2026 American Academy of Neurology Abstract Website

Objective:

To assess neuromuscular junction (NMJ) transmission in pediatric spinal muscular atrophy (SMA) patients using stimulated jitter analysis (stim-JA) and correlate findings with motor function.

Background:

SMA is primarily a motor neuron disorder, but increasing evidence suggests NMJ dysfunction may contribute to muscle weakness. Stim-JA allows objective evaluation of NMJ transmission in children.

Design/Methods:

Nine consecutive SMA patients (6 males, 3 females) underwent stim-JA of the right orbicularis oculi muscle between January-September 2025. Median age at testing was 3.5 years (IQR 2.1-8.3). Six patients had SMA type 1, and three had SMA type 2. Disease-modifying therapies included nusinersen (n=5), risdiplam (n=6), and onasemnogene-abeparvovec (n=6), with some receiving combination or sequential therapies. Five patients were identified through newborn screening (NBS), the remainder were born before NBS initiation. CHOP-INTEND, and highest motor milestones achieved were recorded.

Results:

Seven patients exhibited delayed and two achieved age-appropriate motor milestones. The median CHOP-INTEND scores were 50 (range 42 to 54, max 64) for those with delayed milestones. The mean mean jitter was 64 µs (range 44 to 82µs, normal <24µs) with 78% fibers with increased jitter and blocking in patients with delayed motor milestones; those with age-appropriate milestones had normal mean mean jitter 19.5µs. This difference was statistically significant. No significant differences were observed between type 1 vs. type 2, NBS vs. pre-NBS patients, or those with or without intravenous gene therapy. Pearson analysis revealed significant negative correlations of CHOP-INTEND with mean jitter (r = −0.693, p = 0.039), percentage of abnormal fibers (r = −0.765, p = 0.016), and blocking (r = −0.716, p = 0.030).

Conclusions:

Stim-JA quantifies NMJ abnormalities in children with SMA. Increased mean jitter, abnormal fibers, and blocking correlated with disease severity measured by motor milestones, and CHOP-INTEND. Stim-JA can serve as an objective biomarker for therapies targeting NMJ dysfunction in SMA.