Columbia University
Neurology

Author Of 1 Presentation

Pathogenesis – Immunology Oral Presentation

YI01.01 - Single-cell RNAseq of multiple sclerosis cerebrospinal fluid identifies T cell and myeloid subsets that are over-represented at disease onset

Speakers
Presentation Number
YI01.01
Presentation Topic
Pathogenesis – Immunology
Lecture Time
11:00 - 11:12

Abstract

Background

Immune cells play an important role in the pathogenesis of MS. However, our knowledge of the diversity of immune cell types and states in health and disease has been limited by the restrictions of traditional oligo-marker immunological approaches. Single-cell RNA sequencing (scRNA-seq) provides new means for discovery and characterization of immune cells by measuring expression levels of thousands of genes simultaneously at the single cell level.

Objectives

Here, we investigated the immune cell composition of cerebrospinal fluid (CSF), as the most accessible immune compartment in contact with the central nervous system, using scRNA-seq in MS and non-MS neuroinflammatory conditions (ONID).

Methods

Fresh CSF samples were collected at the time of diagnostic lumbar puncture from 8 untreated RRMS and 7 ONID patients. In addition, to examine the context of the reconstituted CSF after ocrelizumab treatment, we sampled 6 progressive MS patients on ocrelizumab for >1 year, 5 months after their last dose. A replication set of 3 untreated RRMS and 3 ONID are also collected.

Results

After removing doublets, RBCs, and low-quality cells, 59,288 cells were remained for analysis. Data were integrated using canonical correlation analysis. Over-clustering using ‘Seurat’ and iterative merging of clusters with more similar gene expression using ‘SCCAF’ resulted in 13 major clusters: 1 αβ-T cell cluster (consisting of 24 subclusters), 4 other T (NK, NKT, γδ-T), 5 myeloid (microglia-like monocytic, myeloid DC, granulocytes), B cells, plasmablasts and plasmacytoid DC.

Consistent with earlier smaller studies, we observed subsets of myeloid cells with microglia-like features (3% frequency). Using our reference brain-derived microglia scRNA-seq dataset (221,126 cells), we have characterized the microglial subtypes to which the CSF cells most resemble. Interestingly, these are part of the 4 myeloid subtypes which percentage were reduced in newly diagnosed RRMS relative to ONID. In addition, 3 CD4+ and 1 CD8+ memory T cell subsets were increased in RRMS. If replicated, these intriguing differences could guide our understanding of earliest stages of MS vs. other elements of the differential.

B cell component was largely reconstituted in the ocrelizumab group, and the patients had a CD4+ and CD8+ T cell pattern largely similar to ONID (vs RRMS). However, myeloid cell percentages were increased even more in this group. Further studies are needed to resolve whether these changes are due to progression vs. age vs. ocrelizumab.

Conclusions

Our data offer a new level of resolution in cell population shifts and suggest that measuring certain combinations of subsets could be useful clinically. In addition to these results, we will present on gene-level expression differences and a first draft of a CSF molecular network map across the 3 conditions.

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Author Of 10 Presentations

COVID-19 Late Breaking Abstracts

LB1188 - Epidemiology of COVID-19 among persons with neuroimmunological disorders at the Columbia University MS Center in New York City (ID 1987)

Speakers
Presentation Number
LB1188
Presentation Topic
COVID-19

Abstract

Background

The 2019 coronavirus (COVID19) is a novel infectious entity that has incited a global pandemic. Most infected patients experience mild to moderate upper respiratory symptoms but up to 20% have severe pulmonary and multisystem organ involvement. Few studies have assessed the risk for severe COVID19 infection among persons with multiple sclerosis (MS) or other neuroimmunological disorders, many of whom are treated with disease-modifying therapy (DMT).

Objectives

To describe the baseline clinico-sociodemographic characteristics and recent COVID19 epidemiology of patients managed at our center.

Methods

The electronic medical record was queried for patients evaluated at our center with at least two clinical visits within the past 2 years from censure date 1 March 2020. Variables of interest were collected from 1 March to 31 July 2020, and descriptive statistics were obtained.

