Abstract Details

Title Compound Muscle Action Potentials as Potential Motor Outcome Predictors of Spinal Muscular Atrophy in Children with Onasemnogene Abeparvovec-xioi Gene Therapy

Topic Child Neurology and Developmental Neurology

Presentation(s) S24 - State of the Art Diagnostics in Child Neurology (1:36 PM-1:48 PM)

Poster/Presentation
Number 004

Objective This study aims to investigate the potential utility of compound muscle action
potential (CMAP) amplitudes as biomarkers for assessing disease severity in neonates with spinal muscular atrophy (SMA) identified by newborn screening (NBS) and confirmed by genetic testing.

Background We assessed CMAP, CMI, and Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores at baseline with two subsequent follow-up points over one year in newborn-screened SMA infants receiving early gene therapy. The results provide a comprehensive evaluation of functional and neurophysiological outcomes to better define disease progression and treatment response.

Design/Methods We conducted a retrospective review of 21 SMA newborns performed at the median age of 18 days. The analysis included weight, right median, ulnar and fibular motor nerve CMAP amplitudes and functional scores of CHOP-INTEND.

Results The analysis revealed notable findings with statistically significant difference in the motor CMAP amplitudes for the right median (2.6 vs. 3.8 mV, p 0.004), ulnar (2 vs 6.4 mV, p 0.007), and fibular (2.1 vs. 4.05 mV, p 0.007) nerves between 2 vs. 3 SMN2 copy number babies. The baseline ulnar amplitudes positively correlated with CHOP- INTEND scores in patients with 3SMN2 copies (Corr = 0.593, P < 0.05). The differences in weight and CHOP-INTEND scores were insignificant.

Conclusions Reduced motor CMAP amplitudes were able to pick motor neuron loss and disease
severity in NBS positive pre-symptomatic SMA babies. Abnormal CMAP data precedes reduction in weight or CHOP-INTEND. On several occasions, the abnormal CMAP results were available prior to confirmatory genetic testing and SMN2 copy number, highlighting the value of pre-confirmatory neurophysiological testing. Furthermore, the readily available electrodiagnostic test results expedite insurance approval for gene replacement and modifying therapies, which have shown to improve outcomes. We advocate for electrodiagnostic testing to be included in the initial assessment of NBS positive SMA babies.

Authors/Disclosures
Sneha Sadhu PRESENTER	Ms. Sadhu has nothing to disclose.
Bahadir M. Samur, MD	Dr. Samur has nothing to disclose.

��ɫ��

��ɫ��