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Veronica J. Hinton - One of the best experts on this subject based on the ideXlab platform.
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Executive Functioning in the Dystrophinopathies and the Relation to Underlying Mutation Position.
Journal of the International Neuropsychological Society : JINS, 2018Co-Authors: Robert J. Fee, Jacqueline Montes, Veronica J. HintonAbstract:Objectives The aim of this study was to investigate executive skills in children with Dystrophinopathy and to examine the association between executive functions and dystrophin gene mutation position. Methods Fifty boys with Dystrophinopathy (mean age, 11 years 0 months; ages range, 5 to 17 years) completed measures of intellectual functioning (IF), working memory and executive functioning [including Digit Span (working memory) and measures from the NIH Toolbox (selective attention/inhibitory control, set shifting, working memory, and processing speed)]. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF). Mutation positions were categorized into three groups (upstream exon 30, 31-62, and downstream exon 63). Paired-samples t tests compared performance on executive measures to IF, and a one-way (three-group) multivariate analysis of covariance compared cognitive performance with mutation location controlling for motor functioning. Results Mean performance on all executive measures was significantly lower than IF. Parents were also more likely to rate their child with Dystrophinopathy as having clinically significant executive difficulties on the Shift, Emotional Control, and Behavior Regulation indices of the BRIEF. Mutation analyses resulted in small groups limiting power to detect subtle differences. Those with a downstream mutation position had significantly poorer performance on IF and Total Digit Span, but not on other measures of executive function including behavior. Conclusions Individuals with Dystrophinopathy have executive skill deficits, but they are not generally associated with more distal mutations. (JINS, 2019, 25, 146-155).
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Executive Skills and Academic Achievement in the Dystrophinopathies.
Journal of the International Neuropsychological Society : JINS, 2018Co-Authors: Robert J. Fee, Jacqueline Montes, Jennifer L. Stewart, Veronica J. HintonAbstract:OBJECTIVES To examine academic performance in Dystrophinopathy as a function of dystrophin gene mutation position as well as intellectual function, executive skills, socioeconomic status (SES), behavior, and physical ability. METHODS In a cross-sectional study, boys with Dystrophinopathy (ages 5-17; n=50) completed tests of academics (Woodcock-Johnson-III: spelling, reading, calculation and total scores), executive functioning (selective attention/inhibitory control, set shifting, working memory, and processing speed), single word comprehension and nonverbal reasoning. Motor skills were assessed and parents provided demographic information and child behavioral assessments. Dystrophin gene mutation positions were dichotomized into groups (upstream versus downstream of exon 43, location of isoforms previously linked to intellectual impairment). Genetic mutation groups were compared on measures of academic achievement, and multiple regression analyses examined unique and joint contributions of executive skills, intelligence quotient (IQ), SES, motor abilities, behavior, and mutation positions to academic outcomes. RESULTS Academic performance was slightly, yet significantly, lower than IQ and varied as a function of dystrophin gene position, wherein boys possessing the downstream mutation exhibited greater impairment than boys with the upstream mutation. Digit span forward (indexing verbal span), but no other measure of executive function, contributed significant variance to total academic achievement, spelling and calculation. CONCLUSIONS Weak academic performance is associated with Dystrophinopathy and is more common in downstream mutations. A specific deficit in verbal span may underlie inefficiencies observed in children with Dystrophinopathy and may drive deficits impacting academic abilities. (JINS, 2018, 24, 928-938).
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digit span performance in children with Dystrophinopathy a verbal span or working memory contribution
Journal of The International Neuropsychological Society, 2016Co-Authors: Emily B. Leaffer, Veronica J. HintonAbstract:In a large cohort of boys with dystrophinopathies and their unaffected siblings, we examined whether consistently observed performance on digit span is due primarily to a verbal span or executive deficit. We additionally assessed whether digit span performance contributed to the observed variability in reading performance noted in this population.Performance of 170 boys with Dystrophinopathy was compared to 95 unaffected sibling controls on measures of verbal function, reading, and digit span. Maximum digit span forward (DSF) and backward (DSB) lengths were converted to Z-scores using normative data. Independent sample t tests, analysis of variance, and hierarchical multiple regression were run (α=0.05).Probands performed worse than controls on digit span, even after accounting for differences in general verbal function (p<.0001). Differences were significant for both DSF (p<.005) and DSB (p<.0001) span length, and an interaction effect yielded significantly worse DSB compared with DSF (p=.01). Reading performance was also lower in probands (p<.0001). The contribution of general level of verbal function, and forward and backward span lengths, did not vary between groups.In boys with Dystrophinopathy, decreased performance on digit span appears to be due to both decreased span forward (measuring verbal span only) and backward (measuring verbal span and working memory). The extent to which sibling controls exhibited better performance compared to the probands was significantly greater for backward span when compared with forward span. Thus, immediate verbal memory and executive control are differentially compromised among boys with Dystrophinopathy, and both of these abilities independently contribute to reading performance. (JINS, 2016, 22, 777-784).