Results

717 patients were included in the study, comprising 90.7% MS, 5.6% neuromyelitis optica spectrum disorder (NMOSD), 2.0% autoimmune encephalitis (AE), and 1.7% other neuroinflammatory. Median age was 43 (range 14-80), and 69.5% were women. The most commonly reported race and ethnic identities were 14.8% Black, 50.9% Caucasian, and 16.2% Hispanic. The most frequent DMT regimens were anti-CD20 therapy (38.5% ocrelizumab [OCV], 19.8% rituximab [RTX]), dimethyl fumarate (9.8%), and no DMT (8.9%). We found a 9.9% (n=71) report rate of symptoms suspicious for COVID19 of whom 37% (n=26) had confirmatory viral PCR testing. Two subgroups were compared: COVID19 asymptomatic (n=79) and COVID19 symptomatic PCR confirmed. PCR confirmed cases had statistically significant higher rates of Black race (26.9%, p=0.000), Hispanic ethnicity (26.9%, p=0.042), and multiple medical co-morbidities (42%, p=0.002). Most COVID19 symptomatic patients were managed at home (86%). Serious COVID19 infection necessitating hospitalization occurred rarely in patients treated on glatiramer acetate (1), natalizumab (1), OCV (3), or RTX (5). Of those hospitalized (n=10), 4 were admitted to ICU and 5 died (3 MS, 1 NMOSD, 1 AE).

Conclusions

Among a diverse population of patients with neuroimmunological disorders on various DMT regimens residing in one of the epicenters of the COVID19 pandemic, our retrospective observational study found lower rates of hospitalization and mortality compared to the general population of New York City. Significantly higher rates of Black and Hispanic patients tested positive for COVID19 compared to a subgroup who denied symptoms.

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Clinical Trials Late Breaking Abstracts

LB1200 - The SUNLIGHT Study: A telehealth intervention to address mental health in persons with MS during COVID-19  (ID 2034)

Speakers
Presentation Number
LB1200
Presentation Topic
Clinical Trials

Abstract

Background

The arrival of the Covid-19 pandemic in the United States brought a heightened level of anxiety to the general population. Individuals with chronic diseases such as multiple sclerosis (MS) were expected to be particularly affected. To address mental health needs safely and immediately, we conducted a trial of a group-based telehealth treatment of professional online support groups to reduce anxiety in persons with MS, the SUNLIGHT study.

Objectives

To determine feasibility and initial efficacy of a pilot trial of online structured, moderated professional support groups to reduce anxiety in persons with MS during the US outbreak of Covid-19. Trial was registered at clinicaltrials.gov (NCT04379661).

Methods

All procedures were conducted remotely. Thirty-two patients with MS were recruited in March-April 2020 at an MS Center in New York City. Consent was obtained via eConsent. 21 received active treatment: 1 hour/week online structured group therapy; 11 served as an inactive control group (i.e., treatment as usual, TAU). Baseline measures were collected from all participants: anxiety (Stait-Trait Anxiety Inventory, primary efficacy outcome), stress (Perceived Stress Scale), distress (Impact of Event Scale), mood (Patient Health Questionnaire), loneliness (UCLA Loneliness Scale), self-efficacy (General Self-Efficacy Scale), quality of life (Functional Assessment of Multiple Sclerosis).

Results

Sample was diverse: 83% female; 23.3% Hispanic / Latino, 10% Black, 3.3% Asian; age range: 24-72 years; disease duration: .25 -38 years. 30% Major Depressive Disorder, 30% anxiety disorder. At baseline, 36.6% had an anxiety attack within past 4 weeks.

Feasibility: Completion and adherence for treatment group were high; 80.9% completed the intervention; average adherence was 75%.

Efficacy results: Anxiety decreased in the treatment group after 12-weeks (STAI mean change = -2.7 points; p=.09).

Qualitative results: 100% responded YES to 'did you find the SUNLIGHT study to be worth your time,' and 'would you recommend SUNLIGHT study to a friend with MS;' 95% responded YES to 'if it were possible to continue your participation in the SUNLIGHT study, would you choose to do so;' 53% responded YES to 'do you think participation in the SUNLIGHT study contributed to a decrease in any of your MS symptoms?'

