Progressive neurodegeneration following spinal cord injury: Implications for clinical trials

Neurology. 2018 Apr 3;90(14):e1257-e1266. doi: 10.1212/WNL.0000000000005258. Epub 2018 Mar 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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