The Lancet Neurology, Early Online Publication, 2 July 2013
Copyright 2013Elsevier LtdAll rights reserved.
In patients with chronic spinal cord injury, imaging of the spinal cord and brain above the level of the lesion provides evidence of neural degeneration; however, the spatial and temporal patterns of progression and their relation to clinical outcomes are uncertain. New interventions targeting acute spinal cord injury have entered clinical trials but neuroimaging outcomes as responsive markers of treatment have yet to be established. We aimed to use MRI to assess neuronal degeneration above the level of the lesion after acute spinal cord injury.
In our prospective longitudinal study, we enrolled patients with acute traumatic spinal cord injury and healthy controls. We assessed patients clinically and by MRI at baseline, 2 months, 6 months, and 12 months, and controls by MRI at the same timepoints. We assessed atrophy in white matter in the cranial corticospinal tracts and grey matter in sensorimotor cortices by tensor-based analyses of T1-weighted MRI data. We used cross-sectional spinal cord area measurements to assess atrophy at cervical level C2/C3. We used myelin-sensitive magnetisation transfer (MT) and longitudinal relaxation rate (R1) maps to assess microstructural changes associated with myelin. We also assessed associations between MRI parameters and clinical improvement. All analyses of brain scans done with statistical parametric mapping were corrected for family-wise error.
Between Sept 17, 2010, and Dec 31, 2012, we recruited 13 patients and 18 controls. In the 12 months from baseline, patients recovered by a mean of 527 points per log month (95% CI 191863) on the international standards for the neurological classification of spinal cord injury (ISNCSCI) motor score (p=0002) and by 1093 points per log month (6201566) on the spinal cord independence measure (SCIM) score (p<00001). Compared with controls, patients showed a rapid decline in cross-sectional spinal cord area (patients declined by 046 mm per month compared with a stable cord area in controls; p<00001). Patients had faster rates than controls of volume decline of white matter in the cranial corticospinal tracts at the level of the internal capsule (right Z score 521, p=00081; left Z score 412, p=00004) and right cerebral peduncle (Z score 389, p=00302) and of grey matter in the left primary motor cortex (Z score 423, p=0041). Volume changes were paralleled by significant reductions of MT and R1 in the same areas and beyond. Improvements in SCIM scores at 12 months were associated with a reduced loss in cross-sectional spinal cord area over 12 months (Pearson's correlation 077, p=0004) and reduced white matter volume of the corticospinal tracts at the level of the right internal capsule (Z score 430, p=00021), the left internal capsule (Z score 427, p=00278), and left cerebral peduncle (Z score 405, p=00316). Improvements in ISNCSCI motor scores were associated with less white matter volume change encompassing the corticospinal tract at the level of the right internal capsule (Z score 401, p<00001).
Extensive upstream atrophic and microstructural changes of corticospinal axons and sensorimotor cortical areas occur in the first months after spinal cord injury, with faster degenerative changes relating to poorer recovery. Structural volumetric and microstructural MRI protocols remote from the site of spinal cord injury could serve as neuroimaging biomarkers in acute spinal cord injury.
SRH Holding, Swiss National Science Foundation, Clinical Research Priority Program NeuroRehab University of Zurich, Wellcome Trust.
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MRI investigation of the sensorimotor cortex and the corticospinal tract after acute spinal cord injury: a prospective ...
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