Investigating Motor Unit Firing Rate in Individuals with Spinal Muscular Atrophy Receiving Risdiplam: An Exploratory Analysis

Topic:

Other

Poster Number: 96 S

Author(s):

Katie Jira, PT, DPT, Department of Neurology, The Ohio State University Wexner Medical Center, Andrea Jaworek, PT, DPT, Department of Neurology, The Ohio State University Wexner Medical Center, Georgia Cinkay, BS, Department of Neurology, The Ohio State University Wexner Medical Center, Songzhu Zhao, MS, Department of Biomedical Informatics and Center for Biostatistics, The Ohio State University, Kristina Kelly, PT, DPT, NextGen Precision Health, University of Missouri, W. David Arnold, MD, University of Missouri - Columbia, Bakri Elsheikh, MBBS, The Ohio State University Wexner Medical Center

Decomposition electromyography (dEMG) is a reliable, noninvasive method for assessment of motor unit action potential (MUAP) amplitude and firing rate in Spinal Muscular Atrophy (SMA). Previous studies in nusinersen-treated adults showed elevated firing rates in ambulatory individuals, while non-ambulatory individuals showed firing rates similar to healthy controls. The relationship between MUAP firing rate, MUAP amplitude, and risdiplam remains unknown. We conducted dEMG of the abductor digiti minimi (ADM) in ambulatory and non-ambulatory individuals with 5q-SMA. Participants performed three trials of 30-second maximal isometric contractions using multielectrode surface recordings.

We examined 246 MUAPs obtained from eight patients (5 women, 3 men; median age 27.0 years; 6 non-ambulatory and 2 ambulatory; 5 had 3 SMN2 copies, 3 had 4 SMN2 copies, median treatment time 25.5 months). To investigate motor unit firing fatigability, a linear mixed model with a random intercept was used to compare the differences across the three trials. All the firing rates differed by at least 21.0% between non-ambulatory and ambulatory cohorts, except for the mean average firing rate which only differed by 6.0%. The peak motor unit firing rates were higher in the ambulatory cohort compared in the non-ambulatory individuals. To assess motor unit firing fatigability, firing rate differences between trials were analyzed amongst the two cohorts. There were no significant differences between the trials, however the max average firing rate showed the greatest decline (18.4%) between the first and third trials.

We observed a trend of higher average and peak motor unit firing rates in ambulatory adults with 5q-SMA compared to the non-ambulatory individuals. This aligns with previous findings in nusinersen-treated individuals when controlling for ambulatory status. Half of the participants showed a decline in all firing rates between the first and third trial. This suggests that dEMG may be a useful tool for assessing motor unit fatigability.