Sleep disturbance and fatigue in multiple sclerosis: A systematic review and meta-analysis.

Sleep disturbance is common in people with multiple sclerosis and may worsen fatigue; however, the assessment of sleep-fatigue relationships varies across studies. To better understand sleep-fatigue relationships in this population, we conducted a systematic review and random effects meta-analyses for the associations between fatigue and 10 sleep variables: Sleep-disordered breathing, daytime sleepiness, sleep quality, insomnia, restless legs, number of awakenings, sleep efficiency, sleep latency, sleep duration, and wake after sleep onset. Of the 1062 studies screened, 46 met inclusion criteria and provided sufficient data for calculating Hedges' g. Study quality was assessed using the Newcastle-Ottawa Scale. Sample characteristics did not differ between the 10 analyses. Results indicated that sleep quality and insomnia (assessed via self-report or diagnostic criteria) were strongly associated with fatigue (all gs ≥ 0.80 and all ps < .001). In contrast, the number of awakenings and sleep duration (assessed objectively) were not significantly associated with fatigue. Remaining sleep variables yielded moderate, significant effects. Most effects did not vary based on study quality or sample demographics. Results highlight that insomnia and perceptions of poor sleep have a stronger link than objective sleep duration to fatigue in multiple sclerosis and may represent a more effective target for intervention.

Perioperative insomnia trajectories and functional outcomes after total knee arthroplasty.

ABSTRACT: Longitudinal total knee arthroplasty (TKA) studies indicate that a substantial percentage of patients continue to experience clinically significant pain and functional impairment after surgery. Insomnia has been associated with poorer surgical outcomes; however, previous work has largely focused on long-term postsurgical insomnia. This study builds on previous work by examining sleep and pain outcomes about perioperative insomnia trajectories. Insomnia symptoms (using the Insomnia Severity Index) during the acute perioperative period (2 weeks pre-TKA to 6 weeks post-TKA) were used to classify participants into perioperative insomnia trajectories: (1) No Insomnia (ISI < 8), (2) New Insomnia (baseline < 8; postoperative ≥ 8 or ≥6-point increase), (3) Improved Insomnia (baseline ≥ 8, postoperative < 8 or ≥6-point decrease), and (4) Persistent Insomnia (ISI ≥ 8). Insomnia, pain, and physical functioning were assessed in participants with knee osteoarthritis (n = 173; M age = 65 ± 8.3, 57.8% female) at 5 time points: 2 weeks pre-TKA, post-TKA: 6 weeks, 3 months, 6 months, and 12 months. Significant main effects were seen for insomnia trajectory and time, and trajectory-by-time interactions for postoperative insomnia, pain severity, and physical functioning ( P' s < 0.05). The Persistent Insomnia trajectory had the worst postoperative pain at all follow-ups and marked insomnia and physical functioning impairment post-TKA ( P' s < 0.05). The New Insomnia trajectory had notable long-term insomnia (6 weeks to 6 months) and acute (6 weeks) postoperative pain and physical functioning ( P' s < 0.05). Findings indicated a significant relationship between perioperative insomnia trajectory and postoperative outcomes. Results of this study suggest that targeting presurgical insomnia and preventing the development of acute postoperative insomnia may improve long-term postoperative outcomes, with an emphasis on persistent perioperative insomnia due to poorer associated outcomes.

Illness Intrusiveness in Adults with Sickle Cell Disease: The Role of Fatigue.

Chronic illness experiences often interfere with daily functioning (a concept known as illness intrusiveness) and health-related quality of life (HRQoL). However, less is known about the role of specific symptoms in predicting illness intrusiveness in sickle cell disease (SCD). This exploratory study examined associations between common SCD-related symptoms (i.e., pain, fatigue, depression, and anxiety), illness intrusiveness, and HRQoL among adults with SCD (n = 60). Illness intrusiveness significantly correlated with fatigue severity (r = .39, p = .002), depression severity (r = .45, p < .001), anxiety severity (r = .41, p = .001), physical HRQoL (r = - .53, p < .001), and mental HRQoL (r = - .44, p < .001). Multiple regression revealed a significant overall model, (R2 = .28, F(4, 55) = 5.21, p = .001), with fatigue, but not pain, depression, or anxiety, significantly predicting illness intrusiveness (ß = .29, p = .036). Results suggest that fatigue may be a primary factor contributing to illness intrusiveness-a determinant of HRQoL-in individuals with SCD. Given the limited sample size, larger confirmatory studies are warranted.

