Faculty Bibliography
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Effet du traitement par fingolimod chez des enfants ayant une sclerose en plaques (SEP): Resultats complementaires de l'etude PARADIGMS [Meeting Abstract]
Introduction: Dans PARADIGMS, premiere etude phase III en double aveugle dans la SEP pediatrique, le fingolimod a diminue significativement le taux annualise de poussees (TAP) de 82 % versus l'interferon (IFN) beta-1a. Objectifs: Effectuer des analyses dans des sous-groupes (anticorps neutralisants anti-IFN, naifs de traitement); evaluer l'effet chez les patients plus jeunes et prepuberes, la progression du handicap, la qualite de vie. Patients et Methodes: Les analyses de sous-groupes des criteres principal (TAP) et secondaire principal (nouvelles lesions T2, NT2) et post-hoc sur la progression confirmee du handicap ont ete realisees. La qualite de vie (QdV) liee a la sante a ete evaluee par les patients ou les parents a l'aide du questionnaire PedsQL (Quality of Life) avant et a la fin de l'etude (jusqu'a 2 ans): changements du score total et des scores sante physique et sante psychosociale. Resultats: Dans toutes les analyses de sous-groupes, le fingolimod a diminue significativement le TAP (81,5-85,8 %) et NT2 (47,6-53,4 %) versus l'IFNbeta-1a. Le risque de progression du handicap confirmee a 3 mois etait reduit de 77,2 % ([HR] = 0,23, p = 0,007). L'analyse post-hoc a confirme son effet positif sur les scores totaux et de sante physique de QdV rapportes par les patients et les parents, et de sante psychosociale rapporte par les patients versus l'IFN beta-1a (tous p < 0,05). Discussion(s): Le fingolimod dans la SEP pediatrique a ete associe a un controle de l'activite de la maladie dans toutes les analyses complementaires, chez les patients traites precedemment ou non, et ce de maniere plus marquee chez les patients plus jeunes. Des benefices sur la progression du handicap ont ete observes sur une duree de traitement allant jusqu'a 2 ans. Conclusion(s): Le fingolimod versus IFN beta-1a a ete associe a une amelioration significative du controle de l'activite de la maladie et de la qualite de vie liee a la sante.
EMBASE:2001636410
ISSN: 0035-3787
CID: 3789912
Abstract #151: Long Term Outcomes from a Remotely Supervised tDCS Trial for Symptom Management in Multiple Sclerosis [Meeting Abstract]
Introduction: MS is a neurodegenerative, autoimmune disease associated with significant symptom burden such as fatigue, cognitive impairment, motor dysfunction, and depression. Thus, there is a need for therapeutic options for accessible symptom management. tDCS is an emerging neuromodulation treatment that delivers low amperage direct current (=2 mA) to targeted brain regions through scalp electrodes. tDCS is thought to lower the neuronal threshold required for action potentials and is often used to augment the benefit achieved through repetitive stimulation. Recent studies have demonstrated that at-home, remotely supervised tDCS (RS-tDCS) sessions can are successful in reducing fatigue in MS, studies have yet to elucidate the longevity of symptom benefit. Method(s): Participants with MS (N = 26) were recruited to complete a 20 sessions of RS-tDCS over a four-week period (5 sessions per week). We utilized a left anodal dorsolateral prefrontal cortex (DLPFC) montage as the target point for the treatment. The tDCS stimulation was at 2.0 mA. Surveys were completed at least one month following completion of the last RS-tDCS session asking whether any treatment benefit was achieved and whether it was sustained. Half the participants (N =13) received a sham/placebo stimulation, while the other half of the participants (N = 13) received the active stimulation. Both lab technicians and participants were blinded to the participant's conditions. Result(s): 65% of all participants reported treatment benefit. 92% (N =12) among the active participants and 38% (N = 5) among sham participants experienced benefit. The active group experienced a greater rate of benefit compared to the sham group (p<0.001). Furthermore, half of the participants assigned to the active condition that reported experiencing benefit also indicated that the benefit persisted (50%) and only a single participant who experienced benefit in the sham condition indicated that benefit persisted (20%). Conclusion(s): RS-tDCS results in symptom improvement in an MS cohort both immediately after the treatment finishes as well as, for many participants, after one month after treatment finishes. More clinical research should be done to elucidate the mechanism of long-lasting neural change due to tDCS that may help to improve MS symptoms. Longer studies should be done to examine whether self-reported benefit increases with number of sessions.
