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Electrical impedance myography as a potential biomarker in individuals with COL6-related dystrophy
Abstracts / Neuromuscular Disorders 25 (2015) S184–S316 10
S265
surgery performed at a younger age may decrease the progression of respiratory failure in UCMD.
Lyon, Bron, France; USA
http://dx.doi.org/10.1016/j.nmd.2015.06.286
Electrical Impedance Myography is a non-invasive method of measuring muscle health. Resistance is a measured value related to the extracellular and intracellular elements of the muscle such as fibrosis. Reactance is a measured value of the capacitance of the muscle fiber membrane. The phase angle is a calculated value to signify change in voltage output compared to current input and suggestive of the health of the muscle. EIM has been proposed as a meaningful biomarker in the ALS population and is currently being investigated in other neuromuscular diseases (Duchenne Muscular Dystrophy, Spinal Muscular Atrophy). Collagen VI related dystrophy (COL6-RD) is a progressive neuromuscular disease in which individuals present with weakness, contractures, distal joint laxity, respiratory difficulties, with many unable to attain or maintain ambulatory status. The goal of this study was to compare, in individuals with COL6-RD, EIM phase angle measurements with the Motor Function Measure (MFM) 32, North Star Ambulatory Assessment (NSAA) and myometry measurements. Twenty-one individuals with COL6-RD (ages 7–19 years; 12 males; 11 ambulant) participated in this study as part of a natural history study. EIM measurements were assessed unilaterally: deltoids, triceps, biceps, wrist flexors, quadriceps, hamstrings, tibialis anterior and gastrocnemius. MFM32 and NSAA were administered; muscle strength of bilateral elbow flexors/extensors and knee flexors/extensors were measured. EIM scores were totaled as a composite score and compared to total MFM32 and NSAA scores (Spearman’s rho correlation) and compared to myometry sum (Pearson’s correlations). EIM correlated with MFM32 (0.742, p = 0.01), NSAA (0.791, p = 0.01), and myometry (0.622, p = 0.01). Preliminary findings of this study suggest the use of EIM as biomarker in individuals with COL6RD. Future studies should compare EIM measures to ultrasound imaging, muscle biopsy findings, and its sensitivity to change over time.
G.P.263 Comparison of upper extremity measures in individuals with COL6 and LAMA2-muscular dystrophies M. Jain *,1, K. Meilleur 2, C. Nichols 1, M. Waite 1, R. Parks 1, B. Hodsdon 1, R. Bendixen 3, N. Hsia 4, A. Glanzman 4, L. Nelson 5, K. Keller 6, T. Duong 7, M. McGuire 8, J. Dastgir 9, S. Donkervoort 9, M. Leach 9, J. Collins 8, C. Vuillerot 10, A. Rutkowski 11, C. Bönnemann 9 1 National Institutes of Health, Rehabilitation Medicine Department, Bethesda, USA; 2 National Institutes of Health, National Institute of Nursing Research, Bethesda, USA; 3 University of Pittsburgh, Pittsburgh, USA; 4 Children’s Hospital of Philadelphia, Philadelphia, USA; 5 University of Texas Southwestern Medical Center, Dallas, USA; 6 Rady Children’s Hospital, San Diego, USA; 7 Children’s National Medical Center, Washington, DC, USA; 8 Cincinnati Children’s Hospital Medical Center, Cincinnati, USA; 9 National Institutes of Health, NINDS, Bethesda, USA; 10 Hospices Civils de Lyon, Bron, France; 11 Kaiser Permanente SCPMG, Cure CMD, Los Angeles, USA Congenital muscular dystrophies (CMD) are a heterogeneous group of early onset degenerative diseases of the muscle leading to progressive weakness, affecting mobility and respiratory function; Collagen VI-related dystrophies (COL6-RD) and Laminin alpha2-related muscular dystrophy (LAMA2-RD) are 2 of the most common subtypes. Therapeutic interventions targeting both populations are currently under development. In preparation for clinical trials, it is important to select outcome measures to evaluate the efficacy of therapeutic interventions. The goal of this study was to examine the relationships between various upper extremity (UE) measures to determine if they are feasible and reliable in ambulatory and non-ambulatory individuals with COL6-RD and LAMA2-RD. Our cohort included 37 individuals diagnosed with COL6-RD (n = 18) and