Discrepancies between self-report and objective sleep outcomes are associated with cognitive impairment and fatigue in people with multiple sclerosis and insomnia.

OBJECTIVES: The primary aim of this study was to assess the degree to which discrepancies between self-reported and actigraphy-based measures of sleep are associated with specific demographic, disease characteristics, and clinical features in a sample of individuals with multiple sclerosis (MS) reporting clinically significant insomnia symptoms. METHODS: Participants were 90 community-based participants with MS and insomnia. Measures included the Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory-Fast Screen (BDI-FS), Modified Fatigue Impact Scale (MFIS), and MS Neuropsychological Screening Questionnaire (MSNQ), and wrist actigraphy-derived sleep parameters. Discrepancy scores were calculated by subtracting actigraphy-derived values from PSQI-derived values for sleep latency (SL), total sleep time (TST), and sleep efficiency (SE). RESULTS: Correlations between PSQI and actigraphy-derived values were weak. Significant discrepancies, with moderate-to-large effect sizes, were observed between PSQI and actigraphy for SL, TST, and SE, whereby the PSQI yielded longer SL, shorter TST, and less SE than actigraphy. MSNQ elevations correlated with greater PSQI-actigraphy discrepancies in SL and TST. MFIS elevations correlated with greater discrepancies in TST. Discrepancies were not significantly related to BDI-FS, gender, race, education level, or MS type. CONCLUSIONS: Results emphasize the importance of assessing fatigue with sleep, and when feasible, inclusion of both self-report and actigraphy measures.

Eliminating Sleep Health Disparities and Achieving Health Equity: Seven Areas for Action in the Behavioral Sleep Medicine Community.

Racial and ethnically minoritized and under-resourced populations do not reap the same benefits of sufficient sleep as their white counterparts resulting in insufficient sleep and sleep health disparities. Research exploring these disparities have documented a plethora of factors including social determinants of health, community violence, and structural issues - all of which are associated with adverse sleep. There are robust evidence base behavioral intervention that can be leveraged to improve sleep health among racial and ethnic groups. However, EBIs are not well leveraged. In 2021, with participation from members of the society of behavioral sleep medicine, we conducted this report to bring together the field of behavioral sleep medicine including researchers, clinicians and trainees to discuss gaps and opportunities at the intersection of the COVID-19 pandemic, systemic racism, and sleep health. The goals were anchored around seven recommendations toward reducing disparities in the near-term and longer-term approaches to eliminating disparities. Furthermore, we acknowledge that reducing and eliminating disparities in sleep health requires a multifaceted approach that includes a focus on individual, community, health care and societal levels of influence with participation from diverse partners including federal, state and local.

Cognitive and Mood Profiles Among Patients With Stiff Person Syndrome Spectrum Disorders.

An emerging body of evidence suggests that changes in cognitive and emotional function are common aspects of stiff person spectrum disorders (SPSD). We sought to examine the pattern of cognitive impairment and psychiatric symptoms in SPSD. Methods: A retrospective review of medical records was conducted for patients seen at the Johns Hopkins Stiff Person Syndrome (SPS) center from 1997 to January 1st, 2020. Individuals who had received formal cognitive testing as part of routine clinical care for patient-reported cognitive changes were included. Demographics, prevalence of cognitive impairment, psychoactive medication use, and clinically significant psychiatric symptoms were described. Results: Out of 205 patients screened, 20 completed cognitive testing (75% female, mean age 47.4 years). The most common domains of impairment were verbal learning and recall memory (n = 14, 70%), verbal fluency (n = 10, 50%), processing speed (n = 8, 40%), and attention (n = 8, 40%). 9/11 patients assessed for depression reported clinically significant symptoms, and 4/9 patients assessed for anxiety reported clinically significant symptoms. Conclusions: Screening for cognitive impairment in SPSD should utilize testing that assesses verbal learning and recall, phonemic verbal fluency, attention, and processing speed. Moreover, it is important to evaluate for co-existing depression and anxiety symptoms, as these are common in SPSD.

Dialectical behavior therapy skills training for individuals with multiple sclerosis and their support partners: A pilot randomized controlled trial.

