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  • SAGE Publications  (13)
  • Weinstock-Guttman, Bianca  (13)
  • 1
    Online Resource
    Online Resource
    Dietary factors and pediatric multiple sclerosis: A case-control study
    SAGE Publications ; 2018
    In:  Multiple Sclerosis Journal Vol. 24, No. 8 ( 2018-07), p. 1067-1076
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 24, No. 8 ( 2018-07), p. 1067-1076
    Abstract: The role of diet in multiple sclerosis (MS) is largely uncharacterized, particularly as it pertains to pediatric-onset disease. Objective: To determine the association between dietary factors and MS in children. Methods: Pediatric MS patients and controls were recruited from 16 US centers (MS or clinically isolated syndrome onset before age 18, 〈 4 years from symptom onset and at least 2 silent lesions on magnetic resonance imaging). The validated Block Kids Food Screener questionnaire was administered 2011–2016. Chi-squared test compared categorical variables, Kruskal–Wallis test compared continuous variables, and multivariable logistic regression analysis was performed. Results: In total, 312 cases and 456 controls were included (mean ages 15.1 and 14.4 years). In unadjusted analyses, there was no difference in intake of fats, proteins, carbohydrates, sugars, fruits, or vegetables. Dietary iron was lower in cases ( p = 0.04), and cases were more likely to consume below recommended guidelines of iron (77.2% of cases vs 62.9% of controls, p  〈  0.001). In multivariable analysis, iron consumption below recommended guidelines was associated with MS (odds ratio = 1.80, p  〈  0.01). Conclusion: Pediatric MS cases may be less likely to consume sufficient iron compared to controls, and this warrants broader study to characterize a temporal relationship. No other significant difference in intake of most dietary factors was found.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458517713343
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
    detail.hit.zdb_id: 1290669-4
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  • 2
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    Vitamin D genes influence MS relapses in children
    SAGE Publications ; 2020
    In:  Multiple Sclerosis Journal Vol. 26, No. 8 ( 2020-07), p. 894-901
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 26, No. 8 ( 2020-07), p. 894-901
    Abstract: The aim of this study was to determine whether a vitamin D genetic risk score (vitDGRS) is associated with 25-hydroxyvitamin D (25(OH)D) level and multiple sclerosis (MS) relapses in children. Methods: DNA samples were typed for single nucleotide polymorphisms (SNPs) from four genes previously identified to be associated with 25(OH)D levels. SNPs with strong associations with 25(OH)D after multiple comparison correction were used to create a genetic risk score (vitDGRS). Cox regression models tested associations of vitDGRS with relapse hazard. Results: Two independent SNPs within or near GC and NADSYN1/DHCR7 genes were strongly associated with 25(OH)D levels in the discovery cohort ( n = 182) after Bonferroni correction. The vitDGRS of these SNPs explained 4.5% of the variance of 25(OH)D level after adjustment for genetic ancestry. Having the highest versus lowest vitDGRS was associated with 11 ng/mL lower 25(OH)D level (95% confidence interval (CI) = −17.5, −4.5, p = 0.001) in the discovery cohort. Adjusting for ancestry, sex, disease-modifying therapy (DMT), and HLA-DRB1*15 carrier status, the highest versus lowest vitDGRS was associated with 2.6-fold (95% CI = 1.37, 5.03, p = 0.004) and 2.0-fold (95% CI = 0.75, 5.20, p = 0.16) higher relapse hazard in the discovery and replication cohorts, respectively. Conclusion: The vitDGRS identifies children at greater risk of relapse. These findings support a causal role for vitamin D in MS course.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458519845842
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
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  • 3
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    A new look at cognitive functioning in pediatric MS
    SAGE Publications ; 2023
    In:  Multiple Sclerosis Journal Vol. 29, No. 1 ( 2023-01), p. 140-149
