Giorgia Coratti1,2, Sonia Messina3, Simona Lucibello1,2, Maria Carmela Pera1,2, Jacqueline Montes4, Amy Pasternak5, Francesca Bovis6, Jessica Exposito Escudero7, Elena Stacy Mazzone1, Anna Mayhew8, Allan M Glanzman9, Sally Dunaway Young10, Rachel Salazar3, Tina Duong10, Robert Muni Lofra8, Roberto De Sanctis2, Sara Carnicella2, Evelin Milev11, Matthew Civitello12, Marika Pane2, Mariacristina Scoto11, Chiara Marini Bettolo8, Laura Antonaci1,2, Annalia Frongia1,2, Maria Sframeli3, Gian Luca Vita3, Adele D'Amico13, Marleen Van Den Hauwe14, Emilio Albamonte15, Nathalie Goemans14, Basil T Darras5, Enrico Bertini13, Valeria Sansone15, John Day10, Andres Nascimento Osorio7, Claudio Bruno16, Francesco Muntoni11,17, Darryl C De Vivo3, Richard S Finkel12, Eugenio Mercuri1,2. 1. Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy. 2. Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. 3. Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud, University of Messina, Messina, Italy. 4. Departments of Rehabilitation and Regenerative Medicine and Neurology, Columbia University Irving Medical Center, New York, NY. 5. Departments of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA. 6. Department of Health Sciences (DISSAL), University of Genova, Genoa, Italy. 7. Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Hospital Universitari Sant Joan de Déu, ISCIII, CIBERER, Barcelona, Spain. 8. The John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. 9. Department of Physical Therapy, Children's Hospital of Philadelphia, Philadelphia, PA. 10. Department of Neurology, Stanford University, Stanford, CA. 11. Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK. 12. Center for Experimental Neurotherapeutics, St. Jude Children's Research Hospital, Memphis, TN. 13. Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, IRCCS Bambino Gesù Children's Hospital, Rome, Italy. 14. Department of Child Neurology, University Hospitals Leuven, Leuven, Belgium. 15. Neurorehabilitation Unit, University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital, Milan, Italy. 16. Center of Experimental and Translational Myology, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 17. NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.
Abstract
OBJECTIVE: We report natural history data in a large cohort of 199 patients with spinal muscular atrophy (SMA) type III assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE). The aim of the study was to establish the annual rate and possible patterns of progression according to a number of variables, such as age of onset, age at assessment, SMN2 copy number, and functional status. METHODS: HFMSE longitudinal changes were assessed using piecewise linear mixed-effects models. The dependency in the data due to repeated measures was accounted for by a random intercept per individual and an unstructured covariance R matrix was used as correlation structure. An additional descriptive analysis was performed for 123 patients, for a total of 375 12-month assessments. RESULTS: A break point at age 7 years was set for the whole cohort and for SMA IIIA and IIIB. Age, SMA type, and ambulatory status were significantly associated with changes in mean HFMSE score, whereas gender and SMN2 copy number were not. The increase in response before the break point of age 7 years is significant only for SMA IIIA (β = 1.79, p < 0.0001). After the break point, the change in the rate of HFMSE score significantly decrease for both SMA IIIA (β = -1.15, p < 0.0001) and IIIB (β = -0.69, p = 0.002). INTERPRETATION: Our findings contribute to the understanding of the natural history of SMA type III and will be helpful in the interpretation of the real-world data of patients treated with commercially available drugs. ANN NEUROL 2020;88:1109-1117.
OBJECTIVE: We report natural history data in a large cohort of 199 patients with spinal muscular atrophy (SMA) type III assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE). The aim of the study was to establish the annual rate and possible patterns of progression according to a number of variables, such as age of onset, age at assessment, SMN2 copy number, and functional status. METHODS: HFMSE longitudinal changes were assessed using piecewise linear mixed-effects models. The dependency in the data due to repeated measures was accounted for by a random intercept per individual and an unstructured covariance R matrix was used as correlation structure. An additional descriptive analysis was performed for 123 patients, for a total of 375 12-month assessments. RESULTS: A break point at age 7 years was set for the whole cohort and for SMA IIIA and IIIB. Age, SMA type, and ambulatory status were significantly associated with changes in mean HFMSE score, whereas gender and SMN2 copy number were not. The increase in response before the break point of age 7 years is significant only for SMA IIIA (β = 1.79, p < 0.0001). After the break point, the change in the rate of HFMSE score significantly decrease for both SMA IIIA (β = -1.15, p < 0.0001) and IIIB (β = -0.69, p = 0.002). INTERPRETATION: Our findings contribute to the understanding of the natural history of SMA type III and will be helpful in the interpretation of the real-world data of patients treated with commercially available drugs. ANN NEUROL 2020;88:1109-1117.
Authors: Eugenio Mercuri; Charlotte J Sumner; Francesco Muntoni; Basil T Darras; Richard S Finkel Journal: Nat Rev Dis Primers Date: 2022-08-04 Impact factor: 65.038
Authors: Giorgia Coratti; Maria Carmela Pera; Jacqueline Montes; Amy Pasternak; Mariacristina Scoto; Giovanni Baranello; Sonia Messina; Sally Dunaway Young; Allan M Glanzman; Tina Duong; Roberto De Sanctis; Elena Stacy Mazzone; Evelin Milev; Annemarie Rohwer; Matthew Civitello; Marika Pane; Laura Antonaci; Anna Lia Frongia; Maria Sframeli; Gian Luca Vita; Adele DʼAmico; Irene Mizzoni; Emilio Albamonte; Basil T Darras; Enrico Bertini; Valeria A Sansone; Francesca Bovis; John Day; Claudio Bruno; Francesco Muntoni; Darryl C De Vivo; Richard Finkel; Eugenio Mercuri Journal: Muscle Nerve Date: 2021-08-09 Impact factor: 3.852
Authors: Anna Lusakowska; Maria Jedrzejowska; Anna Kaminska; Katarzyna Janiszewska; Przemysław Grochowski; Janusz Zimowski; Janusz Sierdzinski; Anna Kostera-Pruszczyk Journal: Orphanet J Rare Dis Date: 2021-03-24 Impact factor: 4.123
Authors: Maria Carmela Pera; Giorgia Coratti; Francesca Bovis; Marika Pane; Amy Pasternak; Jacqueline Montes; Valeria A Sansone; Sally Dunaway Young; Tina Duong; Sonia Messina; Irene Mizzoni; Adele D'Amico; Matthew Civitello; Allan M Glanzman; Claudio Bruno; Francesca Salmin; Simone Morando; Roberto De Sanctis; Maria Sframeli; Laura Antonaci; Anna Lia Frongia; Annemarie Rohwer; Mariacristina Scoto; Darryl C De Vivo; Basil T Darras; John Day; William Martens; Katia A Patanella; Enrico Bertini; Francesco Muntoni; Richard Finkel; Eugenio Mercuri Journal: Ann Clin Transl Neurol Date: 2021-06-24 Impact factor: 4.511