Cervical Spinal Cord Gray Matter Area is Associated with Motor Unit Number Index in Spinal Muscular Atrophy
Maria Janina Wendebourg1, Eva Kesenheimer2, Claudia Weidensteiner3, Laura Sander1, Matthias Weigel3, Tanja Haas3, Dirk Fischer4, Christoph Neuwirth5, Nathalie Braun5, Markus Weber5, Cristina Granziera1, Michael Sinnreich6, Oliver Bieri3, Regina Schlaeger1
1Departments of Neurology, Clinical Research and Biomedical Engineering, University Hospital Basel, University of Basel, Basel, Switzerland, 2Departments of Neurology, Clinical Research and Biomedical Engineering, University Hospital Basel, University of Basel and RehaB Basel, Basel, Switzerland, 3Division of Radiological Physics, Department of Radiology and Biomedical Engineering, University Hospital Basel and 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 evaluate the association between spinal cord (SC) gray matter (GM) atrophy and Motor Unit Number Index (MUNIX) in patients with 5q-Spinal Muscular Atrophy (SMA).
Background:
There is an unmet need for valid imaging markers to monitor the disease course and therapeutic outcome in SMA. The novel rAMIRA (radially sampled Averaged Magnetization Inversion Recovery Acquisitions) method enables high in-plane resolution MR-imaging with improved contrast of SC GM in clinically feasible acquisition times. MUNIX is an established quantitative neurophysiological measure that provides an index of the number of functioning lower motor neurons that supply a muscle. The association between SC GM area and MUNIX has not been investigated in SMA yet.
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 level C5/C6 perpendicular to the spinal cord. SC GM areas were determined using a semi-automated approach. MUNIX of the biceps brachii (BB) was measured following the ENCALS protocol. The association between SC GM area and MUNIX was assessed using multivariable regression analysis covarying for age and sex.
Results:
SC GM area at C5/6 was significantly reduced in patients compared to HC (mean GM area in mm2 (SD): SMA 17.5 (2.2); HC 21.1 (2.3); relative reduction: 17.1% (p<0.0001)). In multivariable regression analysis SC GM area at C5/6 explained 53% of MUNIX variance of the BB in SMA patients.
Conclusions:
In patients with SMA, SC GM area is strongly associated with motor neuron function quantitated by MUNIX in the corresponding myotome, indicating the functional relevance of this structural marker. Further longitudinal studies are necessary to evaluate the potential of this novel imaging marker for monitoring the disease course and therapeutic outcome.