- Email: [email protected]
P.10.19 Net muscle volumetry using MRI and CT
794
Abstracts / Neuromuscular Disorders 23 (2013) 738–852
years of age). None of the patients had a diagnosis of a primary neuromuscular disease. The specimens were investigated by routine histological techniques and by LX-PCR to identify mtDNA deletions. Morphological alterations in the 26 patients with chronic ischemia that were not present in controls included rimmed vacuoles (12 patients), interstitial fibrosis (14 patients), fiber type grouping (22 patients), group atrophy (19 patients) fibers with glycogen depletion (7 patients), necrotic fibers (6 patients), internalized nuclei (26 pateints), MHC class I upregulation (3 patients) and microangiopathy (13 patients). Cytochrome c oxidase deficient muscle fibres were identified in 25 patients (0.1–1.8% of the fibers) and in 7 controls (0.2–0.5% of the fibers). Multiple mtDNA deletions were identified in 16 patients and one control. None of the alterations were predominant in patients with diabetes. The results demonstrate that chronic ischemia is associated with marked morphological alterations in muscle that may mimic a primary myopathy. Neurogenic changes were frequent both among diabetic and non-diabetic patients. http://dx.doi:10.1016/j.nmd.2013.06.547
P.10.18 Common data elements for muscle biopsy reporting J. Dastgir 1, A. Rutkowski 2, R. Alvarez 2, S. Cossette 2, K. Yan 3, R. Hoffmann 3, C. Sewry 4, Y. Hayashi 5, S.A. Moore 6, H. Goebel 7, C. Bonnemann 1, M.W. Lawlor 8 1 National Institutes of Health/National Institutes of Neurological Disorders and Stroke, Neurogenetics Branch/Neurogenetic and Neuromuscular Disorders of Childhood Section, Bethesda, United States; 2 Cure Congenital Muscular Dystrophy, Olathe, United States; 3 Medical College of Wisconsin, Quantitative Health Sciences Section, Milwaukee, United States; 4 Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital, London, United Kingdom; 5 National Institutes of Neuroscience, NCNP, Tokyo, Japan; 6 University of Iowa, Department of Pathology, Iowa City, United States; 7 Johannes Gutenberg University, Department of Neuropathology, Mainz, Germany; 8 Medical College of Wisconsin, Department of Pathology and Laboratory Medicine, Milwaukee, United States Physicians commonly utilize the muscle biopsy to assist in the diagnosis of neuromuscular diseases. However, there is no current standard for evaluating or reporting on findings, and the resulting variability can impede accurate diagnoses and limit the utility of the muscle biopsy as a tool for clinical care, research, and stratifying patients for clinical trials. The National Institutes of Neurological Disorders and Stroke (NINDS) recently launched a Common Data Element (CDE) in an effort to standardize neuromuscular data collected in clinical reports. For this study, the authors adapted the NINDS Muscle Biopsy CDE to generate a form for prospective muscle biopsy reporting (CDE-R). This form was used to analyze a set of 49 reports from patients with a range of congenital muscle disorders enrolled in the Congenital Muscular Disease International Registry (CMDIR). Using the CDE-R as a checklist, data were extracted from each report and scored to determine the degree to which the report contained the recommended common data elements. Analysis of the data highlighted the lack of consistent reporting of key clinical features from the referring physicians to the pathologist and great variability in the reporting of a range of pertinent positive and negative pathological findings. However, when we used only data extracted to the CDE-R format to characterize these biopsies, we found a >80% concordance between the reported diagnosis and the diagnosis determined by a blinded pathologist, suggesting that the data reformatted to CDE-R can be used to make a diagnosis in most cases. As a result, we propose implementing a combined format for muscle biopsy reporting that consists of the CDE-R checklist elements and a brief narrative comment that interprets the data in support of a final diagnosis. Such a format may assist in more accu-
rately defining and consistently categorizing pertinent positive and negative pathological findings in relation to defined genotypes. http://dx.doi:10.1016/j.nmd.2013.06.548
