Faculty Bibliography

BackgroundMisalignment between actual and perceived balance ability provides relevant information to understand functional deficits and fall risk. However, few studies have provided a continuous quantification of misalignment in neurological populations such as people with Parkinson's disease (PD).ObjectiveDetermine whether a continuous quantification of misalignment between actual and perceived balance ability, discordance, relates to functional outcomes such as quality of life and cognition.MethodsActual (gait velocity), and perceived (Activities of Balance Confidence) balance, cognition (measured via a computer-based cognitive assessment), and mobility-related quality of life were captured in a clinical sample of 95 people with PD. Primary outcomes were quality of life and cognitive domains frequently altered in people with PD (global cognition & executive function). Secondary cognitive domains assessed were attention, memory, visuo-spatial, verbal function, and information processing. Linear and non-linear models assessed the relationship between discordance, quality of life, and cognition.ResultsDiscordance related to mobility-related quality of life, such that under-confidence was related to poorer quality of life. Non-linear (quadratic) models were shown to fit the discordance-Global cognition (p = 0.02) data better than linear models such that over- and under-confidence related to poorer cognition. Secondary cognitive domains were not robustly related to discordance.ConclusionsIn a clinical sample of people with PD, discordance was related to mobility-related quality of life and global cognition. Global cognition further exhibited a possible non-linear relationship to discordance indicating that over- or under-confidence may relate to poorer cognition. This work underscores the functional relevance of misalignment of actual and balance abilities.

BACKGROUND:Cognitive impairment (CI) is prevalent in people with multiple sclerosis (PwMS) and influences employment outcomes independent of physical disability. Although associations between multi-domain CI and employment have been established, less is known about the relative clinical utility of brief cognitive screening tools versus time-efficient multi-domain computerized assessments that can be implemented in routine care. OBJECTIVES/OBJECTIVE:To compare the Symbol Digit Modality Test (SDMT) and NeuroTrax computerized cognitive battery (NT) as predictors of self-reported employment status in PwMS. METHOD/METHODS:109 PwMS (Mean age = 48 years, SD = 10.4; 74 % female) completed the oral SDMT and NT as part of routine clinical care. Employment status was self-reported as "employed" or "unemployed" (including early retirement if <55 years). RESULTS:(3) = 17.862, p < .001), with executive function and attention most frequently impaired. CONCLUSION/CONCLUSIONS:While the SDMT remains a useful screening tool, the NT appears clinically feasible for use in routine care and provides incremental and domain-specific information beyond processing speed alone. Extending assessment in routine care beyond a single screening measure may better characterize cognitive profiles associated with unemployment and inform individualized vocational interventions in PwMS.

BACKGROUND:Cognitive impairment is linked with increased risk of falls in people with multiple sclerosis (pwMS), but it is not clear whether cognitive performance may help to account for the discordance between fall-risk due to actual physiological functioning and the individual's perception of their fall-risk. This study examined the relationship between cognitive performance and the concordance/discordance of physiological and perceived fall-risk in pwMS. METHODS:) fall-risk. Cognitive performance was evaluated using the NeuroTrax computerized cognitive battery, which generates a global cognitive score (GCS) as well as scores for individual cognitive domains. RESULTS:group. CONCLUSION/CONCLUSIONS:In this study, one in 4 pwMS had a discordance between their physiological and perceived fall-risk. This discordance was not explained by cognitive performance.

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.

OBJECTIVE:Evaluate the real-world effect of dimethyl fumarate (DMF) on subclinical biomarkers in patients with relapsing-remitting multiple sclerosis (RRMS) and compare with results from clinical trials. METHODS:Magnetic resonance imaging (MRI) data from 102 RRMS patients were retrospectively collected and processed using icobrain to assess brain atrophy and to assist semi-manual lesion count. RESULTS:Mean (±SD) annualized percent brain volume change in the first 3 years after DMF-initiation were: -0.33 ± 0.68, -0.10 ± 0.60, and - 0.35 ± 0.71%/year, respectively. No new FLAIR lesions were detected in 73.7%, 77.3%, and 73.3% of the patients during years 1, 2, and 3. CONCLUSIONS:Results of this real-world study were consistent with previous DMF phase III clinical trials, supporting the generalizability of the effects observed in clinical trials to the real-world clinical setting.

INTRODUCTION/BACKGROUND: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:cells 1 year after switching (p < 0.05). Similarly, there were no significant changes in CAB, OCT, and PROs. CONCLUSION/CONCLUSIONS: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.

AIM AND RATIONALE/UNASSIGNED: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/METHODS: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:= 0.165, p = 0.001. CONCLUSION/CONCLUSIONS: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).

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/CONCLUSIONS: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.

BACKGROUND:Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient. OBJECTIVE:To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting. METHODS:This was an international, multi-center (11 centers), longitudinal, retrospective, real-word study of people with relapsing-remitting MS (pwRRMS). Brain MRI exams acquired at baseline and follow-up were collected. Cognitive status was evaluated using the Symbol Digit Modalities Test (SDMT). Thalamic volume (TV) measurement was performed on T2-FLAIR, as well as on T1-WI, when available. Thalamic dysconnectivity, T2-lesion volume (T2-LV), and volumes of gray matter (GM), whole brain (WB) and lateral ventricles (LVV) were also assessed. RESULTS:332 pwMS were followed for an average of 2.8 years. At baseline, T2-LV, LVV, TV and thalamic dysconnectivity on T2-FLAIR (p < 0.016), and WB, GM and TV volumes on T1-WI (p < 0.039) were significantly worse in 90 (27.1 %) CI vs. 242 (62.9 %) non-CI pwRRMS. Greater SDMT decline over the follow-up was associated with lower baseline TV on T2-FLAIR (standardized β = 0.203, p = 0.002) and greater thalamic dysconnectivity (standardized β = -0.14, p = 0.028) in a linear regression model. CONCLUSIONS:PwRRMS with thalamic atrophy and worse thalamic dysconnectivity present more frequently with CI and experience greater CW over mid-term follow-up in a real-world setting.

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:) 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.