EMBASE:2001482391
ISSN: 1876-4754
CID: 3634812
Admixture mapping reveals evidence of differential multiple sclerosis risk by genetic ancestry
Multiple sclerosis (MS) is an autoimmune disease with high prevalence among populations of northern European ancestry. Past studies have shown that exposure to ultraviolet radiation could explain the difference in MS prevalence across the globe. In this study, we investigate whether the difference in MS prevalence could be explained by European genetic risk factors. We characterized the ancestry of MS-associated alleles using RFMix, a conditional random field parameterized by random forests, to estimate their local ancestry in the largest assembled admixed population to date, with 3,692 African Americans, 4,915 Asian Americans, and 3,777 Hispanics. The majority of MS-associated human leukocyte antigen (HLA) alleles, including the prominent HLA-DRB1*15:01 risk allele, exhibited cosmopolitan ancestry. Ancestry-specific MS-associated HLA alleles were also identified. Analysis of the HLA-DRB1*15:01 risk allele in African Americans revealed that alleles on the European haplotype conferred three times the disease risk compared to those on the African haplotype. Furthermore, we found evidence that the European and African HLA-DRB1*15:01 alleles exhibit single nucleotide polymorphism (SNP) differences in regions encoding the HLA-DRB1 antigen-binding heterodimer. Additional evidence for increased risk of MS conferred by the European haplotype were found for HLA-B*07:02 and HLA-A*03:01 in African Americans. Most of the 200 non-HLA MS SNPs previously established in European populations were not significantly associated with MS in admixed populations, nor were they ancestrally more European in cases compared to controls. Lastly, a genome-wide search of association between European ancestry and MS revealed a region of interest close to the ZNF596 gene on chromosome 8 in Hispanics; cases had a significantly higher proportion of European ancestry compared to controls. In conclusion, our study established that the genetic ancestry of MS-associated alleles is complex and implicated that difference in MS prevalence could be explained by the ancestry of MS-associated alleles.
PMID: 30653506
ISSN: 1553-7404
CID: 3595382
Brief Computer-Based Information Processing Measures are Linked to White Matter Integrity in Pediatric-Onset Multiple Sclerosis
BACKGROUND AND PURPOSE/OBJECTIVE:Pediatric-onset multiple sclerosis (POMS) is a demyelinating disorder with unique clinical challenges. A brief computer-administered cognitive screening battery measuring processing speed (Cogstate) and the Brief International Cognitive Assessment in MS (BICAMS) detect cognitive impairment in POMS. The neuroanatomic correlates of these deficits are incompletely understood. The purpose of this study is to define the neuroanatomic underpinnings of deficits identified with cognitive screening batteries in POMS. METHODS:Participants with POMS and age-matched healthy controls (HCs) were screened with Cogstate and BICAMS. Diffusion tensor imaging assessed region-wise and tractography-based fractional anisotropy (FA). RESULTS:The POMS (n = 15) and HC (n = 21) groups were matched on age (mean ages 17.9 ± 3.2 vs. 17.8 ± 3.3 years, respectively) and on an estimate of general intellectual functioning. The Cogstate composite revealed significant slowing in POMS relative to HCs (P = .004), but the BICAMS composite did not significantly distinguish the groups (P = .10). The Cogstate composite showed moderate-to-strong correlations with regional FA (r = -.67 to -.82) and significantly associated with uncinate fasciculus FA following multiple comparisons correction (P = .002) in POMS. However, the BICAMS composite measure showed only weak-to-moderate correlations with FA in POMS (r = -.19 to -.57), with none surviving multiple comparisons correction. CONCLUSIONS:Computer-administered measures of cognitive processing are particularly sensitive in POMS and are closely linked to white matter FA.
PMID: 30285300
ISSN: 1552-6569
CID: 3328252
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
Prevalence of isolated cognitive decline in a large, heterogeneous multiple sclerosis population [Meeting Abstract]
Introduction: Performance on the symbol digit modalities test (SDMT) is associated with employment status and activities of daily living. However, most constructs of MS disease progression do not take into account cognitive changes; potentially underestimating disease progression in MS.