P.10.19 Net muscle volumetry using MRI and CT T. Nakayama 1, S. Kuru 2 1 Yokohama Rosai Hospital, Department of Neurology, Yokohama, Japan; 2 NHO Suzuka Hospital, Department of Neurology, Suzuka, Japan Muscle volumetry by MRI has been previously reported using T1 weighted images. We reported muscle volumetry using CT and compared the results obtained by CT and DIXON images. Five patients with muscular dystrophy, 3 patients with myopathy, 2 patients with myositis, and 3 patients with neurogenic amyotrophy were enrolled in this study. CT and MRI DIXON images of the 26 limbs (the thigh or lower leg) of these patients were investigated. The CT and MRI images of fourteen 1-cm and seventy 2-mm thickness slices of the midthigh, 7 cm above and below the midpoint of the trochanter and patella, and ten 1-cm and fifty 2-mm thickness slices of the mid-lower leg, 5 cm above and below the midpoint of the fibula head and lateral malleolus, were analyzed, respectively. A muscle density map was obtained using estimated linear-function. Obvious vessels and skin tissues were excluded manually from the density map and the net muscle volumes of the thighs and lower legs were calculated. Percentage water images were simultaneously calculated using DIXON images, and the sum of the %water images resulted in the net muscle volume from MRI. The results obtained by DIXON closely corresponded to those by CT, with a correlation coefficient of 0.993 and intraclass correlation coefficient of 0.993. There was a significant difference between the two results by the paired t-test (p = 0.001), and the results obtained by DIXON were slightly larger than those by CT, with an SEM of 47.95 cm3. The results obtained by DIXON were correlated to those by CT because these results were calculated from the division of water images by the addition of water images and fat images, and the division procedure reduced the effect of magnetic field inhomogeneity on these images. The results obtained by DIXON were larger than those by CT because the bone marrow was not able to be eliminated on %water images. http://dx.doi:10.1016/j.nmd.2013.06.549
P.10.20 Recent and future additions to the MDA Monoclonal Antibody Resource for Neuromuscular Disorders L. Le Thanh Lam 1, I. Holt 1, E. Humphrey 1, C.A. Sewry 1, M. Nguyen thi Man 1, G.E. Morris 2 1 RJAH Orthopaedic Hospital, Wolfson Centre for Inherited Neuromuscular Disease, Oswestry, United Kingdom; 2 RJAH Orthopaedic Hospital and Keele University, Wolfson Centre for Inherited Neuromuscular Disease, Oswestry, United Kingdom Specific antibodies are vital tools in the fight against neuromuscular disease, but no single antibody can perform all the necessary functions. Over a period of 20 years, we have produced large numbers of well-characterized antibodies for studies of the most common neuromuscular diseases (Duchenne/Becker and Emery–Dreifuss muscular dystrophies, spinal muscular atrophy and myotonic dystrophy), often in close collaboration with other research groups worldwide. This MDA Monoclonal Antibody (mAb) Resource currently contains nearly 400 different mAbs, including 150 exon-specific dystrophin mAbs. The antibody panels are
Abstracts / Neuromuscular Disorders 23 (2013) 738–852
years of age). None of the patients had a diagnosis of a primary neuromuscular disease. The specimens were investigated by routine histological techniques and by LX-PCR to identify mtDNA deletions. Morphological alterations in the 26 patients with chronic ischemia that were not present in controls included rimmed vacuoles (12 patients), interstitial fibrosis (14 patients), fiber type grouping (22 patients), group atrophy (19 patients) fibers with glycogen depletion (7 patients), necrotic fibers (6 patients), internalized nuclei (26 pateints), MHC class I upregulation (3 patients) and microangiopathy (13 patients). Cytochrome c oxidase deficient muscle fibres were identified in 25 patients (0.1–1.8% of the fibers) and in 7 controls (0.2–0.5% of the fibers). Multiple mtDNA deletions were identified in 16 patients and one control. None of the alterations were predominant in patients with diabetes. The results demonstrate that chronic ischemia is associated with marked morphological alterations in muscle that may mimic a primary myopathy. Neurogenic changes were frequent both among diabetic and non-diabetic patients. http://dx.doi:10.1016/j.nmd.2013.06.547
P.10.18 Common data elements for muscle biopsy reporting J. Dastgir 1, A. Rutkowski 2, R. Alvarez 2, S. Cossette 2, K. Yan 3, R. Hoffmann 3, C. Sewry 4, Y. Hayashi 5, S.A. Moore 6, H. Goebel 7, C. Bonnemann 1, M.W. Lawlor 8 1 National Institutes of Health/National Institutes of Neurological Disorders and Stroke, Neurogenetics Branch/Neurogenetic and Neuromuscular Disorders of Childhood Section, Bethesda, United States; 2 Cure Congenital Muscular Dystrophy, Olathe, United States; 3 Medical College of Wisconsin, Quantitative Health Sciences Section, Milwaukee, United States; 4 Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital, London, United Kingdom; 5 National Institutes of Neuroscience, NCNP, Tokyo, Japan; 6 University of Iowa, Department of Pathology, Iowa City, United States; 7 Johannes Gutenberg University, Department of Neuropathology, Mainz, Germany; 8 Medical College of Wisconsin, Department of Pathology and Laboratory Medicine, Milwaukee, United States Physicians commonly utilize the muscle biopsy to assist in the diagnosis of neuromuscular diseases. However, there is no current standard for evaluating or reporting on findings, and the resulting variability can impede accurate diagnoses