Longitudinal assessment of neurocognitive function in people with relapsing multiple sclerosis initiating alemtuzumab in routine clinical practice: LEM-COG study results.

BACKGROUND: Alemtuzumab is effective in reducing relapse rate and disability, but limited data exist on its effect on cognitive function in relapsing multiple sclerosis (RMS). The present study assessed neurocognitive function and safety associated with alemtuzumab treatment in RMS. METHODS: This longitudinal, single-arm, prospective study included people with RMS (aged 25-55 years) who were treated with alemtuzumab in clinical practice in the United States of America and Canada. The first participant was enrolled in December 2016. The primary endpoint was the change from baseline to post-baseline (month [M] 12/24) in MS-COGnitive (MS-COG) composite score. Secondary endpoints included Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R), Selective Reminding Test (SRT), Controlled Oral Word Association Test (COWAT), and Automated Neuropsychological Assessment Metrics (ANAM) scores. Depression and fatigue were assessed using Hamilton Rating Scale-Depression (HAM-D) and Fatigue Severity Scale (FSS)/Modified Fatigue Impact Scale (MFIS), respectively. Magnetic resonance imaging (MRI) parameters were assessed when available. Safety was assessed throughout the study. Descriptive statistics were used for the pre-specified statistical analyses. Since the study was terminated early (November 2019) because of operational and resource difficulties, post hoc analyses for statistical inference were performed among participants who had a baseline value and at least one complete post-baseline assessment for cognitive parameters, fatigue, or depression. RESULTS: Of the 112 participants enrolled, 39 were considered as the primary analysis population at M12. At M12, a mean change of 0.25 (95% confidence interval [CI]: 0.04, 0.45; p = 0.0049; effect size [ES]: 0.39) was observed in the MS-COG composite score. Improvements were observed in processing speed (based on PASAT and SDMT; p < 0.0001; ES: 0.62), as well as in individual PASAT, SDMT and COWAT scores. An improvement was also noted in HAM-D (p = 0.0054; ES: -0.44), but not in fatigue scores. Among MRI parameters, decreases in burden of disease volume (BDV; ES: -0.12), new gadolinium-enhancing lesions (ES: -0.41) and newly active lesions (ES: -0.07) were observed at M12. About 92% of participants showed stable or improved cognitive status at M12. There were no new safety signals reported in the study. The most common adverse events (≥10% of participants) were headache, fatigue, nausea, insomnia, urinary tract infection, pain in extremity, chest discomfort, anxiety, dizziness, arthralgia, flushing, and rash. Hypothyroidism (3.7%) was the most frequent adverse event of special interest. CONCLUSION: The findings from this study suggest that alemtuzumab has a positive impact on cognitive function with significant improvements in processing speed and depression in people with RMS over a period of 12 months. The safety profile of alemtuzumab was consistent with previous studies.

Assessment of cognitive function and its predictors in patients with multiple sclerosis: a case-control study.

INTRODUCTION: Cognitive dysfunction can be seen in patients with MS (PwMS) and has been gaining attention in recent years. This study aimed to assess cognitive function and its determinants in PwMS using Addenbrooke Cognitive Assessment Battery (ACE-R). MATERIAL AND METHODS: This case-control study was conducted at an outpatient MS clinic in Istanbul. The sample consisted of 60 consecutive patients with definite MS and 60 matched controls. Cognitive function was evaluated by using the ACE-R. Subjective cognitive function, anxiety, depression, and fatigue were evaluated by validated scales. RESULTS: The mean age of the patients was 38.8, and the time since diagnosis was nine years. The majority of the patients had relapsing-remitting MS. Compared to age, sex, and education-matched healthy controls, all ACE-R scores, attention/orientation (p = 0.020), memory (p = 0.003), verbal fluency (p = 0.002), language (p = 0.002), visuospatial (p = 0.001), and general cognitive functioning (p < 0.001), were found to be lower in PwMS. The patients obtained the lowest scores in memory and fluency and the highest in the visuospatial domain. Age, education, mobility, subjective cognitive dysfunction, anxiety, depression, and fatigue were associated with cognitive test scores. However, only education, depression, and fatigue remained significant in the multivariable analysis. CONCLUSION: This study revealed impaired domains of cognitive functioning and its predictors in PwMS. Understanding cognitive dysfunction and its predictors in PwMS may enable healthcare providers to identify patients who might benefit from interventions to improve cognitive function. Assessment of PwMS at outpatient clinics with a practical cognitive test that does not require special competence can be suggested.