Objective(s): Describe the prevalence of cognitive decline in multiple sclerosis (MS) in the absence of motor function decline.
Method(s): Patients with MS and clinically isolated syndrome were enrolled in MS PATHS, a network of 10 healthcare institutions in the US (7) and EU (3). During routine visits, patients used the Multiple Sclerosis Performance Test (MSPT) to complete the Processing Speed Test (PST), Manual Dexterity Test (MDT) and Walking Speed Test (WST), which are electronic adaptations of the SDMT, Nine-hole Peg Test and Timed 25 Foot Walk. Patients also completed the Patient Derived Disease Steps (PDDS). This analysis included all patients enrolled in MS PATHS with two or more completed MSPT assessments. Decline between timepoints was defined as a 4 point change on the PST, 20% change on the MDT or WST, or a 1 point change on the PDDS.
Result(s): 2289 patients had 2 or more complete MSPT assessments. At baseline, the average age was 44.9 yrs (SD: 11.2 yrs) and the average disease duration was 10.7 yrs (SD: 8.1 yrs). The average duration of follow-up was 7.5 mos (SD: 4.5 mos) and the average number of MSPT assessments was 2.5 (SD: 0.93). When comparing a patient's first and last MSPT assessment, 33.7% of patients had a decline on either the PST, MDT, or WST. 15.2% of patients had a decline on the PST only, 13.6% had a decline on the WST or MDT only (i.e. motor tests), and 4.9% of patients had decline on both the PST and a motor test. There were no meaningful differences in the distribution of baseline demographics, socioeconomics, or MS sub-types between patients who did or did not experience any decline and within decline sub-groups. PDDS progression was observed in 16.9% of patients with PST decline only, 22.5% of patients with motor decline only, and 30.4% of patients with both PST and motor decline. Further results will be reported at conference.
Conclusion(s): The prevalence of cognitive decline was as common as motor decline. 75.7% of patients with cognitive decline did not have concurrent motor decline. These results highlight the importance of cognitive monitoring in routine clinical care and the need for effective treatment strategies for cognitive decline in MS
Objective(s): Describe the prevalence of cognitive decline in multiple sclerosis (MS) in the absence of motor function decline.
Method(s): Patients with MS and clinically isolated syndrome were enrolled in MS PATHS, a network of 10 healthcare institutions in the US (7) and EU (3). During routine visits, patients used the Multiple Sclerosis Performance Test (MSPT) to complete the Processing Speed Test (PST), Manual Dexterity Test (MDT) and Walking Speed Test (WST), which are electronic adaptations of the SDMT, Nine-hole Peg Test and Timed 25 Foot Walk. Patients also completed the Patient Derived Disease Steps (PDDS). This analysis included all patients enrolled in MS PATHS with two or more completed MSPT assessments. Decline between timepoints was defined as a 4 point change on the PST, 20% change on the MDT or WST, or a 1 point change on the PDDS.
Result(s): 2289 patients had 2 or more complete MSPT assessments. At baseline, the average age was 44.9 yrs (SD: 11.2 yrs) and the average disease duration was 10.7 yrs (SD: 8.1 yrs). The average duration of follow-up was 7.5 mos (SD: 4.5 mos) and the average number of MSPT assessments was 2.5 (SD: 0.93). When comparing a patient's first and last MSPT assessment, 33.7% of patients had a decline on either the PST, MDT, or WST. 15.2% of patients had a decline on the PST only, 13.6% had a decline on the WST or MDT only (i.e. motor tests), and 4.9% of patients had decline on both the PST and a motor test. There were no meaningful differences in the distribution of baseline demographics, socioeconomics, or MS sub-types between patients who did or did not experience any decline and within decline sub-groups. PDDS progression was observed in 16.9% of patients with PST decline only, 22.5% of patients with motor decline only, and 30.4% of patients with both PST and motor decline. Further results will be reported at conference.
