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Validity of the 6 minute walking test in myotonic dystrophy type 1 in a large scale cross-sectional study
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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 the OMMYD outcomes-set proposed for clinical trials in DM1. This study will investigate correlations between walk distance and neuromuscular parameters such as muscle strength, standing balance and reported daily life participation . The study recruited 213 adult patients with genetically confirmed DM1 that could perform at least 10 meters of walking independently (assistive devices allowed) and consent by themselves. Study visits include: 1) patient reported outcomes including the two gold-standards for DM1 (MDHI and DM1-Activ) plus additional questionnaires related to fatigue, pain and quality of life 2) strength assessments (myometry and manual muscle testing) and 3) functional assessments such as the 6MWT. Participants were classified as mild, classic (adult) or juvenile onset phenotype based on the reported age of disease onset. The data has shown a diverse population across all measures of strength, distance and cardiorespiratory function. Significant correlations between 6MWT, strength and burden of illness were identified at baseline. These findings support the knowledge of highly variable DM1 phenoptype but allows for a classification system also applicable for the 6MWT. Correlations presented can assist in future trial design. Some of these baseline findings need to be examined further to understand the differing phenotypes progression. http://dx.doi.org/10.1016/j.nmd.2017.06.475
P.436 Associations between grip strength, myotonia and CTG expansion in myotonic dystrophy type 1 J. Hogrel 1, G. Ollivier 1, I. Ledoux 1, L. Hébert 2, B. Eymard 1, J. Puymirat 2, G. Bassez 1 1 Institute of Myology, Paris, France; 2 Université de Laval, Québec, Canada Myotonia and muscle weakness are two primary impairments in patients suffering from myotonic dystrophy type 1 (DM1). Both myotonia and muscle weakness are generally evidenced during maximal grip contractions and have been used as key biological markers of disease severity. Despite large interindividual variations, the length of CTG repeat is thought to be a rough determinant of disease severity. Leukocyte DNA CTG repeat length has been found to be correlated with myotonia and with muscle strength, while other studies did not report such correlations. However, as the number of patients included in these studies was rather small (between 14 and 38), it is thus still controversial to use myotonia and muscle strength as outcomes related to the CTG repeat length. The aim of this study was to take a second look at this issue in a large cohort of DM1 patients. The data included in the present study were acquired in two centers (Paris, Quebec) from 2009 to 2016 within the frame of several clinical studies or during yearly clinical consultations. We collected CTG repeat length, grip strength and myotonia defined by the relaxation time between 90% and 10% of the strength sustained: RT(90-10)%. The study included 144 DM1 patients (76 females and 68 males aged 42.2 ± 11.0 years) and 44 aged matched controls using the same experimental protocol. CTG repeat length was statistically correlated with muscle strength, expressed either in absolute values (rho=-0.293, p < 0.001) or in percentage of predicted value (rho=-0.269, p = 0.002) with RT (90-10)% (rho = 0.229, p = 0.008). Muscle strength expressed in relative values and RT(90-10)% were also significantly negatively correlated (rho=-0.181, p = 0.031). Even if statistically significant in a large cohort of DM1 patients, the strength of the correlation between CTG repeat length, strength, and myotonia remained weak. The sole CTG repeat length value cannot predict the levels of strength and myotonia at an individual level. http://dx.doi.org/10.1016/j.nmd.2017.06.476
P.437 Clinical outcome study of dysferlinopathy: what are the best outcome measures for dysferlinopathy patients? M. James 1, M. Jacobs 2, A. Mayhew 1, J. Feng 2, S. Spuler 3, J. Day 4, K. Jones 5, D. Bharucha-Goebel 6, E. Salort-Campana 7, A. Pestronk 8, M. Walter 9,
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C. Paradas , T. Stojkovic , M. Mori-Yoshimura , E. Bravver 13, J. Diaz- Manera 14, E. Pegoraro 15, J. Mendell 16, K. Bushby 1, V. Straub 1 1 Newcastle University, Newcastle upon Tyne, UK; 2 Children’s National Health System, Washington, D.C., USA; 3 Charite, Berlin, Germany; 4 Stanford University School of Medicine, Stanford, USA; 5 Children’s Hospital at Westmead, Sydney, Australia; 6 Childen’s National Health System, Washington, D.C., USA; 7 La Timone Hospital, Marseille, France; 8 Washington University School of Medicine, St Louis, USA; 9 Ludwig-Maximilians-University of Munich, Munich, Germany; 10 Hospital U, Virgen del Rocío/Instituto de Biomedicina de Sevilla, Sevilla, Spain; 11 Institut de Myologie, Paris, France; 12 National Center of Neurology and Psychiatry, Tokyo, Japan; 13 Carolinas Healthcare System, Charlotte, USA; 14 Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 15 University of Padova, Padova, Italy; 16 Nationwide Children’s Hospital, Columbus, USA We report on longitudinal functional over the first two years of the 3-year Clinical Outcome Study of Dysferlinopathy. The Clinical outcome study is an international study evaluating patients with genetically confirmed dysferlinopathy with the intention of improving trial readiness in dysferlinopathy. Dysferlinopathy clinically presents with a spectrum of muscle weakness including both distal and proximal phenotypes. This variability presents challenges for developing clinical trial outcome measures. 