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  Tracking the neurodegenerative gradient after spinal cord injury

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.

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 Creators:
Azzarito, Michela1, Author
Seif, Maryam1, Author
Kyathanahally, Sreenath1, Author
Curt, Armin1, Author
Freund, Patrick1, 2, 3, 4, Author              
Affiliations:
1Balgrist Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland, ou_persistent22              
2Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_2205649              
3Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, United Kingdom, ou_persistent22              
4Department of Neurology, University Hospital Zurich, Switzerland, ou_persistent22              

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Free keywords: Spinal cord injury; MRI; Volumetric MRI; MT
 Abstract: Objective 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. Methods 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. Results 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. Conclusions 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.

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Language(s): eng - English
 Dates: 2020-01-212019-10-112020-02-172020-02-25
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.nicl.2020.102221
PMID: 32145681
PMC: PMC7058923
Other: Epub ahead of print
 Degree: -

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Project name : Antibodies against Nogo-A to enhance plasticity, regeneration and functional recovery after acute spinal cord injury, a multicenter European clinical proof of concept trial / NISCI
Grant ID : 681094
Funding program : Horizon 2020
Funding organization : European Commission (EC)
Project name : -
Grant ID : 15.0137
Funding program : -
Funding organization : Swiss State Secretariat for Education, Research and Innovation (SERI)
Project name : -
Grant ID : WFL-CH-007/14
Funding program : INSPIRED project
Funding organization : Wings for Life, Austria
Project name : -
Grant ID : PCEFP3_181362
Funding program : SNF Eccellenza Professorial Fellowship Grant
Funding organization : Swiss National Science Foundation
Project name : -
Grant ID : 091593/Z/10/Z
Funding program : -
Funding organization : Wellcome Trust
Project name : Understanding the mechanisms of atrophy associated with spinal cord injury: the application of MRI-based in vivo histology and ex vivo histology / hMRIofSC
Grant ID : 32NE30_173678
Funding program : ERA-NET NEURON
Funding organization : European Commission (EC)

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Title: NeuroImage: Clinical
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Elsevier
Pages: - Volume / Issue: 26 Sequence Number: 102221 Start / End Page: - Identifier: ISSN: 2213-1582
CoNE: https://pure.mpg.de/cone/journals/resource/2213-1582