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 29, No. 1 ( 2023-01), p. 140-149
    Abstract: Cognitive involvement in pediatric multiple sclerosis (MS) relative to adult MS is less defined. This study advances our understanding by measuring cognitive performances in pediatric MS, adult MS, and pediatric healthy controls. Methods: Consecutive relapsing pediatric MS participants from the United States Network of Pediatric MS Centers were compared with pediatric healthy controls and adults with relapsing MS. Participants were compared on two screening batteries: the Brief International Cognitive Assessment for MS and the Cogstate Brief Battery. Results were transformed to age-normative z scores. Results: The pediatric groups (MS vs. Healthy Controls) did not differ on either battery’s composite mean score or individual test scores ( ps  〉  0.32), nor in the proportions impaired on either battery, Brief International Cognitive Assessment for MS (26% vs. 24%, p = 0.83); Cogstate Brief Battery (26% vs. 32%, p = 0.41). The pediatric versus adult MS group even after controlling for differences in disease duration performed better on the Brief International Cognition Assessment for MS composite ( p = 0.03), Symbol Digit Modalities Test ( p = 0.02), Rey Auditory Verbal Learning Test ( p = 0.01), and Cogstate choice reaction time ( p  〈  0.001). Conclusion: Pediatric MS patients do not differ from healthy pediatric controls on cognitive screens but perform better than adults with MS.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/13524585221123978
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
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  • 4
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    Long-term clinical outcomes in patients with multiple sclerosis who are initiating disease-modifying therapy with natalizumab compared with BRACETD first-line therapies
    SAGE Publications ; 2024
    In:  Therapeutic Advances in Neurological Disorders Vol. 17 ( 2024-01)
    Details
    In: Therapeutic Advances in Neurological Disorders, SAGE Publications, Vol. 17 ( 2024-01)
    Abstract: Aggressive disease control soon after multiple sclerosis (MS) diagnosis may prevent irreversible neurological damage, and therefore early initiation of a high-efficacy disease-modifying therapy (DMT) is of clinical relevance. Objectives: Evaluate long-term clinical outcomes in patients with MS who initiated treatment with either natalizumab or a BRACETD therapy (interferon beta, glatiramer acetate, teriflunomide, or dimethyl fumarate). Design: This retrospective analysis utilized data from MSBase to create a matched population allowing comparison of first-line natalizumab to first-line BRACETD. Methods: This study included patients who initiated treatment either with natalizumab or a BRACETD DMT within 1 year of MS diagnosis and continued treatment for ⩾6 months, after which patients could switch DMTs or discontinue treatment. Patients had a minimum follow-up time of ⩾60 months from initiation. A subgroup analysis compared the natalizumab group to patients in the BRACETD group who escalated therapy after 6 months. Outcomes included unadjusted annualized relapse rates (ARRs), time-to-first relapse, time-to-first confirmed disability improvement (CDI), and time-to-first confirmed disability worsening (CDW). Results: After 1:1 propensity score matching, 355 BRACETD patients were matched to 355 natalizumab patients. Patients initiating natalizumab were less likely to experience a relapse over the duration of follow-up, with ARRs [95% confidence interval (CI)] of 0.080 (0.070–0.092) for natalizumab patients and 0.191 (0.178–0.205) for BRACETD patients ( p  〈  0.0001). A Cox regression model of time-to-first relapse showed a reduced risk of relapse for natalizumab patients [hazard ratio (95% CI) of 0.52 (0.42–0.65); p  〈  0.001] and a more favorable time-to-first CDI. The risk of CDW was similar between groups. The subgroup analysis showed an increased relapse risk as well as a significantly higher risk of CDW for BRACETD patients. Conclusion: Early initiation of natalizumab produced long-term benefits in relapse outcomes in comparison with BRACETD, regardless of a subsequent escalation in therapy.
