Evidence map›Paper›PMID 29514946›Full record

ArticleNeurology2018

Progressive neurodegeneration following spinal cord injury: Implications for clinical trials.

Gabriel Ziegler, Patrick Grabher, Alan Thompson, Daniel Altmann, Markus Hupp, John Ashburner, Karl Friston, Nikolaus Weiskopf, Armin Curt, Patrick Freund

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

80 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Meningeal Lymphatic LTBR Deficiency Links Spinal Cord Injury to Secondary Brain Pathology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  5. Article
  6. Review
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  8. Enhanced Reticulospinal Output in Subacute Spinal Cord Injury Patients with Spasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
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  10. Review
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  12. Imaging Demyelinated Axons After Spinal Cord Injuries with PET Tracer [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025
    Article
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  14. Article
  15. Article
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20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Gabriel ZieglerFrom the Institute of Cognitive Neurology and Dementia Research (G.Z.), Otto-von-Guericke-University Magdeburg; German Center for Neurodegenerative Diseases (G.Z.), Magdeburg, Germany; Spinal Cord Injury Center Balgrist (P.G., M.H., A.C., P.F.), University Hospital Zurich, University of Zurich, Switzerland; Department of Brain Repair & Rehabilitation (A.T., P.F.) and Wellcome Trust Centre for Neuroimaging (J.A., K.F., N.W., P.F.), UCL Institute of Neurology, UCL, London; Queen Square Multiple Sclerosis Centre (D.A.), Institute of Neurology, University College London; Medical Statistics Department (D.A.), London School of Hygiene & Tropical Medicine, London, UK; and Department of Neurophysics (N.W., P.F.), Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Patrick GrabherFrom the Institute of Cognitive Neurology and Dementia Research (G.Z.), Otto-von-Guericke-University Magdeburg; German Center for Neurodegenerative Diseases (G.Z.), Magdeburg, Germany; Spinal Cord Injury Center Balgrist (P.G., M.H., A.C., P.F.), University Hospital Zurich, University of Zurich, Switzerland; Department of Brain Repair & Rehabilitation (A.T., P.F.) and Wellcome Trust Centre for Neuroimaging (J.A., K.F., N.W., P.F.), UCL Institute of Neurology, UCL, London; Queen Square Multiple Sclerosis Centre (D.A.), Institute of Neurology, University College London; Medical Statistics Department (D.A.), London School of Hygiene & Tropical Medicine, London, UK; and Department of Neurophysics (N.W., P.F.), Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Alan ThompsonFrom the Institute of Cognitive Neurology and Dementia Research (G.Z.), Otto-von-Guericke-University Magdeburg; German Center for Neurodegenerative Diseases (G.Z.), Magdeburg, Germany; Spinal Cord Injury Center Balgrist (P.G., M.H., A.C., P.F.), University Hospital Zurich, University of Zurich, Switzerland; Department of Brain Repair & Rehabilitation (A.T., P.F.) and Wellcome Trust Centre for Neuroimaging (J.A., K.F., N.W., P.F.), UCL Institute of Neurology, UCL, London; Queen Square Multiple Sclerosis Centre (D.A.), Institute of Neurology, University College London; Medical Statistics Department (D.A.), London School of Hygiene & Tropical Medicine, London, UK; and Department of Neurophysics (N.W., P.F.), Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Daniel AltmannFrom the Institute of Cognitive Neurology and Dementia Research (G.Z.), Otto-von-Guericke-University Magdeburg; German Center for Neurodegenerative Diseases (G.Z.), Magdeburg, Germany; Spinal Cord Injury Center Balgrist (P.G., M.H., A.C., P.F.), University Hospital Zurich, University of Zurich, Switzerland; Department of Brain Repair & Rehabilitation (A.T., P.F.) and Wellcome Trust Centre for Neuroimaging (J.A., K.F., N.W., P.F.), UCL Institute of Neurology, UCL, London; Queen Square Multiple Sclerosis Centre (D.A.), Institute of Neurology, University College London; Medical Statistics Department (D.A.), London School of Hygiene & Tropical Medicine, London, UK; and Department of Neurophysics (N.W., P.F.), Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Markus HuppFrom the Institute of Cognitive Neurology and Dementia Research (G.Z.), Otto-von-Guericke-University Magdeburg; German Center for Neurodegenerative Diseases (G.Z.), Magdeburg, Germany; Spinal Cord Injury Center Balgrist (P.G., M.H., A.C., P.F.), University Hospital Zurich, University of Zurich, Switzerland; Department of Brain Repair & Rehabilitation (A.T., P.F.) and Wellcome Trust Centre for Neuroimaging (J.A., K.F., N.W., P.F.), UCL Institute of Neurology, UCL, London; Queen Square Multiple Sclerosis Centre (D.A.), Institute of Neurology, University College London; Medical Statistics Department (D.A.), London School of Hygiene & Tropical Medicine, London, UK; and Department of Neurophysics (N.W., P.F.), Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