Validation of the Modified Fatigue Impact Scale in patients with systemic lupus erythematosus.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) experience significant fatigue, a debilitating symptom associated with reduced quality of life. There has not yet been agreed on a simple and reliable method for assessing fatigue in SLE. OBJECTIVES: To investigate the internal consistency, test-retest reliability and construct validity (convergent and discriminant validity) of the Modified Fatigue Impact Scale (MFIS) in patients with SLE. The secondary objective was to investigate the contribution of disease activity and organ damage to fatigue. METHODS: Fatigue was assessed using the MFIS in 61 patients with SLE. Internal consistency of MFIS was assessed with Cronbach's alpha (α) and Principal Component Analysis. Test-retest reliability was evaluated using the intraclass correlation coefficient (ICC). Construct validity was studied using Spearman's rank correlation (rs). Associations between MFIS and disease activity and organ damage were estimated with rs. RESULTS: Internal consistency of the MFIS was excellent with Cronbach's α = 0.97 (95% confidence interval (CI): 0.96-0.98) for the complete scale. Test-retest reliability was good with ICC = 0.89 (95% CI: 0.78-0.95, p < 0.001). Construct validity was confirmed by Spearman's correlation (VT-SF36: rs = -0.73, p < 0.001. MH-SF36: rs = 0.70, p < 0.001). No significant correlation was found between the MFIS and SLEDAI (rs = 0.03, p = 0.83). There was a moderate correlation between MFIS and SLICC Damage Index (rs = 0.43, p < 0.001). CONCLUSION: The present study found the MFIS to be a reliable and valid instrument for assessing fatigue in SLE. Further investigations are needed to clarify if an association between measured fatigue and disease components exists.

Subjective sleep quality and fatigue assessment in Polish adult patients with primary immunodeficiencies: A pilot study.

Introduction: Primary immunodeficiencies (PIDs) are clinically heterogeneous disorders caused by abnormalities in the immune system. However, PIDs are genetically determined and may occur at any age from early childhood to elderly age. Due to chronic patterns, the risk of malignancy and organ damage in patients with PIDs may affect any aspect of life, including sleep patterns. To our knowledge, the prevalence of insomnia and subjective sleep quality have not been investigated in patients with PIDs. Therefore, this pilot study was conducted to investigate sleep quality, the prevalence of sleep disturbances, and fatigue in adult patients with PIDs in Poland. Methods: All participants were surveyed using the Athens Insomnia Scale, Pittsburgh Sleep Quality Index, Fatigue Severity Scale, and a questionnaire concerning general health and demographic data. We included 92 participants: 48 women (52.2%) and 44 men (47.8%). Results: Participants' mean age was 41.9 ± 13.9 years. The mean sleep duration was 7.0 ± 1.5 hours, and the mean sleep latency was 41.2 ± 53.1 minutes. Additionally, 44.6% of patients (n=41) had symptoms of insomnia and 44.6% (n=42) had poor sleep quality. Less than one-fourth (n=22; 23.9%) of the patients reported the use of sleeping pills; moreover, clinically significant fatigue was reported in 52.2% (n=48). Discussion: Our investigation provides insight into the problem of sleep disturbances in patients with PIDs. Data have demonstrated that sleeping disorders with concomitant fatigue are common in patients with PID. Further studies are needed to determine the determinants of poor sleep quality in this specific group of patients.

Associations Between Influencing Factors, Perceived Symptom Burden, and Perceived Overall Function Among Adults Living With HIV.

With adherence to combination antiretroviral therapy, HIV infection is now a chronic, but manageable, disease with associated symptoms and complications. However, there is limited evidence on how symptom burden affects perceived overall function among people living with HIV (PLWH). Furthermore, there is no consensus on the factors that affect symptom burden in PLWH. We examined relationships between factors that may influence symptom burden and perceived overall function, and the association between symptom burden and overall function in 179 adult PLWH. This study was a cross-sectional, secondary analysis using the Theory of Unpleasant Symptoms (Lenz, Pugh, Milligan, Gift, & Suppe, 1997). We found strong evidence that symptoms, especially pain, tiredness, and depression, are prevalent in PLWH, and that symptoms were predicted by perceived social support and the number of comorbidities. Increased symptom burden predicts reduced overall function. Interventions are needed to reduce symptoms and strengthen social support in PLWH. Initiating symptom assessment and management strategies early is paramount.

Sleep Quality, Quality of Life, and Patient-Reported Outcomes.

