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ActiMyo home monitoring in adult patients with limb girdle muscular dystrophy type 2B and facioscapulohumeral muscular dystrophy in study ATYR 1940-C-004
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Abstracts 2017 / Neuromuscular Disorders 27 (2017) S96–S249
P.432 The gross motor function measure is valid for Fukuyama congenital muscular dystrophy T. Sato 1, M. Adachi 1, K. Nakamura 1, M. Zushi 1, K. Goto 1, T. Murakami 1, K. Ishiguro 1, M. Shichiji 1, K. Saito 1, T. Ikai 1, M. Osawa 1, I. Kondo 2, S. Nagata 1, K. Ishigaki 1 1 Tokyo Women’s Medical University, Tokyo, Japan; 2 National Center for Geriatric Medicine and Gerontology, Aichi, Japan Fukuyama congenital muscular dystrophy (FCMD) is the second most common muscular dystrophy in Japan. FCMD is an autosomal recessive disorder caused by mutations in the fukutin gene. The main features of FCMD are a combination of infantile-onset hypotonia, generalized muscle weakness, eye abnormalities, and mental retardation associated with cortical migration defects, and most patients are never able to walk. To date, the development of a quantitative motor scale for FMCD has been difficult due to the moderateto-severe intellectual impairment that accompanies FCMD. Gross motor function measure (GMFM), originally developed as a quantitative motor scale for cerebral palsy, can precisely and quantitatively assess motor function without complicated instructions, and was recently reported to be useful in the assessment of Down syndrome and spinal muscular atrophy. To confirm the validity of GMFM for the assessment of FCMD, 41 FCMD patients (age range: 0.6–24.4 years) were recruited for this study. The GMFM scores correlated significantly with those of two previously used motor scales, and the timedependent change in GMFM scores was consistent with the natural course of FCMD. The inter-rater reliability, based on determinations made by four physiotherapists blinded to each other’s assessment results, was excellent. We concluded GMFM to be a useful and valid measure of motor function in FCMD patients. http://dx.doi.org/10.1016/j.nmd.2017.06.472
P.433 Evaluation of skeletal muscle in patients with Fukuyama congenital muscular dystrophy (FCMD) using bioelectrical impedance analysis T. Murakami 1, K. Ishigai 1, K. Ishiguro 1, T. Sato 1, M. Shichiji 1, M. Ikeda 2, S. Nagata 1, T. Uchida 3, S. Kuru 4, T. Nakayama 5 1 Tokyo Women’s Medical University, Tokyo, Japan; 2 Kobe University Graduate School of Medicine, Kobe, Japan; 3 Tanita Body Weight Scientific Institute, Tokyo, Japan; 4 NHO Suzuka Hospital, Mie, Japan; 5 Yokohama Rosai Hospital, Kanagawa, Japan It was reported that gene therapy can provide a possible basis for the treatment of patients with FCMD. There is now a greater need for safe, noninvasive techniques for assessment of skeletal muscle volume in FCDM patients. We showed the efficacy of muscle volumetry using Bioelectric Impedance Analysis (BIA). The study subjects were 25 FCMD patients between 0.6 and 15.1 years old (F:M = 13:12) who visited the Dept. of Pediatrics, Tokyo Women’s Medical University, from 1 Aug. 2013 to 31 Dec. 2015. Their motor function was assessed using the Gross Motor Function Measurement Manual at intervals of 6 months. Simultaneously, bioelectrical impedance was measured using a BIA device bilaterally at the center of; upper arms, thighs, and lower legs with 10 cm distance between upper and lower electrodes in all patients. We obtained the index; MCAI_BIA, which was reported to closely correlate with muscle cross sectional areas of the central part of the measured section. The skeletal muscle cross sectional area, which was reported as the Muscle Volume Index (MVI), was also assessed using CT scanning at the same time at almost same section region as the BIA in patients who gave specific consent for the investigation. We analyzed the association between FCMD clinical severity and MCAI_BIA. The MCAI_BIA and MVI showed positive correlations at each measured section (Spearman’s rank correlation coefficient). We also found that MCAI_BIA correlated with motor function at each limb location (Spearman’s rank correlation coefficient). At each location, we found that MCAI_BIA decreases according to severity. MCAI_BIA can be measured simply and repeatedly, without radiation exposure to the patients. We thought MCAI_BIA