John AshburnerFrom the Institute of Cognitive Neurology and Dementia Research (G.Z.), Otto-von-Guericke-University Magdeburg; German Center for Neurodegenerative Diseases (G.Z.), Magdeburg, Germany; Spinal Cord Injury Center Balgrist (P.G., M.H., A.C., P.F.), University Hospital Zurich, University of Zurich, Switzerland; Department of Brain Repair & Rehabilitation (A.T., P.F.) and Wellcome Trust Centre for Neuroimaging (J.A., K.F., N.W., P.F.), UCL Institute of Neurology, UCL, London; Queen Square Multiple Sclerosis Centre (D.A.), Institute of Neurology, University College London; Medical Statistics Department (D.A.), London School of Hygiene & Tropical Medicine, London, UK; and Department of Neurophysics (N.W., P.F.), Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Karl FristonFrom the Institute of Cognitive Neurology and Dementia Research (G.Z.), Otto-von-Guericke-University Magdeburg; German Center for Neurodegenerative Diseases (G.Z.), Magdeburg, Germany; Spinal Cord Injury Center Balgrist (P.G., M.H., A.C., P.F.), University Hospital Zurich, University of Zurich, Switzerland; Department of Brain Repair & Rehabilitation (A.T., P.F.) and Wellcome Trust Centre for Neuroimaging (J.A., K.F., N.W., P.F.), UCL Institute of Neurology, UCL, London; Queen Square Multiple Sclerosis Centre (D.A.), Institute of Neurology, University College London; Medical Statistics Department (D.A.), London School of Hygiene & Tropical Medicine, London, UK; and Department of Neurophysics (N.W., P.F.), Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Nikolaus WeiskopfFrom the Institute of Cognitive Neurology and Dementia Research (G.Z.), Otto-von-Guericke-University Magdeburg; German Center for Neurodegenerative Diseases (G.Z.), Magdeburg, Germany; Spinal Cord Injury Center Balgrist (P.G., M.H., A.C., P.F.), University Hospital Zurich, University of Zurich, Switzerland; Department of Brain Repair & Rehabilitation (A.T., P.F.) and Wellcome Trust Centre for Neuroimaging (J.A., K.F., N.W., P.F.), UCL Institute of Neurology, UCL, London; Queen Square Multiple Sclerosis Centre (D.A.), Institute of Neurology, University College London; Medical Statistics Department (D.A.), London School of Hygiene & Tropical Medicine, London, UK; and Department of Neurophysics (N.W., P.F.), Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Armin CurtFrom the Institute of Cognitive Neurology and Dementia Research (G.Z.), Otto-von-Guericke-University Magdeburg; German Center for Neurodegenerative Diseases (G.Z.), Magdeburg, Germany; Spinal Cord Injury Center Balgrist (P.G., M.H., A.C., P.F.), University Hospital Zurich, University of Zurich, Switzerland; Department of Brain Repair & Rehabilitation (A.T., P.F.) and Wellcome Trust Centre for Neuroimaging (J.A., K.F., N.W., P.F.), UCL Institute of Neurology, UCL, London; Queen Square Multiple Sclerosis Centre (D.A.), Institute of Neurology, University College London; Medical Statistics Department (D.A.), London School of Hygiene & Tropical Medicine, London, UK; and Department of Neurophysics (N.W., P.F.), Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Patrick FreundFrom the Institute of Cognitive Neurology and Dementia Research (G.Z.), Otto-von-Guericke-University Magdeburg; German Center for Neurodegenerative Diseases (G.Z.), Magdeburg, Germany; Spinal Cord Injury Center Balgrist (P.G., M.H., A.C., P.F.), University Hospital Zurich, University of Zurich, Switzerland; Department of Brain Repair & Rehabilitation (A.T., P.F.) and Wellcome Trust Centre for Neuroimaging (J.A., K.F., N.W., P.F.), UCL Institute of Neurology, UCL, London; Queen Square Multiple Sclerosis Centre (D.A.), Institute of Neurology, University College London; Medical Statistics Department (D.A.), London School of Hygiene & Tropical Medicine, London, UK; and Department of Neurophysics (N.W., P.F.), Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany. Patrick.Freund@balgrist.ch.

Funding

Wellcome Trust
6 · The paper itself

Abstract

objectiveTo 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.

methodsWe 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.

resultsThe 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.

conclusionThese 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.

Indexed as

AdultAgedAtrophyBrainDisease ProgressionFemaleFollow-Up StudiesHumansLongitudinal StudiesMaleMiddle AgedNerve DegenerationNeuralgiaNeurodegenerative DiseasesRecovery of FunctionSpinal Cord

Identifiers

PMID29514946
PMCPMC5890610

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.