Journal
NEUROLOGY
Volume 90, Issue 17, Pages E1510-E1522Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000005361
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Funding
- Wings for Life, Austria [WFL-CH-007/14]
- International Foundation for Research in Paraplegia [IRP-P158]
- European Union [681094, 658589]
- Clinical Research Priority Program Neurorehab UZH
- European Research Council (ERC) [616905]
- Wellcome Trust [0915/Z/10/Z]
- Deutsche Forschungsgemeinschaft [MO 2397/4-1]
- BMBF [01 EW1711A, 01 EW1711B]
- University College London/University College London Hospitals National Institute of Health Biomedical Research Centre
- Marie Curie Actions (MSCA) [658589] Funding Source: Marie Curie Actions (MSCA)
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Objective To investigate whether gray matter pathology above the level of injury, alongside white matter changes, also contributes to sensorimotor impairments after spinal cord injury. Methods A 3T MRI protocol was acquired in 17 tetraplegic patients and 21 controls. A sagittal T2-weighted sequence was used to characterize lesion severity. At the C2-3 level, a high-resolution T2*-weighted sequence was used to assess cross-sectional areas of gray and white matter, including their subcompartments; a diffusion-weighted sequence was used to compute voxel-based diffusion indices. Regression models determined associations between lesion severity and tissue-specific neurodegeneration and associations between the latter with neurophysiologic and clinical outcome. Results Neurodegeneration was evident within the dorsal and ventral horns and white matter above the level of injury. Tract-specific neurodegeneration was associated with prolonged conduction of appropriate electrophysiologic recordings. Dorsal horn atrophy was associated with sensory outcome, while ventral horn atrophy was associated with motor outcome. White matter integrity of dorsal columns and corticospinal tracts was associated with daily-life independence. Conclusion Our results suggest that, next to anterograde and retrograde degeneration of white matter tracts, neuronal circuits within the spinal cord far above the level of injury undergo trans-synaptic neurodegeneration, resulting in specific gray matter changes. Such improved understanding of tissue-specific cord pathology offers potential biomarkers with more efficient targeting and monitoring of neuroregenerative (i.e., white matter) and neuroprotective (i.e., gray matter) agents.
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