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digit span performance in children with Dystrophinopathy a verbal span or working memory contribution
Journal of The International Neuropsychological Society, 2016Co-Authors: Emily B. Leaffer, Robert J. Fee, Veronica J. HintonAbstract:OBJECTIVES In a large cohort of boys with dystrophinopathies and their unaffected siblings, we examined whether consistently observed performance on digit span is due primarily to a verbal span or executive deficit. We additionally assessed whether digit span performance contributed to the observed variability in reading performance noted in this population. METHODS Performance of 170 boys with Dystrophinopathy was compared to 95 unaffected sibling controls on measures of verbal function, reading, and digit span. Maximum digit span forward (DSF) and backward (DSB) lengths were converted to Z-scores using normative data. Independent sample t tests, analysis of variance, and hierarchical multiple regression were run (α=0.05). RESULTS Probands performed worse than controls on digit span, even after accounting for differences in general verbal function (p<.0001). Differences were significant for both DSF (p<.005) and DSB (p<.0001) span length, and an interaction effect yielded significantly worse DSB compared with DSF (p=.01). Reading performance was also lower in probands (p<.0001). The contribution of general level of verbal function, and forward and backward span lengths, did not vary between groups. CONCLUSIONS In boys with Dystrophinopathy, decreased performance on digit span appears to be due to both decreased span forward (measuring verbal span only) and backward (measuring verbal span and working memory). The extent to which sibling controls exhibited better performance compared to the probands was significantly greater for backward span when compared with forward span. Thus, immediate verbal memory and executive control are differentially compromised among boys with Dystrophinopathy, and both of these abilities independently contribute to reading performance. (JINS, 2016, 22, 777-784).
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Association of Autistic Spectrum Disorders With Dystrophinopathies
Pediatric neurology, 2009Co-Authors: Veronica J. Hinton, Robert J. Fee, Shana E. Cyrulnik, Abigail W. Batchelder, Jacqueline M. Kiefel, Edward Goldstein, Petra Kaufmann, Darryl C. De VivoAbstract:Parents of 85 boys with dystrophinopathies and 51 sibling controls completed the Social Communication Questionnaire, describing child behaviors associated with autism spectrum disorders and a rating of parental stress. Twenty-one boys with dystrophinopathies and no siblings received scores above the cut-point for possible autistic spectrum disorders. Mothers of identified children were given detailed interviews using the Autism Diagnostic Interview-Revised, and 16 boys (about 19% of the sample) met the criteria for autism spectrum disorders. Significant qualitative abnormalities in reciprocal social interactions and communication were evident in all, whereas restricted and repetitive behaviors were generally less pronounced in the group. Moreover, parents of boys with Dystrophinopathy and autism spectrum disorders demonstrated significantly higher ratings of stress than parents of boys with Dystrophinopathy alone. Increased attention to behavioral concerns associated with dystrophinopathies is necessary to ensure the well-being of the whole family.
Kevin M. Flanigan - One of the best experts on this subject based on the ideXlab platform.
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low level dystrophin expression attenuating the Dystrophinopathy phenotype
Neuromuscular Disorders, 2017Co-Authors: Megan A Waldrop, Kevin M. Flanigan, Felecia Gumienny, Saleh El Husayni, Diane E Frank, Robert B WeissAbstract:The reading frame rule suggests that Duchenne muscular dystrophy (DMD) results from DMD mutations causing an out-of-frame transcript, whereas the milder Becker muscular dystrophy results from mutations causing an in-frame transcript. However, predicted nonsense mutations may instead result in altered splicing and an in-frame transcript. Here we report a 10-year-old boy with a predicted nonsense mutation in exon 42 who had a 6-minute walk time of 157% of that of age matched DMD controls, characterized as intermediate muscular dystrophy. RNA sequencing analysis from a muscle biopsy revealed only 6.0-9.8% of DMD transcripts were in-frame, excluding exon 42, and immunoblot demonstrated only 3.2% dystrophin protein expression. Another potential genetic modifier noted was homozygosity for the protective IAAM LTBP4 haplotype. This case suggests that very low levels of DMD exon skipping and dystrophin protein expression may result in amelioration of skeletal muscle weakness, a finding relevant to current dystrophin-restoring therapies.
