597PAligning functional scales with neurophysiological biomarkers in adult SMA: guiding clinical and research scale selection

Abstract

Neurophysiological biomarkers such as Compound Muscle Action Potential (CMAP) and Motor Unit Number Index (MUNIX) are increasingly recognized as objective tools to monitor disease status in spinal muscular atrophy (SMA). However, their relationship with motor function, particularly in adult populations, remains underexplored. Identifying which clinical scale best reflects neurophysiological integrity is essential for outcome selection in both clinical trials and routine care. To investigate correlations between CMAP/MUNIX and three motor function scales—Motor Function Measure (MFM), Hammersmith Functional Motor Scale Expanded (HFMSE), and Revised Upper Limb Module (RULM)—in adults with SMA types 2 and 3, and to identify the most responsive clinical measure. Twenty-eight adults with genetically confirmed SMA types 2 and 3 were evaluated at two timepoints one year apart. CMAP and MUNIX were recorded alongside motor function assessments using MFM, HFMSE, and RULM. Spearman’s correlation coefficients (ρ) were calculated to explore associations between neurophysiological and functional measures. Both CMAP and MUNIX showed strong and consistent correlations with all three motor scales at both visits. Among the scales, MFM demonstrated the highest correlation coefficients (up to ρ = 0.90 with CMAP), outperforming HFMSE and RULM. Longitudinal analysis revealed no significant change in CMAP or MUNIX over one year, whereas MFM scores significantly declined (p = 0.025), suggesting higher sensitivity to disease progression. CMAP and MUNIX are reliable neurophysiological markers of motor unit integrity in adult SMA. The MFM scale demonstrated the strongest and most consistent correlations with these biomarkers and was the only scale to detect significant functional decline over time. Due to its multidimensional structure, encompassing axial, proximal, and distal domains, MFM may offer superior sensitivity in monitoring disease progression in adults with SMA. These findings support the inclusion of MFM as a preferred outcome measure in adult SMA trials and clinical follow-up.

Publication
Neuromuscular Disorders

Related