Outstripping of Motor Unit Compensation with Disease Severity in Adults with Spinal Muscular Atrophy (P3-8.009)

Abstract

<h3>Objective:</h3> To determine relationships between ulnar (hypothenar) multipoint incremental motor unit number estimation (MUNE), single motor unit potential amplitude (SMUP), and compound motor unit potential amplitude (CMAP) versus measures of disease severity in ambulatory (A-SMA) vs non-ambulatory (N-SMA) adults with spinal muscular atrophy (SMA). <h3>Background:</h3> MUNE is an estimate of the number of functioning motor neurons innervating a muscle(s), and SMUP provides an index of motor unit size. Here, we investigated the relationship between MUNE and CMAP in A-SMA versus N-SMA. <h3>Design/Methods:</h3> Cross sectional analysis of electrophysiological and functional outcome data obtained in ambulatory (n=15) and non-ambulatory (n=25) untreated adults with SMA. <h3>Results:</h3> Mean CMAP amplitude for A-SMA vs N-SMA were 8.74 ± 1.82 and 2.37 ± 2.3 (p&lt;0.001). Mean MUNE for A-SMA vs N-SMA were 102.53 ± 30.44 and 34.65 ± 31.83 (p&lt;0.001). Mean SMUP for A-SMA vs N-SMA were 86.3 ± 18.1 and 91.93 ± 37.09 (p=0.96). There was good correlation in N-SMA between MUNE and CMAP (r = 0.93, p&lt;0.001), CMAP and Hammersmith rating scale (r = 0.645, p&lt;0.001), MUNE and Hammersmith rating scale (r = 0.5405, p&lt;0.05), U-CMAP and % Predicted FVC (r = 0.771, p&lt;0.001), MUNE and % Predicted FVC (r = 0.7417, p=0.001). In contrast, these measures did not correlate in A-SMA. <h3>Conclusions:</h3> MUNE and CMAP are useful measures in SMA showing strong correlation with severity and other measures of function. SMUP, a measure of motor unit size providing an index of motor neuron compensation following denervation, did not demonstrate the ability to distinguish severity in adults with SMA. These findings suggest that motor unit compensation is outstripped by motor unit loss across the spectrum of SMA and that motor unit size may an important functional determinant with more severe phenotype. <b>Disclosure:</b> Dr. Deardorff has nothing to disclose. Dr. Guerra Castanon has nothing to disclose. Ms. Zhao has nothing to disclose. Dr. Kelly has nothing to disclose. Marco Tellez has nothing to disclose. Ms. Heintzman has nothing to disclose. Dr. Kolb has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AveXis. Dr. Kolb has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for CureSMA. The institution of Dr. Kolb has received research support from NIH. The institution of Dr. Kolb has received research support from AveXis. The institution of Dr. Kolb has received research support from NIH. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for La Hoffmann Roche. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cadent Therapeutics . Dr. Arnold has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Arnold has received research support from NIH. The institution of Dr. Arnold has received research support from NMD Pharma. The institution of Dr. Arnold has received research support from Gilead Sciences. The institution of Dr. Arnold has received research support from CureSMA. Dr. Arnold has received intellectual property interests from a discovery or technology relating to health care. Dr. Elsheikh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen . Dr. Elsheikh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argnex . The institution of Dr. Elsheikh has received research support from Biogen. The institution of Dr. Elsheikh has received research support from Cure SMA.