CONCLUSIONS: Our results suggest that physical activity timing should be considered in future development and delivery of behavior interventions that focus on increasing physical activity and reducing sedentary behavior among adults with MS who have fatigue.

Discrepancies between self-reported and device-measured sleep parameters in adults with multiple sclerosis.

STUDY OBJECTIVES: Sleep problems are a common consequence of multiple sclerosis; however, there is limited evidence regarding the agreement between device-measured and self-reported sleep parameters in adults with multiple sclerosis. The present study examined the agreement between self-reported and device-measured parameters of sleep quality in a sample of adults with multiple sclerosis. METHODS: Participants (n = 49) completed a 7-day sleep diary and wore a wrist-worn ActiGraph GT3×+ (ActiGraph Corp., Pensecola, FL) for seven consecutive nights to quantify self-reported and device-measured sleep parameters, respectively. RESULTS: There was a significant discrepancy between self-reported and device-measured parameters of total time in bed (mean difference = 19.8 [51.3] min), sleep onset latency (mean difference = 22.2 [19.5] min), and frequency of awakenings during the night (mean difference = 12.8 [6.8]). Intraclass correlation estimates indicated poor agreement between methods on most parameters, except for total time in bed (intraclass correlation = 0.80). Bland-Altman plots suggested that total time in bed and total sleep time had acceptable levels of agreement and linear regression analyses indicated that sleep onset latency (F = 113.91, B = -1.34, P < .001), number of awakenings (F = 543.34, B = 1.85, P < .001), and sleep efficiency (F = 18.39, B = -0.77, P < .001) had significant proportional bias. CONCLUSIONS: Our results draw attention to the discrepancies between sleep parameter measurements and highlight the importance of including both self-report and device-measured outcomes for a complete and accurate representation of sleep in adults with multiple sclerosis. CITATION: Cederberg KLJ, Mathison BG, Schuetz ML, Motl RW. Discrepancies between self-reported and device-measured sleep parameters in adults with multiple sclerosis. J Clin Sleep Med. 2022;18(2):415-421.

Wrist-based accelerometer cut-points for quantifying moderate-to-vigorous intensity physical activity in Parkinson's disease.

BACKGROUND: Persons with Parkinson's disease (PD) participate in low levels of physical activity. This has prompted interest in developing interventions targeting physical activity behavior in PD. However, the current cut-points to quantify moderate-to-vigorous physical activity (MVPA) developed for PD have been derived from a single, vertical axis using hip-worn accelerometers, and this cut-point may not be applicable for wrist-worn devices. Wrist-worn devices might improve accessibility and compliance with physical activity monitoring in PD. RESEARCH QUESTION: What is the relationship between wrist-based activity counts and energy expenditure during treadmill walking in persons with PD? Do cut-points for quantifying time spent in MVPA differ between persons with PD and controls matched by age and sex? METHODS: The sample included 26 persons with mild-to-moderate PD (Hoehn and Yahr stages 2-3) and 27 age- and sex-matched controls. Participants completed three, 6-minute bouts of walking on a treadmill at three increasing speeds. Vector magnitude was measured using ActiGraph GT3X+ accelerometer worn on the more affected side for persons with PD and the non-dominant side for controls. The rate of oxygen consumption, or energy expenditure, was measured using a portable, open-circuit spirometry system. RESULTS: Our results indicated a strong association between activity counts and energy expenditure for persons with PD and controls with R2 values of 0.94(0.07) and 0.95(0.06), respectively. Persons with PD had a cut-point of 2883(871) counts·min-1; this was significantly lower than the cut-point of 4389(1844) counts·min-1 for controls. CONCLUSION: We generated a PD-specific cut-point for wrist-worn ActiGraph accelerometers among persons with PD, and this was lower than controls. This disease-specific cut-point may provide more accurate measurements of time spent in MVPA in PD.

Perceived injustice in multiple sclerosis: An initial, exploratory study.

PURPOSE/OBJECTIVE: The current study represents an initial examination of condition-related perceived injustice (PI) in multiple sclerosis (MS) by examining (a) the structural validity and reliability of the Injustice Experience Questionnaire (IEQ) scores and (b) the associations between IEQ scores and scores from measures of anger, pain, depression, anxiety, fatigue, disability, health-related quality of life (HRQOL), physical activity, and sedentary behavior. Research Method/Design: Persons with MS were recruited through the distribution of letters to a random sample of 1,000 persons from the North American Research Committee on MS registry. Participants who completed the IEQ (N = 139) were included in this analysis. RESULTS: Our results support the structural validity of the 2-factor model of Severity/Irreparability and Blame/Unfairness subscales with a Cronbach's alpha of .917 for the overall scale, and values of .857 and .889 for the subscales, respectively. All measures were meaningfully correlated with IEQ scores. Pain (ρ = .466), fatigue (ρ = .430), disability (ρ = .416), walking impairment (ρ = .446), and physical HRQOL (ρ = .624) were strongly correlated with Severity/Irreparability. Anger; however, was strongly correlated with Blame/Unfairness (ρ = .437). Physical activity and sedentary behavior were similarly correlated with the 2 subscales; however, both moderate-to-vigorous (ρ = -.332) and light physical activity (ρ = -.275) were slightly more correlated with Severity/Irreparability. CONCLUSIONS/IMPLICATIONS: The IEQ is a reliable and valid measure of PI in MS. Physical manifestations of MS are primarily associated with PI, and negative associations were observed between physical activity and IEQ scores. Physical activity may increase self-efficacy and counteract cognitions of permanent disability and frustration concerning limitations that are associated with PI. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Demographic, clinical, and symptomatic correlates of subjective sleep quality in adults with multiple sclerosis.