LAMA2-RD (n = 19) as part of a larger natural history study. Of the 37 individuals, 11 were ambulant; with an equitable gender distribution; males = 18, females = 19. We administered UE measures, including the Jebsen Hand Function Test (Jebsen), myometry (elbow flexors/extensors), grip/hand strength as measured by the Myogrip and Myopinch, and distal hand function as measured by the Moviplate, Motor Function Measure 32 (D3-distal function) and the Brooke Upper Extremity Scale. While all tests were administered bilaterally, maximal scores for each side were totaled and analyzed as a sum of the scores. Spearman’s rho correlations were calculated, resulting in high correlations between D3 measurements and myometry (r = .831), Myogrip (r = .848), Myopinch (r = .837), the Moviplate (r = .721) and there was a large inverse correlation between D3 and the Jebsen (r = −823) and the Brooke (r = −.755, all p < 0.01). These data support the use of these assessments to measure upper extremity/hand function in non-ambulant and ambulant individuals with COL6-RD and LAMA2-RD. http://dx.doi.org/10.1016/j.nmd.2015.06.287
G.P.264 Electrical impedance myography as a potential biomarker in individuals with COL6-related dystrophy C. Nichols 1, T. Lehky 2, M. Waite 1, T. Duong 3, L. Nelson 4, K. Keller 5, D. Lott 6, K. Meilleur 7, J. Collins 8, J. Dastgir 2, C. Vuillerot 9, A. Rutkowski 10, S. Donkervoort 2, M. Leach 2, M. Jain *,1, C. Bönnemann 2 1 National Institutes of Health, Rehabilitation Medicine Department, Bethesda, USA; 2 National Institutes of Health, NINDS, Bethesda, USA; 3 Children’s National Medical Center, Washington, DC, USA; 4 University of Texas Southwestern Medical Center, Dallas, USA; 5 Rady Children’s Hospital, San Diego, USA; 6 University of Florida, Gainesville, USA; 7 National Institutes of Health, National Institute of Nursing Research, Bethesda, USA; 8 Cincinnati Children’s Hospital Medical Center, Cincinnati, USA; 9 Hospices Civils de
Kaiser Permanente SCPMG, Cure CMD, Los Angeles,
http://dx.doi.org/10.1016/j.nmd.2015.06.288
G.P.265 Validation of actiGraph GT3X accelerometers in collagen 6-related muscular dystrophy and LAMA2-related muscular dystrophy K. Meilleur 1, J. Elliott 1, M. Linton 1, C. Vuillerot 2, R. Bendixen 3, I. Arveson 1, F. Tounkara 1, M. Waite 4, C. Nichols 4, K. Yang 5, S. Donkervoort 5, J. Dastgir 6, M. Leach 5, C. Bönnemann 5, M. Jain *,4 1 National Institutes of Health, National Institute of Nursing Research, Bethesda, USA; 2 Hospices Civils de Lyon, Bron, France; 3 University of Pittsburgh, Pittsburgh, USA; 4 National Institutes of Health, Rehabilitation Medicine Department, Bethesda, USA; 5 National Institutes of Health, NINDS, Bethesda, USA; 6 Columbia University, Department of Neurology, New York, USA This study aimed to determine whether ActiGraph GT3X accelerometers (AG) reliably measure energy expenditure for individuals with Collagen VI-Related Muscular Dystrophy (COL6-RD) or LAMA2-Related Muscular Dystrophy (LAMA2-RD). This objective was twofold: 1) to assess the validity of the step-counting function of AG in congenital muscular dystrophy, and 2) to assess criterion validity of AG against clinical measures of motor function. Patients often perform at top motor capacity in clinic. Measuring activity at home may better reflect typical motor performance. AG provides a means of capturing normal activity outside of the clinical setting. AG has not been validated in COL6-RD or LAMA2-RD. In clinic, AG step-count data were validated against a manual step-counter in 11 ambulatory subjects. Motor measures were administered, including the North Star Ambulatory Assessment (NSAA), Motor Function Measure 32 (MFM32), Six-Minute Walk Test (6MWT), and a self-reported measure of limitations of activity (ACTIVLIM). Participants then wore AG at home for seven days. Measurements captured by AG, including vector magnitude counts per minute (VM CPM), steps per minute (SPM), and % moderate-vigorous physical activity (% MVPA), were compared with the motor measures. Data were analyzed by Spearman correlation. The correlation between AG-counted steps and hand-counted steps
S265
surgery performed at a younger age may decrease the progression of respiratory failure in UCMD.