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reliability and validity of active seated an outcome in Dystrophinopathy
Muscle & Nerve, 2015Co-Authors: Linda Lowes, Kevin M. Flanigan, Jerry R. Mendell, L Alfano, Roger Crawfis, Katherine Berry, Han Yin, Igor DvorchikAbstract:Introduction Traditional upper extremity measures typically focus on distal abilities and do not quantify the unique progression of decline in Dystrophinopathy. We designed ACTIVE-seated to meet this need. Our objective was to establish the tool's validity and reliability. Methods ACTIVE-seated uses the Microsoft Kinect gaming interface to quantify functional reaching ability while playing a custom-designed game. A skeletal tracking algorithm was used to determine the furthest arm excursion in all planes in 61 subjects with Dystrophinopathy and 16 controls. Results Total reachable area was scaled based on arm length to standardize comparisons across subjects and accommodate growth. ACTIVE-seated discriminately ranked subjects from normal controls and by Brooke level (P < 0.001). Scores were highly correlated with parent reports of daily activities and mobility (P < 0.05). Test–retest reliability of ACTIVE-seated was excellent (ICC = 0.97, P < 0.0001). Conclusions Initial evaluation of reliability and validity suggests that ACTIVE-seated shows promise as a clinical and research outcome for individuals with Dystrophinopathy. Muscle Nerve 52:356–362, 2015
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Reliability and validity of active‐seated: An outcome in Dystrophinopathy
Muscle & nerve, 2015Co-Authors: Linda Lowes, Kevin M. Flanigan, Lindsay Alfano, Roger Crawfis, Katherine Berry, Han Yin, Igor Dvorchik, Jerry R. MendellAbstract:Introduction Traditional upper extremity measures typically focus on distal abilities and do not quantify the unique progression of decline in Dystrophinopathy. We designed ACTIVE-seated to meet this need. Our objective was to establish the tool's validity and reliability. Methods ACTIVE-seated uses the Microsoft Kinect gaming interface to quantify functional reaching ability while playing a custom-designed game. A skeletal tracking algorithm was used to determine the furthest arm excursion in all planes in 61 subjects with Dystrophinopathy and 16 controls. Results Total reachable area was scaled based on arm length to standardize comparisons across subjects and accommodate growth. ACTIVE-seated discriminately ranked subjects from normal controls and by Brooke level (P
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ataluren treatment of patients with nonsense mutation Dystrophinopathy
Muscle & Nerve, 2014Co-Authors: Katharine Bushby, Richard Finkel, Anne M Connolly, Brenda Wong, Giacomo P Comi, Kevin M. Flanigan, Nathalie Goemans, Richard J Barohn, Craig Campbell, Kristi J JonesAbstract:Introduction: Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. Methods: Randomized, double-blind, placebo-controlled study; males ≥5 years with nm-Dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (N = 57); ataluren 20, 20, 40 mg/kg (N = 60); or placebo (N = 57) for 48 weeks. The primary endpoint was change in 6-Minute Walk Distance (6MWD) at Week 48. Results: Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg versus placebo; the week 48 6MWD Δ = 31.3 meters, post hoc P = 0.056. Secondary endpoints (timed function tests) showed meaningful differences between ataluren 10, 10, 20 mg/kg, and placebo. Conclusions: As the first investigational new drug targeting the underlying cause of nm-Dystrophinopathy, ataluren offers promise as a treatment for this orphan genetic disorder with high unmet medical need. Muscle Nerve 50: 477–487, 2014
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Proof of concept of the ability of the kinect to quantify upper extremity function in Dystrophinopathy.