BACKGROUND: Symptoms of anxiety, depression, and emotion dysregulation are common among individuals with MS and their support partners. Dialectical behavior therapy (DBT) - a type of cognitive behavioral intervention - may be a promising treatment for individuals affected by MS. This pilot randomized controlled trial (RCT) assessed the effects and feasibility of remotely delivered DBT skills on anxiety and depression symptoms and emotion dysregulation in individuals with MS and their support partners. METHODS: This study featured a single-masked, two-arm, parallel group design. Twenty pairs of individuals with MS and their support partners (n = 40) were randomized to 12 weeks of DBT or facilitated peer support (FPS). Masked assessments were completed at weeks 0 (baseline), 13 (post-intervention), and 26 (follow-up). RESULTS: At post-intervention (primary endpoint), participants randomized to DBT exhibited significantly greater reductions in anxiety and depression symptoms compared to FPS (B = 4.45, p = .04, Cohen's d = 0.57). Secondary outcomes of emotion dysregulation and well-being favored the DBT group but did not reach statistical significance (ds = 0.51, ps = 0.07). Effects were not maintained at follow-up. Most (86%) individuals screened were eligible for the trial, and retention (70%) did not differ between study arms. CONCLUSIONS: This pilot RCT provides encouraging evidence that DBT skills is feasible and may improve depression, anxiety, and emotion dysregulation for individuals with MS and their support partners. Future research is needed to optimize maintenance of DBT skills, investigate mechanisms for these improvements, and replicate these promising effects in a fully powered trial.

Reliability and validity of the multiple sclerosis resiliency scale (MSRS).

OBJECTIVE: The objective of this study was to determine the internal reliability and construct validity of the Multiple Sclerosis Resiliency Scale (MSRS) in comparison with a common measure of global resilience. METHODS: Participants were 216 community-dwelling adults with MS (mean age: 48.8 ± 12.5 years; 77% female; median disease duration: 8 years) recruited through a university-affiliated MS Center. Participants completed the MSRS, 10-item Connor Davidson Resilience Scale (CDRS), Perceived Stress Scale (PSS), and depressive and anxious symptom items from the SymptoMScreen. RESULTS: The MSRS exhibited fair to excellent internal consistency (αs 0.74 to 0.91) and divergent validity with disability severity (r = -0.19), MS duration (r = 0.07), and MS subtype (r = -0.01). The MSRS total and Emotional and Cognitive Strategies subscale scores were moderately correlated with the CDRS (rs = 0.50 and 0.62), PSS (rs = -0.56 and - 0.62), depressive symptoms (rs = -0.49 and - 0.54), and anxious symptoms (rs = -0.38 and - 0.047). The MSRS total and Emotional and Cognitive Strategies subscale scores exhibited fair to good accuracy (AUCs = 0.73 to 0.83) for identifying participants in the highest and lowest CDRS quartiles; however, cutoff scores yielded only fair sensitivity and specificity, and the measures differed significantly in classification of participants into highest and lowest quartiles. CONCLUSION: Although the MSRS may be useful in assessing resilience to MS-specific challenges, use of a global resilience measure may still be indicated depending on the clinical and research context.

Physical activity and depression in MS: The mediating role of behavioral activation.

BACKGROUND: Depression is a common comorbid condition among individuals with multiple sclerosis (MS) and is associated with greater overall disease burden and lower quality of life. Numerous clinical trials have supported physical activity interventions versus education, usual care, and attention control conditions for improving depressive symptoms in individuals with MS. However, little is known about the psychological mechanisms that may underlie physical activity-related improvements in depression. Behavioral activation posits that depression may stem from a reduction or loss of personally meaningful and rewarding activity. The process of behavioral activation involves re-engaging with these experiences. Behavioral activation might represent one mechanism by which physical activity interventions improve depression. OBJECTIVE: To examine behavioral activation as a mechanism mediating the effects of physical activity intervention on depressive symptom improvement in individuals with MS. METHODS: Mediational path analysis using data from a randomized controlled trial (N = 64) comparing telephone-based physical activity counseling (TC) to education (EC). RESULTS: Participation in TC resulted in greater improvements in behavioral activation from months 0-3. Improvements in behavioral activation were associated with fewer baseline-adjusted depressive symptoms at month 6. The corresponding indirect (mediational) pathway was significant. CONCLUSION: Behavioral activation may represent one mechanism by which physical activity improves depression in MS. Future physical activity trials should capitalize on this relationship and place additional emphasis on identifying and engaging in personally meaningful life activity. Future trials of therapies focused on behavioral activation might benefit from encouraging physical activity goals. TRIAL REGISTRATION: Trial Registration clinicaltrials.gov Identifier: NCT01198977.

