Faculty Bibliography
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629
Cognitive impairment in pediatric-onset multiple sclerosis is detected by the Brief International Cognitive Assessment for Multiple Sclerosis and computerized cognitive testing
BACKGROUND: Cognitive impairment is a common and troubling feature of pediatric-onset multiple sclerosis (POMS). Brief cognitive assessment in the outpatient setting can identify and longitudinally monitor cognitive involvement so that early intervention is possible. OBJECTIVES: The goal of this study was to measure the sensitivity of two cognitive assessment approaches that are brief, repeatable, and suitable for clinical practice and for multicenter investigation. METHODS: Participants with POMS ( n = 69) were consecutively evaluated as part of outpatient neurologic visits and compared to healthy control participants (HC, n = 66) using the Brief International Cognitive Assessment for MS (BICAMS) approach and timed information processing measures from Cogstate, a computer-based assessment. RESULTS: There was strong agreement in the detection rate of impairment between both assessments, with 26% for the BICAMS and 27% for Cogstate. Two of the Cogstate tasks were the most sensitive individual measures. CONCLUSION: Both the BICAMS and Cogstate timed processing measures offer practical, sensitive, and standardized approaches for cognitive screening assessment in POMS.
PMID: 28322606
ISSN: 1477-0970
CID: 2499402
Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
BACKGROUND:modulator, on disability progression in patients with SPMS. METHODS:This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18-60 years) with SPMS and an Expanded Disability Status Scale score of 3·0-6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. FINDINGS:1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65-0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. INTERPRETATION:Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. FUNDING:Novartis Pharma AG.
PMID: 29576505
ISSN: 1474-547x
CID: 5348122
The Paradigms Study: A Randomized Double-Blind Trial of Fingolimod Versus Interferon beta-1a in Patients with Multiple Sclerosis Aged 10 to < 18 Years [Meeting Abstract]
ISI:000429034600048
ISSN: 1352-4585
CID: 3039262
Patterns and Safety of Newer Disease-Modifying Therapy Use in Pediatric Multiple Sclerosis in the US [Meeting Abstract]
ISI:000429034600091
ISSN: 1352-4585
CID: 3039242
The multiple sclerosis risk allele within the AHI1 gene is associated with relapses in children and adults
BACKGROUND:While common variant non-HLA (human leukocyte antigen) alleles have been associated with MS risk, their role in disease course is less clear. We sought to determine whether established multiple sclerosis (MS) genetic susceptibility factors are associated with relapse rate in children and an independent cohort of adults with MS. METHODS:Genotyping was performed for 182 children with MS or clinically isolated syndrome with high risk for MS from two Pediatric MS Centers. They were prospectively followed for relapses. Fifty-two non-HLA MS susceptibility single nucleotide polymorphisms (SNPs) were evaluated for association with relapse rate. Cox regression models were adjusted for sex, genetic ancestry, disease-modifying therapy (DMT), 25-OH vitamin D level and HLA-DRB1*15:01/03 status. Investigation of pediatric subject SNP results was performed using a second cohort of 141 adult MS subjects of Northern European ancestry from the Southern Tasmanian Multiple Sclerosis Longitudinal Study. RESULTS:For pediatric subjects, 408 relapses were captured over 622 patient-years of follow-up. Four non-HLA risk SNPs (rs11154801, rs650258, rs12212193, rs2303759) were associated with relapses (p < 0.01) in the pediatric subjects. After adjustment for genetic ancestry, sex, age, vitamin D level, DMT use and HLA-DRB1*15 status, having two copies of the MS risk allele within AHI1 (rs11154801) was associated with increased relapses among children (HR = 1.75,95%CI = 1.18-2.48, p = 0.006) and this result was also observed among adults (HR = 1.81,95%CI = 1.05-3.03, p = 0.026). CONCLUSIONS:Our results suggest that the MS genetic risk variant within the gene AHI1 may contribute to disease course in addition to disease susceptibility.
PMCID:5806144
PMID: 29409597
ISSN: 2211-0356
CID: 3257252
Correction: Cognitive function in multiple sclerosis improves with telerehabilitation: Results from a randomized controlled trial [Correction]
[This corrects the article DOI: 10.1371/journal.pone.0177177.].