Measuring health outcomes through patient-reported outcomes is a feasible scenario in the short term, more human, and more linked to the situation that the patient cares about, overcoming limitations of the classic activity scores.

Effects of driver sleepiness and fatigue on violations among truck drivers in India.

This study aims at capturing the influence of driver drowsiness on prevalence of traffic violations among long-haul truck drivers. The study is based on a roadside survey of 453 long-haul truck drivers, stopping at eateries and rest locations on highways connected to three Indian cities- Mumbai, Indore and Nagpur. The survey questionnaire was categorized into three sections: driver demographics, work-rest schedules and safety critical driver behavior (violations and lapses) in the last five years. The questions regarding unsafe driving practices like speeding, overtaking were combined to form a single factor 'violations' using Principal Component Analysis (PCA). A generalized linear model using negative binomial regression predicted young drivers (aged below 25 years), long working hours, insufficient sleeping hours, driving after mid-night, sleepiness on the wheel and frequent traffic violations as significant contributors of violations among the long-haul truck drivers.

How reliable is parental/carer assessment of infant health status?

Problems often arise in cases of lethal inflicted injury in infants and children in determining the chronology of events. However, on occasion it may be assumed that a parent's statement that the child appeared normal at a particular time is correct. It is then inferred that the lethal injury occurred after this time. In a study of infants from Queensland, Australia a significant number of cases occurred where a parent/carer did not actually recognise that an infant was deceased or in extremis despite handling of the infants, some of whom had established rigor mortis. Assessment of their infant's health status was quite flawed, presumably due to inattention, fatigue, or confirmatory bias (seeing what is expected). This could also apply to infants with head injuries who may manifest quite non-specific signs such as lethargy, somnolence or alteration in conscious state, manifestations that could easily be confused with normal drowsiness or sleep. Thus, the evaluation of parent/carer statements must be tempered by the knowledge that their opinions may not always (for completely understandable reasons) be reliable, and should not be uncritically accepted as a basis for deciding the time course for a lethal process.

Evaluating dalfampridine for the treatment of relapsing-remitting multiple sclerosis: does it add to the treatment armamentarium?

Introduction: Multiple sclerosis (MS) is a demyelinating disease, causing axonal damage and disability. Dalfampridine (DAL) is an extended-release formulation of 4-aminopyridine (4AP) and broad-spectrum voltage-dependent potassium channel blocker that is reported to improve motor, visual and cognitive functions. Furthermore, it is presently the only approved drug for walking impairment in MS. Areas covered: Herein, the authors evaluate DAL as a relapsing-remitting MS treatment, reporting and commenting on all aspects of the drug including its chemistry, safety, pharmacokinetics, and cost-effectiveness. A bibliographic search was performed on PubMed using the terms 'dalfampridine OR fampridine OR 4-aminopyridine'. Expert opinion: Evidence from post-marketing studies suggests that DAL, consistent with the effects of 4AP, may not only improve walking speed, but also arm function, fatigue, mood and cognition through restored nerve conduction in central nervous system demyelinated areas. Long-term safety data confirm that the approved dose of 10 mg twice daily is generally well tolerated. However, despite the reported efficacy, the extent of the benefits is limited in real life activities, although significant improvements have been demonstrated in the clinical setting. Patients often complain of side effects (such as cramps and painful paraesthesia) or lack of efficacy. Also, its considerably higher pricing in comparison to 4AP represents an important limitation.

The association of fatigue and social participation in multiple sclerosis as assessed using two different instruments.

INTRODUCTION: Fatigue is an important aspect of health-related quality of life and a commonly reported symptom by many persons with multiple sclerosis (MS). There are multiple validated instruments available to assess fatigue in MS with differing benefits for each instrument. OBJECTIVE: We aimed to assess the relationship between the PROMIS Fatigue instrument and the Fatigue Performance Scale (FPS) in the NARCOMS registry. Additionally, we aimed to examine the association of fatigue with social participation. METHODS: The NARCOMS registry is a voluntary, self-report registry, which has enrolled participants with MS who provide semi-annual updates regarding their MS. The Fall 2016 semi-annual survey included the PROMIS Fatigue and Ability to Participate in Social Roles and Activities questionnaires, in addition to demographic and clinical information. We examined the association between instruments using Spearman correlations. Linear and ordinal regression models were used to evaluate associations with fatigue using the PROMIS Fatigue and the FPS. RESULTS: Of the 7,006 Fall 2016 respondents, 6,883 (98.2%) completed the PROMIS instruments. Respondents were mostly female (79.5%) and Caucasian (87.4%), had a mean (SD) age of 59.9 (10.2) years and moderate disability level (median Patient Determined Disease Steps [PDDS] 4 [early cane]). The mean (SD) PROMIS Fatigue T-score was 56.8 (11.0) and median (25th, 75th) FPS was 3 [moderate] (1 [minimal], 4 [severe]). Fatigue measures were strongly correlated (r = 0.83, 95% CI: [0.827, 0.842]). Factors consistently associated with fatigue were PDDS level, depression and pain functionality scales, and symptoms worsening. The ability to participate in social roles and activities was strongly associated with fatigue and had an independent effect on fatigue after adjusting for PDDS, depression and pain levels. CONCLUSION: A high proportion of respondents experience some level of fatigue and it is independently associated with reduced social participation.

