The moderating roles of self-efficacy and depression in dual-task walking in multiple sclerosis: A test of self-awareness theory.

OBJECTIVE: Multiple sclerosis (MS) is a debilitating neurological disease associated with a variety of psychological, cognitive, and motoric symptoms. Walking is among the most important functions compromised by MS. Dual-task walking (DTW), an everyday activity in which people walk and engage in a concurrent, discrete task, has been assessed in MS, but little is known about how it relates to other MS symptoms. Self-awareness theory suggests that DTW may be a function of the interactions among psychological, cognitive, and motor processes. METHOD: Cognitive testing, self-report assessments for depression and falls self-efficacy (FSE), and walk evaluations [DTW and single-task walk (STW)] were assessed in seventy-three people with MS in a clinical care setting. Specifically, we assessed whether psychological factors (depression and FSE) that alter subjective evaluations regarding one's abilities would moderate the relationships between physical and cognitive abilities and DTW performance. RESULTS: DTW speed is related to diverse physical and cognitive predictors. In support of self-awareness theory, FSE moderated the relationship between STW and DTW speeds such that lower FSE attenuated the strength of the relationship between them. DTW costs - the change in speed normalized by STW speed - did not relate to cognitive and motor predictors. DTW costs did relate to depressive symptoms, and depressive symptoms moderated the effect of information processing on DTW costs. CONCLUSIONS: Findings indicate that an interplay of physical ability and psychological factors - like depression and FSE - may enhance understanding of walking performance under complex, real-world, DTW contexts.

The association between MRI brain volumes and computerized cognitive scores of people with multiple sclerosis.

BACKGROUND: Computerized cognitive assessment facilitates the incorporation of multi-domain cognitive monitoring into routine clinical care. The predictive validity of computerized cognitive assessment among people with multiple sclerosis (PwMS) has scarcely been investigated. OBJECTIVE: To explore the associations between brain volumes and cognitive scores from a computerized cognitive assessment battery (CAB, NeuroTrax) among PwMS. METHODS: PwMS were evaluated with the CAB and underwent brain MRI within 40 days. Cognitive assessment yielded age- and education-adjusted scores in 9 cognitive domains: memory, executive function, attention, information processing speed, visual spatial, verbal function, motor skills, problem solving, and working memory. The global cognitive score (GCS) is the average of all domain scores. MRI brain and lesion volumes were assessed with icobrain ms, a fully automated tissue and lesion segmentation and quantification software. RESULTS: 91 PwMS were included [Age: 52.1 ± 11.7 years, 64 (70%) female, EDSS: 3.4 ± 2.0, 79 (87%) with a relapsing remitting course]. Significant correlations were found between the GCS and whole brain, white matter, grey matter, thalamic, lateral ventricles, hippocampal and lesion volumes (Correlation coefficients: 0.46, 0.40, 0.25, 0.42, -0.36, 0.21, -0.3, respectively). Regression analysis revealed that lateral ventricles and thalamic volumes were the most consistent predictors of all cognitive domain scores. CONCLUSION: Computerized cognitive scores were significantly associated with quantified MRI. These findings support the predictive validity of multi-domain computerized cognitive assessment for people with multiple sclerosis.

The impact of subjective cognitive fatigue and depression on cognitive function in patients with multiple sclerosis.

BACKGROUND: The association between subjective cognitive fatigue and objective cognitive dysfunction in patients with multiple sclerosis (PwMS) has been studied, with conflicting results. OBJECTIVE: To explore the impact of fatigue on cognitive function, while controlling for the influence of depression, disability, comorbidities, and psychotropic medications. METHODS: PwMS completed a computerized cognitive testing battery with age- and education-adjusted cognitive domain scores. Disability (Expanded Disability Status Scale (EDSS)), cognitive fatigue, and depression were concurrently evaluated. RESULTS: In all, 699 PwMS were included. Both cognitive fatigue and depression were significantly and negatively correlated with the same cognitive domains: information processing speed, executive function, attention, motor function, and memory (-0.15 ⩽ r ⩽ -0.14 for cognitive fatigue; -0.24 ⩽ r ⩽ -0.19 for depression). Multivariate analysis revealed significant but small independent correlations only between depression and neuropsychological test results, while cognitive fatigue had no independent correlation with objective cognitive function except for a trend toward impaired motor function in highly fatigued PwMS. Depression and cognitive fatigue accounted for no more than 6% of the variance in objective cognitive domain scores. CONCLUSION: Cognitive fatigue is not independently related to objective cognitive impairment. Depression may influence cognitive function of PwMS primarily when it is severe. Cognitive impairment in PwMS should not be ascribed to fatigue or mild depression.

Shifting paradigms in multiple sclerosis: from disease-specific, through population-specific toward patient-specific.

