Spinal cord markers in ALS: Diagnostic and biomarker considerations

Despite considerable involvement of the spinal cord in amyotrophic lateral sclerosis (ALS), current biomarker research is primarily centred on brain imaging and CSF proteomics. In clinical practice, spinal cord imaging in ALS is performed primarily to rule out alternative conditions in the diagnostic phase of the disease. Quantitative spinal cord imaging has traditionally been regarded as challenging, as it requires high spatial resolution while minimizing partial volume effects, physiological motion and susceptibility distortions. In recent years however, as acquisition and post-processing methods have been perfected, a number of exciting and promising quantitative spinal imaging and electrophysiology techniques have been developed. We performed a systematic review of the trends, methodologies, limitations and conclusions of recent spinal cord studies in ALS to explore the diagnostic and prognostic potential of spinal markers. Novel corrective techniques for quantitative spinal cord imaging are systematically reviewed. Recent findings demonstrate that imaging techniques previously used in brain imaging, such as diffusion tensor, functional and metabolic imaging can now be successfully applied to the human spinal cord. Optimized electrophysiological approaches make the non-invasive assessment of corticospinal pathways possible, and multimodal spinal techniques are likely to increase the specificity and sensitivity of proposed spinal markers. In conclusion, spinal cord imaging is an emerging area of ALS biomarker research. Novel quantitative spinal modalities have already been successfully used in ALS animal models and have the potential for development into sensitive ALS biomarkers in humans.