203 adults with dysferlinopathy have been recruited across 15 sites in 8 countries. Patients attended five visits over two years and in this time underwent physiotherapy assessments, medical and MRI assessments. Physiotherapy assessments included muscle strength (manual muscle testing, MMT; hand held dynamometry, HHD) and functional ability evaluations (North Star assessment for dysferlinopathy and performance of upper limb), as well as timed tests (rise from floor, 10 metre walk / run, four stair climb and descend; Timed Up and Go, TUG; Six Minute Walk Distance, 6MWD) and respiratory function testing (forced vital capacity and mouth inspiratory pressure). Significant change has been detected in several outcome measures in both functional and MRI measures after one year. Here we examine the physiotherapy data for change after two years. Data collected at baseline, six month, one and two year visits have been analysed to calculate the change for the cohort between each visit. Generalized estimating equations (GEE) have been used to model longitudinal change in outcomes. The data were examined to identify and quantify groups demonstrating differing rate of progress. Power calculations on a range of measures have also been calculated. http://dx.doi.org/10.1016/j.nmd.2017.06.477
P.438 Is grip strength compared to lower extremity measurements sufficient for capturing changes in muscle strength in chronic inflammatory demyelinating polyneuropathy? K. Knak 1, L. Andersen 1, L. Markvardsen 2 1 Rigshospitalet, Copenhagen, Denmark; 2 Aarhus University Hospital, Aarhus, Denmark Chronic inflammatory demyelinating polyneuropathy (CIDP) is a sensomotoric disorder with proximal and distal muscle weakness in upper and lower extremities. Grip strength measures muscle strength in the distal upper extremities and is a commonly used outcome measure in patients with CIDP. However, several patients with CIDP present with predominant lower extremity weakness. So far, no studies have investigated the relationship between grip strength and outcome measures of lower extremity muscle strength and function. The objective in this study was to investigate the ability to capture changes in muscle strength in patients with CIDP by comparing grip strength with isokinetic muscle strength of the lower extremities. Moreover, grip strength was compared to general muscle strength (Medical research council, MRC), walking performance (40 meter walk test) and disability (Overall disability sum score, ODSS). Seventy patients with CIDP from our previous studies of intravenous and subcutaneous immunoglobulin treatment were included. All measurements were collected at the same time points. Difference scores of all measurements between week 0–2 and week 0–10/12 were used for
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 the OMMYD outcomes-set proposed for clinical trials in DM1. This study will investigate correlations between walk distance and neuromuscular parameters such as muscle strength, standing balance and reported daily life participation . The study recruited 213 adult patients with genetically confirmed DM1 that could perform at least 10 meters of walking independently (assistive devices allowed) and consent by themselves. Study visits include: 1) patient reported outcomes including the two gold-standards for DM1 (MDHI and DM1-Activ) plus additional questionnaires related to fatigue, pain and quality of life 2) strength assessments (myometry and manual muscle testing) and 3) functional assessments such as the 6MWT. Participants were classified as mild, classic (adult) or juvenile onset phenotype based on the reported age of disease onset. The data has shown a diverse population across all measures of strength, distance and cardiorespiratory function. Significant correlations between 6MWT, strength and burden of illness were identified at baseline. These findings support the knowledge of highly variable DM1 phenoptype but allows for a classification system also applicable for the 6MWT. Correlations presented can assist in future trial design. Some of these baseline findings need to be examined further to understand the differing phenotypes progression. http://dx.doi.org/10.1016/j.nmd.2017.06.475
P.436 Associations between grip strength, myotonia and CTG expansion in myotonic dystrophy type 1 J. Hogrel 1, G. Ollivier 1, I. Ledoux 1, L. Hébert 2, B. Eymard 1, J. Puymirat 2, G. Bassez 1 1 Institute of Myology, Paris, France; 2 Université de Laval, Québec, Canada Myotonia and muscle weakness are two primary impairments in patients suffering from myotonic dystrophy type 1 (DM1). Both myotonia and muscle weakness are generally evidenced during maximal grip contractions and have been used as key biological markers of disease severity. Despite large interindividual variations, the length of CTG repeat is thought to be a rough determinant of disease severity. Leukocyte DNA CTG repeat length has been found to be correlated with myotonia and with muscle strength, while other studies did not report such correlations. However, as the number of patients included in these studies was rather small (between 14 and 38), it is thus still controversial to use myotonia and muscle strength as outcomes related to the CTG repeat length. The aim of this study was to take a second look at this issue in a large cohort of DM1 patients. The data included in the present study were acquired in two centers (Paris, Quebec) from 2009 to 2016 within the