Cognitive Assessment of Individuals with Multiple Sclerosis in the Arab World: a Systematic Review.

The prevalence of multiple sclerosis (MS) is on the rise globally, and recent epidemiological studies have observed increased rates in the Arab world (i.e., countries of North Africa and the Middle East where Arabic is the primary language). However, assessment of cognitive impairment and its relevant covariates (e.g., fatigue and depressive symptomatology) in the Arab world has not been rigorously reviewed. Thus, the objective of the present study was to systematically review the current use of cognitive assessment measures in observational and interventional studies of individuals with MS in the Arab world. A systematic review of studies that assessed cognitive function in adults with MS in the Arab world was conducted using PubMed, PsycINFO, CINAHL, The Cochrane Library, Embase, WHO Global Index Medicus, and Ovid Global Health. Studies that featured at least one objective cognitive measure were included. Eligible studies were reviewed for bias and study quality using the QUADAS-2 and NIH QAT. Study characteristics and finding were extracted by two independent reviewers, with results confirmed by a third reviewer. A total of 13 (N = 846) studies met inclusion criteria. Risk of bias and included measures varied across studies. Results demonstrated inconsistent availability and use of MS cognitive assessment tools across the Arab world. An Arabic version of the BICAMS was the only cognitive battery that was evaluated with regard to psychometric properties. The most common individual test include in reviewed studies was the SDMT. However, validation studies are still needed for this and a number of other measures. Other measures are still in the early stages of translation and cultural-linguistic norming. This review of cognitive assessment of individuals with MS in the Arab world was limited by variable study quality and measure selection. The present review provides a summary of the tests most commonly used in this region and recommendations for future investigation.

Brief and cost-effective tool for assessing verbal learning in multiple sclerosis: Comparison of the Rey Auditory Verbal Learning Test (RAVLT) to the California Verbal Learning Test - II (CVLT-II).

BACKGROUND: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is a common cognitive screening tool. However, administration and scoring can be time-consuming, and its use of proprietary subtests like the California Verbal Learning Test - II (CVLT-II) is financially limiting. Use of the non-proprietary Rey Auditory Verbal Learning Test (RAVLT) may be provide a valid alternative. OBJECTIVES: To compare the RAVLT and CVLT-II in terms of diagnostic accuracy for detecting cognitive impairment, and to determine optimal cut-scores for the RAVLT. METHODS: 100 participants with MS completed the five learning trials from the RAVLT and CVLT-II. Receiver operating characteristic analyses were used to compare the measures' sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV), and to identify optimal cut-scores. RESULTS: Using a criterion of 1.5 SD below the normative sample mean, the RAVLT showed fair to good (κs = 0.21-0.41) agreement with the CVLT-II. A cut-score of 12 on Trials 1 + 2 of the RAVLT showed fair sensitivity (75%) and specificity (76%) and did not differ significantly from the CVLT-II (p > .05). CONCLUSIONS: Performance on initial learning trials of the RAVLT may provide a brief, valid, and cost-effective alternative to the CVLT-II for screening verbal learning impairments in MS.

Depressive symptoms and fatigue as predictors of objective-subjective discrepancies in cognitive function in multiple sclerosis.