PLoS currents, 2013Co-Authors: Linda Lowes, Kevin M. Flanigan, Lindsay Alfano, Brent A Yetter, Lise Worthen-chaudhari, William Hinchman, Jordan Savage, Patrick Samona, Jerry R. MendellAbstract:Introduction: Individuals with Dystrophinopathy lose upper extremity strength in proximal muscles followed by those more distal. Current upper extremity evaluation tools fail to fully capture changes in upper extremity strength and function across the disease spectrum as they tend to focus solely on distal ability. The Kinect by Microsoft is a gaming interface that can gather positional information about an individuals upper extremity movement which can be used to determine functional reaching volume, velocity of movement, and rate of fatigue while playing an engaging video game. The purpose of this study was to determine the feasibility of using the Kinect platform to assess upper extremity function in individuals with Dystrophinopathy across the spectrum of abilities. Methods: Investigators developed a proof-of-concept device, ACTIVE (Abilities Captured Through Interactive Video Evaluation), to measure functional reaching volume, movement velocity, and rate of fatigue. Five subjects with Dystrophinopathy and 5 normal controls were tested using ACTIVE during one testing session. A single subject with Dystrophinopathy was simultaneously tested with ACTIVE and a marker-based motion analysis system to establish preliminary validity of measurements. Results: ACTIVE proof-of-concept ranked the upper extremity abilities of subjects with Dystrophinopathy by Brooke score, and also differentiated them from performance of normal controls for the functional reaching volume and velocity tests. Preliminary test-retest reliability of the ACTIVE for 2 sequential trials was excellent for functional reaching volume (ICC=0.986, p Discussion: The data from our pilot study with ACTIVE proof-of- concept demonstrates that newly available gaming technology has potential to be used to create a low-cost, widely-accessible and functional upper extremity outcome measure for use with children and adults with Dystrophinopathy. Abstract Introduction: Individuals with Dystrophinopathy lose upper extremity strength in proximal muscles followed by those more distal. Current upper extremity evaluation tools fail to fully capture changes in upper extremity strength and function across the disease spectrum as they tend to focus solely on distal ability. The Kinect by Microsoft is a gaming interface that can gather positional information about an individuals upper extremity movement which can be used to determine functional reaching volume, velocity of movement, and rate of fatigue while playing an engaging video game. The purpose of this study was to determine the feasibility of using the Kinect platform to assess upper extremity function in individuals with Dystrophinopathy across the spectrum of abilities. Methods: Investigators developed a proof-of-concept device, ACTIVE (Abilities Captured Through Interactive Video Evaluation), to measure functional reaching volume, movement velocity, and rate of fatigue. Five subjects with Dystrophinopathy and 5 normal controls were tested using ACTIVE during one testing session. A single subject with Dystrophinopathy was simultaneously tested with ACTIVE and a marker-based motion analysis system to establish preliminary validity of measurements. Results: ACTIVE proof-of-concept ranked the upper extremity abilities of subjects with Dystrophinopathy by Brooke score, and also differentiated them from performance of normal controls for the functional reaching volume and velocity tests. Preliminary test-retest reliability of the ACTIVE for 2 sequential trials was excellent for functional reaching volume (ICC=0.986, p Discussion: The data from our pilot study with ACTIVE proof-of- concept demonstrates that newly available gaming technology has potential to be used to create a low-cost, widely-accessible and functional upper extremity outcome measure for use with children and adults with Dystrophinopathy. Abstract Introduction: Individuals with Dystrophinopathy lose upper extremity strength in proximal muscles followed by those more distal. Current upper extremity evaluation tools fail to fully capture changes in upper extremity strength and function across the disease spectrum as they tend to focus solely on distal ability. The Kinect by Microsoft is a gaming interface that can gather positional information about an individuals upper extremity movement which can be used to determine functional reaching volume, velocity of movement, and rate of fatigue while playing an engaging video game. The purpose of this study was to determine the feasibility of using the Kinect platform to assess upper extremity function in individuals with Dystrophinopathy across the spectrum of abilities. Methods: Investigators developed a proof-of-concept device, ACTIVE (Abilities Captured Through Interactive Video Evaluation), to measure functional reaching volume, movement velocity, and rate of fatigue. Five subjects with Dystrophinopathy and 5 normal controls were tested using ACTIVE during one testing session. A single subject with Dystrophinopathy was simultaneously tested with ACTIVE and a marker-based motion analysis system to establish preliminary validity of measurements. Results: ACTIVE proof-of-concept ranked the upper extremity abilities of subjects with Dystrophinopathy by Brooke score, and also differentiated them from performance of normal controls for the functional reaching volume and velocity tests. Preliminary test-retest reliability of the ACTIVE for 2 sequential trials was excellent for functional reaching volume (ICC=0.986, p Discussion: The data from our pilot study with ACTIVE proof-of- concept demonstrates that newly available gaming technology has potential to be used to create a low-cost, widely-accessible and functional upper extremity outcome measure for use with children and adults with Dystrophinopathy.
