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  Progressive neurodegeneration following spinal cord injury: Implications for clinical trials

Ziegler, G., Grabher, P., Thompson, A., Altmann, D., Hupp, M., Ashburner, J., et al. (2018). Progressive neurodegeneration following spinal cord injury: Implications for clinical trials. Neurology, 90(14), e1257-e1266. doi:10.1212/WNL.0000000000005258.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0000-D487-8 Version Permalink: https://hdl.handle.net/21.11116/0000-0006-5689-F
Genre: Journal Article

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 Creators:
Ziegler, Gabriel1, 2, Author
Grabher, Patrick3, Author
Thompson, Alan4, Author
Altmann, Daniel5, 6, Author
Hupp, Markus3, Author
Ashburner, John7, Author
Friston, Karl7, Author
Weiskopf, Nikolaus7, 8, Author           
Curt, Armin3, Author
Freund, Patrick3, 4, 7, 8, Author           
Affiliations:
1Institute of Cognitive Neurology and Dementia Research, Otto von Guericke University Magdeburg, Germany, ou_persistent22              
2German Center for Neurodegenerative Diseases, Magdeburg, Germany, ou_persistent22              
3Balgrist Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland, ou_persistent22              
4Department of Brain Repair & Rehabilitation, University College London, United Kingdom, ou_persistent22              
5Queen Square Multiple Sclerosis Centre, Institute of Neurology, University College London, United Kingdom, ou_persistent22              
6Medical Statistics Department, London School of Hygiene and Tropical Medicine, University of London, United Kingdom, ou_persistent22              
7Wellcome Trust Centre for Neuroimaging, University College London, United Kingdom, ou_persistent22              
8Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_2205649              

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 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.

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Language(s): eng - English
 Dates: 2017-07-142018-01-042018-03-072018-04-03
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1212/WNL.0000000000005258
PMID: 29514946
PMC: PMC5890610
Other: Epub 2018
 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 (H2020-PHC-2014-2015)
Funding organization : European Commission (EC)
Project name : -
Grant ID : -
Funding program : Clinical Research Priority Program (CRPP)
Funding organization : University Zurich
Project name : -
Grant ID : WFL-CH-007/14
Funding program : -
Funding organization : Wings for Life, Austria
Project name : -
Grant ID : 088130/Z/09/Z
Funding program : Wellcome Trust Principal Research Fellowship
Funding organization : Wellcome Trust
Project name : -
Grant ID : -
Funding program : -
Funding organization : UCL/UCLH National Institute for Health Research (NIHR) Biomedical Research Centre (BRC)

Source 1

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Title: Neurology
Source Genre: Journal
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Publ. Info: Cleveland, Ohio [etc.] : Advanstar Communications [etc.]
Pages: - Volume / Issue: 90 (14) Sequence Number: - Start / End Page: e1257 - e1266 Identifier: ISSN: 0028-3878
CoNE: https://pure.mpg.de/cone/journals/resource/954925246073