    Type of Medium: Online Resource
    ISSN: 1756-2864 , 1756-2864
    URL: Article
    DOI: 10.1177/17562864231221331
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2024
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  • 5
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    Effect of dimethyl fumarate on lymphocyte subsets in patients with relapsing multiple sclerosis
    SAGE Publications ; 2020
    In:  Multiple Sclerosis Journal - Experimental, Translational and Clinical Vol. 6, No. 2 ( 2020-04), p. 205521732091861-
    Details
    In: Multiple Sclerosis Journal - Experimental, Translational and Clinical, SAGE Publications, Vol. 6, No. 2 ( 2020-04), p. 205521732091861-
    Abstract: In patients treated with dimethyl fumarate, absolute lymphocyte count decline typically occurs during the first year and then plateaus; early drops have been associated with the development of severe prolonged lymphopenia. Objective We investigated the effect of dimethyl fumarate on absolute lymphocyte counts and CD4+/CD8+ T cells in patients with relapsing–remitting multiple sclerosis treated with dimethyl fumarate in routine practice. Methods Lymphocyte data were collected via medical chart abstraction. Primary endpoint: change from baseline in absolute lymphocyte count and CD4+/CD8+ counts at 6‐month intervals following dimethyl fumarate initiation. Results Charts of 483 patients were abstracted and 476 patients included in the analysis. Mean baseline absolute lymphocyte count (2.23 × 10 9 /l) decreased by ∼39% (95% confidence interval: –41.1 to –37.2) by month 6 and 44% (95% confidence interval: –46.6 to –42.1) by month 12. CD4+ and CD8+ T-cell subsets strongly correlated with absolute lymphocyte count, with greater decreases from baseline to 6 months vs 6–12 months, and in CD8+ vs CD4+ T cells. Prior natalizumab was not a risk factor for lymphopenia. Conclusion Dimethyl fumarate-associated decline in absolute lymphocyte count in the first 12 months correlated with decline in CD4+ and CD8+ T cells and was independent of prior natalizumab. Absolute lymphocyte count monitoring continues to be an effective strategy to identify patients at risk of prolonged lymphopenia.
    Type of Medium: Online Resource
    ISSN: 2055-2173 , 2055-2173
    URL: Article
    DOI: 10.1177/2055217320918619
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
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  • 6
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    Ocrelizumab treatment for relapsing-remitting multiple sclerosis after a suboptimal response to previous disease-modifying therapy: A nonrandomized controlled trial
    SAGE Publications ; 2022
    In:  Multiple Sclerosis Journal Vol. 28, No. 5 ( 2022-04), p. 790-800
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 28, No. 5 ( 2022-04), p. 790-800
    Abstract: Many patients with multiple sclerosis (MS) experience suboptimal disease control despite the use of disease-modifying therapy (DMT). Objective: To assess the efficacy and safety of ocrelizumab (OCR) in patients with relapsing-remitting MS (RRMS) and suboptimal response to prior DMTs. Methods: Patients with RRMS and suboptimal responses (one clinically reported relapse and/or lesion activity) after ⩾ 6 months on another DMT were enrolled. OCR 600 mg was given intravenously every 24 weeks. The primary outcome was no evidence of disease activity (NEDA), defined as the absence of protocol-defined relapse, confirmed disability progression (CDP), T1 Gd-enhancing lesions, and new/enlarging T2 lesions. Results: The intention-to-treat (ITT) population included 608 patients; NEDA was analyzed in a modified ITT (mITT) population ( n = 576 (94.7%)). Over 96 weeks, 48.1% of mITT patients achieved NEDA, and most were free from protocol-defined relapse (89.6%), CDP (89.6%), and T1 Gd-enhancing lesions (95.5%); 59.5% had no new/enlarging T2 lesions. Safety observations were consistent with findings in the pivotal trials. Conclusion: Consistent efficacy of OCR on clinical and magnetic resonance imaging (MRI) disease activity measures and progression was shown in patients with RRMS and a suboptimal response to prior DMTs; no new safety signals were observed.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/13524585211035740
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
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  • 7
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    Gene–environment interactions increase the risk of pediatric-onset multiple sclerosis associated with ozone pollution
    SAGE Publications ; 2022
    In:  Multiple Sclerosis Journal Vol. 28, No. 9 ( 2022-08), p. 1330-1339
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 28, No. 9 ( 2022-08), p. 1330-1339