Emily B. Leaffer - One of the best experts on this subject based on the ideXlab platform.
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digit span performance in children with Dystrophinopathy a verbal span or working memory contribution
Journal of The International Neuropsychological Society, 2016Co-Authors: Emily B. Leaffer, Veronica J. HintonAbstract:In a large cohort of boys with dystrophinopathies and their unaffected siblings, we examined whether consistently observed performance on digit span is due primarily to a verbal span or executive deficit. We additionally assessed whether digit span performance contributed to the observed variability in reading performance noted in this population.Performance of 170 boys with Dystrophinopathy was compared to 95 unaffected sibling controls on measures of verbal function, reading, and digit span. Maximum digit span forward (DSF) and backward (DSB) lengths were converted to Z-scores using normative data. Independent sample t tests, analysis of variance, and hierarchical multiple regression were run (α=0.05).Probands performed worse than controls on digit span, even after accounting for differences in general verbal function (p<.0001). Differences were significant for both DSF (p<.005) and DSB (p<.0001) span length, and an interaction effect yielded significantly worse DSB compared with DSF (p=.01). Reading performance was also lower in probands (p<.0001). The contribution of general level of verbal function, and forward and backward span lengths, did not vary between groups.In boys with Dystrophinopathy, decreased performance on digit span appears to be due to both decreased span forward (measuring verbal span only) and backward (measuring verbal span and working memory). The extent to which sibling controls exhibited better performance compared to the probands was significantly greater for backward span when compared with forward span. Thus, immediate verbal memory and executive control are differentially compromised among boys with Dystrophinopathy, and both of these abilities independently contribute to reading performance. (JINS, 2016, 22, 777-784).
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digit span performance in children with Dystrophinopathy a verbal span or working memory contribution
Journal of The International Neuropsychological Society, 2016Co-Authors: Emily B. Leaffer, Robert J. Fee, Veronica J. HintonAbstract:OBJECTIVES In a large cohort of boys with dystrophinopathies and their unaffected siblings, we examined whether consistently observed performance on digit span is due primarily to a verbal span or executive deficit. We additionally assessed whether digit span performance contributed to the observed variability in reading performance noted in this population. METHODS Performance of 170 boys with Dystrophinopathy was compared to 95 unaffected sibling controls on measures of verbal function, reading, and digit span. Maximum digit span forward (DSF) and backward (DSB) lengths were converted to Z-scores using normative data. Independent sample t tests, analysis of variance, and hierarchical multiple regression were run (α=0.05). RESULTS Probands performed worse than controls on digit span, even after accounting for differences in general verbal function (p<.0001). Differences were significant for both DSF (p<.005) and DSB (p<.0001) span length, and an interaction effect yielded significantly worse DSB compared with DSF (p=.01). Reading performance was also lower in probands (p<.0001). The contribution of general level of verbal function, and forward and backward span lengths, did not vary between groups. CONCLUSIONS In boys with Dystrophinopathy, decreased performance on digit span appears to be due to both decreased span forward (measuring verbal span only) and backward (measuring verbal span and working memory). The extent to which sibling controls exhibited better performance compared to the probands was significantly greater for backward span when compared with forward span. Thus, immediate verbal memory and executive control are differentially compromised among boys with Dystrophinopathy, and both of these abilities independently contribute to reading performance. (JINS, 2016, 22, 777-784).
Jerry R. Mendell - One of the best experts on this subject based on the ideXlab platform.
