Degenerative disc disease, a term frequently referred to as spondylosis, 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 (SCI), is the most debilitating type of degenerative disc disease, and is the most common acquired cause of spinal cord dysfunction in adults greater than 50 years of age. In many ways, its impact on society is greater than traumatic SCI due to the substantially larger number of patients afflicted with this disorder. There are several critical gaps in our understanding of CSM pathogenesis and treatment, in part due to the fact that the vast majority of CSM research has investigated the spinal cord in isolation, and not assayed other supraspinal structures within the CNS that are anatomically and functionally interrelated. Moreover, many of these isolated cervical spine studies have utilized standard MRI, which provides excellent macroscopic detail, but little information regarding the spinal cord microstructure, cellular physiology, or metabolism. Recent studies have demonstrated the role of cerebral reorganization and neural plasticity as compensatory mechanisms to preserve neurological function following traumatic SCI. We have previously elucidated similar findings in CSM patients utilizing both task based and resting functional MRI. During our previous funding period, we established Diffusion Tensor Imaging and MR spectroscopy as suitable techniques for assessing the spinal cord microstructure and biochemistry, and demonstrated correlations with these biomarkers to degree of neurological impairment. We now propose to build upon our previous work by developing a multi-modality imaging paradigm that probes the impact of supraspinal plasticity on CSM pathogenesis and recovery in tandem with advanced spinal cord imaging techniques MRS and DTI to yield a complete view of the entire sensorimotor network. In addition to greatly enhancing our knowledge base regarding chronic SCI pathogenesis and recovery, we seek to utilize these advanced imaging techniques to bridge current clinical gaps in the monitoring of CSM patients managed nonoperatively, as well as prediction of surgical outcome in those treated with surgery.

Public Health Relevance

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 advanced brain and spinal cord imaging techniques to assess abnormalities within the central nervous system found in these patients, and determine the ability of these techniques 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 #
5R01NS078494-09
Application #
10134439
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Bambrick, Linda Louise
Project Start
2012-09-26
Project End
2023-02-28
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
9
Fiscal Year
2021
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
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 :
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 :
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; Holly, Langston T (2015) Advances in MR imaging for cervical spondylotic myelopathy. Eur Spine J 24 Suppl 2:197-208
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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