Spinal Cord Injury: How Can We Improve the Classification and Quantification of Its Severity and Prognosis?

Abstract

The preservation of functional neural tissue after spinal cord injury (SCI) is the basis for spontaneous neurological recovery. Some injured patients in the acute phase have more potential for recovery than others. This fact is problematic for the construction of clinical trials because enrollment of subjects with variable recovery potential makes it difficult to detect effects, requires large sample sizes, and risks Type II errors. In addition, the current methods to assess injury and recovery are non-quantitative and not sensitive. It is likely that therapeutic combinations will be necessary to cause substantially improved function after SCI, thus we need highly sensitive techniques to evaluate changes in motor, sensory, autonomic and other functions. We review several emerging neurophysiological techniques with high sensitivity. Quantitative methods to evaluate residual tissue sparing after severe acute SCI have not entered widespread clinical use. This reduces the ability to correlate structural preservation with clinical outcome following SCI resulting in enrollment of subjects with varying patterns of tissue preservation and injury into clinical trials. We propose that the inclusion of additional measures of injury severity, pattern, and individual genetic characteristics may enable stratification in clinical trials to make the testing of therapeutic interventions more effective and efficient. New imaging techniques to assess tract injury and demyelination and methods to quantify tissue injury, inflammatory markers, and neuroglial biochemical changes may improve the evaluation of injury severity, and the correlation with neurological outcome, and measure the effects of treatment more robustly than is currently possible. The ability to test such a multimodality approach will require a high degree of collaboration between clinical and research centers and government research support. When the most informative of these assessments is determined, it may be possible to identify patients with substantial recovery potential, improve selection criteria and conduct more efficient clinical trials.

New evidence for preserved somatosensory pathways in complete spinal cord injury: A fMRI study

“…While sacral sparing has been shown to better predict injury stability [Waters et al, ], it does not meet the need for more detailed research identifying those more likely to benefit from interventions or potentially at higher risk of developing persistent pain. The need for more detailed methods to quantify severity and to classify SCI type has been expressed for some time [Krishna et al, ]. Inclusion of discomplete SCI subgroups (motor and sensory) in the international SCI taxonomy (ISNCSCI) [Kirshblum et al, ] is essential to consider for its potential to improve the prediction of neurological outcome, enhance the interpretation of therapy effects and better select people with SCI for reparative trials [Krishna et al, ].…”

“…However, larger controlled studies are required to provide further objective evidence of partially preserved somatosensory preservation. While a consensus approach to identify preserved pathways would need to be determined [Krishna et al, ], the inclusion of discomplete SCI subgroups (motor and sensory) in the international SCI taxonomy (ISNCSCI) [Kirshblum et al, ] has potential benefits. It would facilitate research aiming to (1) improve the selection of people with acute SCI more likely to benefit from enhanced reparative rehabilitation [Gerasimenko et al, ; Donati et al, ]; (2) protect against injury [Awad et al, ]; and (3) explain how SCI injury type influences the development of pain [Cruz‐Almeida et al, ; Finnerup et al, ; Wasner et al, ; Widerström‐Noga et al, ].…”

Are midsagittal tissue bridges predictive of outcome after cervical spinal cord injury?

“…Residual tissue bridges spanning the lesion has been less studied, although these tissue bridges may be associated with improved recovery . Treatments aiming at the repair of the injured spinal cord will likely depend on such tissue bridges …”

A prospective serial MRI study following acute traumatic cervical spinal cord injury

“…More recently, there has been much interest in utilizing objective measures derived from MRI scans to characterize the severity of neurologic impairment and to predict outcome. The large heterogeneity amongst SCI patients, especially with regard to extent of neurological deficit, injury pattern, overall injury severity, comorbidities, surgical strategies, and rehabilitation care, makes prediction of neurological outcome very difficult [3]. Current methods for predicting outcome based on the initial functional neurologic examination are limited, and there is a great need for objective measures to better classify injury severity and predict outcome.…”