Faculty Bibliography

BACKGROUND:Visual evoked potential (VEP) P100 latency is routinely used to assess optic nerve demyelination. However, there is no established methodology for disentangling whether shifts in VEP P100 latency may reflect upstream changes in the visual pathway, such as the level of the retina, or whether these delays could be reflective of downstream disturbances in broader brain structure and functioning. OBJECTIVE:To determine the relationship between VEP-based P100 and MRI-based outcomes in people with MS (PwMS) after accounting for structural retinal changes assessed by spectral domain optical coherence tomography (OCT). METHODS:64 study participants underwent OCT, VEP, and MRI. Standardized VEP assessment derived monocular P100 latency for both eyes. Similarly, OCT performed on Heidelberg Spectralis hardware provided peripapillary retinal nerve fiber layer (pRNFL) thickness. Mediation analyses were performed to assess the relationship between P100 and MRI-based outcomes, adjusting for mediating effects of pRNFL and age. RESULTS:VEP-based P100 was significantly associated with lower whole brain volume (WBV) (p=0.0037), with 87.8% of the total effect being both direct and independent from RNFL and the significant age-WBV covariate effect. Similarly, greater VEP-based P100 latency was directly and independently predictive of lower gray matter volume (GMV) (p=0.015) and greater T2-FLAIR LV (p=0.0036) after adjusting for RNFL and age mediating effects. CONCLUSION/CONCLUSIONS:VEP-based P100 latency shows both age- and RNFL-independent associations with MRI-based MS outcomes. In addition to their established diagnostic utility, VEP measures may provide a neurophysiological, objective metric to assess neurodegeneration.

BACKGROUND:People with multiple sclerosis (PwMS) frequently experience invisible symptoms, including cognitive impairment, fatigue, depression, anxiety, and psychosocial factors such as stigma, which can substantially affect social role participation (SRP). These factors are often under-recognized in clinical care despite their functional impact. OBJECTIVE:To examine the unique contributions of invisible MS-related symptoms to SRP after accounting for demographic characteristics and objective cognitive performance. METHODS:A cross-sectional sample of 434 PwMS was recruited from a large outpatient neurology clinic specializing in MS care. The sample was predominantly female (75%), largely white (85%), and middle-aged (M = 51.0, SD = 11.7), with mild-to-moderate disability. Participants completed a computerized cognitive battery and validated patient-reported outcome measures assessing disease impact, mood, fatigue, stigma, and SRP. Hierarchical regression models evaluated the variance explained by demographics, cognitive performance, and patient-reported symptoms. RESULTS:Demographic variables were not significant predictors of SRP. Cognitive performance accounted for 13.3% of the variance. Adding patient-reported outcomes increased explained variance to 70.6%. Depression, disease impact, fatigue, and executive functioning remained significant predictors, whereas stigma did not. CONCLUSIONS:Patient-reported symptom burden showed strong associations with SRP and explained more variance than demographic factors and most cognitive measures, while executive functioning also contributed independently.

INTRODUCTION/BACKGROUND:Although word-finding difficulties (WFD) are prevalent in multiple sclerosis (MS), they remain poorly understood. This cross-sectional study aimed to identify several important practical and theoretical challenges, including key knowledge gaps related to understanding and measuring aspects of language deficit in MS (i.e., WFD). Further investigations of possible correlates of deficits with other symptoms of MS (i.e., such as depression, fatigue and cognitive impairment) were also carried out as part of this study to find out if WFD is a standalone symptom or is a part of a broader and complex symptom of MS. METHODS:In this cohort study, all data from 586 consecutive Persons with MS (PwMS) (137 males and 449 females), with a mean age of 47.1 (SD±10.34) and a median EDSS score of 2.0, were included. A standardized naming task was used as part of a computerized cognitive assessment battery (CAB, NeuroTrax™) with computer-based administration and off-site scoring that has been validated for use in PwMS to determine the associations between cognitive impairment (CI), fatigue, and depression in WFD. RESULTS:A significant correlation (r = 0.327) was noted in this study between cognitive impairment and WFD (p < 0.001). PwMS with CI had a higher rate of WFD (i.e., 43.2%) as compared to individuals with WFD despite not having CI (i.e., 13.9%). Disability (EDSS), disease duration, depression and fatigue, were not correlated with WFD. CONCLUSION/CONCLUSIONS:WFD are most likely part of a larger underlying problem (i.e., CI), but there is a small group of persons with MS and WFD who have isolated WFD. Findings of this study have implications for activities of daily living (ADLs) and therapy for rehabilitation professionals working with PwMS.

OBJECTIVE:Fatigue and depression are common and disabling symptoms in people with Multiple Sclerosis (PwMS). This study aimed to examine the relationship between discordant fatigue measures and depression severity in PwMS. METHODS:A retrospective analysis was conducted on 712 PwMS evaluated over 14 years at a comprehensive MS center. All participants completed the Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), and Beck Depression Inventory (BDI) as part of routine clinical care. Fatigue score concordance was defined as both FSS and MFIS being above or below the threshold; discordance was defined as one above and one below. Statistical analyses compared demographic, clinical, and depression-related variables between groups. RESULTS:Of the 712 patients (75.3% female; mean EDSS 2.8), 78.9% demonstrated concordant fatigue scores, while 21.1% showed discordance-most commonly with elevated MFIS and low FSS. The discordant group had significantly higher mean BDI scores (23.0 vs. 9.8; P < 0.0001) and elevated suicidality scores, despite similar clinical characteristics. CONCLUSIONS:PwMS with discordant fatigue profiles, particularly those with higher MFIS than FSS scores, exhibit significantly greater depressive symptoms. Discordance between fatigue measures may serve as a clinical marker for underlying depression, supporting the need for comprehensive psychosocial evaluation in this subgroup.

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: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.

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.