Tracking trauma-induced structural and functional changes above the level of spinal cord injury

Huber, Eveline; Curt, Armin; Freund, Patrick

doi:10.1097/wco.0000000000000224

Cited by 15 publications

(18 citation statements)

References 77 publications

(86 reference statements)

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“…S pinal cord injury (SCI) results in permanent sensorimotor deficits and remote neurodegeneration and reorganization along the neuroaxis, all of which have strong relationships with clinical outcomes (1,2). These relationships are of high clinical relevance because in vivo neuroimaging assessing volumetric and microstructural changes of the central nervous system might help to improve prediction of outcome and stratification of patients in future interventional trials (3).…”

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confidence: 99%

MR Spectroscopy of the Cervical Spinal Cord in Chronic Spinal Cord Injury

Wyss¹,

Huber²,

Curt³

et al. 2019

Radiology

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Purpose To investigate metabolic changes in chronic spinal cord injury (SCI) by applying MR spectroscopy in the cervical spinal cord. Materials and Methods Single-voxel short-echo spectroscopic data in study participants with chronic SCI and healthy control subjects were prospectively acquired in the cervical spinal cord at C2 above the level of injury between March 2016 and January 2017 and were compared between groups. Concentrations of total N-acetylaspartate (tNAA), myo-inositol (mI), total choline-containing compounds (tCho), creatine, and glutamine and glutamate complex were estimated from the acquired spectra. Participants were assessed with a comprehensive clinical evaluation investigating sensory and motor deficits. Correlation analysis was applied to investigate relationships between observed metabolic differences, lesion severity, and clinical outcome. Results There were 18 male study participants with chronic SCI (median age, 51 years; range, 30-68 years) and 11 male healthy control subjects (median age, 45 years; range, 30-67 years). At cervical level C2, tNAA/mI and tCho/mI ratios were lower in participants with SCI (tNAA/mI: -26%, P = .003; tCho/mI: -18%; P = .04) than in healthy control subjects. The magnitude of difference was greater with the severity of cord atrophy (tNAA/mI: R = 0.44, P = .003; tCho/mI: R = 0.166, P = .09). Smaller tissue bridges at the lesion site correlated with lower ratios of tNAA/mI (R = 0.69, P = .006) and tCho/mI (R = 0.51, P = .03) at the C2 level. Lower tNAA/mI and tCho/mI ratios were associated with worse sensory and motor outcomes (P < .05). Conclusion Supralesional metabolic alterations are observed in chronic spinal cord injury, likely reflecting neurodegeneration, demyelination, and astrocytic gliosis in the injured cervical cord. Lesion severity and greater clinical impairment are both linked to the biochemical changes in the atrophied cervical cord after spinal cord injury. • Content codes:Purpose: To investigate metabolic changes in chronic spinal cord injury (SCI) by applying MR spectroscopy in the cervical spinal cord. Materials and Methods:Single-voxel short-echo spectroscopic data in study participants with chronic SCI and healthy control subjects were prospectively acquired in the cervical spinal cord at C2 above the level of injury between March 2016 and January 2017 and were compared between groups. Concentrations of total N-acetylaspartate (tNAA), myo-inositol (mI), total choline-containing compounds (tCho), creatine, and glutamine and glutamate complex were estimated from the acquired spectra. Participants were assessed with a comprehensive clinical evaluation investigating sensory and motor deficits. Correlation analysis was applied to investigate relationships between observed metabolic differences, lesion severity, and clinical outcome.Results: There were 18 male study participants with chronic SCI (median age, 51 years; range, 30-68 years) and 11 male healthy control subjects (median age, 45 years; range, 30-67 years). At cervical level C2, tNAA/m...

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MR Spectroscopy of the Cervical Spinal Cord in Chronic Spinal Cord Injury

Wyss¹,

Huber²,

Curt³

et al. 2019

Radiology

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“…22 Recent advances in quantitative neuroimaging of the spinal cord and brain provide the possibility of monitoring temporal changes of the macrostructure as well as the microstructure from the earliest onset of SCI. 23,24 In a longitudinal prospective design, we used advanced magnetic resonance imaging (MRI) outcome measures to assess the spontaneous time course of structural progressive changes within the sensory system above the spinal level of the lesion (ie, cervical cord and brain). We measured next to cross-sectional spinal cord area 9 the anterior-posterior width (APW) and left-right width (LRW) at the identical cord level to provide detailed insights into morphometric cord changes.…”

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Tracking sensory system atrophy and outcome prediction in spinal cord injury

Grabher

Callaghan

Ashburner

et al. 2015

Annals of Neurology

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117

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ObjectiveIn patients with subacute spinal cord injury (SCI), the motor system undergoes progressive structural changes rostral to the lesion, which are associated with motor outcome. The extent to which the sensory system is affected and how this relates to sensory outcome are uncertain.MethodsChanges in the sensory system were prospectively followed by applying a comprehensive magnetic resonance imaging (MRI) protocol to 14 patients with subacute traumatic SCI at baseline, 2 months, 6 months, and 12 months after injury, combined with a full neurological examination and comprehensive pain assessment. Eighteen controls underwent the same MRI protocol. T1‐weighted volumes, myelin‐sensitive magnetization transfer saturation (MT), and longitudinal relaxation rate (R1) mapping provided data on spinal cord and brain morphometry and microstructure. Regression analysis assessed the relationship between MRI readouts and sensory outcomes.ResultsAt 12 months from baseline, sensory scores were unchanged and below‐level neuropathic pain became prominent. Compared with controls, patients showed progressive degenerative changes in cervical cord and brain morphometry across the sensory system. At 12 months, MT and R1 were reduced in areas of structural decline. Sensory scores at 12 months correlated with rate of change in cord area and brain volume and decreased MT in the spinal cord at 12 months.InterpretationThis study has demonstrated progressive atrophic and microstructural changes across the sensory system with a close relation to sensory outcome. Structural MRI protocols remote from the site of lesion provide new insights into neuronal degeneration underpinning sensory disturbance and have potential as responsive biomarkers of rehabilitation and treatment interventions. Ann Neurol 2015;78:Ann Neurol 2015;78:679–696

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“…1 ). Clinical observations typically reveal that downstream plasticity associated with functional improvements below complete or subcomplete spinal cord lesions remains ineffective ( Huber et al , 2015 ). Clinically less appreciated are consequences of lesion-induced plasticity in the reverse (upstream) direction—i.e.…”

Section: Embodiment and Neurologymentioning

confidence: 99%

“…Clinically less appreciated are consequences of lesion-induced plasticity in the reverse (upstream) direction—i.e. deafferentation of cortical regions (due to loss or impaired sensory and proprioceptive inputs)—although they may show marked neuropathological consequences, including cortical atrophy, plastic cortical map changes, or axonal retraction ( Huber et al , 2015 ).…”

Section: Embodiment and Neurologymentioning

confidence: 99%

“…The embodied nature of the complex interactive sensorimotor system suggests that even successful repair of focally damaged fibre tracts through a regenerative treatment [like anti-Nogo-A antibodies in spinal cord injury ( Huber et al , 2015 )] may not lead to complete recovery. This is because even though tissues and organs are exterior to the CNS they are inevitably impacted upon by the consequences of the central lesion (e.g.…”

Section: Embodiment and Neurologymentioning

confidence: 99%

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