Conclusions

Telehealth provides an acceptable, accessible, safe vehicle for delivering mental health treatment to chronic disease populations during Covid-19. High adherence and completion, and initial evidence showing reduced anxiety bolster professional support groups as a promising treatment option for individuals with MS. Low cost, high return solutions such as online support groups should be further explored in future large-scale trials. Rigorous clinical trail evidence is needed to elevate the priority given to telehealth behavioral treatments.

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COVID-19 Late Breaking Abstracts

LB1244 - Manifestations and Impact of the COVID-19 Pandemic in Neuroinflammatory Diseases (ID 2130)

Abstract

Background

We have limited understanding of the risks and impact of COVID-19 in neuroinflammatory diseases (NID) of the central nervous system, particularly among patients receiving disease modifying therapies (DMTs).

Objectives

To report initial results of a planned multi-center year-long prospective study examining the risk and impact of COVID-19 among persons with NID.

Methods

In April 2020, we deployed online questionnaires to individuals in their home environment to assess the prevalence and potential risk factors of COVID-19 symptoms in persons with and without NID.

Results

Our cohort included 1,115 participants (630 NID, 98% MS; 485 reference) as of April 30, 2020. 202 (18%) participants, residing in areas with high COVID-19 case prevalence, met the April 2020 CDC symptom criteria for suspected COVID-19, but only 4% of all participants received testing given testing shortages. Among all participants, those with suspected COVID-19 were younger, more racially diverse, and reported more depression and liver disease. Persons with NID had the same rate of suspected COVID-19 as the reference group. Early changes in disease management included telemedicine visits in 21% and treatment changes in 9% of persons with NID. After adjusting for potential confounders, increasing neurological disability was associated with a greater likelihood of suspected COVID-19 (ORadj=1.45, 1.17-1.84).

Conclusions

Our study of real-time, patient-reported experience during the COVID-19 pandemic complements physician-reported MS case registries that capture an excess of severe cases. Overall, persons with NID seem to have a risk of suspected COVID-19 similar to the reference population.

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Biomarkers and Bioinformatics Late Breaking Abstracts

LB1250 - Neuronal integrity is associated to peripheral leukocyte dysfunction in asymptomatic Multiple Sclerosis (MS) first-degree relatives (ID 2136)

Speakers
Presentation Number
LB1250
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Genetic studies suggest that peripheral immune dysfunctions occurs first in the causal chain of events leading to MS. However, these changes are typically not appreciated when patients present with their first symptom or with an asymptomatic inflammatory lesion; we have only sparsely characterized individuals before they develop disease. Thus, the earliest molecular events leading to damage of the CNS parenchyma remain unknown.

Objectives

To investigate the correlation between a marker of neuronal integrity (Neurofilament light chain, NfL) and the transcriptional profile of peripheral immune cells during the pre-symptomatic phase in a cohort of first-degree family members of MS patients.

Methods

Blood samples were collected from 124 asymptomatic first-degree relatives of MS patients part of the Genes & Environment in MS (GEMS) study, 7 MS patients, and 11 patients with other neuroimmune diseases (ONID), age (20-54). Serum samples were used to assess NfL levels using the SIMOA platform. Cryopreserved peripheral blood mononuclear cells (PBMC) were used to generate RNA-sequencing data. ‘CIBERSORT’ was used to estimate the proportions of major PBMC cell types (CD4 and CD8 T, monocyte, B, and NK) from the gene expression data. ‘WGCNA’ was used to to identify PBMC co-expressed gene modules. Available genotyping data were used to calculate a polygenic MS risk score for each individual.

Results

Serum NfL levels from GEMS individuals increased with age (p=2E-14), and were significantly lower than MS and ONID patients, adjusting for the effects of age and sex. NfL was not elevated in high-risk (high polygenic score) vs. low-risk family member subgroups.

After batch variation and technical variable correction 114 GEMS subjects qualified for PBMC bulk RNA-sequencing analysis. ‘WGCNA’ identified 37 co-expressed gene modules, 4 of which were associated with NfL levels (FDR-adjusted p<0.05), adjusting for effects of age, sex and estimated cell type proportions. One particular module is enriched in myeloid cells, and myeloid-mediated immunity and myeloid activation pathways; an association that persisted after accounting for the proportion of different cell types. The other 3 modules were all enriched for genes upregulated in chronic myelogenous leukemia and downregulated gene targets of KLF1 transcription factor.

