Electrophysiological Multimodal Assessments Improve Outcome Prediction in Traumatic Cervical Spinal Cord Injury

Abstract

Outcome prediction after spinal cord injury (SCI) is essential for early counseling and orientation of the rehabilitative intervention. Moreover, prognostication of outcome is crucial to achieving meaningful stratification when conceiving clinical trials. Neurophysiological examinations are commonly employed for prognostication after SCI, but whether neurophysiology could improve the functional prognosis based on clinical predictors remains an open question. Data of 224 patients included in the European Multicenter Study about Spinal Cord Injury were analyzed with bootstrapping analysis and multivariate logistical regression to derive prediction models of complete functional recovery in the chronic stage after traumatic cervical SCI. Within 40 days after SCI, we evaluated age, gender, the motor and sensory cumulative scores of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), and neurophysiological variables (motor evoked potentials, sensory evoked potentials, nerve conduction study) as possible predictors. Positive outcome was defined by a Spinal Cord Independence Measure total score of 100. Analyzing clinical variables, we derived a prediction model based on the ISNCSCI total motor score and age: the area under the receiver operating curve (AUC) was 0.936 (95% confidence interval [CI]: 0.904-0.968). Adding neurophysiological variables to the model, the AUC increased significantly: 0.956 (95% CI: 0.930-0.982; p = 0.019). More patients could be correctly classified by adding the electrophysiological data. Our study demonstrates that neurophysiological assessment improves the prediction of functional prognosis after traumatic cervical SCI, and suggests the use of neurophysiology to optimize patient information, rehabilitation, and discharge planning and the design of future clinical trials.

MRI in traumatic spinal cord injury: from clinical assessment to neuroimaging biomarkers

“…9 At the microstructural level, a worse ISNCSCI pin-prick score was associated with a greater increase in GM R2* in the thalamus, 9 a better ISNCSCI lower extremity motor recovery was predicted by a smaller decrease in MT in the somatosensory cortex 9 and a greater decrease R2* in the right cerebellum, 10 and increased functional connectivity between primary motor cortex and supplementary motor and premotor cortices. 46 More substantial grey matter atrophy in the cerebellum was associated with impaired light-touch sensation, 10 while greater increases in neuropathic pain intensity were associated with more extensive microstructural changes (increased R2*) in the secondary sensory cortex, anterior cingulate cortex, and cerebellum. 9 These longitudinal qMRI studies within a two-year follow-up point to three important and clinically relevant findings: (i) while clinical recovery levels off at two years post-SCI, progressive changes in macroscopic and microstructural markers continue; (ii) while macrostructrual changes slow down at the level of the spinal cord, both macroscopic and microstructural measures of neurodegeneration show sustained changes in the brain; (iii) the changes that have the greatest predictive validity in relation to clinical outcome appear to be those at the level of the spinal cord, brainstem and cortex (e.g.…”

“…Neurorehabilitation per se is believed to promote neurological changes such as cortical and spinal cord neural circuit reorganisation, which is assumed to translate into improved function. A few longitudinal qMRI studies within the range of one to two years post-SCI follow-up have found that better ISNCSCI lower extremity motor score recovery was predicted by less cervical spinal cord atrophy, 9,10 and cord diffusion alterations. 72 Early after SCI (<2 months post-injury) and at the level of the brain, greater ISNCSCI lower extremity motor recovery was associated with less cranial corticospinal tract atrophy.…”

“…spinal cord atrophy, cranial CST atrophy, lower MT in the primary motor cortex) over the first 6 months. 9,10 Implication for clinical trials…”

“…[6][7][8][9][10][11][12][13][14] These qMRI protocols provide quantitative measures of spinal cord 15,16 and brain integrity 17 that reflect atrophy, demyelination, and iron deposition of tissue. They have been used to demonstrate widespread [6][7][8][9][10][11][12][13][14] and progressive neurodegeneration; [7][8][9] the magnitude of which predicts clinical recovery. 9,10 qMRI therefore offers improved assessments of underlying neural integrity and can provide insights into the relationship between clinical recovery and neural plasticity, within the spinal cord and the brain.…”

“…They have been used to demonstrate widespread [6][7][8][9][10][11][12][13][14] and progressive neurodegeneration; [7][8][9] the magnitude of which predicts clinical recovery. 9,10 qMRI therefore offers improved assessments of underlying neural integrity and can provide insights into the relationship between clinical recovery and neural plasticity, within the spinal cord and the brain. 18 Additionally, task-based (fMRI) and resting state (rs-fMRI) functional MRI, although non-quantitative, can probe plasticity at the level of the brain, [19][20][21] and within the spinal cord.…”