    Abstract: We previously reported a relationship between air pollutants and increased risk of pediatric-onset multiple sclerosis (POMS). Ozone is an air pollutant that may play a role in multiple sclerosis (MS) pathoetiology. CD86 is the only non-HLA gene associated with POMS for which expression on antigen-presenting cells (APCs) is changed in response to ozone exposure. Objectives: To examine the association between county-level ozone and POMS, and the interactions between ozone pollution, CD86, and HLA- DRB1*15, the strongest genetic variant associated with POMS. Methods: Cases and controls were enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers. County-level-modeled ozone data were acquired from the CDC’s Environmental Tracking Network. Participants were assigned ozone values based on county of residence. Values were categorized into tertiles based on healthy controls. The association between ozone tertiles and having MS was assessed by logistic regression. Interactions between tertiles of ozone level and the GG genotype of the rs928264 (G/A) single nucleotide polymorphism (SNP) within CD86, and the presence of DRB1*15:01 ( DRB1*15) on odds of POMS were evaluated. Models were adjusted for age, sex, genetic ancestry, and mother’s education. Additive interaction was estimated using relative excess risk due to interaction (RERI) and attributable proportions (APs) of disease were calculated. Results: A total of 334 POMS cases and 565 controls contributed to the analyses. County-level ozone was associated with increased odds of POMS (odds ratio 2.47, 95% confidence interval (CI): 1.69–3.59 and 1.95, 95% CI: 1.32–2.88 for the upper two tertiles, respectively, compared with the lowest tertile). There was a significant additive interaction between high ozone tertiles and presence of DRB1*15, with a RERI of 2.21 (95% CI: 0.83–3.59) and an AP of 0.56 (95% CI: 0.33–0.79). Additive interaction between high ozone tertiles and the CD86 GG genotype was present, with a RERI of 1.60 (95% CI: 0.14–3.06) and an AP of 0.37 (95% CI: 0.001–0.75) compared to the lowest ozone tertile. AP results indicated that approximately half of the POMS risk in subjects can be attributed to the possible interaction between higher county-level ozone carrying either DRB1*15 or the CD86 GG genotype. Conclusions: In addition to the association between high county-level ozone and POMS, we report evidence for additive interactions between higher county-level ozone and DRB1*15 and the CD86 GG genotype. Identifying gene–environment interactions may provide mechanistic insight of biological processes at play in MS susceptibility. Our work suggests a possible role of APCs for county-level ozone-induced POMS risk.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/13524585211069926
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
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  • 8
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    Gene–environment interactions: Epstein–Barr virus infection and risk of pediatric-onset multiple sclerosis
    SAGE Publications ; 2024
    In:  Multiple Sclerosis Journal Vol. 30, No. 3 ( 2024-03), p. 308-315
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 30, No. 3 ( 2024-03), p. 308-315
    Abstract: Prior Epstein–Barr virus (EBV) infection is associated with an increased risk of pediatric-onset multiple sclerosis (POMS) and adult-onset multiple sclerosis (MS). It has been challenging to elucidate the biological mechanisms underlying this association. We examined the interactions between candidate human leukocyte antigen (HLA) and non-HLA variants and childhood EBV infection as it may provide mechanistic insights into EBV-associated MS. Methods: Cases and controls were enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers. Participants were categorized as seropositive and seronegative for EBV-viral capsid antigen (VCA). The association between prior EBV infection and having POMS was estimated with logistic regression. Interactions between EBV serostatus, major HLA MS risk factors, and non-HLA POMS risk variants associated with response to EBV infection were also evaluated with logistic regression. Models were adjusted for sex, age, genetic ancestry, and the mother’s education. Additive interactions were calculated using relative risk due to interaction (RERI) and attributable proportions (APs). Results: A total of 473 POMS cases and 702 controls contributed to the analyses. Anti-VCA seropositivity was significantly higher in POMS cases compared to controls (94.6% vs 60.7%, p  〈  0.001). There was evidence for additive interaction between childhood EBV infection and the presence of the HLA-DRB1*15 allele (RERI = 10.25, 95% confidence interval (CI) = 3.78 to 16.72; AP = 0.61, 95% CI = 0.47 to 0.75). There was evidence for multiplicative interaction ( p  〈  0.05) between childhood EBV infection and the presence of DRB1*15 alleles (odds ratio (OR) = 3.43, 95% CI = 1.06 to 11.07). Among the pediatric MS variants also associated with EBV infection, we detected evidence for additive interaction ( p = 0.02) between prior EBV infection and the presence of the GG genotype in risk variant (rs2255214) within CD86 (AP = 0.30, 95% CI = 0.03 to 0.58). Conclusion: We report evidence for interactions between childhood EBV infection and DRB1*15 and the GG genotype of CD86 POMS risk variant. Our results suggest an important role of antigen-presenting cells (APCs) in EBV-associated POMS risk.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/13524585231224685