OBJECTIVE: To examine the degree to which depressive symptoms and fatigue in individuals with multiple sclerosis (MS) are associated with discrepancies between subjective and objective cognitive impairment. METHODS: Ninety-nine adults with MS who were receiving care in a university-affiliated MS center completed the Patient Health Questionnaire-8 (PHQ-8), Fatigue Severity Scale (FSS), MS Neuropsychological Screening Questionnaire (MSNQ), and Brief International Cognitive Assessment for MS (BICAMS). Participants were classified as "Accurates," "Underestimators," or "Overestimators" based on discrepancies between their MSNQ (subjective) and BICAMS (objective) scores. Underestimators were individuals whose subjective scores were significantly worse than their objective scores. Overestimators exhibited the opposite profile. RESULTS: The PHQ-8 (r = 0.58) and FSS (r = 0.48) significantly correlated with the MSNQ, but not with the BICAMS (rs < 0.07). Underestimators (i.e., participants who underestimated their objective cognitive functioning) exhibited higher PHQ-8 and FSS scores compared to Accurates (ps < 0.01) and Overestimators (ps < 0.01). Optimal cut-scores of ≥6 on the PHQ-8 and ≥36 on the FSS provided fair accuracy (78% and 74%) for identifying Underestimators. Identification of Underestimators based on PHQ-8 and FSS scores was not moderated by any demographic or MS clinical variables. CONCLUSIONS: In the presence of mild levels of depression or significant fatigue, subjective cognitive measures are unlikely to provide accurate estimates of objective cognitive functioning. Objective cognitive measures are required for accurate identification of cognitive impairment.

Diagnostic and Clinical Utility of the GAD-2 for Screening Anxiety Symptoms in Individuals With Multiple Sclerosis.

OBJECTIVE: To assess the diagnostic and clinical utility of the 2-item Generalized Anxiety Disorder Scale (GAD-2) for screening anxiety symptoms in individuals with multiple sclerosis (MS). DESIGN: Cross-sectional. SETTING: University-affiliated MS neurology and rehabilitation center. PARTICIPANTS: The sample comprised adults (N=99) (ages 19-72; mean ± SD=46.2±13.0; 75% women) with a physician-confirmed MS diagnosis who were receiving care in a university-affiliated MS center. Disease durations ranged from 1 to 37 years (mean ± SD=10.7±8.4). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants completed the 7-item Generalized Anxiety Disorder Scale (GAD-7) and GAD-2. Internal consistency was calculated for both measures. Area under the receiver operating characteristics curve (AUC), the 95% confidence interval for the AUC, and Youden's J were calculated to determine the optimal GAD-2 cutoff score for identifying clinically significant anxiety symptoms, as defined by the previously validated GAD-7 cutoff score of ≥8. RESULTS: Internal consistency was excellent for the GAD-7 (Cronbach α=.91) and acceptable for the GAD-2 (α=.77), and the measures were highly correlated (r=.94). The GAD-2 had excellent overall accuracy for identifying clinically significant anxiety symptoms (AUC=0.97; 95% confidence interval, 0.94-1.00). A GAD-2 cutoff score of ≥3 provided an optimal balance of good sensitivity (0.87) and excellent specificity (0.92) for detecting clinically significant anxiety symptoms. Alternatively, a cutoff score of ≥2 provided excellent sensitivity (1.00) and fair specificity (0.76). CONCLUSIONS: The GAD-2 is a clinically useful and psychometrically valid tool for screening anxiety symptoms in MS rehabilitation and neurology care settings. Importantly, this tool has the potential to identify individuals with MS who are at risk for anxiety disorders and who may benefit from rehabilitation psychology interventions to ultimately improve functioning and quality of life.

Cognitive and affective mechanisms of pain and fatigue in multiple sclerosis.

OBJECTIVE: To examine the extent to which pain catastrophizing, fatigue catastrophizing, positive affect, and negative affect simultaneously mediated the associations between common symptoms of multiple sclerosis (MS; i.e., pain, fatigue) and impact on daily life, depressive symptoms, and resilience. METHOD: Participants were community-dwelling adults with MS (N = 163) reporting chronic pain, fatigue, and/or moderate depressive symptoms. Multiple mediation path analysis was used to model potential mediators of pain and fatigue separately, using baseline data from a randomized controlled trial comparing two symptom self-management interventions. RESULTS: In the pain model, pain catastrophizing was a mediator of pain intensity with pain interference and depression. Negative affect was a mediator of pain intensity with depression and resilience. In the fatigue model, fatigue catastrophizing was a mediator of fatigue intensity with fatigue impact and depression. Positive affect was a mediator of fatigue intensity with depression and resilience. CONCLUSIONS: These findings provide preliminary support for the presence of differential effects of cognitive-affective mediators and suggest potential targets for psychological interventions based on an individual's clinical presentation. The differential mediating effects also support the inclusion of both positive and negative aspects of psychological health in models of pain and fatigue, which would not be otherwise apparent if negative constructs were examined in isolation. To our knowledge, this is the first study to utilize a multivariate path analysis approach to examine cognitive-affective mediators of pain and fatigue in MS, while also examining positive and negative constructs concurrently. (PsycINFO Database Record

Sleep Disturbance and Cognitive Dysfunction in Multiple Sclerosis: a Systematic Review.