can be a potential indicator for the assessment of skeletal muscle volume, and that it will change with the disease severity of motor function in patients with FCMD. http://dx.doi.org/10.1016/j.nmd.2017.06.473
P.434 ActiMyo home monitoring in adult patients with limb girdle muscular dystrophy type 2B and facioscapulohumeral muscular dystrophy in study ATYR 1940-C-004 T. Gidaro 1, A. Moraux 2, M. Grelet 3, E. Gasnier 1, M. Villeret 1, M. Annoussamy 1, J. Vissing 4, S. Attarian 5, T. Mozaffar 6, S. Iyadurai 7, K. Wagner 8, G. Walker 9, A. Richiardi 9, S. Shukla 9, D. Vissière 3, L. Servais 1 1 I-Motion, Paris, France; 2 Institut of Myology. Pitie-Salpetriere Hospital, Paris, France; 3 Sysnav, Vernon, France; 4 Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 5 Centre d’nvestigation Clinique – Centre de Pharmacologie Clinique et d’Evaluations Thérapeutiques (CICCPCET), Marseille, France; 6 University of California, ALS and Neuromuscular Center, Irvine, CA, USA; 7 OSU Wexner Medical Center, Columbus, Ohio, USA; 8 Kennedy Krieger Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; 9 aTyr Pharma, Inc, San Diego, CA, USA To evaluate the feasibility of home-monitoring changes in functional activity using ActiMyo in a subset of patients with LGMD2B and FSHD in study ATYR 1940-C-004. ActiMyo is composed of two watch-like devices that record magneto-inertial sensors used to compute activity and gait variables in controlled and non-controlled setting. ATYR1940-C-004 is a multicenter, openlabel study evaluating intra-patient dose escalations of intravenous ATYR1940 in patients with genetically confirmed FSHD and LGMD2B. ActiMyo was provided to patients at baseline. Patients wore the device every day at home for the duration of the study (approximately four months). For each patient, gait variables were calculated from the data recorded in 30-day sub-periods using the ActiMyo sensor worn at the ankle, and the wrist. For each sub-period, gait parameters were compared between FSHD and LGMD2B patients using a non-parametric Mann-Whitney test. Change from baseline over the four month period was assessed using Friedman analysis of variance for paired samples. Of the eighteen patients enrolled in the study, ten were ambulant and sufficiently compliant for analysis. Median step speed and step length were significantly lower in FSHD patients compared to LGMD2B patients at baseline. Longitudinal analyses of those completing the assessment showed a visit effect with a mild decrement of median step speed after 3 months in 8 patients (p = 0.03) and after 4 months in 6 patients (p = 0.04). In contrast, cumulative variables such as total number of meters/step were highly variable from month to month, and no visit effect were found in this variable, or other like duration of walking episodes, step length or step height. The present study shows the feasibility of monitoring gait activity at home in ambulant FSHD and LGMD2B patients. In this limited number of patients, Actimyo could detect statistically significant mild decreases in median step speed over a four month period. http://dx.doi.org/10.1016/j.nmd.2017.06.474
P.435 Validity of the 6 minute walking test in myotonic dystrophy type 1 in a large scale cross-sectional study D. Moat 1, C. Jimenez-Moreno 1, A. Mayhew 1, C. Massey 2, N. Nikolenko 1, C. Turner 2, H. Lochmüller 1 1 Institute of Genetics, Newcastle, UK; 2 Queens Square, London, UK This study is part of the ongoing multicentre natural history study for myotonic dystrophy type 1 (DM1) -pheno-DM1 study- which aims for a deep phenotyping of a cohort of patients with DM1 and to assist in the planning, design and recruitment of clinical trials. Six-minute walk test (6MWT) is a commonly used functional outcome in neuromuscular disorders and is part of