The effect of increased physical activity on symptom burden in older persons living with HIV.

Advancements in antiretroviral therapy have extended the longevity of people living with HIV (PLWH). However, they often experience symptoms that negatively impact their quality of life, including fatigue, weight change, depression, pain, and memory loss. Although there is a dearth of data on the effect of physical activity (PA) for HIV-associated symptom management, increased PA has generally been associated with improvements in strength and overall quality of life. In this study, we enrolled 40 participants (mean age = 51.5; 40% female; 17.4 mean years living with HIV) and used Omron pedometers to measure daily step counts over 12 weeks. The 20-item HIV Symptom Index was administered at baseline and week 12. Increased PA was not associated with improvement in overall HIV symptom burden. However, bothersome symptoms were reduced, and total symptom burden was highly correlated with PA level at week 12 (r = -.48, p = .01), such that participants with  higher step counts reported lower symptom burden. Significant gender differences in symptom burden were noted: males on average reported lower symptom burden. Further research is needed to examine associations between PA and HIV symptom burden and to further explore gender differences in HIV symptom burden to improve overall quality of life for all older PLWH.

Lessons Learned to Aid in Developing Fatigue Risk Management Plans for Resident Physicians.

Phenomenon: Fatigue is a significant risk factor for deterioration in performance, which may lead to medical errors and reduced well-being in resident physicians (residents). Sleep deprivation, which has been studied extensively, is only one contributor to fatigue. Given the complexity of fatigue and its relationship with resident performance, the National Steering Committee on Resident Duty Hours in Canada recommends that all residency education programs develop a fatigue risk management plan (FRMP) for their residents. The purpose of this study was to explore the impact of residents' experiences of fatigue and the strategies they use to manage it. Approach: This single-site study investigated the perceptions of resident physicians. Residents were recruited through purposive sampling to ensure representation from a variety of programs, postgraduate year level, and gender. Recruitment was managed with support from the residency programs; however, data collection and analysis were conducted by the Office of Postgraduate Medical Education to ensure participant anonymity. Program directors and administrators assisted in relaying the information about the study to the residents; however, they were not made aware if their residents participated in the study. Interview and focus group data were collected all at once, then transcribed, and then subsequent thematic analysis of these data was conducted using a quasi-constant comparison approach until thematic saturation was reached. Two researchers coded the data using thematic content analysis. Findings: Fifty-seven residents participated in a focus group or interview. There was representation from more than half of the 58 residency programs and from 15 of 16 departments. Overall, there was consensus that fatigue impacts residents' physical, cognitive, and emotional states. These impacts were reported as influencing resident performance including those related to patient care. Residents reported that fatigue led them to be less productive in their personal and professional lives. Three major themes were identified for which strategies could be developed for fatigue risk management: self, program, and system. Together with self-, program-, and system-level strategies that complement and enhance each other, specific targeted FRMPs could be developed. Insights: Fatigue is a multifaceted phenomenon experienced by residents that requires management beyond extended duty hours and adequate amounts of sleep. FRMPs that encompass strategies used by the resident, the residency-training program, and the healthcare system in which they work could assist with managing fatigue in residents and support enhanced resident well-being and patient care.

General Population Norms for the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale.