PMCID:5790288
PMID: 29381774
ISSN: 1932-6203
CID: 2989072
Examining the contributions of environmental quality to pediatric multiple sclerosis
BACKGROUND: Multiple sclerosis (MS) is a presumed autoimmune disease caused by genetic and environmental factors. It is hypothesized that environmental exposures (such as air and water quality) trigger the innate immune response thereby activating a pro-inflammatory cascade. OBJECTIVE: To examine potential environmental factors in pediatric MS using geographic information systems (GIS). METHODS: Pediatric MS cases and healthy controls were identified as part of an ongoing multicenter case-control study. Subjects' geographic locations were mapped by county centroid to compare to an Environmental Quality Index (EQI). The EQI examines 5 individual environmental components (air, land, water, social, built factors). A composite EQI score and individual scores were compared between cases and controls, stratified by median proximity to enrollment centers (residence <20 or >/=20 miles from the recruiting center), using logistic regression. RESULTS: Of the 287 MS cases and 445 controls, 46% and 49% respectively live in areas where the total EQI is the highest (worst environmental quality). Total EQI was not significantly associated with the odds for MS (p = 0.90 < 20 miles from center; p = 0.43 >/= 20 miles); however, worsening air quality significantly impacted the odds for MS in those living near a referral center (OR = 2.83; 95%CI 1.5, 5.4) and those who reside >/= 20 miles from a referral center (OR = 1.61; 95%CI 1.2, 2.3). CONCLUSION: Among environmental factors, air quality may contribute to the odds of developing MS in a pediatric population. Future studies will examine specific air constituents and other location-based air exposures and explore potential mechanisms for immune activation by these exposures.
PMCID:5720353
PMID: 29141802
ISSN: 2211-0356
CID: 2784602
Remotely supervised transcranial direct current stimulation (RS-tDCS) improves fatigue in multiple sclerosis [Meeting Abstract]
Background: Fatigue is known for being one of the most debilitating and common symptoms of multiple sclerosis (MS). Despite its prevalence, though, reliable treatment options are lacking. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation treatment that uses low amperage (2.0 mA) electric current to stimulate cortical regions. tDCS has been shown to improve fatigue in MS following consecutive daily treatment sessions. We have recently developed and shown the feasibility of a remotely supervised tDCS (RS-tDCS) protocol to ease the burden of daily sessions and allow patients to complete the treatment at home. We aim to evaluate the efficacy of RS-tDCS in fatigue management for patients with MS. Methods: We enrolled n = 31 patients with MS (all subtypes) into a randomly controlled, double-blind trial; n = 27 patients provided data for analysis with n = 15 randomized to the active group and n = 12 in the placebo or "sham" group. Participants came to the clinic for baseline and follow-up measures including self-report forms on fatigue. At baseline they were also trained in operating the tDCS headset. Participants then took the device home where they complete 20 sessions of tDCS (20 minutes, 2.0 mA, dorsolateral prefrontal cortex montage, left anodal) paired with cognitive training. Results: Our primary outcome measure was the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue scale. When comparing change in PROMIS Fatigue between the active and sham tDCS groups we found that active tDCS participants had significantly greater reductions in fatigue (mean change in Active =-5.6 +/- 8.9 vs. Sham = 0.9 +/- 1.9, p = 0.02 conditions). We analyzed the within-subject effect tDCS had and found a significant, beneficial effect in the active group (pre-treatment mean = 26.6 +/- 9.2, post-treatment mean = 21.0 +/- 6.4, p = 0.04) and no such effect in the sham group (pre-treatment mean = 22.9 +/- 7.9, post-treatment mean = 23.8 +/- 8.4, p = 0.15). Finally, we calculated Cohen's d effect size (Active d =-0.71, Sham d = 0.11). Conclusions: These data suggest that RS-tDCS provides significant reduction in MS-related fatigue
EMBASE:619358784
ISSN: 1477-0970
CID: 2871622
Journal of the International Neuropsychological Society. 2017:23(9-10):832-842.DOI: 10.1017/S1355617717000959
Neuropsychology of Multiple Sclerosis: Looking Back and Moving Forward
The neuropsychological aspects of multiple sclerosis (MS) have evolved over the past three decades. What was once thought to be a rare occurrence, cognitive dysfunction is now viewed as one of the most disabling symptoms of the disease, with devastating effects on patients' quality of life. This selective review will highlight major innovations and scientific discoveries in the areas of neuropathology, neuroimaging, diagnosis, and treatment that pertain to our understanding of the neuropsychological aspects of MS. Specifically, we focus on the recent discovery that MS produces pathogical lesions of gray matter (GM) that have consequences for cognitive functions. Methods for imaging these GM lesions in MS are discussed along with multimodal imaging studies that integrate structural and functional imaging methods to provide a better understanding of the relationship between cognitive test performance and functional reserve. Innovations in the screening and comprehensive assessment of cognitive disorders are presented along with recent research that examines cognitive dysfunction in pediatric MS. Results of innovative outcome studies in cognitive rehabilitation are discussed. Finally, we highlight trends for potential future innovations over the next decade. (JINS, 2017, 23, 832-842).
PMID: 29198279
ISSN: 1469-7661
CID: 3062372
REVIEW OF THE EPIDEMIOLOGY AND TREATMENT LANDSCAPE IN PEDIATRIC MULTIPLE SCLEROSIS IN THE UNITED STATES [Meeting Abstract]
ISI:000405448002342
ISSN: 1524-4733
CID: 2650212
