Cervical Spinal Cord Gray Matter Atrophy as an Emerging Imaging Marker in Spinal Muscular Atrophy (P2-8.014)

Abstract

<h3>Objective:</h3> To prospectively evaluate cervical spinal cord (SC) gray matter (GM) area and its association with upper limb function in patients with 5q-Spinal Muscular Atrophy (SMA) using rAMIRA (radially sampled Magnetization Inversion Recovery Acquisitions) MR-imaging. <h3>Background:</h3> With the approval of the first disease modifying treatments for SMA, there is an increasing need for biomarkers that allow easy to perform, reliable, and valid disease course- and therapeutic response monitoring. The novel rAMIRA method enables high in-plane resolution MR-imaging with improved contrast of SC GM in clinically feasible acquisition times at 3 Tesla. <h3>Design/Methods:</h3> Using axial 2D rAMIRA imaging, we prospectively investigated 21 patients with 5q-SMA, types 2 and 3 (mean age/SD 41.3/11.6y, 9 women) and 21 age- and sex-matched healthy controls (HC) (mean age/SD 41.7/11.4y, 9 women) at the intervertebral disc levels C2/C3-C5/C6 perpendicular to the cord. SC GM areas were determined using a semi-automated approach. The associations between SC GM area and Revised Upper Limb Module (RULM), an established measure of upper limb disability in SMA, were assessed using multivariable regression analysis covarying for age. <h3>Results:</h3> Compared to HC cervical SC GM areas were significantly reduced in patients with SMA at C3/C4 with a relative reduction (RR) of 13.6% (p&lt;0.0001), at C4/5 RR = 16.7%, (p&lt;0.0001), at C5/6 RR = 17.1% (p&lt;0.0001), but not significantly at C2/C3 RR = 5.3% (p=0.071). In multivariable regression analysis covarying for age, GM area at C3/C4 explained 28% of RULM variance in patients with SMA. <h3>Conclusions:</h3> Cervical SC GM atrophy is detectable in patients with 5q SMA compared to HC and correlates with clinical measures of upper limb function, namely RULM. Further longitudinal investigations are necessary next steps to evaluate the potential of this novel and easy to assess imaging marker for monitoring the disease course and therapeutic response. <b>Disclosure:</b> Dr. Kesenheimer has nothing to disclose. Dr. Wendebourg has nothing to disclose. An immediate family member of Dr. Weidensteiner has received personal compensation for serving as an employee of Siemens Healthineers. Dr. Sander has nothing to disclose. The institution of Matthias Weigel, PhD has received research support from Biogen. Matthias Weigel, PhD has received intellectual property interests from a discovery or technology relating to health care. Tanja Haas has nothing to disclose. The institution of Dirk Fischer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hoffmann La Roche AG. The institution of Dirk Fischer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann La Roche AG. Christoph Neuwirth has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen USA. Christoph Neuwirth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen Switzerland. Nathalie Braun has nothing to disclose. Dr. Weber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen Idec. Dr. Weber has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Granziera has nothing to disclose. Prof. Sinnreich has nothing to disclose. The institution of Oliver Bieri has received research support from Swiss National Science Foundation. The institution of Oliver Bieri has received research support from MIAC Foundation. The institution of Oliver Bieri has received research support from Biogen. Oliver Bieri has received intellectual property interests from a discovery or technology relating to health care. Regina Schlaeger has nothing to disclose.