title: Revised Hammersmith Scale for spinal muscular atrophy: A SMA specific clinical outcome assessment tool.
abstract: Recent translational research developments in Spinal Muscular Atrophy (SMA), outcome measure design and demands from regulatory authorities require that clinical outcome assessments are 'fit for purpose'. An international collaboration (SMA REACH UK, Italian SMA Network and PNCRN USA) undertook an iterative process to address discontinuity in the recorded performance of the Hammersmith Functional Motor Scale Expanded and developed a revised functional scale using Rasch analysis, traditional psychometric techniques and the application of clinical sensibility via expert panels. Specifically, we intended to develop a psychometrically and clinically robust functional clinician rated outcome measure to assess physical abilities in weak SMA type 2 through to strong ambulant SMA type 3 patients. The final scale, the Revised Hammersmith Scale (RHS) for SMA, consisting of 36 items and two timed tests, was piloted in 138 patients with type 2 and 3 SMA in an observational cross-sectional multi-centre study across the three national networks. Rasch analysis demonstrated very good fit of all 36 items to the construct of motor performance, good reliability with a high Person Separation Index PSI 0.98, logical and hierarchical scoring in 27/36 items and excellent targeting with minimal ceiling. The RHS differentiated between clinically different groups: SMA type, World Health Organisation (WHO) categories, ambulatory status, and SMA type combined with ambulatory status (all p < 0.001). Construct and concurrent validity was also confirmed with a strong significant positive correlation with the WHO motor milestones rs = 0.860, p < 0.001. We conclude that the RHS is a psychometrically sound and versatile clinical outcome assessment to test the broad range of physical abilities of patients with type 2 and 3 SMA. Further longitudinal testing of the scale with regards change in scores over 6 and 12 months are required prior to its adoption in clinical trials.
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
authors.forename: Danielle
authors.identifier: http://orcid.org/0000-0003-1275-2640
authors.initials: D
authors.lastname: Ramsey
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Scoto
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Mayhew
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
authors.forename: Marion
authors.initials: M
authors.lastname: Main
authors.affiliation: Department of Child Neurology, Catholic University in Rome, Rome, Italy.
authors.forename: Elena S
authors.initials: ES
authors.lastname: Mazzone
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Montes
authors.affiliation: Department of Child Neurology, Catholic University in Rome, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: de Sanctis
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Sally
authors.initials: S
authors.lastname: Dunaway Young
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Rachel
authors.initials: R
authors.lastname: Salazar
authors.affiliation: Department of Physical Therapy, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Allan M
authors.initials: AM
authors.lastname: Glanzman
authors.affiliation: Departments of Neurology and Physical Therapy and Occupational Therapy Services, Boston Children's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Amy
authors.initials: A
authors.lastname: Pasternak
authors.affiliation: Departments of Neurology and Physical Therapy and Occupational Therapy Services, Boston Children's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Janet
authors.initials: J
authors.lastname: Quigley
authors.affiliation: Departments of Neurology and Physical Therapy and Occupational Therapy Services, Boston Children's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mirek
authors.affiliation: Department of Neurology, Stanford University, Palo Alto, California, United States of America.
authors.forename: Tina
authors.initials: T
authors.lastname: Duong
authors.affiliation: Lucille Packard Children's Hospital, Stanford University, Palo Alto, California, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Gee
authors.affiliation: Nemours Children's Hospital, University of Central Florida College of Medicine, Orlando, Florida, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Civitello
authors.affiliation: Department of Neurology, The Children's Hospital of Philadelphia and the Pearlman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Gihan
authors.initials: G
authors.lastname: Tennekoon
authors.affiliation: Department of Child Neurology, Catholic University in Rome, Rome, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Pane
authors.affiliation: Department of Child Neurology, Catholic University in Rome, Rome, Italy.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Pera
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom.
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.affiliation: Department of Neurology, Stanford University, Palo Alto, California, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Day
authors.affiliation: Departments of Neurology and Physical Therapy and Occupational Therapy Services, Boston Children's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Basil T
authors.initials: BT
authors.lastname: Darras
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Darryl
authors.initials: D
authors.lastname: De Vivo
authors.affiliation: Nemours Children's Hospital, University of Central Florida College of Medicine, Orlando, Florida, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Finkel
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.|Department of Child Neurology, Catholic University in Rome, Rome, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mercuri
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D051346:Mobility Limitation; D009043:Motor Activity; D017063:Outcome Assessment, Health Care / Q000379:methods*; D010865:Pilot Projects; D011594:Psychometrics; D012720:Severity of Illness Index; D014897:Spinal Muscular Atrophies of Childhood; D055815:Young Adult