Conclusions

The transcriptional programs of some peripheral immune cells strongly correlate with NfL levels; ongoing data replication. These results implicate a cross-talk between the peripheral immune system and the CNS that could provide additional insights into MS pathophysiology; the direction of the association is being explored.

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Clinical Outcome Measures Poster Presentation

P0165 - Social Matters: Social support is linked to mental health, quality of life, and motor function in multiple sclerosis (ID 1219)

Speakers
Presentation Number
P0165
Presentation Topic
Clinical Outcome Measures

Abstract

Background

We are social animals who naturally seek the companionship of others as an essential part of our physical and psychological well-being. Patients with multiple sclerosis (MS) who are dealing with a chronic and often debilitating disease are at higher risk for social isolation, which may be particularly detrimental to their health.

Objectives

We investigated associations of social support with mental health, cognition, and motor functioning in cross-sectional data from two independent cohorts of patients with MS. We further explored sex differences in these relationships, based on a bioevolutionary theoretical justification.

Methods

Social support was assessed in 185 recently diagnosed patients (RADIEMS cohort), and in an independent validation sample (MEM CONNECT cohort, n = 62). Patients also completed a comprehensive neurobehavioral evaluation including measures of mental health, fatigue, quality of life, cognition and motor function. Correlations tested links between social support and these variables, along with potential gender differences.

Results

In both samples, higher social support was associated with better mental health, quality of life, subjective cognitive function, and less fatigue. In the RADIEMS cohort, correlations showed positive associations between social support and motor functions. The most robust relationships were observed for gross motor functions (gait, grip strength), especially in women.

Conclusions

These findings highlight associations of social support to overall psychological health and motor functioning in persons with MS, underlining the potential opportunity of evaluating and promoting social engagement as a novel treatment strategy.

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Clinical Trials Poster Presentation

P0190 - ASPIRE Study: Protocol for a double-blind RCT of aspirin for overheating during exercise in MS (ID 666)

Speakers
Presentation Number
P0190
Presentation Topic
Clinical Trials

Abstract

Background

Background Exercise holds many benefits for persons with multiple sclerosis (MS), yet many MS patients are heat sensitive and therefore avoid exercise due to overheating and exhaustion that result. The exercise literature in MS to date is likely subject to bias by predominant representation of patients who are not heat sensitive and may not be a representative sample. Finding ways to facilitate comfortable engagement in exercise for persons with MS is a key priority. Our pilot trial of aspirin as a cooling pretreatment for exercise in MS showed favorable results: after aspirin, participants who experience overheating during exercise were able to exercise longer and the amount of body temperature increase they experienced was reduced by 56%.

Objectives

Objective Conduct a large-scale double-blind randomized controlled trial of aspirin (acetylsalicylic acid, ASA) pretreatment as a convenient and inexpensive method to prevent overheating and improve exercise performance in persons with MS, compared to placebo and acetaminophen.

Methods

Methods Participants are seen for three separate sessions (separated by at least one week) for a laboratory maximal exercise test. At each session, body temperature is measured tympanically before oral administration of a standard adult dose (650 mg) of aspirin, acetaminophen (APAP), or placebo. Participants then perform a maximal ramp test on a cycle ergometer. Primary outcomes are (a) time to exhaustion (TTE, i.e., time spent cycling to peak exertion) and (b) body temperature change. Secondary outcomes include patient reported outcomes including pain, fatigue, and mood. Cross-over analyses will include tests for effects of treatment, period, treatment–period interaction (carryover effect) and sequence.

Results

Results Enrollment in the ASPIRE trial was begun in February 2019. Adherence and acceptability of the treatment are high. To date, 35 participants have been enrolled; of these, 16 have completed all 3 study visits. There have been 6 drop-outs and 7 non-serious adverse events. Heterogeneity of sample is notable, with 26% men, 9% Black, 6% Hispanic/Latinx. Study data will not be unblinded until completion of all participants (target N=60).

