1. Development of new outcome measures for adult SMA type III and IV: a multimodal longitudinal study
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Rabab Debs, Jean-Yves Hogrel, Gaëlle Bruneteau, Nadine Le Forestier, Peter Bede, Pascal Laforêt, Sophie Blancho, Anthony Behin, Timothée Lenglet, Véronique Marchand-Pauvert, François Salachas, Giorgia Querin, Pierre-François Pradat, Tanya Stojkovic, Maria del Mar Amador, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Etudes sur les sciences et les techniques (EST), Université Paris-Saclay, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [AP-HP], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), H&R BLOCK, HRB: EIA-2017-019 Association Française contre les Myopathies, AFM Health Research Board, HRB Iris O'Brien Foundation Irish Institute of Clinical Neuroscience, IICN AFM-Téléthon: NCT0288587, This study was sponsored by the Association française contre les myopathies (AFM-Téléthon). Dr. Giorgia Querin, Dr. Timothée Lenglet, Dr. Rabab Debs, Dr. Tanya Stojkovic, Dr. Anthony Behin, Dr. François Salachas, Dr. Nadine Le Forestier, Dr. Maria del Mar Amador, Dr. Gaëlle Bruneteau, Dr. Sophie Blancho, Dr. Véronique Marchand-Pauvert: report no disclosures. Prof Pascal Laforêt receives funding for research and as an advisor or speaker from Sanofi Genzyme and Spark Therapeutics. Dr. Peter Bede is supported by the Health Research Board (HRB EIA-2017-019), the Andrew Lydon scholarship, the Irish Institute of Clinical Neuroscience (IICN), the Irish Motor Neuron Disease Association (IMNDA) and the Iris O'Brien Foundation. Dr. Jean-Yves Hogrel is co-inventor of the Myogrip and MyoPinch devices and did consultancy for Biogen and Sarepta. Dr Pierre- François Pradat receives funding as an advisor and speaker from Biogen., We are grateful for the generosity of all SMA patients who have kindly participated in this study. This study was supported by the Association Française contre les Myopathies (AFM-Téléthon). We also thank the Institut pour la Recherche sur la Moelle Épinière et l’Encephale (IRME) for their support of this the study. Peter Bede is supported by the Health Research Board (HRB EIA-2017-019), the Andrew Lydon scholarship, the Irish Institute of Clinical Neuroscience (IICN), the Irish Motor Neuron Disease Association (IMNDA) and the Iris O'Brien Foundation. The rest of the authors have no specific sponsors to declare., Supported by the Association Française contre les Myopathies (AFM-Téléthon, NCT0288587)., Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Myologie, Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Association française contre les myopathies (AFM-Téléthon). Dr. Giorgia Querin, Dr. Timothée Lenglet, Dr. Rabab Debs, Dr. Tanya Stojkovic, Dr. Anthony Behin, Dr. François Salachas, Dr. Nadine Le Forestier, Dr. Maria del Mar Amador, Dr. Gaëlle Bruneteau, Dr. Sophie Blancho, Dr. Véronique Marchand-Pauvert: report no disclosures. Prof Pascal Laforêt receives funding for research and as an advisor or speaker from Sanofi Genzyme and Spark Therapeutics. Dr. Peter Bede is supported by the Health Research Board (HRB EIA-2017-019), the Andrew Lydon scholarship, the Irish Institute of Clinical Neuroscience (IICN), the Irish Motor Neuron Disease Association (IMNDA) and the Iris O'Brien Foundation. Dr. Jean-Yves Hogrel is co-inventor of the Myogrip and MyoPinch devices and did consultancy for Biogen and Sarepta. Dr Pierre- François Pradat receives funding as an advisor and speaker from Biogen.
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Adult ,medicine.medical_specialty ,Longitudinal study ,Neurology ,[SDV]Life Sciences [q-bio] ,Deltoid curve ,Spinal Muscular Atrophies of Childhood ,Outcome measures ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Outcome Assessment, Health Care ,Humans ,Medicine ,Longitudinal Studies ,Muscle Strength ,030212 general & internal medicine ,Muscle, Skeletal ,Neuroradiology ,Longitudinal progression ,business.industry ,SMA ,Spinal cord ,3. Good health ,Clinical trial ,medicine.anatomical_structure ,Sample size determination ,Adult SMA ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,MUNIX - Abstract
International audience; Objective: The aim of this study was the comprehensive characterisation of longitudinal clinical, electrophysiological and neuroimaging measures in type III and IV adult spinal muscular atrophy (SMA) with a view to propose objective monitoring markers for future clinical trials. Methods: Fourteen type III or IV SMA patients underwent standardised assessments including muscle strength testing, functional evaluation (SMAFRS and MFM), MUNIX (abductor pollicis brevis, APB; abductor digiti minimi, ADM; deltoid; tibialis anterior, TA; trapezius) and quantitative cervical spinal cord MRI to appraise segmental grey and white matter atrophy. Patients underwent a follow-up assessment with the same protocol 24 months later. Longitudinal comparisons were conducted using the Wilcoxon-test for matched data. Responsiveness was estimated using standardized response means (SRM) and a composite score was generated based on the three most significant variables. Results: Significant functional decline was observed based on SMAFRS (p = 0.019), pinch and knee flexion strength (p = 0.030 and 0.027), MUNIX and MUSIX value in the ADM (p = 0.0006 and 0.043) and in TA muscle (p = 0.025). No significant differences were observed based on cervical MRI measures. A significant reduction was detected in the composite score (p = 0.0005, SRM = −1.52), which was the most responsive variable and required a smaller number of patients than single variables in the estimation of sample size for clinical trials. Conclusions: Quantitative strength testing, SMAFRS and MUNIX readily capture disease progression in adult SMA patients. Composite multimodal scores increase predictive value and may reduce sample size requirements in clinical trials.
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- 2021