Author Of 3 Presentations
P0167 - Ten-Foot Tandem Walk: Detection of subtle gait changes and future fall risk in MS (ID 1534)
Abstract
Background
Gait disturbance is common and often begins early in multiple sclerosis (MS). We have previously identified higher-challenge balance tasks as more sensitive than gait speed tasks (Timed 25 Foot Walk [T25FW], Two-Minute-Walk-Test [2MWT]) to patient-reported gait change and fall risk in a cohort of persons with early relapsing MS (<5 years diagnosed).
Objectives
To assess whether a clinically-feasible, quantifiable higher-challenge dynamic balance task is sensitive to subtle patient-reported gait changes and falls in persons with relapsing MS of varied disease duration and with normal gait speed as measured by the T25FW.
Methods
Persons with relapsing MS or clinically isolated syndrome (n=218, aged 18-65 years) with normal gait speed (T25FW <5.0s) reported gait disturbance (MS Walking Scale-12 [MSWS-12]) and recent falls/near-falls (within the past month); healthy controls (n=200) also reported recent falls/near-falls. Dynamic balance was assessed with the novel 10-Foot Tandem Walk (10FTW) task requiring patients to tandem walk on a 10-foot straight line with arms across their chest; number of quarters successfully completed across three trials was recorded (0-12). For comparison, patients also performed the 2MWT as a high-challenge gait speed task.
Results
Nearly half of patients (48.2%) reported at least mild walking difficulty despite normal T25FW, and MS patients reported twice as many falls as controls (11.5% vs. 5.5%). Among MS patients, logistic regression revealed that worse 10FTW (p=.006), but not 2MWT (p=.121), independently predicted falls. Percent of MS patients reporting falls across 10FTW quartiles was 22.4%, 11.7%, 9.5%, 2.5%. Supplemental analyses replicated findings when considering near-falls and when controlling for mood.
Conclusions
Many MS patients report gait disturbance despite normal walking speed (T25FW). Dynamic balance assessed with the clinically-feasible and quantifiable 10FTW was sensitive to subtle walking difficulties and fall risk in these patients. These findings replicate our previous work identifying balance tasks as more sensitive to gait disturbance and fall risk than speeded walking tasks. The 10FTW may hold promise as an clinical trial outcome measure, especially among patients with more mild disability.
P0340 - High-dimensional immune profiling of dimethyl fumarate and ocrelizumab in multiple sclerosis (ID 1007)
Abstract
Background
Dimethyl fumarate (DMF) and ocrelizumab are two effective immunomodulators for multiple sclerosis (MS). Identifying overlapping mechanisms of action between the drugs may elucidate common pathways in preventing disease activity.
Objectives
In this study we analyzed cytokine and immune-profiling data to evaluate the similarities and differences between these two disease-modifying therapies in MS.
Methods
Plasma and PBMCs from MS patients were collected at baseline, 3 months and 6 months after treatment with DMF (n=16) and ocrelizumab (n=13). Immunophenotyping was performed with mass cytometry (CyTOF) and analyzed with gating based on cell surface markers. Cytokine analysis from plasma was performed with Olink assays and analyzed with linear mixed effects models.
Results
DMF reduced both effector T and memory B cell populations while increasing CD56bright natural killer (NK) cells. Ocrelizumab exerted its main immunomodulatory effect by reducing the frequency of all B cells and increasing frequency of NK cells. At 6 months, naïve B-cells began to reconstitute; however, memory B cells remain depleted. DMF treatment was associated with a significant reduction of plasma cytokines involved in inflammatory pathways, such as IL-6 and IL-12 signaling in MS and Dectin-1 signaling. In addition, DMF lowered plasma cytokines that are dysregulated in psoriasis and involved in allograft rejection pathways. Ocrelizumab treatment led to the upregulation of neurotropic proteins in the plasma of MS patients, including proteins involved in NAD biosynthesis and tryptophan metabolism.
Conclusions
Our high-dimensional immunophenotyping results suggest that DMF and ocrelizumab both increase NK cells in addition to affecting different immune cell populations and cytokine pathways to exert their effects in MS patients. Detecting similarities between the mechanisms of the two drugs may contribute to identifying more specific therapeutic targets.
P0827 - Speed of Lexical Access Contributes to Verbal Memory Retrieval in MS. (ID 1060)
Abstract
Background
Verbal memory deficits are common in persons with multiple sclerosis (MS). Memory deficits associated with hippocampal pathology may contribute; however, the hippocampus encodes verbal memories by binding together semantic content present within the cortex. Recent evidence for early parietal cortical atrophy and subtle language-related deficits (i.e. speed of lexical access) in MS suggest that individual differences in language function may contribute to verbal memory.