Abstracts 2017 / Neuromuscular Disorders 27 (2017) S96–S249
P.432 The gross motor function measure is valid for Fukuyama congenital muscular dystrophy T. Sato 1, M. Adachi 1, K. Nakamura 1, M. Zushi 1, K. Goto 1, T. Murakami 1, K. Ishiguro 1, M. Shichiji 1, K. Saito 1, T. Ikai 1, M. Osawa 1, I. Kondo 2, S. Nagata 1, K. Ishigaki 1 1 Tokyo Women’s Medical University, Tokyo, Japan; 2 National Center for Geriatric Medicine and Gerontology, Aichi, Japan Fukuyama congenital muscular dystrophy (FCMD) is the second most common muscular dystrophy in Japan. FCMD is an autosomal recessive disorder caused by mutations in the fukutin gene. The main features of FCMD are a combination of infantile-onset hypotonia, generalized muscle weakness, eye abnormalities, and mental retardation associated with cortical migration defects, and most patients are never able to walk. To date, the development of a quantitative motor scale for FMCD has been difficult due to the moderateto-severe intellectual impairment that accompanies FCMD. Gross motor function measure (GMFM), originally developed as a quantitative motor scale for cerebral palsy, can precisely and quantitatively assess motor function without complicated instructions, and was recently reported to be useful in the assessment of Down syndrome and spinal muscular atrophy. To confirm the validity of GMFM for the assessment of FCMD, 41 FCMD patients (age range: 0.6–24.4 years) were recruited for this study. The GMFM scores correlated significantly with those of two previously used motor scales, and the timedependent change in GMFM scores was consistent with the natural course of FCMD. The inter-rater reliability, based on determinations made by four physiotherapists blinded to each other’s assessment results, was excellent. We concluded GMFM to be a useful and valid measure of motor function in FCMD patients. http://dx.doi.org/10.1016/j.nmd.2017.06.472
P.433 Evaluation of skeletal muscle in patients with Fukuyama congenital muscular dystrophy (FCMD) using bioelectrical impedance analysis T. Murakami 1, K. Ishigai 1, K. Ishiguro 1, T. Sato 1, M. Shichiji 1, M. Ikeda 2, S. Nagata 1, T. Uchida 3, S. Kuru 4, T. Nakayama 5 1 Tokyo Women’s Medical University, Tokyo, Japan; 2 Kobe University Graduate School of Medicine, Kobe, Japan; 3 Tanita Body Weight Scientific Institute, Tokyo, Japan; 4 NHO Suzuka Hospital, Mie, Japan; 5 Yokohama Rosai Hospital, Kanagawa, Japan It was reported that gene therapy can provide a possible basis for the treatment of patients with FCMD. There is now a greater need for safe, noninvasive techniques for assessment of skeletal muscle volume in FCDM patients. We showed the efficacy of muscle volumetry using Bioelectric Impedance Analysis (BIA). The study subjects were 25 FCMD patients between 0.6 and 15.1 years old (F:M = 13:12) who visited the Dept. of Pediatrics, Tokyo Women’s Medical University, from 1 Aug. 2013 to 31 Dec. 2015. Their motor function was assessed using the Gross Motor Function Measurement Manual at intervals of 6 months. Simultaneously, bioelectrical impedance was measured using a BIA device bilaterally at the center of; upper arms, thighs, and lower legs with 10 cm distance between upper and lower electrodes in all patients. We obtained the index; MCAI_BIA, which was reported to closely correlate with muscle cross sectional areas of the central part of the measured section. The skeletal muscle cross sectional area, which was reported as the Muscle Volume Index (MVI), was also assessed using CT scanning at the same time at almost same section region as the BIA in patients who gave specific consent for the investigation. We analyzed the association between FCMD clinical severity and MCAI_BIA. The MCAI_BIA and MVI showed positive correlations at each measured section (Spearman’s rank correlation coefficient). We also found that MCAI_BIA correlated with motor function at each limb location (Spearman’s rank correlation coefficient). At each location, we found that MCAI_BIA decreases according to severity. MCAI_BIA can be measured simply and repeatedly, without radiation exposure to the patients. We thought MCAI_BIA
