title: Patterns of disease progression in type 2 and 3 SMA: Implications for clinical trials.
abstract: The aim of the study was to establish 12-month changes in the Hammersmith Functional motor scale in a large cohort of SMA patients, to identify patterns of disease progression and the effect of different variables. 268 patients were included in this multicentric study. Their age ranged between 2.5 and 55.5 years at baseline, 68 were ambulant and 200 non-ambulant. The baseline scores ranged between 0 and 66 (mean 23.91, SD 20.09). The 12-month change was between -14 and +9 (mean -0.56, SD 2.72). Of the 268 patients, 206 (76.86%) had changes between -2 and +2 points. Ambulant and non-ambulant subjects had a different relationship between baseline values and age (p for age X ambulation interaction = 0.007). There was no association with age in ambulant subjects, while there was a significant heterogeneity at different age for non-ambulant patients (p < 0.001). The 12-month change (adjusted for baseline) was not associated with age in ambulant patients (p = 0.34), but it was significantly different among various age groups in non-ambulant patients. Our results suggest that there are different profiles of progression in ambulant and non-ambulant patients, and that age may play an important role in the progression of non-ambulant patients.
authors.affiliation: Department of Paediatric Neurology, Catholic University, Rome, Italy. Electronic address: mercuri@rm.unicatt.it.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mercuri
authors.affiliation: Nemours Children's Hospital, University of Central Florida College of Medicine, Orlando, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Finkel
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Montes
authors.affiliation: Department of Paediatric Neurology, Catholic University, Rome, Italy.
authors.forename: Elena S
authors.initials: ES
authors.lastname: Mazzone
authors.affiliation: Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK.
authors.forename: Marion
authors.initials: M
authors.lastname: Main
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK.
authors.forename: Danielle
authors.initials: D
authors.lastname: Ramsey
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Mayhew
authors.affiliation: Department of Physical Therapy, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Allan M
authors.initials: AM
authors.lastname: Glanzman
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, USA.
authors.forename: Sally
authors.initials: S
authors.lastname: Dunaway
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Salazar
authors.affiliation: Departments of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Pasternak
authors.affiliation: Departments of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Quigley
authors.affiliation: Department of Paediatric Neurology, Catholic University, Rome, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Pane
authors.affiliation: Department of Paediatric Neurology, Catholic University, Rome, Italy.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Pera
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK.
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Scoto
authors.affiliation: Department of Neurosciences and Nemo Sud Clinical Centre, University of Messina, Messina, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Messina
authors.affiliation: Department of Neurosciences and Nemo Sud Clinical Centre, University of Messina, Messina, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Sframeli
authors.affiliation: Department of Neurosciences and Nemo Sud Clinical Centre, University of Messina, Messina, Italy.
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Vita
authors.affiliation: Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: D'Amico
authors.affiliation: Department of Child Neurology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Marleen
authors.initials: M
authors.lastname: van den Hauwe
authors.affiliation: Department of Paediatric Neurology, Catholic University, Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Sivo
authors.affiliation: Department of Child Neurology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Goemans
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, USA.
authors.forename: Petra
authors.initials: P
authors.lastname: Kaufmann
authors.affiliation: Departments of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Basil T
authors.initials: BT
authors.lastname: Darras
authors.affiliation: Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, USA.
authors.forename: Darryl C
authors.initials: DC
authors.lastname: De Vivo
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051346:Mobility Limitation; D012189:Retrospective Studies; D014897:Spinal Muscular Atrophies of Childhood / Q000503:physiopathology*; D055815:Young Adult
keywords: Hammersmith Functional Motor Scale; Outcome measures; Spinal muscular atrophy