PURPOSE OF REVIEW: The present review summarizes recent research on the association between sleep disturbance and cognitive dysfunction in MS. Assessment methodology, domain-specific associations between sleep disturbance and cognitive dysfunction, and implications for future research and treatment are discussed. RECENT FINDINGS: All 12 studies included in this review found significant associations between sleep disturbance and cognitive dysfunction; however, results varied considerably depending on the assessment method used and the cognitive domain assessed. Self-reported sleep disturbance generally predicted self-report but not objective measures of cognitive dysfunction. Objective sleep measures (e.g., polysomnography, actigraphy) generally predicted objective impairments in processing speed and attention; however, objective sleep disturbance was more variable in predicting performance in other cognitive domains (e.g., memory, executive function). Sleep disturbance may help predict future cognitive decline in MS. Results highlight the need to integrate sleep assessment into routine MS care. Interventions aimed treating sleep disturbance may offer promise for improving cognitive dysfunction in MS.

Moderators of Treatment Outcomes After Telehealth Self-Management and Education in Adults With Multiple Sclerosis: A Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: To examine moderators of treatment effects in a randomized controlled trial comparing a telehealth self-management intervention with a telehealth multiple sclerosis (MS) education intervention for fatigue, pain, and mood in adults with MS. DESIGN: Secondary analysis of a single-blind randomized controlled trial. SETTING: Community. PARTICIPANTS: Adults with MS and chronic fatigue, chronic pain, and/or moderate depressive symptoms (N=163) recruited from across the United States. INTERVENTIONS: Two 8-week, telephone-delivered symptom interventions delivered 1:1: a self-management intervention (n=75) and an MS education intervention (n=88). MAIN OUTCOME MEASURES: Outcome measures were fatigue impact pain interference, and depressive symptom severity assessed at baseline and posttreatment. Potential moderators of treatment effects assessed at baseline were demographics (age, sex, and education), clinical characteristics (disease duration and disability severity), symptoms (perceived cognitive impairment and pain intensity), baseline levels of the treatment outcomes (pain interference, fatigue impact and depressive symptom severity), and cognitive behavioral factors (pain catastrophizing, fatigue catastrophizing, self-efficacy, and patient activation). RESULTS: Moderation analyses found significant moderation for fatigue impact but not for pain intensity or depressive symptom severity. Baseline patient activation interacted with treatment group to predict fatigue impact at posttreatment (P=.049). Among participants with high baseline patient activation, the self-management group reported significantly less fatigue at posttreatment than the education group. No other variables moderated the study outcomes. CONCLUSIONS: At the group level, participants responded to both interventions, regardless of disease characteristics, demographics, symptom levels, and cognitive behavioral factors. Self-management and education are both potentially beneficial symptom treatments that may be recommended to individuals with MS and chronic pain, fatigue, and/or depressive symptoms.

In vivo evidence of oxidative stress in brains of patients with progressive multiple sclerosis.

BACKGROUND: The oxidative stress hypothesis links neurodegeneration in the later, progressive stages of multiple sclerosis (MS) to the loss of a major brain antioxidant, glutathione (GSH). OBJECTIVE: We measured GSH concentrations among major MS subtypes and examined the relationships with other indices of disease status including physical disability and magnetic resonance imaging (MRI) measures. METHODS: GSH mapping was performed on the fronto-parietal region of patients with relapsing-remitting multiple sclerosis (RRMS, n = 21), primary progressive multiple sclerosis (PPMS, n = 20), secondary progressive multiple sclerosis (SPMS, n = 20), and controls ( n = 28) using GSH chemical shift imaging. Between-group comparisons were performed on all variables (GSH, T2-lesion, atrophy, Expanded Disability Status Scale (EDSS)). RESULTS: Patients with MS had substantially lower GSH concentrations than controls, and GSH was lower in progressive MS (PPMS and SPMS) compared with RRMS. GSH concentrations were not significantly different between PPMS and SPMS, or between RRMS and controls. Brain atrophy was significant in both RRMS and progressive MS compared with controls. CONCLUSION: Markedly lower GSH in progressive MS than RRMS indicates more prominent involvement of oxidative stress in the progressive stage of MS than the inflammatory stage. The association between GSH and brain atrophy suggests the important role of oxidative stress contributing to neurodegeneration in progressive MS, as suggested in other neurodegenerative diseases.