Conclusions

Conclusions Exercise is highly beneficial for persons with MS, but only if they do it. Positive findings from this trial would yield an effective, inexpensive, readily available, unobtrusive treatment to allow many more persons with MS access to the benefits of exercise via a cooling mechanism. Thus far, enrollment and adherence in the ASPIRE trial, as well as diversity of our sample suggest good acceptibiliity of aspirin as a treatment, and favorable generalizability of trial results.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0374 - Progressive MS patients of older age on ocrelizumab: real-world experience at Columbia University Irving Medical Center (ID 1059)

Speakers
Presentation Number
P0374
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Seminal trials evaluating ocrelizumab in multiple sclerosis (MS) have primarily shown benefit in patients with younger age, lower baseline EDSS, shorter disease duration, and evidence of higher inflammatory disease activity. The risk/benefit profile in patients who do not fit this description, accounting for a significant proportion of patients with progressive MS on this therapy, is unknown.

Objectives

To describe our experience with older primary progressive MS (PPMS) and secondary progressive MS (SPMS) patients on ocrelizumab.

Methods

The Genentech My Patient Solutions® online database was queried for patients at our center at least 55 years old at the time of ocrelizumab enrollment. Patients with PPMS or SPMS were entered into a database for retrospective chart review. Descriptive statistics were performed.

Results

A total of 56 patients with progressive forms of MS (33% PPMS, 66% SPMS) ages 55 years and older (median 64, range 56-77) at the time of ocrelizumab initiation were identified. At baseline, 46% of patients had more than three documented comorbidities, median EDSS was 6.0 (range 2 - 7.5) and disease duration was 17.7 years. 87% of patients had exposure to at least one prior DMT (most commonly rituximab n=27; glatiramer acetate n=18; interferon beta-1a n=17). At two years, 44% of patients with a baseline EDSS < 5.5 had >1-point increase (n=4, delta-EDSS 1.5) and 39% with a baseline EDSS >5.5 had >0.5-point increase (n=11; delta-EDSS 0.5) confirmed on sequential visits >12 weeks apart. EDSS remained stable in 57% (n=21) and improved in 3.0% (n=1). T25FW increased by >20% in 21% of patients (n=8; delta-T25FW 33%); though data was limited by ambulatory status and variable testing. Subjectively, 46% of patients reported feeling worse, 17% stable, 13% equivocal, and 5% improved at two years. Infections were reported in 27% (n=15) of patients, 2 of which were severe. No neoplasms were diagnosed during treatment. 13 patients discontinued therapy due to progression of disease (n=4), infection (n=4), clinical trial enrollment (n=2), hypogammaglobulinemia (n=1), infusion-related reaction (n=1), and poor venous access (n=1).

Conclusions

In this small, retrospective study of older progressive patients on ocrelizumab, 40% (n=15) had clinically meaningful disability progression at two years. This is a higher rate than reported in younger, less disabled patients with PPMS in clinical trials. More research is still needed to clarify the risk/benefit profile in this understudied MS subpopulation with a high rate of comorbidities and unique disease trajectory contributing to functional decline.

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Comorbidities Poster Presentation

P0442 - Cerebrovascular disease and Alzheimer’s disease neuropathology in multiple sclerosis. (ID 422)

Speakers
Presentation Number
P0442
Presentation Topic
Comorbidities

Abstract

Background

Multiple sclerosis (MS) is associated with an increased risk of ischemic stroke and this association is not accounted for by traditional vascular risk factors. Few neuropathologic human studies have examined the relation of MS to cerebrovascular disease (CVD) and other common neuropathology of aging.

Objectives

To examine associations of MS with pathologically-proven CVD and Alzheimer’s disease (AD), among community-dwelling persons with and without MS who died and came to autopsy.