frame of several clinical studies or during yearly clinical consultations. We collected CTG repeat length, grip strength and myotonia defined by the relaxation time between 90% and 10% of the strength sustained: RT(90-10)%. The study included 144 DM1 patients (76 females and 68 males aged 42.2 ± 11.0 years) and 44 aged matched controls using the same experimental protocol. CTG repeat length was statistically correlated with muscle strength, expressed either in absolute values (rho=-0.293, p < 0.001) or in percentage of predicted value (rho=-0.269, p = 0.002) with RT (90-10)% (rho = 0.229, p = 0.008). Muscle strength expressed in relative values and RT(90-10)% were also significantly negatively correlated (rho=-0.181, p = 0.031). Even if statistically significant in a large cohort of DM1 patients, the strength of the correlation between CTG repeat length, strength, and myotonia remained weak. The sole CTG repeat length value cannot predict the levels of strength and myotonia at an individual level. http://dx.doi.org/10.1016/j.nmd.2017.06.476
P.437 Clinical outcome study of dysferlinopathy: what are the best outcome measures for dysferlinopathy patients? M. James 1, M. Jacobs 2, A. Mayhew 1, J. Feng 2, S. Spuler 3, J. Day 4, K. Jones 5, D. Bharucha-Goebel 6, E. Salort-Campana 7, A. Pestronk 8, M. Walter 9,
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C. Paradas , T. Stojkovic , M. Mori-Yoshimura , E. Bravver 13, J. Diaz- Manera 14, E. Pegoraro 15, J. Mendell 16, K. Bushby 1, V. Straub 1 1 Newcastle University, Newcastle upon Tyne, UK; 2 Children’s National Health System, Washington, D.C., USA; 3 Charite, Berlin, Germany; 4 Stanford University School of Medicine, Stanford, USA; 5 Children’s Hospital at Westmead, Sydney, Australia; 6 Childen’s National Health System, Washington, D.C., USA; 7 La Timone Hospital, Marseille, France; 8 Washington University School of Medicine, St Louis, USA; 9 Ludwig-Maximilians-University of Munich, Munich, Germany; 10 Hospital U, Virgen del Rocío/Instituto de Biomedicina de Sevilla, Sevilla, Spain; 11 Institut de Myologie, Paris, France; 12 National Center of Neurology and Psychiatry, Tokyo, Japan; 13 Carolinas Healthcare System, Charlotte, USA; 14 Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 15 University of Padova, Padova, Italy; 16 Nationwide Children’s Hospital, Columbus, USA We report on longitudinal functional over the first two years of the 3-year Clinical Outcome Study of Dysferlinopathy. The Clinical outcome study is an international study evaluating patients with genetically confirmed dysferlinopathy with the intention of improving trial readiness in dysferlinopathy. Dysferlinopathy clinically presents with a spectrum of muscle weakness including both distal and proximal phenotypes. This variability presents challenges for developing clinical trial outcome measures. 203 adults with dysferlinopathy have been recruited across 15 sites in 8 countries. Patients attended five visits over two years and in this time underwent physiotherapy assessments, medical and MRI assessments. Physiotherapy assessments included muscle strength (manual muscle testing, MMT; hand held dynamometry, HHD) and functional ability evaluations (North Star assessment for dysferlinopathy and performance of upper limb), as well as timed tests (rise from floor, 10 metre walk / run, four stair climb and descend; Timed Up and Go, TUG; Six Minute Walk Distance, 6MWD) and respiratory function testing (forced vital capacity and mouth inspiratory pressure). Significant change has been detected in several outcome measures in both functional and MRI measures after one year. Here we examine the physiotherapy data for change after two years. Data collected at baseline, six month, one and two year visits have been analysed to calculate the change for the cohort between each visit. Generalized estimating equations (GEE) have been used to model longitudinal change in outcomes. The data were examined to identify and quantify groups demonstrating differing rate of progress. Power calculations on a range of measures have also been calculated. http://dx.doi.org/10.1016/j.nmd.2017.06.477
P.438 Is grip strength compared to lower extremity measurements sufficient for capturing changes in muscle strength in chronic inflammatory demyelinating polyneuropathy? K. Knak 1, L. Andersen 1, L. Markvardsen 2 1 Rigshospitalet, Copenhagen, Denmark; 2 Aarhus University Hospital, Aarhus, Denmark Chronic inflammatory demyelinating polyneuropathy (CIDP) is a sensomotoric disorder with proximal and distal muscle weakness in upper and lower extremities. Grip strength measures muscle strength in the distal upper extremities and is a commonly used outcome measure in patients with CIDP. However, several patients with CIDP present with predominant lower extremity weakness. So far, no studies have investigated the relationship between grip strength and outcome measures of lower extremity muscle strength and function. The objective in this study was to investigate the ability to capture changes in muscle strength in patients with CIDP by comparing grip strength with isokinetic muscle strength of the lower extremities. Moreover, grip strength was compared to general muscle strength (Medical research council, MRC), walking performance (40 meter walk test) and disability (Overall disability sum score, ODSS). Seventy patients with CIDP from our previous studies of intravenous and subcutaneous immunoglobulin treatment were included. All measurements were collected at the same time points. Difference scores of all measurements between week 0–2 and week 0–10/12 were used for