TY  - JOUR
AU  - Ziegler, Gabriel
AU  - Grabher, Patrick
AU  - Thompson, Alan
AU  - Altmann, Daniel
AU  - Hupp, Markus
AU  - Ashburner, John
AU  - Friston, Karl
AU  - Weiskopf, Nikolaus
AU  - Curt, Armin
AU  - Freund, Patrick
TI  - Progressive neurodegeneration following spinal cord injury: Implications for clinical trials.
JO  - Neurology
VL  - 90
IS  - 14
SN  - 0028-3878
CY  - [S.l.]
PB  - Ovid
M1  - DZNE-2020-06414
SP  - e1257-e1266
PY  - 2018
AB  - 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.
KW  - Adult
KW  - Aged
KW  - Atrophy
KW  - Brain: diagnostic imaging
KW  - Brain: pathology
KW  - Disease Progression
KW  - Female
KW  - Follow-Up Studies
KW  - Humans
KW  - Longitudinal Studies
KW  - Male
KW  - Middle Aged
KW  - Nerve Degeneration: diagnostic imaging
KW  - Nerve Degeneration: etiology
KW  - Nerve Degeneration: physiopathology
KW  - Neuralgia: diagnostic imaging
KW  - Neuralgia: etiology
KW  - Neuralgia: physiopathology
KW  - Neurodegenerative Diseases: diagnostic imaging
KW  - Neurodegenerative Diseases: etiology
KW  - Neurodegenerative Diseases: physiopathology
KW  - Recovery of Function
KW  - Spinal Cord: diagnostic imaging
KW  - Spinal Cord: pathology
KW  - Spinal Cord Injuries: complications
KW  - Spinal Cord Injuries: diagnostic imaging
KW  - Spinal Cord Injuries: physiopathology
KW  - Young Adult
LB  - PUB:(DE-HGF)16
C6  - pmid:29514946
C2  - pmc:PMC5890610
DO  - DOI:10.1212/WNL.0000000000005258
UR  - https://pub.dzne.de/record/140092
ER  -