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2024
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  • 9
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    Cognitive processing speed in pediatric-onset multiple sclerosis: Baseline characteristics of impairment and prediction of decline
    SAGE Publications ; 2020
    In:  Multiple Sclerosis Journal Vol. 26, No. 14 ( 2020-12), p. 1938-1947
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 26, No. 14 ( 2020-12), p. 1938-1947
    Abstract: Cognitive impairment occurs in approximately one-third of pediatric-onset multiple sclerosis (POMS) patients. The Symbol Digit Modalities Test (SDMT), a widely used cognitive screen in adults, has yet to be incorporated early into the standard care of POMS. Objective: To screen for cognitive impairment early in the course of POMS and analyze predictive factors. Methods: Of the 955 POMS or clinically isolated syndrome (CIS) patients prospectively assessed from March 2014 to July 2018, 500 POMS and 116 CIS patients met inclusion criteria (disease onset before the age of 18, one or more SDMTs, and 8 years or older at the time of testing). Those with relapse were analyzed separately from those who were relapse-free. Results: At initial assessment, the mean (interquartile range (IQR)) age at symptom onset was 13.5 years (12.0, 15.9) and the mean (±SD) disease duration was 3.0 ± 2.9 years. Impaired processing speed occurred in 23.4% of POMS and in 16.4% of CIS. On serial testing ( n = 383, mean follow-up: 1.8 years), 14.1% had clinically meaningful decline predicted by older age of multiple sclerosis (MS) onset and male gender. Disease relapse or steroid use led to transient worsening on the SDMT. Conclusion: Early in the disease, some POMS and CIS patients are at risk for cognitive impairment and subsequent decline.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458519891984
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
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  • 10
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    Antibody response to common viruses and human leukocyte antigen-DRB1 in pediatric multiple sclerosis
    SAGE Publications ; 2013
    In:  Multiple Sclerosis Journal Vol. 19, No. 7 ( 2013-06), p. 891-895
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 19, No. 7 ( 2013-06), p. 891-895
    Abstract: As remote infections with common herpes viruses are associated with modulation of the risk of multiple sclerosis (MS), we hypothesized that antibody concentrations against these viruses may further modify risk. As many common viruses are first encountered during childhood, pediatric MS offer a unique opportunity to investigate more closely their influence on susceptibility. Our aim was to determine if MS patients who were positive for these viruses had higher levels of antibodies to these viruses. We also assessed whether human leukocyte antigen (HLA)-DRB1*1501 genotype influenced viral antibody levels. Methods: Antibody response levels toward Epstein Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV)-1, and HLA-DRB1*1501 status were determined in pediatric MS patients ( n=189) and controls ( n=38). Multivariate analyses were used, adjusted for age, gender, race, ethnicity and use of disease-modifying therapies. Results: The antibody concentrations against EBV (Epstein-Barr nuclear antigen 1 (EBNA-1), viral capsid antigen (VCA) and early antigen (EA)), CMV and HSV-1 were similar between pediatric MS patients and controls positive for seroconversion against the virus of interest. EBNA-1 humoral responses were higher in HLA-DRB1 positive individuals ( p=0.005) whereas other viral humoral responses were similar in HLA-DRB1 positive and negative individuals. Conclusion: Among those positive for EBNA-1, MS patients did not have higher levels of antibody response to EBNA-1: however, titers for EBNA-1 were higher in those who were HLA-DRB1 positive. This suggests that genotype might influence the humoral response to EBV. Whether other genotypes influence antibody response to other viruses remains to be determined.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458512469693
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2013
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