Objectives
To investigate whether language ability independently contributes to verbal memory performance in persons with MS.
Methods
Analyses were performed on independent research and clinical samples of relapsing-remitting MS. In the research sample (n=185), word-list memory was assessed by the Selective Reminding Test (SRT), and in the clinical sample (n=227), word-list memory was assessed by the Hopkins Verbal Learning Test, Revised (HVLT-R). In both samples when controlling for age, sex, premorbid verbal IQ, and word-list Total Learning, stepwise regression (entry p<.05) predicted word-list delayed recall with Symbol Digit Modalities Test (SDMT), processing speed (Stroop, Pattern Comparison, Decision Speed in research sample; Wechsler Adult Intelligence Scale, Fourth Edition [WAIS-IV] Symbol Search subtest in clinical sample), nonverbal memory (CANTAB Paired Associate Learning [PAL]), and language tasks (rapid automatized naming [RAN], animal naming). The Brief Visuospatial Memory Test, Revised (BVMT-R) was also used in the research sample to assess nonverbal memory. Healthy controls (n=50) were assessed using the same battery as the research sample.
Results
In the research sample, SRT delayed recall was independently predicted by Total Learning (partial r (rp)=.658, p<.001), nonverbal memory (BVMT-R, rp=.204, p=.006), and language (RAN, rp=.204, p=.006). These findings were replicated in the clinical sample: HVLT-R delayed recall was independently predicted by Total Learning (rp=.659, p<.001), language (RAN, rp=.206, p=.002), and nonverbal memory (rp=.144, p=.032), but also SDMT (rp=.135, p=.044). Demonstrating specificity to MS, there was no relationship between word-list delayed recall and RAN among healthy controls (rp=.020, p=.894).
Conclusions
Results suggest that language ability (speed of lexical access assessed by RAN) contributes to delayed recall of word lists independent of initial total learning scores in both research and replication clinical samples. These findings highlight the need to consider language changes as a component of verbal memory in MS.
Presenter Of 1 Presentation
P0167 - Ten-Foot Tandem Walk: Detection of subtle gait changes and future fall risk in MS (ID 1534)
Abstract
Background
Gait disturbance is common and often begins early in multiple sclerosis (MS). We have previously identified higher-challenge balance tasks as more sensitive than gait speed tasks (Timed 25 Foot Walk [T25FW], Two-Minute-Walk-Test [2MWT]) to patient-reported gait change and fall risk in a cohort of persons with early relapsing MS (<5 years diagnosed).
Objectives
To assess whether a clinically-feasible, quantifiable higher-challenge dynamic balance task is sensitive to subtle patient-reported gait changes and falls in persons with relapsing MS of varied disease duration and with normal gait speed as measured by the T25FW.
Methods
Persons with relapsing MS or clinically isolated syndrome (n=218, aged 18-65 years) with normal gait speed (T25FW <5.0s) reported gait disturbance (MS Walking Scale-12 [MSWS-12]) and recent falls/near-falls (within the past month); healthy controls (n=200) also reported recent falls/near-falls. Dynamic balance was assessed with the novel 10-Foot Tandem Walk (10FTW) task requiring patients to tandem walk on a 10-foot straight line with arms across their chest; number of quarters successfully completed across three trials was recorded (0-12). For comparison, patients also performed the 2MWT as a high-challenge gait speed task.
Results
Nearly half of patients (48.2%) reported at least mild walking difficulty despite normal T25FW, and MS patients reported twice as many falls as controls (11.5% vs. 5.5%). Among MS patients, logistic regression revealed that worse 10FTW (p=.006), but not 2MWT (p=.121), independently predicted falls. Percent of MS patients reporting falls across 10FTW quartiles was 22.4%, 11.7%, 9.5%, 2.5%. Supplemental analyses replicated findings when considering near-falls and when controlling for mood.
Conclusions
Many MS patients report gait disturbance despite normal walking speed (T25FW). Dynamic balance assessed with the clinically-feasible and quantifiable 10FTW was sensitive to subtle walking difficulties and fall risk in these patients. These findings replicate our previous work identifying balance tasks as more sensitive to gait disturbance and fall risk than speeded walking tasks. The 10FTW may hold promise as an clinical trial outcome measure, especially among patients with more mild disability.