Conclusion(s): The prevalence of cognitive decline was as common as motor decline. 75.7% of patients with cognitive decline did not have concurrent motor decline. These results highlight the importance of cognitive monitoring in routine clinical care and the need for effective treatment strategies for cognitive decline in MS
EMBASE:629481367
ISSN: 1477-0970
CID: 4131392
Adults with MS show earlier cognitive changes than those with pediatric MS [Meeting Abstract]
Introduction: Cognitive impairment is common and often disabling in multiple sclerosis (MS), but the risk factors and mechanisms underlying cognitive decline remain poorly understood. Pediatric MS (MS onset < 18 years of age) is unique due to the demyelinating process occurring in the context of development.
Objective(s): To compare cognitive functions in newly diagnosed patients with either adult- or pediatric-onset MS (AOMS vs. POMS).
Aim(s): To test performance in newly diagnosed MS patients using the Symbol Digit Modalities Test (SDMT) and a computer-based measure sensitive to processing speed deficits (Cogstate).
Method(s): As part of an ongoing multi-center longitudinal cognition trial, AOMS and POMS participants were recruited from outpatient visits and matched by years of disease. At the baseline evaluation, all participants were administered the Wide Range Achievement Test-4 (WRAT-4), the SDMT and the Cogstate Brief Battery, which includes three measures of information processing speed tasks:simple (DET) and choice (IDN) reaction time and working memory (ONB). Cogstate scores were converted to z-scores and then averaged for one composite z-score.
Result(s): A total of n=64 participants completed baseline assessments with n= 32 in the AOMS group (mean age 33.36 ?+/- 5.82) and n= 32 in the POMS group (mean age 11.31 ?+/- 3.64). All participants had relapsing remitting disease and the groups were matched for disease duration (4.91 ?+/- 3.05 years for AOMS vs. 6.38 ?+/- 3.54 for POMS). The POMS group had higher estimated premorbid IQ (WRAT-4 reading 112.7 ?+/- 18.5 vs. 105.4 ?+/- 13.4), though the result did not reach significance (p=0.07). Neither group's cognitive performances fell into the impaired range relative to age-normative means. However, the AOMS compared to the POMS group consistently performed significantly worse on the SDMT (mean z-score -0.26 ?+/- 1.15 for AOMS vs. 0.68 ?+/- 1.53 for POMS, p=0.01) and slower on the Cogstate composite (mean z-score of -1.04 ?+/- 1.09 for AOMS vs. 0.35 ?+/- 1.15 for POMS, p=0.04). Estimated premorbid IQ was correlated with SDMT, but not Cogstate performance (r=0.56 p=0.001 and r=0.13 p=0.35, respectively). Age of disease onset was significantly negatively correlated with cognitive processing (SDMT: r= -0.32, p= 0.01 and Cogstate DET: r= -0.33, p=0.02), further indicating that older age of onset is associated with greater cognitive impairment.
Conclusion(s): Adult MS is associated with larger cognitive involvement than pediatric MS
Objective(s): To compare cognitive functions in newly diagnosed patients with either adult- or pediatric-onset MS (AOMS vs. POMS).
Aim(s): To test performance in newly diagnosed MS patients using the Symbol Digit Modalities Test (SDMT) and a computer-based measure sensitive to processing speed deficits (Cogstate).
Method(s): As part of an ongoing multi-center longitudinal cognition trial, AOMS and POMS participants were recruited from outpatient visits and matched by years of disease. At the baseline evaluation, all participants were administered the Wide Range Achievement Test-4 (WRAT-4), the SDMT and the Cogstate Brief Battery, which includes three measures of information processing speed tasks:simple (DET) and choice (IDN) reaction time and working memory (ONB). Cogstate scores were converted to z-scores and then averaged for one composite z-score.
