Abstract
Objective To quantify atrophy, demyelination, and iron accumulation over 2 years following acute spinal cord injury and to identify MRI predictors of clinical outcomes and determine their suitability as surrogate markers of therapeutic intervention.
Methods We assessed 156 quantitative MRI datasets from 15 patients with spinal cord injury and 18 controls at baseline and 2, 6, 12, and 24 months after injury. Clinical recovery (including neuropathic pain) was assessed at each time point. Between-group differences in linear and nonlinear trajectories of volume, myelin, and iron change were estimated. Structural changes by 6 months were used to predict clinical outcomes at 2 years.
Results The majority of patients showed clinical improvement with recovery stabilizing at 2 years. Cord atrophy decelerated, while cortical white and gray matter atrophy progressed over 2 years. Myelin content in the spinal cord and cortex decreased progressively over time, while cerebellar loss decreases decelerated. As atrophy progressed in the thalamus, sustained iron accumulation was evident. Smaller cord and cranial corticospinal tract atrophy, and myelin changes within the sensorimotor cortices, by 6 months predicted recovery in lower extremity motor score at 2 years. Whereas greater cord atrophy and microstructural changes in the cerebellum, anterior cingulate cortex, and secondary sensory cortex by 6 months predicted worse sensory impairment and greater neuropathic pain intensity at 2 years.
Conclusion These results draw attention to trauma-induced neuroplastic processes and highlight the intimate relationships among neurodegenerative processes in the cord and brain. These measurable changes are sufficiently large, systematic, and predictive to render them viable outcome measures for clinical trials.
Glossary
- ACC=
- anterior cingulate cortex;
- AIS=
- American Spinal Injury Association Impairment Scale;
- APW=
- anterior-posterior width;
- CI=
- confidence interval;
- CST=
- corticospinal tract;
- GM=
- gray matter;
- LRW=
- cord left-right width;
- M1=
- primary motor cortices;
- MT=
- magnetization transfer saturation;
- R2*=
- effective transverse relaxation rate;
- ROI=
- region of interest;
- S2=
- secondary sensory cortices;
- SCI=
- spinal cord injury;
- SCIM=
- Spinal Cord Independence Measure;
- SPM=
- statistical parametric mapping;
- WM=
- white matter
Footnotes
↵* These authors contributed equally to this work as first authors.
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
The Article Processing Charge was funded by Wellcome Trust.
- Received July 14, 2017.
- Accepted in final form January 4, 2018.
- Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Disputes & Debates: Rapid online correspondence
- Author response to Dr. Domingue
- Reader response: Progressive neurodegeneration following spinal cord injury
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