Clinical Variability in Spinal Muscular Atrophy Type III
Giorgia Coratti PT
Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
These authors contributed equally to this work and should be considered co-first authors.
Search for more papers by this authorSonia Messina MD, PhD
Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud, University of Messina, Messina, Italy
These authors contributed equally to this work and should be considered co-first authors.
Search for more papers by this authorSimona Lucibello MD
Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
These authors contributed equally to this work and should be considered co-first authors.
Search for more papers by this authorMaria Carmela Pera MD, PhD
Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Search for more papers by this authorJacqueline Montes PT, EdD
Departments of Rehabilitation and Regenerative Medicine and Neurology, Columbia University Irving Medical Center, New York, NY
Search for more papers by this authorAmy Pasternak PT
Departments of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA
Search for more papers by this authorFrancesca Bovis STAT, PhD
Department of Health Sciences (DISSAL), University of Genova, Genoa, Italy
Search for more papers by this authorJessica Exposito Escudero MD
Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Hospital Universitari Sant Joan de Déu, ISCIII, CIBERER, Barcelona, Spain
Search for more papers by this authorElena Stacy Mazzone PT
Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy
Search for more papers by this authorAnna Mayhew PT, PhD
The John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Search for more papers by this authorAllan M. Glanzman PT
Department of Physical Therapy, Children's Hospital of Philadelphia, Philadelphia, PA
Search for more papers by this authorSally Dunaway Young PT
Department of Neurology, Stanford University, Stanford, CA
Search for more papers by this authorRachel Salazar PT
Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud, University of Messina, Messina, Italy
Search for more papers by this authorTina Duong PT, PhD
Department of Neurology, Stanford University, Stanford, CA
Search for more papers by this authorRobert Muni Lofra PT
The John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Search for more papers by this authorRoberto De Sanctis PT
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Search for more papers by this authorSara Carnicella PT
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Search for more papers by this authorEvelin Milev PT
Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK
Search for more papers by this authorMatthew Civitello PT
Center for Experimental Neurotherapeutics, St. Jude Children's Research Hospital, Memphis, TN
Search for more papers by this authorMarika Pane MD, PhD
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Search for more papers by this authorMariacristina Scoto MD, PhD
Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK
Search for more papers by this authorChiara Marini Bettolo MD, PhD
The John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Search for more papers by this authorLaura Antonaci MD
Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Search for more papers by this authorAnnalia Frongia MD
Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Search for more papers by this authorMaria Sframeli MD, PhD
Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud, University of Messina, Messina, Italy
Search for more papers by this authorGian Luca Vita MD, PhD
Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud, University of Messina, Messina, Italy
Search for more papers by this authorAdele D'Amico MD, PhD
Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, IRCCS Bambino Gesù Children's Hospital, Rome, Italy
Search for more papers by this authorMarleen Van Den Hauwe PT
Department of Child Neurology, University Hospitals Leuven, Leuven, Belgium
Search for more papers by this authorEmilio Albamonte MD
Neurorehabilitation Unit, University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital, Milan, Italy
Search for more papers by this authorNathalie Goemans MD, PhD
Department of Child Neurology, University Hospitals Leuven, Leuven, Belgium
Search for more papers by this authorBasil T. Darras MD
Departments of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA
Search for more papers by this authorEnrico Bertini MD, PhD
Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, IRCCS Bambino Gesù Children's Hospital, Rome, Italy
Search for more papers by this authorValeria Sansone MD, PhD
Neurorehabilitation Unit, University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital, Milan, Italy
Search for more papers by this authorJohn Day MD, PhD
Department of Neurology, Stanford University, Stanford, CA
Search for more papers by this authorAndres Nascimento Osorio MD
Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Hospital Universitari Sant Joan de Déu, ISCIII, CIBERER, Barcelona, Spain
Search for more papers by this authorClaudio Bruno MD, PhD
Center of Experimental and Translational Myology, IRCCS Istituto Giannina Gaslini, Genoa, Italy
Search for more papers by this authorFrancesco Muntoni MD, PhD
Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK
NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK
Search for more papers by this authorDarryl C. De Vivo MD, PhD
Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud, University of Messina, Messina, Italy
Search for more papers by this authorRichard S. Finkel MD
Center for Experimental Neurotherapeutics, St. Jude Children's Research Hospital, Memphis, TN
Search for more papers by this authorCorresponding Author
Eugenio Mercuri MD, PhD
Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Address correspondence to Prof. Eugenio Mercuri, Pediatric Neurology, Catholic University, Largo Gemelli 8, 00168 Rome, Italy. E-mail: [email protected]
Search for more papers by this authorGiorgia Coratti PT
Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
These authors contributed equally to this work and should be considered co-first authors.
Search for more papers by this authorSonia Messina MD, PhD
Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud, University of Messina, Messina, Italy
These authors contributed equally to this work and should be considered co-first authors.
Search for more papers by this authorSimona Lucibello MD
Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
These authors contributed equally to this work and should be considered co-first authors.
