The Natural History of Traumatic Spinal Cord Injury Using fMRI, MRS and DTI

Study Overview
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Brief Summary
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Traumatic spinal cord injury is a common injury to the spine and can lead to a clinical syndrome called central cord syndrome (CCS). CCS is an incomplete spinal cord injury where one starts to lose more motor function in the upper rather than lower extremities. It affects a wide range of the population from the young to the old. However, the natural history of CCS is poorly understood. Research has shown that the injury resulting in CCS might be due to the pinching or compressing of the spinal cord. This creates damage to a part of the spinal cord and creates difficulties in the signal getting through. We believe that we can gain a better understanding of the natural history of incomplete spinal cord injury as well as the recovery process. It is possible to track many changes in the brain and motor function through a variety of methods. One can track the concentrations of different chemicals (metabolites) by using magnetic resonance spectroscopy (MRS), changes in brain activation by using functional magnetic resonance imaging (fMRI) and thread-like nerve fibers in the spine by using diffusion tensor imaging (DTI). In our study we will be detecting differences in brain metabolism and activation of different parts of the brain during specific movement and in the nerve fibers in the brain. We hypothesize that there will be decreased levels of N-acetylaspartate (NAA, a putative marker of neuronal function) and decreased levels of glutamate (the primary excitatory neurotransmitter) in the motor cortex in patients with CCS when compared with controls. Over time, we hypothesize that the normalization of metabolite levels will correlate with the extent of neurologic recovery. We also hypothesize a reorganization of brain activation patterns with time such that patients will show increased volumes of activation in the motor cortex with recovery and that this will correlate with the extent of neurologic outcome. Over time, we predict that there will be normalization of the fibre track anatomy that will correlate with neurological recovery.

Detailed Description
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The long-term goal of this project is to develop predictors of neurological recovery based on brain metabolism, brain activation patterns, and fibre tracks in patients with traumatic CCS. The objective of this preliminary study is to evaluate metabolic changes, brain activation pattern reorganization and altered spinal cord fibre tracks in patients suffering from traumatic CCS to gain a better understanding of the natural history of this condition. Magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI) will be used to investigate the changes in brain metabolite concentrations, cerebral cortical activation, and fibre tract anatomy, respectively, in patients and controls. Ten patients having traumatic CCS will be recruited from the Clinical Neurological Sciences Department at the London Health Sciences Centre, University Campus. All participants will undergo an fMRI, MRS and DTI scan of the motor cortex to measure the volume of activation, signal intensity and levels of NAA and glutamate. The CCS participants will have three scans, one acutely (up to 48 hours after injury), one subacutely (15 days after injury), and one late (6 months after injury). Healthy volunteers will have two scans six months apart to determine reproducibility. Clinical changes will be measured using validated disease specific scoring instruments including the Japanese Orthopedic Association scale (JOA), ASIA/ISCOS Impairment Scale, and the Neck Disability Index (NDI). General quality of life will be measured using the 36-item Short-Form Health Survey (SF-36). A blinded investigator will administer these instruments prior to the scan at all time points.

Official Title
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Mapping the Natural History of Traumatic Spinal Cord Injury in the Sensorimotor Cortex Using Functional Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging

Conditions
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Central Cord Syndrome

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: between 30 and 85 years of age right handed with normal/corrected hearing and vision fluent in reading and speaking Canadian or American English able to follow simple task instructions able to maintain standardized movements available to return for the 15 day and 6 month imaging sessions competent to give consent Exclusion Criteria: must not have any other neurological disorder or systemic disease that may affect neurologic function not have any potential magnetic metal fragments in their body suffering from claustrophobia having a pacemaker or other electronic implants have been or currently is a welder or soldier have been injured by a metallic object that has not been removed pregnant or trying to conceive have cerebral aneurysm clips

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control<br>Controls (healthy volunteers) will have two scans (fMRI, MRS and DTI) six months apart to determine reproducibility. A blinded investigator will administer JOA, ASIA/ISCOS, NDI and SF-36 prior to the scan at all time points. | |
| CCS Participants<br>CCS participants will have three scans (fMRI, MRS and DTI), one acutely (up to 48 hours after injury), one subacutely (15 days after injury), and one late (6 months after injury). A blinded investigator will administer JOA, ASIA/ISCOS, NDI and SF-36 prior to the scan at all time points. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure the volume of activation, signal intensity and levels of NAA and glutamate using fMRI, MRS and DTI. |  | acutely (up to 48 hours after injury), subacutely (15 days after injury), and late (6 months after injury) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical changes will be measured using validated disease specific scoring instruments including the Japanese Orthopedic Association scale (JOA), ASIA/ISCOS Impairment Scale, and the Neck Disability Index (NDI). |  | Acutely (up to 48 hours after injury), subacutely (15 days after injury), and late (6 months after injury) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical spondylotic myelopathy, spinal cord compression, magnetic resonance spectroscopy, functional magnetic resonance imaging, brain plasticity