BACKGROUND: The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale is an internationally used validated measure. General population-based age- and sex-specific percentile norms are, however, not published to date, although these are needed as reference for the interpretation of clinical research data. OBJECTIVES: To assess the FACIT-Fatigue Scale in a large representative sample of the German general population to examine psychometric characteristics and factorial structure and to provide population-based norms. METHODS: A nationally representative face-to-face household survey was conducted in Germany using the FACIT-Fatigue Scale. Item characteristics were examined. Internal consistency was determined using the Cronbach α. Dimensionality was analyzed using confirmatory factor analysis (CFA) and bifactor analysis. Scale score differences relating to sex and age were assessed. Sex- and age-specific percentiles were computed for the entire scale range. RESULTS: Of 2426 participants, 55.7% were women, and the mean age was 49.8 ± 17.4 years. The FACIT-Fatigue Scale mean was 43.5 ± 8.3. Cronbach α was high at 0.92. Although fit indices of the CFA were below desired levels (root mean squared error of approximation = 0.144, comparative fit index = 0.846, and Tucker-Lewis index = 0.815), item loadings in the CFA and bifactor analysis confirm the scale's unidimensionality. Women were more fatigued than men, and participants who were 70 years or older showed higher fatigue scores than younger respondents. Thus, sex- and age-specific population-based percentiles were provided. CONCLUSIONS: Reliability and validity of the German translation of the FACIT-Fatigue Scale were confirmed. This study provides general population-based sex- and age-specific FACIT-Fatigue Scale percentile norms for the first time, thereby contributing to a meaningful interpretation of clinical research data.

Fatigue Incident Antecedents, Consequences, and Aviation Operational Risk Management Resources.

BACKGROUND: Flight crew fatigue is an important factor in aviation, leading organizations to implement fatigue risk management programs to reduce risk. The U.S. Air Force Air Mobility Command (AMC) has implemented the Aviation Operational Risk Management (AvORM) program to aid mission schedulers and flight crews in mitigating flight risks and identifying appropriate levels of risk. The AvORM program uses a scheduling tool and underpinning biomathematical fatigue model. This study examined self-reported fatigue-related incidents within AMC, which provides some indirect and anecdotal evidence as to the effectiveness of the scheduling tool. METHODS: Archival data from the AMC Aviation Safety Action Program (ASAP) Safety Reporting System was examined. Report content themes were created through an inductive approach in terms of fatigue prevalence, antecedents, and consequences. RESULTS: Fatigue was estimated as a factor in 4% of the reports. The two most commonly referenced fatigue antecedents were associated with mission/duty length and mission scheduling/planning factors. Factors associated with aircraft operation violations were the most cited consequences of fatigue. Fatigue was almost twice as likely to be reported as a secondary rather than primary contributing factor. Aircrew reported both positive and negative aspects of AvORM resources in mission planning and fatigue mitigation. DISCUSSION: Examination of ASAP reports suggests that fatigue is a contributing factor to safety incidents. Although the AvORM program highlights potential flight risks by utilizing a scheduling tool built upon an underlying biomathematical fatigue model, human fatigue continues to impact safety, suggesting an ongoing need for improved fatigue risk management and mitigation.Morris MB, Wiedbusch MD, Gunzelmann G. Fatigue incident antecedents, consequences, and aviation operational risk management resources. Aerosp Med Hum Perform. 2018; 89(8):708-716.

Household chores as the main source of physical activity: Perspectives of pregnant Pakistani women.

OBJECTIVE: To understand the level of physical activity in pregnant women and to identify perceived facilitators and barriers faced by them. METHODS: This cross-sectional study was conducted from January to June 2016 at Aga Khan Maternity and Child Care Centre, Hyderabad, Pakistan, and comprised pregnant women attending the antenatal clinics. They were administered the pregnancy physical activity questionnaire while additional questions were asked to assess perceived barriers and facilitators in pregnancy. SPSS 19 was used for data analysis. RESULTS: Of the 455 subjects, 179(36%) were physically active. Their median metabolic equivalent of task hours per week was 14.65 (interquartile range=0-105.8). The overall mean age of subjects was 26±4.47 years, while the mean gestational age was 24±10 weeks. Household activity had a strong positive correlation with total activity (p<0.05). Reported barriers included lack of energy and lack of information regarding benefits of physical activity, and facilitators included support from family and affordable facilities in the area of residence. CONCLUSIONS: Majority of the pregnant women failed to meet the daily recommendations for physical activity..

Smart watch, smarter EDSS: Improving disability assessment in multiple sclerosis clinical practice.