Lyon, Bron, France; USA
http://dx.doi.org/10.1016/j.nmd.2015.06.286
Electrical Impedance Myography is a non-invasive method of measuring muscle health. Resistance is a measured value related to the extracellular and intracellular elements of the muscle such as fibrosis. Reactance is a measured value of the capacitance of the muscle fiber membrane. The phase angle is a calculated value to signify change in voltage output compared to current input and suggestive of the health of the muscle. EIM has been proposed as a meaningful biomarker in the ALS population and is currently being investigated in other neuromuscular diseases (Duchenne Muscular Dystrophy, Spinal Muscular Atrophy). Collagen VI related dystrophy (COL6-RD) is a progressive neuromuscular disease in which individuals present with weakness, contractures, distal joint laxity, respiratory difficulties, with many unable to attain or maintain ambulatory status. The goal of this study was to compare, in individuals with COL6-RD, EIM phase angle measurements with the Motor Function Measure (MFM) 32, North Star Ambulatory Assessment (NSAA) and myometry measurements. Twenty-one individuals with COL6-RD (ages 7–19 years; 12 males; 11 ambulant) participated in this study as part of a natural history study. EIM measurements were assessed unilaterally: deltoids, triceps, biceps, wrist flexors, quadriceps, hamstrings, tibialis anterior and gastrocnemius. MFM32 and NSAA were administered; muscle strength of bilateral elbow flexors/extensors and knee flexors/extensors were measured. EIM scores were totaled as a composite score and compared to total MFM32 and NSAA scores (Spearman’s rho correlation) and compared to myometry sum (Pearson’s correlations). EIM correlated with MFM32 (0.742, p = 0.01), NSAA (0.791, p = 0.01), and myometry (0.622, p = 0.01). Preliminary findings of this study suggest the use of EIM as biomarker in individuals with COL6RD. Future studies should compare EIM measures to ultrasound imaging, muscle biopsy findings, and its sensitivity to change over time.
G.P.263 Comparison of upper extremity measures in individuals with COL6 and LAMA2-muscular dystrophies M. Jain *,1, K. Meilleur 2, C. Nichols 1, M. Waite 1, R. Parks 1, B. Hodsdon 1, R. Bendixen 3, N. Hsia 4, A. Glanzman 4, L. Nelson 5, K. Keller 6, T. Duong 7, M. McGuire 8, J. Dastgir 9, S. Donkervoort 9, M. Leach 9, J. Collins 8, C. Vuillerot 10, A. Rutkowski 11, C. Bönnemann 9 1 National Institutes of Health, Rehabilitation Medicine Department, Bethesda, USA; 2 National Institutes of Health, National Institute of Nursing Research, Bethesda, USA; 3 University of Pittsburgh, Pittsburgh, USA; 4 Children’s Hospital of Philadelphia, Philadelphia, USA; 5 University of Texas Southwestern Medical Center, Dallas, USA; 6 Rady Children’s Hospital, San Diego, USA; 7 Children’s National Medical Center, Washington, DC, USA; 8 Cincinnati Children’s Hospital Medical Center, Cincinnati, USA; 9 National Institutes of Health, NINDS, Bethesda, USA; 10 Hospices Civils de Lyon, Bron, France; 11 Kaiser Permanente SCPMG, Cure CMD, Los Angeles, USA Congenital muscular dystrophies (CMD) are a heterogeneous group of early onset degenerative diseases of the muscle leading to progressive weakness, affecting mobility and respiratory function; Collagen VI-related dystrophies (COL6-RD) and Laminin alpha2-related muscular dystrophy (LAMA2-RD) are 2 of the most common subtypes. Therapeutic interventions targeting both populations are currently under development. In preparation for clinical trials, it is important to select outcome measures to evaluate the efficacy of therapeutic interventions. The goal of this study was to examine the relationships between various upper extremity (UE) measures to determine if they are feasible and reliable in ambulatory and non-ambulatory individuals with COL6-RD and LAMA2-RD. Our cohort included 37 individuals diagnosed with COL6-RD (n = 18) and LAMA2-RD (n = 19) as part of a larger natural history study. Of the 37 individuals, 11 were ambulant; with an