Association Between Sleep Problems and Perceived Cognitive Dysfunction Over 12 Months in Individuals with Multiple Sclerosis.

Sleep problems are highly prevalent among individuals with multiple sclerosis (MS); however, the relationship between sleep problems and cognitive dysfunction is poorly understood in this population. In the present study, 163 individuals with MS and depression, fatigue, or pain completed self-report measures of sleep, cognitive dysfunction, and relevant demographic and clinical characteristics (e.g., disability severity, depressive symptomatology, pain intensity, fatigue impact) at four time points over 12 months. Mixed-effects regression demonstrated that poorer sleep was independently associated with worse perceived cognitive dysfunction (ß = -0.05, p = .001), beyond the influence of depressive symptomatology. Fatigue impact was found to partially mediate this relationship. Results suggest that for individuals with MS and depression, fatigue, or pain, self-reported sleep problems are related to perceived cognitive dysfunction, and that fatigue impact accounts for part of this relationship.

Proposed cut scores for tests of the Brief International Cognitive Assessment of Multiple Sclerosis (BICAMS).

OBJECTIVE: Cognitive impairment (CI) is common in multiple sclerosis (MS). An international consensus committee developed the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) to screen for CI commonly seen in MS. BICAMS cut scores would allow clinicians to, efficiently and effectively, identify patients with possible CI and could aid in clinical decision-making. The aim of this study was to establish cut scores for the neuropsychological tests of the BICAMS. METHODS: This study utilized data collected from MS Centers in the United States. ROC curve analysis identified cut scores yielding the best balance of sensitivity and specificity. We tested two definitions of impairment: 1.5 and 2 standard deviations (SD) below the normative mean. RESULTS: All cut scores yielded excellent or good sensitivity and specificity for identifying impaired cognitive performance. The following cut scores yielded the best balance between sensitivity and specificity: On the Symbol Digit Modalities Test, 44 for 1.5 SD below the mean and 38 for 2 SD below the mean; on the California Verbal Learning Test - II learning trials, 39 (1.5 SD) and 35 (2 SD); and on the Brief Visuospatial Memory Test-Revised learning trials, 17 (1.5 SD) and 16 (2 SD). CONCLUSIONS: Cut scores can accurately identify cognitive impairment on all subtests of the BICAMS. Use of cut scores may improve the efficiency of screening for cognitive impairment by reducing administrative burden and simplifying interpretation.

Sleep and its associations with perceived and objective cognitive impairment in individuals with multiple sclerosis.

Problems with sleep and cognitive impairment are common among people with multiple sclerosis (MS). The present study examined the relationship between self-reported sleep and both objective and perceived cognitive impairment in MS. Data were obtained from the baseline assessment of a multi-centre intervention trial (NCT00841321). Participants were 121 individuals with MS. Nearly half (49%) of participants met the criteria for objective cognitive impairment; however, cognitively impaired and unimpaired participants did not differ on any self-reported sleep measures. Nearly two-thirds (65%) of participants met the criteria for 'poor' sleep, and poorer sleep was significantly associated with greater levels of perceived cognitive impairment. Moreover, the relationships between self-reported sleep and perceived cognitive impairment were significant beyond the influence of clinical and demographic factors known to influence sleep and cognitive functioning (e.g. age, sex, education level, disability severity, type of MS, disease duration, depression and fatigue). However, self-reported sleep was not associated with any measures of objective cognitive impairment. Among different types of perceived cognitive impairment, poor self-reported sleep was most commonly related to worse perceived executive function (e.g. planning/organization) and prospective memory. Results from the present study emphasize that self-reported sleep is significantly and independently related to perceived cognitive impairment in MS. In terms of clinical implications, interventions focused on improving sleep may help improve perceived cognitive function and quality of life in this population; however, the impact of improved sleep on objective cognitive function requires further investigation.