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@ARTICLE{Ziegler:140092,
      author       = {Ziegler, Gabriel and Grabher, Patrick and Thompson, Alan
                      and Altmann, Daniel and Hupp, Markus and Ashburner, John and
                      Friston, Karl and Weiskopf, Nikolaus and Curt, Armin and
                      Freund, Patrick},
      title        = {{P}rogressive neurodegeneration following spinal cord
                      injury: {I}mplications for clinical trials.},
      journal      = {Neurology},
      volume       = {90},
      number       = {14},
      issn         = {0028-3878},
      address      = {[S.l.]},
      publisher    = {Ovid},
      reportid     = {DZNE-2020-06414},
      pages        = {e1257-e1266},
      year         = {2018},
      abstract     = {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.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.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.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.},
      keywords     = {Adult / Aged / Atrophy / Brain: diagnostic imaging / Brain:
                      pathology / Disease Progression / Female / Follow-Up Studies
                      / Humans / Longitudinal Studies / Male / Middle Aged / Nerve
                      Degeneration: diagnostic imaging / Nerve Degeneration:
                      etiology / Nerve Degeneration: physiopathology / Neuralgia:
                      diagnostic imaging / Neuralgia: etiology / Neuralgia:
                      physiopathology / Neurodegenerative Diseases: diagnostic
                      imaging / Neurodegenerative Diseases: etiology /
                      Neurodegenerative Diseases: physiopathology / Recovery of
                      Function / Spinal Cord: diagnostic imaging / Spinal Cord:
                      pathology / Spinal Cord Injuries: complications / Spinal
                      Cord Injuries: diagnostic imaging / Spinal Cord Injuries:
                      physiopathology / Young Adult},
      cin          = {AG Düzel},
      ddc          = {610},
      cid          = {I:(DE-2719)5000006},
      pnm          = {344 - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29514946},
      pmc          = {pmc:PMC5890610},
      doi          = {10.1212/WNL.0000000000005258},
      url          = {https://pub.dzne.de/record/140092},
}