equitable gender distribution; males = 18, females = 19. We administered UE measures, including the Jebsen Hand Function Test (Jebsen), myometry (elbow flexors/extensors), grip/hand strength as measured by the Myogrip and Myopinch, and distal hand function as measured by the Moviplate, Motor Function Measure 32 (D3-distal function) and the Brooke Upper Extremity Scale. While all tests were administered bilaterally, maximal scores for each side were totaled and analyzed as a sum of the scores. Spearman’s rho correlations were calculated, resulting in high correlations between D3 measurements and myometry (r = .831), Myogrip (r = .848), Myopinch (r = .837), the Moviplate (r = .721) and there was a large inverse correlation between D3 and the Jebsen (r = −823) and the Brooke (r = −.755, all p < 0.01). These data support the use of these assessments to measure upper extremity/hand function in non-ambulant and ambulant individuals with COL6-RD and LAMA2-RD. http://dx.doi.org/10.1016/j.nmd.2015.06.287
G.P.264 Electrical impedance myography as a potential biomarker in individuals with COL6-related dystrophy C. Nichols 1, T. Lehky 2, M. Waite 1, T. Duong 3, L. Nelson 4, K. Keller 5, D. Lott 6, K. Meilleur 7, J. Collins 8, J. Dastgir 2, C. Vuillerot 9, A. Rutkowski 10, S. Donkervoort 2, M. Leach 2, M. Jain *,1, C. Bönnemann 2 1 National Institutes of Health, Rehabilitation Medicine Department, Bethesda, USA; 2 National Institutes of Health, NINDS, Bethesda, USA; 3 Children’s National Medical Center, Washington, DC, USA; 4 University of Texas Southwestern Medical Center, Dallas, USA; 5 Rady Children’s Hospital, San Diego, USA; 6 University of Florida, Gainesville, USA; 7 National Institutes of Health, National Institute of Nursing Research, Bethesda, USA; 8 Cincinnati Children’s Hospital Medical Center, Cincinnati, USA; 9 Hospices Civils de
Kaiser Permanente SCPMG, Cure CMD, Los Angeles,
http://dx.doi.org/10.1016/j.nmd.2015.06.288
G.P.265 Validation of actiGraph GT3X accelerometers in collagen 6-related muscular dystrophy and LAMA2-related muscular dystrophy K. Meilleur 1, J. Elliott 1, M. Linton 1, C. Vuillerot 2, R. Bendixen 3, I. Arveson 1, F. Tounkara 1, M. Waite 4, C. Nichols 4, K. Yang 5, S. Donkervoort 5, J. Dastgir 6, M. Leach 5, C. Bönnemann 5, M. Jain *,4 1 National Institutes of Health, National Institute of Nursing Research, Bethesda, USA; 2 Hospices Civils de Lyon, Bron, France; 3 University of Pittsburgh, Pittsburgh, USA; 4 National Institutes of Health, Rehabilitation Medicine Department, Bethesda, USA; 5 National Institutes of Health, NINDS, Bethesda, USA; 6 Columbia University, Department of Neurology, New York, USA This study aimed to determine whether ActiGraph GT3X accelerometers (AG) reliably measure energy expenditure for individuals with Collagen VI-Related Muscular Dystrophy (COL6-RD) or LAMA2-Related Muscular Dystrophy (LAMA2-RD). This objective was twofold: 1) to assess the validity of the step-counting function of AG in congenital muscular dystrophy, and 2) to assess criterion validity of AG against clinical measures of motor function. Patients often perform at top motor capacity in clinic. Measuring activity at home may better reflect typical motor performance. AG provides a means of capturing normal activity outside of the clinical setting. AG has not been validated in COL6-RD or LAMA2-RD. In clinic, AG step-count data were validated against a manual step-counter in 11 ambulatory subjects. Motor measures were administered, including the North Star Ambulatory Assessment (NSAA), Motor Function Measure 32 (MFM32), Six-Minute Walk Test (6MWT), and a self-reported measure of limitations of activity (ACTIVLIM). Participants then wore AG at home for seven days. Measurements captured by AG, including vector magnitude counts per minute (VM CPM), steps per minute (SPM), and % moderate-vigorous physical activity (% MVPA), were compared with the motor measures. Data were analyzed by Spearman correlation. The correlation between AG-counted steps and hand-counted steps