Marni B Jacobs1,2, Meredoith K James3, Linda P Lowes4, Lindsay N Alfano4, Michelle Eagle3, Robert Muni Lofra3, Ursula Moore3, Jia Feng1, Laura E Rufibach5, Kristy Rose6, Tina Duong7,8, Luca Bello9, Irene Pedrosa-Hernández10, Scott Holsten11, Chikako Sakamoto12, Aurélie Canal13, Nieves Sanchez-Aguilera Práxedes14, Simone Thiele15, Catherine Siener16, Bruno Vandevelde17, Brittney DeWolf7, Elke Maron18, Michela Guglieri3, Jean-Yves Hogrel13, Andrew M Blamire19, Pierre G Carlier20, Simone Spuler21, John W Day22, Kristi J Jones6, Diana X Bharucha-Goebel23,24, Emmanuelle Salort-Campana17, Alan Pestronk16, Maggie C Walter15, Carmen Paradas25, Tanya Stojkovic13, Madoka Mori-Yoshimura26, Elena Bravver11, Jordi Díaz-Manera27,28, Elena Pegoraro9, Jerry R Mendell4, Anna G Mayhew3, Volker Straub3. 1. Center for Translational Science, Division of Biostatistics and Study Methodology, Children's National Health System, Washington, DC. 2. Pediatrics, Epidemiology, and Biostatistics, George Washington University, Washington, DC. 3. The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Central Parkway, Newcastle upon Tyne, UK. 4. The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH. 5. The Jain Foundation, Seattle, WA. 6. The Children's Hospital at Westmead, The University of Sydney, Sydney, Australia. 7. Cooperative International Neuromuscular Research Group (CINRG), Children's National Health System, Washington, DC. 8. Lucile Salter Packard Children's Hospital at Stanford, Palo Alto, CA. 9. Department of Neuroscience, University of Padova, Padova, Italy. 10. Physical Medicine and Rehabilitation, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 11. Neuroscience Institute, Carolinas Neuromuscular/ALS-MDA Center, Carolinas HealthCare System, Charlotte, NC. 12. Department of Physical Rehabilitation, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan. 13. Institut de Myologie, AP-HP, GH Pitié-Salpêtrière, Paris, France. 14. Neurorehabilitation Unit, Rehabilitation Hospital Universitario Virgen del Rocío, Sevilla, Spain. 15. Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians University of Munich, Munich, Germany. 16. Department of Neurology Washington University School of Medicine, St. Louis, MO. 17. Service des Maladies Neuromusculaire et de la SLA, Hôpital de La Timone, Marseille, France. 18. ELAN-PHYSIO, Praxis für Physiotherapie Maron, Berlin, Germany. 19. Magnetic Resonance Centre, Institute for Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. 20. AIM & CEA NMR Laboratory, Institute of Myology, Pitié-Salpêtrière University Hospital, Paris, France. 21. Charite Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation of the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine, Berlin, Germany. 22. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA. 23. Department of Neurology Children's National Health System, Washington, DC. 24. National Institutes of Health (NINDS), Bethesda, MD. 25. Neuromuscular Unit, Department of Neurology, Hospital U. Virgen del Rocío/Instituto de Biomedicina de Sevilla, Sevilla, Spain. 26. Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan. 27. Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Barcelona, Spain. 28. Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Abstract
OBJECTIVE: Dysferlinopathy is a muscular dystrophy with a highly variable clinical presentation and currently unpredictable progression. This variability and unpredictability presents difficulties for prognostication and clinical trial design. The Jain Clinical Outcomes Study of Dysferlinopathy aims to establish the validity of the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) scale and identify factors that influence the rate of disease progression using NSAD. METHODS: We collected a longitudinal series of functional assessments from 187 patients with dysferlinopathy over 3 years. Rasch analysis was used to develop the NSAD, a motor performance scale suitable for ambulant and nonambulant patients. Generalized estimating equations were used to evaluate the impact of patient factors on outcome trajectories. RESULTS: The NSAD detected significant change in clinical progression over 1 year. The steepest functional decline occurred during the first 10 years after symptom onset, with more rapid decline noted in patients who developed symptoms at a younger age (p = 0.04). The most rapidly deteriorating group over the study was patients 3 to 8 years post symptom onset at baseline. INTERPRETATION: The NSAD is the first validated limb girdle specific scale of motor performance, suitable for use in clinical practice and clinical trials. Longitudinal analysis showed it may be possible to identify patient factors associated with greater functional decline both across the disease course and in the short-term for clinical trial preparation. Through further work and validation in this cohort, we anticipate that a disease model incorporating functional performance will allow for more accurate prognosis for patients with dysferlinopathy. ANN NEUROL 2021;89:967-978.