Search for more papers by this authorMaria Carmela Pera MD, PhD
Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Search for more papers by this authorJacqueline Montes PT, EdD
Departments of Rehabilitation and Regenerative Medicine and Neurology, Columbia University Irving Medical Center, New York, NY
Search for more papers by this authorAmy Pasternak PT
Departments of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA
Search for more papers by this authorFrancesca Bovis STAT, PhD
Department of Health Sciences (DISSAL), University of Genova, Genoa, Italy
Search for more papers by this authorJessica Exposito Escudero MD
Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Hospital Universitari Sant Joan de Déu, ISCIII, CIBERER, Barcelona, Spain
Search for more papers by this authorElena Stacy Mazzone PT
Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy
Search for more papers by this authorAnna Mayhew PT, PhD
The John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Search for more papers by this authorAllan M. Glanzman PT
Department of Physical Therapy, Children's Hospital of Philadelphia, Philadelphia, PA
Search for more papers by this authorSally Dunaway Young PT
Department of Neurology, Stanford University, Stanford, CA
Search for more papers by this authorRachel Salazar PT
Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud, University of Messina, Messina, Italy
Search for more papers by this authorTina Duong PT, PhD
Department of Neurology, Stanford University, Stanford, CA
Search for more papers by this authorRobert Muni Lofra PT
The John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Search for more papers by this authorRoberto De Sanctis PT
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Search for more papers by this authorSara Carnicella PT
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Search for more papers by this authorEvelin Milev PT
Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK
Search for more papers by this authorMatthew Civitello PT
Center for Experimental Neurotherapeutics, St. Jude Children's Research Hospital, Memphis, TN
Search for more papers by this authorMarika Pane MD, PhD
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Search for more papers by this authorMariacristina Scoto MD, PhD
Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK
Search for more papers by this authorChiara Marini Bettolo MD, PhD
The John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Search for more papers by this authorLaura Antonaci MD
Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Search for more papers by this authorAnnalia Frongia MD
Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Search for more papers by this authorMaria Sframeli MD, PhD
Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud, University of Messina, Messina, Italy
Search for more papers by this authorGian Luca Vita MD, PhD
Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud, University of Messina, Messina, Italy
Search for more papers by this authorAdele D'Amico MD, PhD
Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, IRCCS Bambino Gesù Children's Hospital, Rome, Italy
Search for more papers by this authorMarleen Van Den Hauwe PT
Department of Child Neurology, University Hospitals Leuven, Leuven, Belgium
Search for more papers by this authorEmilio Albamonte MD
Neurorehabilitation Unit, University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital, Milan, Italy
Search for more papers by this authorNathalie Goemans MD, PhD
Department of Child Neurology, University Hospitals Leuven, Leuven, Belgium
Search for more papers by this authorBasil T. Darras MD
Departments of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA
Search for more papers by this authorEnrico Bertini MD, PhD
Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, IRCCS Bambino Gesù Children's Hospital, Rome, Italy
Search for more papers by this authorValeria Sansone MD, PhD
Neurorehabilitation Unit, University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital, Milan, Italy
Search for more papers by this authorJohn Day MD, PhD
Department of Neurology, Stanford University, Stanford, CA
Search for more papers by this authorAndres Nascimento Osorio MD
Neuromuscular Unit, Neuropaediatrics Department, Institut de Recerca Hospital Universitari Sant Joan de Déu, ISCIII, CIBERER, Barcelona, Spain
Search for more papers by this authorClaudio Bruno MD, PhD
Center of Experimental and Translational Myology, IRCCS Istituto Giannina Gaslini, Genoa, Italy
Search for more papers by this authorFrancesco Muntoni MD, PhD
Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK
NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK
Search for more papers by this authorDarryl C. De Vivo MD, PhD
Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud, University of Messina, Messina, Italy
Search for more papers by this authorRichard S. Finkel MD
Center for Experimental Neurotherapeutics, St. Jude Children's Research Hospital, Memphis, TN
Search for more papers by this authorCorresponding Author
Eugenio Mercuri MD, PhD
Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Address correspondence to Prof. Eugenio Mercuri, Pediatric Neurology, Catholic University, Largo Gemelli 8, 00168 Rome, Italy. E-mail: [email protected]
Search for more papers by this authorAbstract
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
Potential Conflicts of Interest
Authors have nothing to report as potential conflict of interest relative to this study. Full disclosures can be found in the ICMJE conflict of interest forms.
Supporting Information
| Filename | Description |
|---|---|
| ana25900-sup-0001-TableS1.docxWord 2007 document , 55.2 KB | Table S1. Descriptive statistics (N, mean, SD, min and max) of the 375 assessments reporting age, Hammersmith Functional Motor Scale Expanded (HFMSE) at baseline, HFMSE at 12 months, and HFMSE changes values of the whole cohort, subdivided by spinal muscular atrophy (SMA) type III A or B and subgrouped by ambulatory status and age groups. |
| ana25900-sup-0002-TableS2.docxWord 2007 document , 38.8 KB | Table S2. Analysis of the 375 assessments reporting clinical meaningful changes frequency on the whole cohort, subdivided by spinal muscular atrophy (SMA) type III A or B and subgrouped by ambulatory status and age groups. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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