Degenerative disc disease occurs as part of the normal aging process and its treatment costs run in the many billions of dollars per year. Cervical spondylotic myelopathy (CSM), a form of chronic spinal cord injury, is the most debilitating form of degenerative disc disease, and is the most common acquired cause of spinal cord dysfunction in adults greater than 50 years of age. Both surgical and nonoperative management have been advocated for this condition with varying results, and the optimal treatment strategy is frequently debated. MR spectroscopy (MRS) has become widely accepted as a method to provide pertinent information regarding cellular physiology and integrity in the central nervous system, and is commonly used in the evaluation of disorders affecting the brain. Our laboratory has adapted this technology for spinal applications, and we were the first to describe its use in the evaluation of CSM. We have also been pioneers in the development and implementation of Diffusion Tensor Imaging (DTI) biomarker for evaluating spinal cord microstructure and functional impairment, and have recently adopted these biomarkers to CSM patients. Due to the poor natural history of CSM, inherent risks of treatment, and individual/societal cost associated with this disorder, there is a distinct need to develop more accurate, noninvasive methods to predict lesion severity and potential for neurological recovery following operative intervention. Additionally, in those patients treated nonoperatively, the development of non-invasive modalities to monitor subclinical disease progression is of high priority. Accordingly, we plan to investigate a novel, comprehensive approach to evaluate and treat CSM patients that could potentially have a major impact in our field, and would be easily translatable to widespread clinical application. Using the advanced spinal imaging techniques MRS and DTI, we plan to identify the time course of the relevant biochemical and microstructural changes that occur during the pathogenesis of CSM. These cellular and microstructural alterations will be used as biomarkers to monitor asymptomatic patients for signs of cellular signs of spinal cord injury that are likely to precede neurological deterioration. Lasty, these biomarkers will be investigated to determine if they can be used to predict outcome following surgical intervention.

Public Health Relevance

Health Cervical spondylotic myelopathy (CSM) is a form of chronic spinal cord injury caused by degenerative spine disease, and is the most common acquired cause of spinal cord dysfunction in adults. The neurological recovery and clinical response from both surgical and nonsurgical treatment can be quite variable and inconsistent. The proposed study will use MR Spectroscopy and Diffusion Tensor Imaging to evaluate the cellular spinal cord damage, and determine if this technique can be used to predict and monitor response to surgical and nonsurgical treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
4R01NS078494-05
Application #
9093864
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Jakeman, Lyn B
Project Start
2012-09-26
Project End
2017-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Ellingson, Benjamin M; Salamon, Noriko; Woodworth, Davis C et al. (2018) Reproducibility, temporal stability, and functional correlation of diffusion MR measurements within the spinal cord in patients with asymptomatic cervical stenosis or cervical myelopathy. J Neurosurg Spine 28:472-480
Woodworth, Davis C; Holly, Langston T; Mayer, Emeran A et al. (2018) Alterations in Cortical Thickness and Subcortical Volume are Associated With Neurological Symptoms and Neck Pain in Patients With Cervical Spondylosis. Neurosurgery :
Woodworth, Davis C; Holly, Langston T; Salamon, Noriko et al. (2018) Resting-State Functional Magnetic Resonance Imaging Connectivity of the Brain Is Associated with Altered Sensorimotor Function in Patients with Cervical Spondylosis. World Neurosurg 119:e740-e749
Holly, Langston T; Ellingson, Benjamin M; Salamon, Noriko (2016) Metabolic Imaging Using Proton Magnetic Spectroscopy as a Predictor of Outcome Following Surgery for Cervical Spondylotic Myelopathy. Clin Spine Surg :
Ashana, Adedayo O; Cohen, Jeremiah R; Evans, Brandon et al. (2016) Regression of Anterior Disc-osteophyte Complex Following Cervical Laminectomy and Fusion for Cervical Spondylotic Myelopathy. Clin Spine Surg :
Ellingson, Benjamin M; Salamon, Noriko; Holly, Langston T (2015) Advances in MR imaging for cervical spondylotic myelopathy. Eur Spine J 24 Suppl 2:197-208
Chang, Victor; Ellingson, Benjamin M; Salamon, Noriko et al. (2015) The Risk of Acute Spinal Cord Injury After Minor Trauma in Patients With Preexisting Cervical Stenosis. Neurosurgery 77:561-5; discussion 565
Ellingson, Benjamin M; Salamon, Noriko; Woodworth, Davis C et al. (2015) Correlation between degree of subvoxel spinal cord compression measured with super-resolution tract density imaging and neurological impairment in cervical spondylotic myelopathy. J Neurosurg Spine 22:631-8
Ellingson, Benjamin M; Salamon, Noriko; Hardy, Anthony J et al. (2015) Prediction of Neurological Impairment in Cervical Spondylotic Myelopathy using a Combination of Diffusion MRI and Proton MR Spectroscopy. PLoS One 10:e0139451
Ellingson, Benjamin M; Salamon, Noriko; Grinstead, John W et al. (2014) Diffusion tensor imaging predicts functional impairment in mild-to-moderate cervical spondylotic myelopathy. Spine J 14:2589-97

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