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Journal Article

Tracking the neurodegenerative gradient after spinal cord injury


Freund,  Patrick
Balgrist Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland;
Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, United Kingdom;
Department of Neurology, University Hospital Zurich, Switzerland;

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Azzarito, M., Seif, M., Kyathanahally, S., Curt, A., & Freund, P. (2020). Tracking the neurodegenerative gradient after spinal cord injury. NeuroImage: Clinical, 26: 102221. doi:10.1016/j.nicl.2020.102221.

Cite as: https://hdl.handle.net/21.11116/0000-0005-BF9B-6

To quantify neurodegenerative changes along the cervical spinal cord rostral to a spinal cord injury (SCI) by means of quantitative MRI (qMRI) and to determine its relationship with clinical impairment.


Thirty chronic SCI patients (15 tetraplegics and 15 paraplegics) and 23 healthy controls underwent a high-resolution T1-weighted and myelin-sensitive magnetization transfer (MT) MRI. We assessed macro- and microstructural changes along the cervical cord from levels C1 to C4, calculating cross-sectional spinal cord area, its anterior-posterior and left-right width and myelin content (i.e. MT). Regression analysis determined associations between qMRI parameters and clinical impairment.


In SCI patients, cord area decreased by 2.67 mm2 (p=0.004) and left-right width decreased by 0.35 mm (p=0.002) per level in caudal direction when compared to the healthy controls. This gradient of neurodegeneration was greater in tetraplegic than paraplegics in the cord area (by 3.28 mm2, p=0.011), left-right width (by 0.36 mm, p=0.03), and MT (by 0.13%, p=0.04), but independant of lesion severity (p>0.05). Higher lesion level was associated with greater magnitudes of neurodegeneration. Greater loss in myelin content in the dorsal columns and spinothalamic tract was associated with worse light touch (p=0.016) and pin prick score (p=0.024), respectively.


A gradient of neurodegeneration is evident in the high cervical cord remote from a SCI. Tract-specific associations with appropriate clinical outcomes highlight that remote neurodegenerative changes are clinically eloquent. Monitoring the neurodegenerative gradient could be used to track treatment effects of regenerative and neuroprotective agents, both in trials targeting cervical and thoracic SCI patients.