PURPOSE OF REVIEW: In recent years we notice paradigm shifts in the understanding of multiple sclerosis (MS), leading to important transition in the patients' management. This review discusses some of the recent findings and developments underlying the conceptual changes being translated from 'treating the disease' to 'treating the patient' with MS (PwMS). RECENT FINDINGS: Applying advanced technologies combined with cross-disciplinary efforts in the fields of neuropathology, neuroimmunology, neurobiology, and neuroimaging, together with clinical neurology provided support for the notion that MS is not a single disease but rather a spectrum. Predictive markers of disease subtypes, disease activity and response to therapy are being developed; some already applied to practice, allowing informed management. In parallel, population-specific issues, some genetic-driven, others caused by environmental (sun-exposure, life-style, etc.), gender-related (hormones) and epigenetic factors, are being elucidated. Additionally, patient empowerment-based approaches, including integration of patient-reported outcome measures (PRO) as well as tools to enhance patients' adherence to medications, are being developed, some already provided as part of emerging mobile-health technologies. SUMMARY: Developments in the MS field, elucidating disease subtypes and interpopulation diversities, together with integration of patient-centered approaches, allow transition toward precision medicine in MS clinical trials and patient care.

[FROM STATISTICAL ASSOCIATIONS TO SCIENTIFIC CAUSALITY].

The pathogenesis of most chronic diseases is complex and probably involves the interaction of multiple genetic and environmental risk factors. One way to learn about disease triggers is from statistically significant associations in epidemiological studies. However, associations do not necessarily prove causation. Associations can commonly result from bias, confounding and reverse causation. Several paradigms for causality inference have been developed. Henle-Koch postulates are mainly applied for infectious diseases. Austin Bradford Hill's criteria may serve as a practical tool to weigh the evidence regarding the probability that a single new risk factor for a given disease is indeed causal. These criteria are irrelevant for estimating the causal relationship between exposure to a risk factor and disease whenever biological causality has been previously established. Thus, it is highly probable that past exposure of an individual to definite carcinogens is related to his cancer, even without proving an association between this exposure and cancer in his group. For multifactorial diseases, Rothman's model of interacting sets of component causes can be applied.

Polysomnography parameters in a large cohort of people with multiple sclerosis.

BACKGROUND: Disordered and disturbed sleep is quite common among people with multiple sclerosis (PwMS). It is associated with fatigue one of most disabling symptoms in MS. This study aims at comparing polysomnographic (PSG) sleep parameters in a large single cohort of PwMS from a single center to that of the published norms. Hence establishing PSG parameters in PwMS. METHODS: This is a retrospective review of 299 consecutive adult PwMS who were seen and evaluated with an overnight PSG at a Comprehensive MS Care Center between 11/19/2001 to 9/17/2014. Data extracted from the PSG included Total Sleep Time (TST), sleep efficiency (SE), sleep onset latency (SOL), Relative REM latency, total apnea-hypopnea indices (AHI), spontaneous arousal indices (AI), total periodic leg movements indices (PLMI) and, sleep architecture metrics including percentage spent in stages N1/N2, N3, and REM. RESULTS: PwMS, compared to normative data, had, on average, 85.9 min shorter TST (p < 0.001), 27.3 min longer SOL (p < 0.0001), 62.1 min longer REM latency (p < 0.0001), 10.7 % lower SE (p < 0.0001), 16.4 % more N1/N2 (p < 0.0001) and 11.4 % less N3 (p < 0.0001). REM latency The prevalence of Obstructive Sleep Apnea (OSA) was high at 60.7 % and the mean AHI was higher by 11.1 events per hour (p < 0.0001). CONCLUSIONS: This study establishes PSG parameters in the largest PwMS cohort reported to date. It is important to be vigilant of sleep complaints in PwMS. Future prospective large single cohort studies with standardized methods are needed to further understand sleep disturbances in PwMS as well as their causes and implications.

Multiple Sclerosis, Fatigue, Expanded Disability Status Scale: A Cross-Sectional Exploration of Sleep Efficiency and Quantitative Sleep Parameters.

BACKGROUND: Poor sleep quality and sleep disorders are more prevalent in individuals with multiple sclerosis (MS) than in the general population. Poor sleep has been correlated with worse MS outcomes. Sleep efficiency (SE) is one of the most sensitive markers of sleep quality. There is very little written about SE and other polysomnography (PSG) parameters and MS measures. METHODS: This is a retrospective review of 280 consecutive individuals with MS evaluated by PSGs and other standardized MS measures over 13 years at a comprehensive MS center. In addition, the cohort was assessed with 2 fatigue scales, the Epworth Sleepiness Scale, and the Expanded Disability Status Scale. A comparison of means test (independent t test) and a correlation coefficient (r) were used. RESULTS: The PSG measures of SE and Total Sleep Time were significantly different between a group of individuals with MS with a disease duration of more than 5 years vs a group of individuals with MS with a disease duration less than or equal to 5 years. Prevalence of obstructive sleep apnea was 63%, higher than reported in the literature while the prevalence of moderate to severe obstructive sleep apnea was 33.4%, which was lower than reported. CONCLUSIONS: Longer disease duration and worse disability correlate with sleep quality as measured by SE.

Peering further into the mind's eye: combining visual evoked potential and optical coherence tomography measures enhances insight into the variance in cognitive functioning in multiple sclerosis.

