Electrodiagnostic and Functional Biomarkers for Non-Ambulatory Children With Late-Onset Spinal Muscular Atrophy

Identifying sensitive response measures is crucial for evaluating treatment efficacy in SMA patients. Current electrodiagnostic (EDX) measures include compound muscle action potential (CMAP), motor unit number index (MUNIX), and motor unit size index (MUSIX). Functional measures include Hammersmith functional motor scale extended (HFMSE), Children's Hospital of Philadelphia infant test of neuromuscular disorders (CHOP-INTEND), and the revised upper limb module (RULM). Here, we compared EDX to traditional functional measures for monitoring treatment response in pediatric SMA.

A retrospective chart review of 16 non-ambulatory, late-onset (> 6 months of age) SMA children seen between January 2017 and June 2024 was performed. Motor nerve conduction study (NCS) recordings from the right median-abductor pollicis brevis (APB) and ulnar-abductor digiti minimi (ADM) nerve muscle pairs and functional scores were compared using Spearman correlation and a generalized linear mixed model (GLMM).

EDX measures were significantly reduced in SMA children compared to healthy, age-matched controls (p < 0.05). Median abductor pollicis brevis (APB) CMAP amplitudes demonstrated moderate to strong correlations with CHOP-INTEND (r = 0.64, p < 0.05) and RULM (r = 0.77, p < 0.05) scores, and the GLMM revealed that APB CMAP significantly decreased over time (Beta = -0.02, p < 0.05) in the non-treatment compared to the treatment group. HMFSE showed a declining trend in patients who received only risdiplam.

Median-APB CMAP amplitude demonstrated sensitivity in capturing treatment response. A prospective study comparing nusinersen and risdiplam in a larger, clinically diverse cohort with a longer follow-up period is needed.