and limit the utility of the muscle biopsy as a tool for clinical care, research, and stratifying patients for clinical trials. The National Institutes of Neurological Disorders and Stroke (NINDS) recently launched a Common Data Element (CDE) in an effort to standardize neuromuscular data collected in clinical reports. For this study, the authors adapted the NINDS Muscle Biopsy CDE to generate a form for prospective muscle biopsy reporting (CDE-R). This form was used to analyze a set of 49 reports from patients with a range of congenital muscle disorders enrolled in the Congenital Muscular Disease International Registry (CMDIR). Using the CDE-R as a checklist, data were extracted from each report and scored to determine the degree to which the report contained the recommended common data elements. Analysis of the data highlighted the lack of consistent reporting of key clinical features from the referring physicians to the pathologist and great variability in the reporting of a range of pertinent positive and negative pathological findings. However, when we used only data extracted to the CDE-R format to characterize these biopsies, we found a >80% concordance between the reported diagnosis and the diagnosis determined by a blinded pathologist, suggesting that the data reformatted to CDE-R can be used to make a diagnosis in most cases. As a result, we propose implementing a combined format for muscle biopsy reporting that consists of the CDE-R checklist elements and a brief narrative comment that interprets the data in support of a final diagnosis. Such a format may assist in more accu-
rately defining and consistently categorizing pertinent positive and negative pathological findings in relation to defined genotypes. http://dx.doi:10.1016/j.nmd.2013.06.548
P.10.19 Net muscle volumetry using MRI and CT T. Nakayama 1, S. Kuru 2 1 Yokohama Rosai Hospital, Department of Neurology, Yokohama, Japan; 2 NHO Suzuka Hospital, Department of Neurology, Suzuka, Japan Muscle volumetry by MRI has been previously reported using T1 weighted images. We reported muscle volumetry using CT and compared the results obtained by CT and DIXON images. Five patients with muscular dystrophy, 3 patients with myopathy, 2 patients with myositis, and 3 patients with neurogenic amyotrophy were enrolled in this study. CT and MRI DIXON images of the 26 limbs (the thigh or lower leg) of these patients were investigated. The CT and MRI images of fourteen 1-cm and seventy 2-mm thickness slices of the midthigh, 7 cm above and below the midpoint of the trochanter and patella, and ten 1-cm and fifty 2-mm thickness slices of the mid-lower leg, 5 cm above and below the midpoint of the fibula head and lateral malleolus, were analyzed, respectively. A muscle density map was obtained using estimated linear-function. Obvious vessels and skin tissues were excluded manually from the density map and the net muscle volumes of the thighs and lower legs were calculated. Percentage water images were simultaneously calculated using DIXON images, and the sum of the %water images resulted in the net muscle volume from MRI. The results obtained by DIXON closely corresponded to those by CT, with a correlation coefficient of 0.993 and intraclass correlation coefficient of 0.993. There was a significant difference between the two results by the paired t-test (p = 0.001), and the results obtained by DIXON were slightly larger than those by CT, with an SEM of 47.95 cm3. The results obtained by DIXON were correlated to those by CT because these results were calculated from the division of water images by the addition of water images and fat images, and the division procedure reduced the effect of magnetic field inhomogeneity on these images. The results obtained by DIXON were larger than those by CT because the bone marrow was not able to be eliminated on %water images. http://dx.doi:10.1016/j.nmd.2013.06.549
P.10.20 Recent and future additions to the MDA Monoclonal Antibody Resource for Neuromuscular Disorders L. Le Thanh Lam 1, I. Holt 1, E. Humphrey 1, C.A. Sewry 1, M. Nguyen thi Man 1, G.E. Morris 2 1 RJAH Orthopaedic Hospital, Wolfson Centre for Inherited Neuromuscular Disease, Oswestry, United Kingdom; 2 RJAH Orthopaedic Hospital and Keele University, Wolfson Centre for Inherited Neuromuscular Disease, Oswestry, United Kingdom Specific antibodies are vital tools in the fight against neuromuscular disease, but no single antibody can perform all the necessary functions. Over a period of 20 years, we have produced large numbers of well-characterized antibodies for studies of the most common neuromuscular diseases (Duchenne/Becker and Emery–Dreifuss muscular dystrophies, spinal muscular atrophy and myotonic dystrophy), often in close collaboration with other research groups worldwide. This MDA Monoclonal Antibody (mAb) Resource currently contains nearly 400 different mAbs, including 150 exon-specific dystrophin mAbs. The antibody panels are