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reliability and validity of active seated an outcome in Dystrophinopathy
Muscle & Nerve, 2015Co-Authors: Linda Lowes, Kevin M. Flanigan, Jerry R. Mendell, L Alfano, Roger Crawfis, Katherine Berry, Han Yin, Igor DvorchikAbstract:Introduction Traditional upper extremity measures typically focus on distal abilities and do not quantify the unique progression of decline in Dystrophinopathy. We designed ACTIVE-seated to meet this need. Our objective was to establish the tool's validity and reliability. Methods ACTIVE-seated uses the Microsoft Kinect gaming interface to quantify functional reaching ability while playing a custom-designed game. A skeletal tracking algorithm was used to determine the furthest arm excursion in all planes in 61 subjects with Dystrophinopathy and 16 controls. Results Total reachable area was scaled based on arm length to standardize comparisons across subjects and accommodate growth. ACTIVE-seated discriminately ranked subjects from normal controls and by Brooke level (P < 0.001). Scores were highly correlated with parent reports of daily activities and mobility (P < 0.05). Test–retest reliability of ACTIVE-seated was excellent (ICC = 0.97, P < 0.0001). Conclusions Initial evaluation of reliability and validity suggests that ACTIVE-seated shows promise as a clinical and research outcome for individuals with Dystrophinopathy. Muscle Nerve 52:356–362, 2015
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Reliability and validity of active‐seated: An outcome in Dystrophinopathy
Muscle & nerve, 2015Co-Authors: Linda Lowes, Kevin M. Flanigan, Lindsay Alfano, Roger Crawfis, Katherine Berry, Han Yin, Igor Dvorchik, Jerry R. MendellAbstract:Introduction Traditional upper extremity measures typically focus on distal abilities and do not quantify the unique progression of decline in Dystrophinopathy. We designed ACTIVE-seated to meet this need. Our objective was to establish the tool's validity and reliability. Methods ACTIVE-seated uses the Microsoft Kinect gaming interface to quantify functional reaching ability while playing a custom-designed game. A skeletal tracking algorithm was used to determine the furthest arm excursion in all planes in 61 subjects with Dystrophinopathy and 16 controls. Results Total reachable area was scaled based on arm length to standardize comparisons across subjects and accommodate growth. ACTIVE-seated discriminately ranked subjects from normal controls and by Brooke level (P
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Proof of concept of the ability of the kinect to quantify upper extremity function in Dystrophinopathy.
PLoS currents, 2013Co-Authors: Linda Lowes, Kevin M. Flanigan, Lindsay Alfano, Brent A Yetter, Lise Worthen-chaudhari, William Hinchman, Jordan Savage, Patrick Samona, Jerry R. MendellAbstract:Introduction: Individuals with Dystrophinopathy lose upper extremity strength in proximal muscles followed by those more distal. Current upper extremity evaluation tools fail to fully capture changes in upper extremity strength and function across the disease spectrum as they tend to focus solely on distal ability. The Kinect by Microsoft is a gaming interface that can gather positional information about an individuals upper extremity movement which can be used to determine functional reaching volume, velocity of movement, and rate of fatigue while playing an engaging video game. The purpose of this study was to determine the feasibility of using the Kinect platform to assess upper extremity function in individuals with Dystrophinopathy across the spectrum of abilities. Methods: Investigators developed a proof-of-concept device, ACTIVE (Abilities Captured Through Interactive Video Evaluation), to measure functional reaching volume, movement velocity, and rate of fatigue. Five subjects with Dystrophinopathy and 5 normal controls were tested using ACTIVE during one testing session. A single subject with Dystrophinopathy was simultaneously tested with ACTIVE and a marker-based motion analysis system to establish preliminary validity of measurements. Results: ACTIVE proof-of-concept ranked the upper extremity abilities of subjects with Dystrophinopathy by Brooke score, and also differentiated them from performance of normal controls for the functional reaching volume and velocity tests. Preliminary test-retest reliability of the ACTIVE for 2 sequential trials was excellent for functional reaching volume (ICC=0.986, p Discussion: The data from our pilot study with ACTIVE proof-of- concept demonstrates that newly available gaming technology has potential to be used to create a low-cost, widely-accessible and functional upper extremity outcome measure for use with children and adults with Dystrophinopathy. Abstract Introduction: Individuals with Dystrophinopathy lose upper extremity strength in proximal muscles followed by those more distal. Current upper extremity evaluation tools fail to fully capture changes in upper extremity strength and function across the disease spectrum as they tend to focus solely on distal ability. The Kinect by Microsoft is a gaming interface that can gather positional information about an individuals upper extremity movement which can be used to determine functional reaching volume, velocity of movement, and rate of fatigue while playing an engaging video game. The purpose of this study was