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.

Fatigability in spinal muscular atrophy: validity and reliability of endurance shuttle tests

“…These and previously published data of motor function and endurance suggest that current performance measures are not sensitive to capture possible changes at the extreme ends of the spectrum of physical abilities [25,29]. A commonly used method to counteract this problem in functional scales, adding items to both ends of the hierarchical scale, is not applicable to exercise testing [26,30,31]. The second objective of this study was to develop a combined score that would allow comparison of patients with varying severity on their individual most relevant endurance test, thereby increasing sensitivity and circumventing subgroup analysis with less statistical power.…”

A Sensitive and Selective Immunoassay for the Quantitation of Serum Latent Myostatin after In Vivo Administration of SRK-015, a Selective Inhibitor of Myostatin Activation

“…15 Thus, measuring this pool of latent myostatin may provide insight into the kinetics of target engagement and saturation in SRK-015-treated subjects. In addition, when paired with wellcharacterized protocols for evaluating muscle function and basic motor skills, [17][18][19][20] accurate measurement of latent myostatin may inform dose selection and frequency for clinical trials that aim to evaluate the efficacy of this inhibitor of myostatin activation.…”

A retrospective cohort study of children with spinal muscular atrophy type 2 receiving anesthesia for intrathecal administration of nusinersen

“…Source data were de‐identified and entered into a secure database registry REDCap (https://www.project-redcap.org), which is a secure web application for creating and managing online surveys and databases and subsequently analyzed with Microsoft Excel for descriptive statistical parameters. Information recorded included patient demographics including age at time of procedure, gender, American Society of Anesthesiologist's (ASA) Physical Status, most recent Expanded Hammersmith Functional Motor Scale for SMA, anesthesia induction method, anesthesia maintenance method, duration of anesthesia, duration of postanesthesia care unit (PACU) stay, discharge destination, preprocedure SaO 2 , PACU discharge oxygen saturation (SaO 2 ), and occurrence of unanticipated admission or postdischarge hospitalization …”

“…or sham procedure (Table 1). Patients underwent a median of 8 (5)(6)(7)(8)(9) procedures. A propofol infusion at 250-300 μg/kg/min was used in 58 cases, while the remainder were maintained with inhalational anesthetics.…”