BACKGROUND: This study examined a comprehensive set of demographic, clinical, and symptomatic variables as correlates of subjective sleep quality in adults with multiple sclerosis (MS). METHODS: Participants with MS(N=485) completed the Pittsburgh Sleep Quality Index(PSQI), a demographics and clinical characteristics questionnaire, the Patient Determined Disease Steps Scale(PDDS), the Fatigue Severity Scale, and the Hospital Anxiety and Depression Scale. We conducted bivariate Spearman's rho (ρ) correlation analyses and multiple linear regression analysis for identifying variables associated with PSQI scores. RESULTS: Participants had a mean (standard deviation) age of 55.4 (12.6) years and were mostly female (78%) with a median [interquartile range] PDDS of 2.0[3.0]. Higher levels of fatigue (ρ=0.32), more symptoms of anxiety (ρ=0.39) and depression (ρ=0.36), younger age (ρ=-0.12), lower income status (ρ=-0.13), shorter MS disease duration (ρ=-0.11), being in a minority group (ρ=0.09), and being unemployed (ρ=-0.10) were associated with worse sleep quality. There were no significant associations between gender, marital status, parental status, education level, disability status, or MS disease type and sleep quality. The overall regression model accounted for 26.3% of variance in sleep quality (F[8,229.8]=20.25) and there were significant coefficients for anxiety(ß=0.25), fatigue(ß=0.18), depression(ß=0.16), and employment status(ß=-0.12), but not disease duration, age, race, or income level. DISCUSSION: Participants with higher levels of anxiety, fatigue, and depression and who were unemployed reported worse sleep quality in our sample of adults with MS. These results may identify specific subgroups of the MS population that experience more sleep problems, and therefore are in greatest need for interventions designed to improve sleep impairment.

Do physical activity and social cognitive theory variable scores differ across symptom cluster severity groups in multiple sclerosis?

BACKGROUND: Persons with multiple sclerosis (MS) experience co-occurring symptoms termed "symptom clusters" that can be distinguished based on mild, moderate, or severe symptom severity termed "symptom cluster severity." Physical activity (PA) may be an approach for improving co-occurring symptoms. OBJECTIVE: To examined if PA and social cognitive theory (SCT) variables differed by symptom cluster groups, and if associations between SCT variables and PA were moderated by symptom cluster groups. METHODS: Secondary analysis of participants with MS (N = 205) enrolled in a cross-sectional study. Trend analyses were conducted to determine if device-measured and self-reported PA and SCT variables (i.e., social support, self-efficacy, outcome expectations, goal setting, planning, and impediments) decreased with increased symptom cluster severity. Spearman rho rank-order correlations were conducted between PA measures and SCT variables within each symptom cluster group. RESULTS: Linear trend analyses indicated that self-reported PA declined with increased symptom cluster severity groups (F = 4.90,p = 0.03). Linear trend analyses indicated significant differences among symptom cluster severity groups in social support (F = 31.43,p = 0.001), exercise self-efficacy (F = 22.55,p = 0.001), barrier self-efficacy (F = 11.48,p = 0.001), outcome expectations (F = 6.98,p = 0.009), and impediments (F = 34.41,p = 0.001). There were differential associations of moderate magnitude in correlations, such that three SCT variables were associated with PA in the mild group (i.e., self-efficacy, goal setting and planning), two in the moderate group (i.e., social support and goal setting), and four in the severe group (i.e., self-efficacy, outcome expectations, planning, and social support). CONCLUSIONS: Further research is warranted examining the use of SCT-based behavior change techniques for promoting PA and improving symptom clusters in persons with MS.

Validity and reliability of the suggested immobilization test for measurement of restless legs syndrome severity in adults with multiple sclerosis.

OBJECTIVE/BACKGROUND: Adults with multiple sclerosis (MS) often present with conditions that mimic restless legs syndrome (RLS), thereby adding complexity into the assessment of RLS severity. The current gold-standard measures of RLS severity rely on a fixed seven-day time frame, which limits the ability of these measures for studying acute changes in RLS severity. The present study examined if subjective and objective scores from the suggested immobilization test (SIT) provide a valid and reliable acute measure of RLS severity in persons with MS. PATIENTS/METHODS: Participants with MS and RLS (n = 20) and MS without RLS (n = 20) were matched by age, gender, and disability. All participants completed validated questionnaires for RLS severity followed by the SIT, conducted at 18:00 (±15 min) on the same day of the week for two consecutive weeks. Participants wore accelerometer devices for seven nights to capture periodic limb movements (PLMs) during the night. RESULTS: Self-reported RLS severity during the SIT had excellent construct validity and convergent validity, but moderate test-retest reliability. Device-measured PLMs, while not themselves a direct measure of RLS severity, were significantly associated with PLMs during the night and had excellent test-retest reliability during the SIT in adults with MS. CONCLUSIONS: Our results suggest that the SIT represents a valid acute measure for capturing self-reported sensory aspects of RLS severity and should be considered in future research and clinical practice as a standardized acute measure of subjective RLS severity in adults with MS who present with RLS.