Result(s): A total of n=64 participants completed baseline assessments with n= 32 in the AOMS group (mean age 33.36 ?+/- 5.82) and n= 32 in the POMS group (mean age 11.31 ?+/- 3.64). All participants had relapsing remitting disease and the groups were matched for disease duration (4.91 ?+/- 3.05 years for AOMS vs. 6.38 ?+/- 3.54 for POMS). The POMS group had higher estimated premorbid IQ (WRAT-4 reading 112.7 ?+/- 18.5 vs. 105.4 ?+/- 13.4), though the result did not reach significance (p=0.07). Neither group's cognitive performances fell into the impaired range relative to age-normative means. However, the AOMS compared to the POMS group consistently performed significantly worse on the SDMT (mean z-score -0.26 ?+/- 1.15 for AOMS vs. 0.68 ?+/- 1.53 for POMS, p=0.01) and slower on the Cogstate composite (mean z-score of -1.04 ?+/- 1.09 for AOMS vs. 0.35 ?+/- 1.15 for POMS, p=0.04). Estimated premorbid IQ was correlated with SDMT, but not Cogstate performance (r=0.56 p=0.001 and r=0.13 p=0.35, respectively). Age of disease onset was significantly negatively correlated with cognitive processing (SDMT: r= -0.32, p= 0.01 and Cogstate DET: r= -0.33, p=0.02), further indicating that older age of onset is associated with greater cognitive impairment.
Conclusion(s): Adult MS is associated with larger cognitive involvement than pediatric MS
EMBASE:629478950
ISSN: 1477-0970
CID: 4131502
Diffusion tensor imaging in pediatric onset multiple sclerosis: Differential links to information processing speed and memory functioning [Meeting Abstract]
Introduction: Pediatric onset multiple sclerosis (POMS) is a demyelinating disorder occurring in the context of neurodevelopment with unique clinical challenges due to the potential for disease-related cognitive impairment. A brief cognitive screening battery of computer administered measures of processing speed (Cogstate) and the Brief International Cognitive Assessment in MS (BICAMS) detects cognitive impairment in POMS. However, the neuroanatomic correlates of these deficits are incompletely understood. We have sought to define the neuroimaging correlates of deficits identified with a cognitive screening battery in POMS.
Objective(s): To test the links between white matter integrity and cognitive functioning in pediatric MS patients and matched healthy controls.
Aim(s): Participants cognitive performance as measured by the BICAMS and Cogstate assessments was compared to magnetic resonance imaging (MRI) outcomes.
Method(s): Participants with POMS and age-matched healthy controls (HC) completed cognitive screening with Cogstate and the BICAMS along with 64-direction MRI based diffusion tensor imaging (DTI).
Result(s): The POMS group (n= 15, mean age 17.9+/-3.2 years) compared to the HC group (n= 21, mean age 17.8+/-3.3 years) were significantly slower on a composite Cogstate score (p=0.004), but the groups did not significantly differ using a composite BICAMS score (p = 0.10). The POMS group also presented with increased fractional anisotropy (FA) in the thalamus (p=0.01) and reduced FA in the corpus callosum (p=0.05) and temporal lobe white matter (p=0.03) relative to HCs. Controlling for age and sex within groups, the measured slowed processing speed (Cogstate composite) significantly negatively correlated with regional fractional anisotropy (FA) in the corpus callosum, temporal and occipital lobe white matter, and in the tractography-based uncinate fasciculus in the POMS sample (p=0.002 to 0.025), whereas the reduced verbal learning (RAVLT) was significantly negatively correlated with thalamic FA (p = 0.046). Of these effects, only the relationship between the Cogstate composite and temporal lobe FA was significant in the HCs (p=0.013).
Conclusion(s): Computer administered measures of cognitive processing speed are particularly sensitive to slowing in POMS and are closely linked to MRI diffusion measures
Objective(s): To test the links between white matter integrity and cognitive functioning in pediatric MS patients and matched healthy controls.
Aim(s): Participants cognitive performance as measured by the BICAMS and Cogstate assessments was compared to magnetic resonance imaging (MRI) outcomes.
Method(s): Participants with POMS and age-matched healthy controls (HC) completed cognitive screening with Cogstate and the BICAMS along with 64-direction MRI based diffusion tensor imaging (DTI).
Result(s): The POMS group (n= 15, mean age 17.9+/-3.2 years) compared to the HC group (n= 21, mean age 17.8+/-3.3 years) were significantly slower on a composite Cogstate score (p=0.004), but the groups did not significantly differ using a composite BICAMS score (p = 0.10). The POMS group also presented with increased fractional anisotropy (FA) in the thalamus (p=0.01) and reduced FA in the corpus callosum (p=0.05) and temporal lobe white matter (p=0.03) relative to HCs. Controlling for age and sex within groups, the measured slowed processing speed (Cogstate composite) significantly negatively correlated with regional fractional anisotropy (FA) in the corpus callosum, temporal and occipital lobe white matter, and in the tractography-based uncinate fasciculus in the POMS sample (p=0.002 to 0.025), whereas the reduced verbal learning (RAVLT) was significantly negatively correlated with thalamic FA (p = 0.046). Of these effects, only the relationship between the Cogstate composite and temporal lobe FA was significant in the HCs (p=0.013).
