UCLA

Degenerative cervical myelopathy (DCM) is a chronic, progressive disorder characterized by the age-related degeneration of osseocartilaginous structures within the cervical spine resulting in narrowing of the spinal canal and chronic compression of the spinal cord. Chronic spinal cord compression can result in persisting neck pain and neurological deficits including loss of fine motor skills, weakness or numbness in the upper limbs, and gait abnormalities and imbalance, ultimately requiring surgical intervention to relieve cord compression. DCM is the most common form of spinal cord injury in adults and as the elderly population continues to grow, incidence of DCM will rise alongside an increased demand on healthcare resources. Further investigation into the neural response to chronic spinal cord compression may not only inform disease progression and prognosis but may benefit patient monitoring and treatment planning.This dissertation aims to elucidate how symptom presentation, degree of spinal compression, microstructural and cellular integrity of the affected cord, and sex impact supraspinal structure and function in patients with DCM. To address the goals of the dissertation, we implemented a multimodal neuroimaging approach including anatomical, functional, and diffusion imaging of the brain and T2-weighted, diffusion, and metabolic imaging of the spine. First, we characterized and compared spinal cord compression induced alterations in cerebral morphometry and functional connectivity between symptomatic DCM and asymptomatic spinal cord compression (ASCC) patients to further uncover potential compensatory neural mechanisms driving symptom presentation and disease progression. Because the degree of cervical cord compression is not strongly linked to symptom severity, we investigated whether macrostructural, microstructural, and metabolic properties of the cervical spinal cord result in conventional anatomical and functional alterations within the brains of patients with DCM. Lastly, we identified sex-specific differences on cerebral structure and functional connectivity in patients with DCM. In summary, the dissertation revealed unique cerebral signatures between symptomatic and asymptomatic patients, novel insights into the interrelationship between spinal and supraspinal alterations, and sex-specific supraspinal reorganization in patients with DCM. Findings from this work contribute to our knowledge of disease characteristics and compensatory neural mechanisms; and may benefit future development of non-invasive imaging biomarkers, more precise predicative models to inform disease progression, and novel pharmacological strategies to enhance neuroprotective mechanisms and functional recovery in patients with DCM.