to determine the feasibility of using the Kinect platform to assess upper extremity function in individuals with Dystrophinopathy across the spectrum of abilities. Methods: Investigators developed a proof-of-concept device, ACTIVE (Abilities Captured Through Interactive Video Evaluation), to measure functional reaching volume, movement velocity, and rate of fatigue. Five subjects with Dystrophinopathy and 5 normal controls were tested using ACTIVE during one testing session. A single subject with Dystrophinopathy was simultaneously tested with ACTIVE and a marker-based motion analysis system to establish preliminary validity of measurements. Results: ACTIVE proof-of-concept ranked the upper extremity abilities of subjects with Dystrophinopathy by Brooke score, and also differentiated them from performance of normal controls for the functional reaching volume and velocity tests. Preliminary test-retest reliability of the ACTIVE for 2 sequential trials was excellent for functional reaching volume (ICC=0.986, p Discussion: The data from our pilot study with ACTIVE proof-of- concept demonstrates that newly available gaming technology has potential to be used to create a low-cost, widely-accessible and functional upper extremity outcome measure for use with children and adults with Dystrophinopathy. Abstract Introduction: Individuals with Dystrophinopathy lose upper extremity strength in proximal muscles followed by those more distal. Current upper extremity evaluation tools fail to fully capture changes in upper extremity strength and function across the disease spectrum as they tend to focus solely on distal ability. The Kinect by Microsoft is a gaming interface that can gather positional information about an individuals upper extremity movement which can be used to determine functional reaching volume, velocity of movement, and rate of fatigue while playing an engaging video game. The purpose of this study was to determine the feasibility of using the Kinect platform to assess upper extremity function in individuals with Dystrophinopathy across the spectrum of abilities. Methods: Investigators developed a proof-of-concept device, ACTIVE (Abilities Captured Through Interactive Video Evaluation), to measure functional reaching volume, movement velocity, and rate of fatigue. Five subjects with Dystrophinopathy and 5 normal controls were tested using ACTIVE during one testing session. A single subject with Dystrophinopathy was simultaneously tested with ACTIVE and a marker-based motion analysis system to establish preliminary validity of measurements. Results: ACTIVE proof-of-concept ranked the upper extremity abilities of subjects with Dystrophinopathy by Brooke score, and also differentiated them from performance of normal controls for the functional reaching volume and velocity tests. Preliminary test-retest reliability of the ACTIVE for 2 sequential trials was excellent for functional reaching volume (ICC=0.986, p Discussion: The data from our pilot study with ACTIVE proof-of- concept demonstrates that newly available gaming technology has potential to be used to create a low-cost, widely-accessible and functional upper extremity outcome measure for use with children and adults with Dystrophinopathy.
Robert J. Fee - One of the best experts on this subject based on the ideXlab platform.
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Executive Functioning in the Dystrophinopathies and the Relation to Underlying Mutation Position.
Journal of the International Neuropsychological Society : JINS, 2018Co-Authors: Robert J. Fee, Jacqueline Montes, Veronica J. HintonAbstract:Objectives The aim of this study was to investigate executive skills in children with Dystrophinopathy and to examine the association between executive functions and dystrophin gene mutation position. Methods Fifty boys with Dystrophinopathy (mean age, 11 years 0 months; ages range, 5 to 17 years) completed measures of intellectual functioning (IF), working memory and executive functioning [including Digit Span (working memory) and measures from the NIH Toolbox (selective attention/inhibitory control, set shifting, working memory, and processing speed)]. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF). Mutation positions were categorized into three groups (upstream exon 30, 31-62, and downstream exon 63). Paired-samples t tests compared performance on executive measures to IF, and a one-way (three-group) multivariate analysis of covariance compared cognitive performance with mutation location controlling for motor functioning. Results Mean performance on all executive measures was significantly lower than IF. Parents were also more likely to rate their child with Dystrophinopathy as having clinically significant executive difficulties on the Shift, Emotional Control, and Behavior Regulation indices of the BRIEF. Mutation analyses resulted in small groups limiting power to detect subtle differences. Those with a downstream mutation position had significantly poorer performance on IF and Total Digit Span, but not on other measures of executive function including behavior. Conclusions Individuals with Dystrophinopathy have executive skill deficits, but they are not generally associated with more distal mutations. (JINS, 2019, 25, 146-155).
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Executive Skills and Academic Achievement in the Dystrophinopathies.