Conclusion(s): Computer administered measures of cognitive processing speed are particularly sensitive to slowing in POMS and are closely linked to MRI diffusion measures
EMBASE:629481935
ISSN: 1477-0970
CID: 4131352
Transcranial direct current stimulation (tDCS) enhances cognitive remediation outcomes in multiple sclerosis: Results from a randomized clinical trial of telerehabilitation with 40 at-home treatment sessions [Meeting Abstract]
Introduction: Cognitive impairment represents a frequent and troubling symptom of multiple sclerosis (MS) in need of treatment options. Transcranial direct current stimulation (tDCS) uses scalpbased electrodes to pass mild electrical current (< 4mA) through target cortical brain regions and is a safe and well-tolerated treatment. We have developed a protocol to deliver remotely supervised cognitive remediation paired with tDCS to individuals with MS at home.
Objective(s): To test whether at-home cognitive remediation augmented with tDCS will lead to improved training outcomes in MS.
Aim(s): Cognitive processing speed was assessed at baseline and study end by the Cogstate Brief Battery. Age normative z scores were computed for the Cogstate Brief Battery scores, with outcome measured by change in the average z score of information processing assessments.
Method(s): MS participants with cognitive impairment were recruited and randomized to complete 40 sessions of either active or sham tDCS paired with either adaptive or non-adaptive cognitive training (aCT or nCT). Training was completed at home using study-provided equipment and remotely supervised via videoconference using our established probed (RS-tDCS). Training was 20 minutes in duration and was completed five times a week (M-F) for approximately eight weeks. Participants were blinded and received active (2.5mA) or sham stimulation and cognitive training simultaneously during each session.
Result(s): To date, n=19 MS participants have successfully complete the 40 session training program at home: n=6 in active/aCT, n=8 in Sham/aCT, and n=5 in active/nCT. Mean age was 49+/-15 years of age and mean years of education was 16.5+/-2.1. The majority of participants had the RRMS subtype (63%, with 11% PPMS, and 26% SPMS). The participants were matched on cognitive status as measured by the symbol digit modality test (ANOVA p=0.09). tDCS and the cognitive training were uniformly well tolerated with no safety concerns. At the group level, all three groups showed improvement from baseline (0.75, 0.56, 0.59 z-score improvement for each condition respectively), indicating that both tDCS and aCT can be of benefit. Further, as predicted, the active tDCS paired with aCT experienced the greatest benefit (Cohen's d = 0.51).
Conclusion(s): Our telerehabiltiation protocol allows for participants to receive extended cognitive training paired with tDCS at home, resulting in improved outcomes from cognitive remediation
Objective(s): To test whether at-home cognitive remediation augmented with tDCS will lead to improved training outcomes in MS.
Aim(s): Cognitive processing speed was assessed at baseline and study end by the Cogstate Brief Battery. Age normative z scores were computed for the Cogstate Brief Battery scores, with outcome measured by change in the average z score of information processing assessments.
Method(s): MS participants with cognitive impairment were recruited and randomized to complete 40 sessions of either active or sham tDCS paired with either adaptive or non-adaptive cognitive training (aCT or nCT). Training was completed at home using study-provided equipment and remotely supervised via videoconference using our established probed (RS-tDCS). Training was 20 minutes in duration and was completed five times a week (M-F) for approximately eight weeks. Participants were blinded and received active (2.5mA) or sham stimulation and cognitive training simultaneously during each session.
