2-year Change in Revised Hammersmith Scale scores in a large cohort of untreated paediatric type 2 and 3 SMA participants

Abstract

The Revised Hammersmith Scale (RHS) is a 36-item ordinal scale developed using clinical expertise and sound psychometrics to investigate motor function in participants with Spinal Muscular Atrophy (SMA). In this study, we investigate median change in the RHS score up to two years in paediatric SMA 2 and 3 participants and contextualise it to the Hammersmith Functional Motor Scale-Expanded (HFMSE). These change scores were considered by SMA type, motor function and baseline RHS score. We consider a new transitional group, spanning crawlers, standers and walkers-with-assistance, and analyse that alongside non-sitters, sitters and walkers. The transitional group exhibit the most definitive change score trend, with an average 1-year decline of 3 points. The RHS has a reduced floor effect compared to the HFMSE, although we show that the RHS should be used in conjunction with the RULM for participants scoring less than 20 points on the RHS. In the stronger participants (between 10 and 42 on the RHS) in the 5-7 age group, both the RHS and HFMSE can detect 1-year change. The timed items in the RHS have high between-participant variability, so participants with the same RHS total can be differentiated by their timed test items.

Disease Trajectories in the Revised Hammersmith Scale in a Cohort of Untreated Patients with Spinal Muscular Atrophy types 2 and 3

“…In the RHS we observe a stable peak in the SMA type 2 s between 3.25-6 years and in the SMA 3a between 5.6-7.7 years. Previous work on the RHS has reported positive slopes before the age of 5 in those with type 2 SMA followed by a negative slope, whereas the patients with SMA 3a demonstrated an increase in scores before 5 years, stability between ages 5-7 and then a negative trend after 7 years [15].…”

“…This leads to a discontinuity when patients undergo scoliosis but due to the visiting process, it wasn't possible to model the impact of scoliosis surgery on motor function with respect to time. The ages for yearly change estimates are the mid-points of the age group summaries previously presented [15]. RStudio version 2022.07.2 Build 576 was used for this analysis.…”

“…All participants had a genetically confirmed diagnosis of SMA, clinically classified as type 2, 3a or 3b, were receiving SMA Standards of Care treatment [20], had no previous involvement in clinical trials, and had at least two RHS assessments performed between the 17th of March 2015 and the 29th of July 2019. This study is a longitudinal reanalysis of previously published cross-sectional natural history data [15]. The inclusion criteria included those who had all fully completed HFMSE and RHS assessments, known spinal surgery status and known sex.…”

“…The SMA specific outcome measures commonly used to assess gross motor function for clinical trials in patients with later-onset type 2 and 3 SMA are the Hammersmith Functional Motor Scale Expanded (HFMSE) and more recently the Revised Hammersmith Scale (RHS) [13,14]. The RHS was developed more recently to expand the HFMSE at both ends of the scale, including an item from the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) which has been shown to reduce floor effect and several items including timed tests from the North Star Ambulatory Assessment (NSAA) to reduce the ceiling effect [13,15]. Upper limb function is assessed using the Revised Upper Limb Module (RULM) [16,17].…”

Determining minimal clinically important differences in the Hammersmith Functional Motor Scale Expanded for untreated spinal muscular atrophy patients: An international study

“…For the distribution-based MDC calculation, to maximize the number of participants, multiple 12-month observation intervals were defined for each participant, where 12 months was defined as two visits that were at least 304.2 days (47.3 weeks) and no more than 425.8 days (64.7 weeks) apart [30,39].…”