can be a potential indicator for the assessment of skeletal muscle volume, and that it will change with the disease severity of motor function in patients with FCMD. http://dx.doi.org/10.1016/j.nmd.2017.06.473
P.434 ActiMyo home monitoring in adult patients with limb girdle muscular dystrophy type 2B and facioscapulohumeral muscular dystrophy in study ATYR 1940-C-004 T. Gidaro 1, A. Moraux 2, M. Grelet 3, E. Gasnier 1, M. Villeret 1, M. Annoussamy 1, J. Vissing 4, S. Attarian 5, T. Mozaffar 6, S. Iyadurai 7, K. Wagner 8, G. Walker 9, A. Richiardi 9, S. Shukla 9, D. Vissière 3, L. Servais 1 1 I-Motion, Paris, France; 2 Institut of Myology. Pitie-Salpetriere Hospital, Paris, France; 3 Sysnav, Vernon, France; 4 Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 5 Centre d’nvestigation Clinique – Centre de Pharmacologie Clinique et d’Evaluations Thérapeutiques (CICCPCET), Marseille, France; 6 University of California, ALS and Neuromuscular Center, Irvine, CA, USA; 7 OSU Wexner Medical Center, Columbus, Ohio, USA; 8 Kennedy Krieger Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; 9 aTyr Pharma, Inc, San Diego, CA, USA To evaluate the feasibility of home-monitoring changes in functional activity using ActiMyo in a subset of patients with LGMD2B and FSHD in study ATYR 1940-C-004. ActiMyo is composed of two watch-like devices that record magneto-inertial sensors used to compute activity and gait variables in controlled and non-controlled setting. ATYR1940-C-004 is a multicenter, openlabel study evaluating intra-patient dose escalations of intravenous ATYR1940 in patients with genetically confirmed FSHD and LGMD2B. ActiMyo was provided to patients at baseline. Patients wore the device every day at home for the duration of the study (approximately four months). For each patient, gait variables were calculated from the data recorded in 30-day sub-periods using the ActiMyo sensor worn at the ankle, and the wrist. For each sub-period, gait parameters were compared between FSHD and LGMD2B patients using a non-parametric Mann-Whitney test. Change from baseline over the four month period was assessed using Friedman analysis of variance for paired samples. Of the eighteen patients enrolled in the study, ten were ambulant and sufficiently compliant for analysis. Median step speed and step length were significantly lower in FSHD patients compared to LGMD2B patients at baseline. Longitudinal analyses of those completing the assessment showed a visit effect with a mild decrement of median step speed after 3 months in 8 patients (p = 0.03) and after 4 months in 6 patients (p = 0.04). In contrast, cumulative variables such as total number of meters/step were highly variable from month to month, and no visit effect were found in this variable, or other like duration of walking episodes, step length or step height. The present study shows the feasibility of monitoring gait activity at home in ambulant FSHD and LGMD2B patients. In this limited number of patients, Actimyo could detect statistically significant mild decreases in median step speed over a four month period. http://dx.doi.org/10.1016/j.nmd.2017.06.474
P.435 Validity of the 6 minute walking test in myotonic dystrophy type 1 in a large scale cross-sectional study D. Moat 1, C. Jimenez-Moreno 1, A. Mayhew 1, C. Massey 2, N. Nikolenko 1, C. Turner 2, H. Lochmüller 1 1 Institute of Genetics, Newcastle, UK; 2 Queens Square, London, UK This study is part of the ongoing multicentre natural history study for myotonic dystrophy type 1 (DM1) -pheno-DM1 study- which aims for a deep phenotyping of a cohort of patients with DM1 and to assist in the planning, design and recruitment of clinical trials. Six-minute walk test (6MWT) is a commonly used functional outcome in neuromuscular disorders and is part of