Methods

Participants were enrolled in one of two clinical-pathologic studies of aging, the Rush Memory and Aging Project and the Religious Orders Study. We matched (1:2) all autopsied MS subjects (n=14) with persons without MS (n =28), on gender, balancing by race, years of education, and age of death. MS was identified by the medical history or postmortem neuropathological examination. Pathological diagnosis of MS was made when one or more areas of primary demyelination were encountered in the periventricular white matter in the cerebrum or brainstem. Uniform neuropathologic examination documented brain infarcts, and separately gross and microscopic infarcts, and cerebral vessel pathologies including atherosclerosis. A global AD score was based on a modified Bielschowsky silver stain detecting plaques and neurofibrillary tangles, and immunohistochemistry documented amyloid load and tangle density. Analyses employed the generalized estimating equation for categorical variables and linear mixed model of a logarithmic scale for continuous variables.

Results

In the total group (n=42), participants were 79% female, 93% white, with a mean age-at-death of 85.0 years (SD=8.2). Five patients had a clinical diagnosis of MS, seven a pathological diagnosis, and two both diagnoses. MS cases were more likely to have one or more brain infarcts (10/14 (71.4%) MS cases and 7/28 (25.0%) controls, OR=7.02, 95% CI[2.44, 20.17], p=0.0003), and more likely to have one or more gross infarcts (8/14 (57.1%) MS cases and 5/28 (17.9%) controls, OR=5.92, 95% CI [2.49, 14.10], p=<0.0001). There was no difference in number of microinfarcts (p=0.07) or severity level of vessel pathologies including atherosclerosis (p=0.56), arteriolosclerosis (p=0.99), or cerebral amyloid angiopathy (p=0.09). Cases had higher levels of global AD pathology than controls (Coefficient (SE)=1.10(0.49), p=0.03). There were no significant differences in amyloid load (p=0.13) or tangles density (p=0.50).

Conclusions

In keeping with clinical studies showing that MS is associated with stroke, we found that persons with MS were more likely to have neuropathologically-confirmed brain infarcts, and gross infarcts in particular. There was no difference in cerebral vessel pathology. MS was also associated with AD pathology. This study was limited by a small sample size. Further studies will elucidate pathways linking MS to neuropathology of aging, stroke, and cognitive impairment.

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Pediatric MS Poster Presentation

P1081 - Social networks in pediatric multiple sclerosis are associated with academic performance (ID 1056)

Speakers
Presentation Number
P1081
Presentation Topic
Pediatric MS

Abstract

Background

Social connectivity is known to impact health and cognition. In adults with multiple sclerosis (MS), close-knit social networks have been associated with worsened physical function (Levin et al, ECTRIMS 2019). To date, no studies have explored social networks in pediatric MS, a disease that occurs during a period of formative learning, social exploration, and personal identity.

Objectives

To analyze social networks in a small cohort of adolescents with MS and examine how these networks relate to academic performance.

Methods

We deployed a structured social network questionnaire to 14 adolescents with MS. We assessed academic performance using either the Woodcock Johnson Test of Academic Achievement (WJ) or performance on a statewide standardized achievement test. We defined academic impairment as a z score ≤1.5 standard deviations on the WJ or a score <65 on any statewide exam. Using graph theoretical statistics, we calculated three structural metrics for each individual’s social network: size, constraint, and effective size. Size is the number of network members, excluding the patient. Constraint is the extent to which network members have connections to each other. Effective size, conceptually the inverse of constraint, is the number of members who occupy structurally unique positions. We explored the association between network size, constraint, and effective size and academic impairment using a student t test.

Results

13 out of 14 subjects (93%) were female with a mean age of 16.4 (±3.25) years. Median EDSS was 1 (range 0-3). Median grade level was 12 (range 7-14). 8 of 14 (57%) subjects were academically impaired. Subjects who were academically impaired had a lower mean network size than those without academic impairment (9.75 vs 17.2, p = 0.028). The group with academic impairment had a trend towards higher network constraint (mean 54.9 vs. 30.4, p = 0.0507). Academic impairment was associated with lower average network effective size (3.94 vs 7.16, p = 0.004).

Conclusions

In this small cohort of adolescents with MS, we found that academic performance was inversely related to social network size and effective size. Taken together, these findings suggest that small, closely-knit social networks are associated with lower scholastic performance. These social network trends in children with MS are in line with physical disability data in adults with MS. Future plans include analyzing a dataset of 60 pediatric MS subjects and comparing to healthy controls. Larger, longitudinal studies are needed to determine the full impact of social networks on academic achievement in youth with MS.