OBJECTIVE:Dysferlinopathy is a muscular dystrophy with a highly variable clinical presentation and currently unpredictable progression. This variability and unpredictability presents difficulties for prognostication and clinical trial design. The Jain Clinical Outcomes Study of Dysferlinopathy aims to establish the validity of the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) scale and identify factors that influence the rate of disease progression using NSAD. METHODS: We collected a longitudinal series of functional assessments from 187 patients with dysferlinopathy over 3 years. Rasch analysis was used to develop the NSAD, a motor performance scale suitable for ambulant and nonambulant patients. Generalized estimating equations were used to evaluate the impact of patient factors on outcome trajectories. RESULTS: The NSAD detected significant change in clinical progression over 1 year. The steepest functional decline occurred during the first 10 years after symptom onset, with more rapid decline noted in patients who developed symptoms at a younger age (p = 0.04). The most rapidly deteriorating group over the study was patients 3 to 8 years post symptom onset at baseline. INTERPRETATION: The NSAD is the first validated limb girdle specific scale of motor performance, suitable for use in clinical practice and clinical trials. Longitudinal analysis showed it may be possible to identify patient factors associated with greater functional decline both across the disease course and in the short-term for clinical trial preparation. Through further work and validation in this cohort, we anticipate that a disease model incorporating functional performance will allow for more accurate prognosis for patients with dysferlinopathy. ANN NEUROL 2021;89:967-978.
Authors: Anna G Mayhew; Meredith K James; Ursula Moore; Helen Sutherland; Marni Jacobs; Jia Feng; Linda Pax Lowes; Lindsay N Alfano; Robert Muni Lofra; Laura E Rufibach; Kristy Rose; Tina Duong; Luca Bello; Irene Pedrosa-Hernández; Scott Holsten; Chikako Sakamoto; Aurélie Canal; Nieves Sánchez-Aguilera Práxedes; Simone Thiele; Catherine Siener; Bruno Vandevelde; Brittney DeWolf; Elke Maron; Heather Gordish-Dressman; Heather Hilsden; Michela Guglieri; Jean-Yves Hogrel; Andrew M Blamire; Pierre G Carlier; Simone Spuler; John W Day; Kristi J Jones; Diana X Bharucha-Goebel; Emmanuelle Salort-Campana; Alan Pestronk; Maggie C Walter; Carmen Paradas; Tanya Stojkovic; Madoka Mori-Yoshimura; Elena Bravver; Jordi Díaz-Manera; Elena Pegoraro; Jerry R Mendell; Volker Straub Journal: Front Neurol Date: 2022-03-10 Impact factor: 4.003
Authors: Harmen Reyngoudt; Fiona E Smith; Ericky Caldas de Almeida Araújo; Ian Wilson; Roberto Fernández-Torrón; Meredith K James; Ursula R Moore; Jordi Díaz-Manera; Benjamin Marty; Noura Azzabou; Heather Gordish; Laura Rufibach; Tim Hodgson; Dorothy Wallace; Louise Ward; Jean-Marc Boisserie; Julien Le Louër; Heather Hilsden; Helen Sutherland; Aurélie Canal; Jean-Yves Hogrel; Marni Jacobs; Tanya Stojkovic; Kate Bushby; Anna Mayhew; Volker Straub; Pierre G Carlier; Andrew M Blamire Journal: J Cachexia Sarcopenia Muscle Date: 2022-04-03 Impact factor: 12.063
Authors: Ursula Moore; Roberto Fernandez-Torron; Marni Jacobs; Heather Gordish-Dressman; Jordi Diaz-Manera; Meredith K James; Anna G Mayhew; Elizabeth Harris; Michela Guglieri; Laura E Rufibach; Jia Feng; Andrew M Blamire; Pierre G Carlier; Simone Spuler; John W Day; Kristi J Jones; Diana X Bharucha-Goebel; Emmanuelle Salort-Campana; Alan Pestronk; Maggie C Walter; Carmen Paradas; Tanya Stojkovic; Madoka Mori-Yoshimura; Elena Bravver; Elena Pegoraro; Linda Pax Lowes; Jerry R Mendell; Kate Bushby; John Bourke; Volker Straub Journal: Muscle Nerve Date: 2022-03-05 Impact factor: 3.852