Cervical Spinal Cord Gray Matter Atrophy as an Emerging Imaging Marker in Spinal Muscular Atrophy
Eva Kesenheimer1, Maria Janina Wendebourg2, Claudia Weidensteiner3, Laura Sander2, Matthias Weigel3, Tanja Haas3, Dirk Fischer4, Christoph Neuwirth5, Nathalie Braun5, Markus Weber5, Cristina Granziera2, Michael Sinnreich6, Oliver Bieri3, Regina Schlaeger2
1Departments of Neurology, Clinical Research and Biomedical Engineering, University Hospital Basel, University of Basel and Rehab Basel, Basel, Switzerland, 2Departments of Neurology, Clinical Research and Biomedical Engineering, University Hospital Basel, University of Basel, Basel, Switzerland, 3Division of Radiological Physics, Departments of Radiology and Biomedical Engineering, University Hospital Basel, University of Basel, Basel, Switzerland, 4Division of Neuropediatrics and Developmental Medicine, University Childrens` Hospital of Basel (UKBB), University of Basel, Basel, Switzerland, 5Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, St. Gallen, Switzerland, 6Departments of Neurology and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
Objective:
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.
Background:
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.
Design/Methods:
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.
Results:
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<0.0001), at C4/5 RR = 16.7%, (p<0.0001), at C5/6 RR = 17.1% (p<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.
Conclusions:
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.