BACKGROUND: Patients' walking ability is critical for assessing the EDSS, the disability scale commonly used in MS clinical practice. Such assessment is usually based on patients' estimates or on the measures the neurologists observe during periodic visits. OBJECTIVES AND METHODS: We evaluated the agreement between patients' and neurologists' estimates of maximum walking ability and patients' mean maximum walking ability measured in their daily life through a GPS smartwatch, and assessed limitations of the current methods. RESULTS: Seventy-three patients with a median walking ability of 500m (IQR 400-800) were enrolled in the study. The agreement between patients' estimates and GPS measurements was modest (ICC 0.29, 95% CIs 0.06-0.49) and was influenced by course of the disease, patients' mood and inaccuracy at estimating long distances. A better reliability was found between neurologists' and GPS measures (ICC 0.68, 95% CIs 0.53-0.78), but the variability increased for longer distances and was influenced by patients' depressive symptoms, fatigue and course of the disease. CONCLUSIONS: This study showed a poor agreement between patients' and neurologists' estimates of maximum walking ability and patients' mean maximum walking ability measured in their daily life through a GPS smartwatch, with many factors affecting patient's and neurologists' estimates of the EDSS. The use of remote measurement technologies may provide a better understanding of the impact of MS in a patient's life.

Improving Provision of Care for Long-term Survivors of Lymphoma.

The progressive improvement of lymphoma therapies has led to a significant prolongation of patient survival and life expectancy. However, lymphoma survivors are at high risk of experiencing a range of early and late adverse effects associated with the extent of treatment exposure. Among these, second malignancies and cardiopulmonary diseases can be fatal, and neurocognitive dysfunction, endocrinopathy, muscle atrophy, and persistent fatigue can affect patients' quality of life for decades after treatment. Early recognition and reduction of risk factors and proper monitoring and treatment of these complications require well-defined follow-up criteria, close coordination among specialists of different disciplines, and a tailored model of survivorship care. We have summarized the major aspects of therapy-related effects in lymphoma patients, reviewed the current recommendations for follow-up protocols, and described a new hospital-based model of survivorship care provision from a recent multicenter Italian experience.

Barriers and facilitators to epilepsy self-management for patients with physical and psychological co-morbidity.

Objectives This exploratory study identifies barriers and facilitators to self-management to inform future epilepsy self-management interventions for persons who have epilepsy complicated by co-morbid mental health conditions and serious medical events. Methods Focus group methods were used in a series of community advisory board meetings. Analysis was conducted using a thematic, constant comparative approach aiming to describe the range of barriers and facilitators salient to participants. There were a total of 22 participants, including 8 health professionals, 9 patients with epilepsy, and 5 care partners. Mean age was 49.1 (SD = 11.0, range 32-69), 11 (50%) were female, and 11 (50%) were male. For those with epilepsy, mean years having epilepsy was 24.7 (SD = 19.9, range 1-58 years). Results Individual psychological barriers (mental illness, fatigue, and psychological distress) prominently interfered with health behaviors. Community and family barriers included stigma, lack of epilepsy knowledge, and poor social support. Facilitators included planning for seizures, learning about medications, stress management, socializing with others, and talking with other epilepsy patients. Discussion Qualitative evidence in this study suggests a linkage between social integration and positive health behaviors. Future efforts to embed patients with epilepsy and their caregivers into clinical care processes could offset barriers and enhance facilitators.

Tracking daily fatigue fluctuations in multiple sclerosis: ecological momentary assessment provides unique insights.

Studies investigating the prevalence, cause, and consequence of multiple sclerosis (MS) fatigue typically use single measures that implicitly assume symptom-stability over time, neglecting information about if, when, and why severity fluctuates. We aimed to examine the extent of moment-to-moment and day-to-day variability in fatigue in relapsing-remitting MS and healthy individuals, and identify daily life determinants of fluctuations. Over 4 weekdays, 76 participants (38 relapsing-remitting MS; 38 controls) recruited from multiple sites provided real-time self-reports six times daily (n = 1661 observations analyzed) measuring fatigue severity, stressors, mood, and physical exertion, and daily self-reports of sleep quality. Fatigue fluctuations were evident in both groups. Fatigue was highest in relapsing-remitting MS, typically peaking in late-afternoon. In controls, fatigue started lower and increased steadily until bedtime. Real-time stressors and negative mood were associated with increased fatigue, and positive mood with decreased fatigue in both groups. Increased fatigue was related to physical exertion in relapsing-remitting MS, and poorer sleep quality in controls. In relapsing-remitting MS, fatigue fluctuates substantially over time. Many daily life determinants of fluctuations are similar in relapsing-remitting MS and healthy individuals (stressors, mood) but physical exertion seems more relevant in relapsing-remitting MS and sleep quality most relevant in healthy individuals.