Result(s): To date, n=19 MS participants have successfully complete the 40 session training program at home: n=6 in active/aCT, n=8 in Sham/aCT, and n=5 in active/nCT. Mean age was 49+/-15 years of age and mean years of education was 16.5+/-2.1. The majority of participants had the RRMS subtype (63%, with 11% PPMS, and 26% SPMS). The participants were matched on cognitive status as measured by the symbol digit modality test (ANOVA p=0.09). tDCS and the cognitive training were uniformly well tolerated with no safety concerns. At the group level, all three groups showed improvement from baseline (0.75, 0.56, 0.59 z-score improvement for each condition respectively), indicating that both tDCS and aCT can be of benefit. Further, as predicted, the active tDCS paired with aCT experienced the greatest benefit (Cohen's d = 0.51).
Conclusion(s): Our telerehabiltiation protocol allows for participants to receive extended cognitive training paired with tDCS at home, resulting in improved outcomes from cognitive remediation
EMBASE:629479666
ISSN: 1477-0970
CID: 4131422
Effect of fingolimod on quality of life in paediatric MS: Results of the phase 3 PARADIGMS study [Meeting Abstract]
Introduction: In PARADIGMS, a double-blind phase 3 trial of 215 paediatric MS patients (age 10-< 18 years), fingolimod administered up to 2 years significantly reduced the annualised relapse rate by 81.9%, the annualised rate of new/newly enlarged T2 lesions by 52.6%, and the number of Gadolinium-enhancing T1 lesions by 66.0% compared to interferon (IFN) beta-1a.
Objective(s): To evaluate the effect of fingolimod versus IFN beta-1a on quality of life in this paediatric MS population.
Method(s): Health-related quality of life was assessed using the Pediatric Quality of Life (PedsQL) inventory. Summary statistics of change in patient-or parent-reported PedsQL scores from baseline until study end (up to 2 years) were pre-planned. Inferential testing on between group differences in PedsQL scores was performed as a post-hoc analysis. The change from baseline in Total Scale score, Physical Health Summary score, and Psychosocial Health Summary score was compared by visit for patient-and parent-reported PedsQL using a parametric analysis of covariance (ANCOVA) model adjusted by treatment, region, pubertal status, and the corresponding baseline score.
Result(s): Numerical improvements in PedsQL scores in both patient-and parent-reported Total Scale, Physical Health, and Psychosocial Health Summary scores were observed in fingolimod-treated patients compared with consistent worsening observed in the IFN beta-1a-treated patients. The post-hoc inferential statistical analysis confirmed that treatment with fingolimod resulted in a positive effect on quality of life in both patient-and parent-reported Total score and Physical Health Summary score, as well as in patient-reported Psychosocial Health Summary score compared with IFN beta-1a (all p< 0.05).
Conclusion(s): Consistent with the primary efficacy results, treatment with fingolimod versus IFN beta-1a was associated with a significant improvement in all measures of health-related quality of life as reported by the patients, and in Total score and Physical Health score as reported by their parents
Objective(s): To evaluate the effect of fingolimod versus IFN beta-1a on quality of life in this paediatric MS population.
Method(s): Health-related quality of life was assessed using the Pediatric Quality of Life (PedsQL) inventory. Summary statistics of change in patient-or parent-reported PedsQL scores from baseline until study end (up to 2 years) were pre-planned. Inferential testing on between group differences in PedsQL scores was performed as a post-hoc analysis. The change from baseline in Total Scale score, Physical Health Summary score, and Psychosocial Health Summary score was compared by visit for patient-and parent-reported PedsQL using a parametric analysis of covariance (ANCOVA) model adjusted by treatment, region, pubertal status, and the corresponding baseline score.
Result(s): Numerical improvements in PedsQL scores in both patient-and parent-reported Total Scale, Physical Health, and Psychosocial Health Summary scores were observed in fingolimod-treated patients compared with consistent worsening observed in the IFN beta-1a-treated patients. The post-hoc inferential statistical analysis confirmed that treatment with fingolimod resulted in a positive effect on quality of life in both patient-and parent-reported Total score and Physical Health Summary score, as well as in patient-reported Psychosocial Health Summary score compared with IFN beta-1a (all p< 0.05).
Conclusion(s): Consistent with the primary efficacy results, treatment with fingolimod versus IFN beta-1a was associated with a significant improvement in all measures of health-related quality of life as reported by the patients, and in Total score and Physical Health score as reported by their parents
EMBASE:629479063
ISSN: 1477-0970
CID: 4131362
