Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy

Objective To assess in adult spinal muscular atrophy (SMA) patients the construct validity and responsiveness of several outcome measures. Methods Patients older than 15 years and followed-up at least for 6 months, between October 2015 and August 2020, with one motor function scale (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb module, RULM) in five referral centers were included. Bedside functional scales (Egen Klassification, EK2; Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, ALSFRS-R) were also collected when available. Correlations and regression models were performed to evaluate the construct validity. The monthly slopes of change were used to calculate their responsiveness. Results The study included 79 SMA patients, followed up for a mean of 16 months. All scales showed strong or very strong correlations with each other. A floor effect in motor function scales was found in weakest patients (HFMSE < 5 and RULM<10), and a ceiling effect in stronger patients (with HFMSE >55 and RULM > 35), when compared with other scales. ALSFRS-R (B=0.72) showed a strong discriminating ability between walkers, sitters, and non-sitters, and HFMSE (B=0.86) between walkers and sitters. The responsiveness was overall low, although in treated patients a moderate responsiveness was found for ALSFRS-R and HFMSE in walkers (0.69 and 0.61 respectively), and for EK2 in sitters (0.65) and non-sitters (0.60). Conclusions This study shows the validity in SMA adult patients of commonly used scales. Overall, bedside functional scales showed some advantages over motor function scales, although all scales showed low responsiveness in untreated patients.