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Invited Presentations Invited Abstracts

TC20.01 - Presentation 01 (ID 647)

Speakers
Authors
Presentation Number
TC20.01
Presentation Topic
Invited Presentations

Abstract

Abstract

Over the last twenty years, there has been a rapid expansion of high-throughput molecular profiling techniques for human samples as well as of their deployment at proper scale to generate highly significant, reproducible results. This experience and the resulting insights have laid a strong foundation that now informs the design of a new generation of studies. Specifically, no single dimension of information is sufficient to capture the onset or course of MS: an integrated multi-modal approach is necessary. In this section of the course, we will briefly review human genetic studies that have largely led the conceptual framework of high-dimensional analyses, especially the concept of data reduction and rigorous statistical methodologies that are essential for these studies. We will then move on to discuss their integration with the epigenome in an effort to systematically map the functional consequences of genetic variants. We will also touch on transcriptomic data, and their systematic analyses Then, using cerebrospinal fluid data, we will introduce new concepts of population structure and communication among cell subtype that are central to single cell analyses. However, all of these approaches are dependent on robust outcome measures that are often the limiting factor in MS studies. Thus, with a rapid tour of different modalities, we will review key concepts and study designs that can guide the development of new experiments to generate high-dimensional data that will enhance our understanding of MS.

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Presenter Of 1 Presentation

Invited Presentations Invited Abstracts

TC20.01 - Presentation 01 (ID 647)

Speakers
Authors
Presentation Number
TC20.01
Presentation Topic
Invited Presentations

Abstract

Abstract

Over the last twenty years, there has been a rapid expansion of high-throughput molecular profiling techniques for human samples as well as of their deployment at proper scale to generate highly significant, reproducible results. This experience and the resulting insights have laid a strong foundation that now informs the design of a new generation of studies. Specifically, no single dimension of information is sufficient to capture the onset or course of MS: an integrated multi-modal approach is necessary. In this section of the course, we will briefly review human genetic studies that have largely led the conceptual framework of high-dimensional analyses, especially the concept of data reduction and rigorous statistical methodologies that are essential for these studies. We will then move on to discuss their integration with the epigenome in an effort to systematically map the functional consequences of genetic variants. We will also touch on transcriptomic data, and their systematic analyses Then, using cerebrospinal fluid data, we will introduce new concepts of population structure and communication among cell subtype that are central to single cell analyses. However, all of these approaches are dependent on robust outcome measures that are often the limiting factor in MS studies. Thus, with a rapid tour of different modalities, we will review key concepts and study designs that can guide the development of new experiments to generate high-dimensional data that will enhance our understanding of MS.

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Moderator Of 1 Session

Teaching Course Fri, Sep 11, 2020

Invited Speaker Of 1 Presentation

Invited Presentations Invited Abstracts

TC20.01 - Presentation 01 (ID 647)

Speakers
Authors
Presentation Number
TC20.01
Presentation Topic
Invited Presentations

Abstract

Abstract

Over the last twenty years, there has been a rapid expansion of high-throughput molecular profiling techniques for human samples as well as of their deployment at proper scale to generate highly significant, reproducible results. This experience and the resulting insights have laid a strong foundation that now informs the design of a new generation of studies. Specifically, no single dimension of information is sufficient to capture the onset or course of MS: an integrated multi-modal approach is necessary. In this section of the course, we will briefly review human genetic studies that have largely led the conceptual framework of high-dimensional analyses, especially the concept of data reduction and rigorous statistical methodologies that are essential for these studies. We will then move on to discuss their integration with the epigenome in an effort to systematically map the functional consequences of genetic variants. We will also touch on transcriptomic data, and their systematic analyses Then, using cerebrospinal fluid data, we will introduce new concepts of population structure and communication among cell subtype that are central to single cell analyses. However, all of these approaches are dependent on robust outcome measures that are often the limiting factor in MS studies. Thus, with a rapid tour of different modalities, we will review key concepts and study designs that can guide the development of new experiments to generate high-dimensional data that will enhance our understanding of MS.

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