Faculty Bibliography
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630
Genetic predictors of relapse rate in pediatric MS
BACKGROUND: Genetic ancestry, sex, and individual alleles have been associated with multiple sclerosis (MS) susceptibility. OBJECTIVE: To determine whether established risk factors for disease onset are associated with relapse rate in pediatric MS. METHODS: Whole-genome genotyping was performed for 181 MS or high-risk clinically isolated syndrome patients from two pediatric MS centers. Relapses and disease-modifying therapies were recorded as part of continued follow-up. Participants were characterized for 25-hydroxyvitamin D serum status. Ancestral estimates (STRUCTURE v2.3.1), human leukocyte antigen (HLA)-DRB1*15 carrier status (direct sequencing), sex, and a genetic risk score (GRS) of 110 non-HLA susceptibility single-nucleotide polymorphisms (SNPs) were evaluated for association with relapse rate with Cox and negative binomial regression models. RESULTS: Over 622 patient-years, 408 relapses were captured. Girls had greater relapse rate than boys (incident rate ratio (IRR) = 1.40, 95% confidence interval (CI) = 1.04-1.87, p = 0.026). Participants were genetically diverse; ~40% (N = 75) had <50% European ancestry. HLA-DRB1*15 status modified the association of vitamin D status (pixn = 0.022) with relapse rate (per 10 ng/mL, in DRB1*15+ hazard ratio (HR) = 0.72, 95% CI = 0.58-0.88, p = 0.002; in DRB1*15- HR = 0.96, 95% CI = 0.83-1.12, p = 0.64). Neither European ancestry nor GRS was associated with relapse rate. CONCLUSION: We demonstrate that HLA-DRB1*15 modifies the association of vitamin D status with relapse rate. Our findings emphasize the need to pursue disease-modifying effects of MS genes in the context of environmental factors.
PMCID:4945462
PMID: 26769066
ISSN: 1477-0970
CID: 2043122
Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study
OBJECTIVE:To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study. METHODS:CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 patients with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 patients (MRI cohort). RESULTS:DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance. CONCLUSIONS:The robust effects on MRI active lesion counts and total lesion volume in patients with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS. CLASSIFICATION OF EVIDENCE/METHODS:This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment.
PMCID:4371413
PMID: 25681448
ISSN: 1526-632x
CID: 5348212
[S.l. : American Psychological Society, New York, 2015]
Cognitive impairment and real-world functioning in multiple sclerosis (MS) : test of everyday cognitive ability (TECA)
(Website)CID: 2238962
A case-control study of dietary salt intake and risk of pediatric multiple sclerosis (MS) [Meeting Abstract]
ORIGINAL:0011416
ISSN: 1526-632x
CID: 2236592
Gut microbiome in early pediatric MS : a case-control study [Meeting Abstract]
ORIGINAL:0011420
ISSN: 1526-632x
CID: 2236632
Higher weight in adolescence and young adulthood is associated with an earlier age at multiple sclerosis onset
BACKGROUND: Growing evidence suggests an association between adolescent obesity and increased risk of multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to investigate whether weight or body mass index (BMI) in adolescence and young adulthood was associated with age at MS symptom onset. METHODS: Our cohort is comprised of a sub-group of 184 women enrolled in the New York State MS Consortium registry. Individuals were asked to recall their weight at the time of first menstruation and at age 25. BMI was calculated accordingly for age 25. Regression analyses were carried out to investigate the association between weight or BMI and age at onset. RESULTS: Weight at menarche was significantly related to younger age at symptom onset (beta = -0.073, p = 0.001). These results were also found at age 25 for weight (beta = -0.080, p < 0.001) and BMI (beta = -0.448, p = 0.001). Significantly earlier disease onset (26.9 years +/-9.9) was observed in individuals who were overweight at 25 compared to those who were not overweight (32.1 years +/-9.2, p = 0.006). CONCLUSIONS: Women who reported higher weight in adolescence and BMI in early adulthood were younger at MS onset. Future research should investigate whether there is a causal link between body weight and MS, as prevention lifestyle and dietary interventions could be implemented.
PMID: 25392327
ISSN: 1477-0970
CID: 2237042
The Montreal Cognitive Assessment (MoCA) in Multiple Sclerosis: Relation to Clinical Features
ORIGINAL:0011415
ISSN: 2376-0389
CID: 2236582
Assessing cognition in MS clinical trials : the cognitive assessment interview (CAI) [Meeting Abstract]
ORIGINAL:0011418
ISSN: 1526-632x
CID: 2236612
Fat, fiber and pediatric MS [Meeting Abstract]
ORIGINAL:0011421
ISSN: 1526-632x
CID: 2236642
Cognition in MS across the lifespan [Meeting Abstract]
ORIGINAL:0011417
ISSN: 1526-632x
CID: 2236602
