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

Area of Science:

• Neurology
• Pediatrics
• Biomedical Engineering

Background:

• Sensitive response measures are vital for evaluating treatment efficacy in spinal muscular atrophy (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 like HFMSE, CHOP-INTEND, and RULM are also used.

Purpose of the Study:

• To compare electrodiagnostic (EDX) measures with traditional functional measures for monitoring treatment response in pediatric SMA patients.
• To assess the sensitivity of EDX measures in capturing treatment effects in SMA.
• To evaluate the correlation between specific EDX parameters and functional scores.

Main Methods:

• Retrospective chart review of 16 non-ambulatory, late-onset SMA children (January 2017 - June 2024).
• Comparison of motor nerve conduction study (NCS) recordings (median-APB and ulnar-ADM) with functional scores.
• Statistical analysis using Spearman correlation and generalized linear mixed model (GLMM).

Main Results:

• EDX measures were significantly reduced in SMA children compared to controls (p < 0.05).
• Median abductor pollicis brevis (APB) CMAP amplitudes correlated moderately to strongly with CHOP-INTEND (r=0.64) and RULM (r=0.77) scores (p < 0.05).
• APB CMAP significantly decreased over time in the non-treatment group compared to the treatment group (Beta = -0.02, p < 0.05).

Conclusions:

• Median-APB CMAP amplitude is a sensitive measure for capturing treatment response in pediatric SMA.
• Further prospective studies with larger cohorts and longer follow-up are needed to compare specific treatments like nusinersen and risdiplam.