BACKGROUND: Spectral Optical Coherence Tomography (OCT) and Visual Evoked Potentials (VEPs) have both emerged as potentially useful biomarkers of cognitive decline in people with multiple sclerosis (PwMS). Their combined use may provide additional predictive value for identifying disease impact, progression, and remyelination capacity above-and-beyond what is captured using either approach alone. OBJECTIVE: We examined the relationship between OCT/VEP measures and cognitive functioning in 205 PwMS. OCT measures included Retinal Nerve Fiber Layer Volume (RNFLV), Papillo-Macular Bundle Volume (PBMV), and Macular Volume (MV). VEP measures included latency of the P100, and inter-ocular latency. Cognitive performance was evaluated across seven separate domains of performance, and for overall cognition, using the NeuroTrax computerized testing battery. RESULTS: Both OCT and VEP measures were significantly correlated with cognitive performance across several domains. Linear regression models that controlled for the influence of visual acuity revealed (1) that reduced MV was significantly predictive of poorer visual-spatial functioning, and (2) that delayed VEP latency was significantly predictive of performance in global cognitive functioning and visual-spatial functioning, after controlling for multiple comparisons. Among PwMS with normal visual acuity, PwMS with a combination of both relatively low MV and delayed VEP latency tended to have poorer performance in the domains of global, executive, and visual-spatial functioning compared to PwMS with both high MV and normal VEP latency. CONCLUSION: Approaches that combine the use of OCT and VEP measures can enhance insight into underlying factors that contribute to variance in cognitive functioning in PwMS.

De-escalation of Disease-Modifying Therapy for People with Multiple Sclerosis Due to Safety Considerations: Characterizing 1-Year Outcomes in 25 People Who Switched from Ocrelizumab to Diroximel Fumarate.

INTRODUCTION: Switching disease-modifying therapy (DMT) may be considered for relapsing-remitting multiple sclerosis (RRMS) if a patient's current therapy is no longer optimal. This was particularly important during the recent COVID-19 pandemic because of considerations around immune deficiency and impaired vaccine response associated with B cell-depleting DMTs. This real-world, single-center study aimed to evaluate change or decline in functional ability and overall disease stability in people with RRMS who were switched from B cell-depleting ocrelizumab (OCRE) to diroximel fumarate (DRF) because of safety concern related to the COVID-19 pandemic. METHODS: Adults with RRMS were included if they had been clinically stable for ≥ 1 year on OCRE. Data collected at baseline and 1 year post switch included relapse rate, magnetic resonance imaging (MRI), blood work for assessment of peripheral immune parameters, the Cognitive Assessment Battery (CAB), optical coherence tomography (OCT), and patient-reported outcomes (PROs). RESULTS: Participants (N = 25) had a mean (SD) age of 52 (9) years, and a mean (SD) duration of 26 (8) months' treatment with OCRE before the switch to DRF. Median washout duration since the last OCRE infusion was 7 months (range 4-18 months). No participants relapsed on DRF during follow-up, and all remained persistent on DRF after 1 year. There were no significant changes in peripheral immune parameters, other than an increase in the percentage of CD19+ cells 1 year after switching (p < 0.05). Similarly, there were no significant changes in CAB, OCT, and PROs. CONCLUSION: These preliminary findings suggest that transition to DRF from OCRE may be an effective treatment option for people with RRMS who are clinically stable but may need to switch for reasons unrelated to effectiveness. Longer follow-up times on larger samples are needed to confirm these observations.

Exploring the relationship between manual dexterity and cognition in people with multiple sclerosis: 9-hole peg and multiple cognitive functions.

AIM AND RATIONALE: Problems with manual dexterity and cognition impact the everyday performance of people with multiple sclerosis (PwMS). Accumulated findings point to the relationship between deficits in manual dexterity and auditory domains of cognition with a lack of evidence on visuospatial and verbal aspects of cognitive functioning. Therefore, this study explores the relationship between manual dexterity and cognition in a cohort of PwMS. METHOD: This cross-sectional study collected data from 63 PwMS aged 22 to 55 through a convenient sampling method. Participants were diagnosed with relapsing-remitting multiple sclerosis (RRMS). Cognition was measured using a multi-domain computerized cognitive testing, NeuroTrax, and manual dexterity was measured using a 9-hole peg assessment. Spearman correlation was used to identify the correlation among cognition subtests as well as with manual dexterity. Linear regression analysis was also conducted to identify whether manual dexterity predicts cognitive functioning. RESULTS: A significant negative correlation was found between 9-hole peg scores and global cognitive scores (GCS), r = -0.34, p = 006. The manual dexterity scores were also shown to predict GCS, R2= 0.165, p = 0.001. CONCLUSION: Manual dexterity was found to not only predict cognitive dysfunction but was also associated with multiple cognitive domains. Understanding the relationship between manual dexterity and cognition and the inferred progression of deficits can assist clinicians to provide interventions at earlier stages of disease progression to potentially increase daily functioning and quality of life (QoL).