Journal of the International Neuropsychological Society : JINS, 2018Co-Authors: Robert J. Fee, Jacqueline Montes, Jennifer L. Stewart, Veronica J. HintonAbstract:OBJECTIVES To examine academic performance in Dystrophinopathy as a function of dystrophin gene mutation position as well as intellectual function, executive skills, socioeconomic status (SES), behavior, and physical ability. METHODS In a cross-sectional study, boys with Dystrophinopathy (ages 5-17; n=50) completed tests of academics (Woodcock-Johnson-III: spelling, reading, calculation and total scores), executive functioning (selective attention/inhibitory control, set shifting, working memory, and processing speed), single word comprehension and nonverbal reasoning. Motor skills were assessed and parents provided demographic information and child behavioral assessments. Dystrophin gene mutation positions were dichotomized into groups (upstream versus downstream of exon 43, location of isoforms previously linked to intellectual impairment). Genetic mutation groups were compared on measures of academic achievement, and multiple regression analyses examined unique and joint contributions of executive skills, intelligence quotient (IQ), SES, motor abilities, behavior, and mutation positions to academic outcomes. RESULTS Academic performance was slightly, yet significantly, lower than IQ and varied as a function of dystrophin gene position, wherein boys possessing the downstream mutation exhibited greater impairment than boys with the upstream mutation. Digit span forward (indexing verbal span), but no other measure of executive function, contributed significant variance to total academic achievement, spelling and calculation. CONCLUSIONS Weak academic performance is associated with Dystrophinopathy and is more common in downstream mutations. A specific deficit in verbal span may underlie inefficiencies observed in children with Dystrophinopathy and may drive deficits impacting academic abilities. (JINS, 2018, 24, 928-938).
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digit span performance in children with Dystrophinopathy a verbal span or working memory contribution
Journal of The International Neuropsychological Society, 2016Co-Authors: Emily B. Leaffer, Robert J. Fee, Veronica J. HintonAbstract:OBJECTIVES In a large cohort of boys with dystrophinopathies and their unaffected siblings, we examined whether consistently observed performance on digit span is due primarily to a verbal span or executive deficit. We additionally assessed whether digit span performance contributed to the observed variability in reading performance noted in this population. METHODS Performance of 170 boys with Dystrophinopathy was compared to 95 unaffected sibling controls on measures of verbal function, reading, and digit span. Maximum digit span forward (DSF) and backward (DSB) lengths were converted to Z-scores using normative data. Independent sample t tests, analysis of variance, and hierarchical multiple regression were run (α=0.05). RESULTS Probands performed worse than controls on digit span, even after accounting for differences in general verbal function (p<.0001). Differences were significant for both DSF (p<.005) and DSB (p<.0001) span length, and an interaction effect yielded significantly worse DSB compared with DSF (p=.01). Reading performance was also lower in probands (p<.0001). The contribution of general level of verbal function, and forward and backward span lengths, did not vary between groups. CONCLUSIONS In boys with Dystrophinopathy, decreased performance on digit span appears to be due to both decreased span forward (measuring verbal span only) and backward (measuring verbal span and working memory). The extent to which sibling controls exhibited better performance compared to the probands was significantly greater for backward span when compared with forward span. Thus, immediate verbal memory and executive control are differentially compromised among boys with Dystrophinopathy, and both of these abilities independently contribute to reading performance. (JINS, 2016, 22, 777-784).
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Association of Autistic Spectrum Disorders With Dystrophinopathies
Pediatric neurology, 2009Co-Authors: Veronica J. Hinton, Robert J. Fee, Shana E. Cyrulnik, Abigail W. Batchelder, Jacqueline M. Kiefel, Edward Goldstein, Petra Kaufmann, Darryl C. De VivoAbstract:Parents of 85 boys with dystrophinopathies and 51 sibling controls completed the Social Communication Questionnaire, describing child behaviors associated with autism spectrum disorders and a rating of parental stress. Twenty-one boys with dystrophinopathies and no siblings received scores above the cut-point for possible autistic spectrum disorders. Mothers of identified children were given detailed interviews using the Autism Diagnostic Interview-Revised, and 16 boys (about 19% of the sample) met the criteria for autism spectrum disorders. Significant qualitative abnormalities in reciprocal social interactions and communication were evident in all, whereas restricted and repetitive behaviors were generally less pronounced in the group. Moreover, parents of boys with Dystrophinopathy and autism spectrum disorders demonstrated significantly higher ratings of stress than parents of boys with Dystrophinopathy alone. Increased attention to behavioral concerns associated with dystrophinopathies is necessary to ensure the well-being of the whole family.
