Microstructural Changes in the Brain During Recovery After Mild Traumatic Brain Injury

Study Overview
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Brief Summary
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This study examines the possible microstructural changes in the brain during recovery after mTBI using diffusion MRI.

Detailed Description
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This study is embedded in a larger randomized controlled trial (RCT) (ClinicalTrials.gov ID: NCT02337101) from which the subjects are recruited and will separately examine the possible microstructural changes in the brain during recovery after mild traumatic brain injury (mTBI) in subjects with ongoing symptoms more than 2 month after mTBI in both groups from the RCT. Several biomarkers and brain areas has been investigated as possible sites of injury after mTBI. The nature of the diffuse chronic post-concussion symptoms (PCS) makes corpus callosum (CC), thalamus (THA) and hippocampus (HIP) interesting because of their central position and connection to widespread motor, sensory and cognitive processes and other brain areas. In most prior studies conventional magnetic resonance imaging (MRI) has failed to detect pathology especially in the chronic phase after mTBI. Diffusional Kurtosis Imaging (DKI) and Diffusional Tensor Imaging (DTI) are more sensitive to microstructural changes and might serve as biomarkers in the brain after mTBI. We hypothesized that a change in symptoms (as measured by cognitive performance and self reported symptoms) will correlate with a change in microstructural changes (as measured with DKI) in thalamus, corpus callosum and hippocampus from baseline 2-6 month after mTBI to follow up 6 month after. Separate correlations will also be made for both treatment and control group within the cohort.

Official Title
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Microstructural Changes in the Brain During Recovery After Mild Traumatic Brain Injury

Conditions
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Brain Concussion

Intervention / Treatment
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* Behavioral: Graded and behavevial theraphy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Concussion caused by a head trauma according to the diagnostic criteria recommended by the Danish Consensus Report on Commotio Cerebri within the last 2-6 months. The criteria are based on recommendations by the WHO Task Force, but with the amendment, that there must have been a direct contact between the head and an object in order to rule out pure acceleration - deceleration traumas. Age 18 to 30 years at the time of the head trauma. Able to understand, speak and read Danish. Patients with symptoms on at least three items on the Rivermead Post Concussion Symptoms Questionnaire (RPQ) rated as moderate or severe problem. PCS have to be subjectively rated as causing substantial impairment in daily life. Suitable for MRI examination Exclusion Criteria: Objective neurological findings from neurological examination and / or acute trauma CT scan, indicating other neurological diseases or brain damage. Previous concussion leading to persistent PCS within the last two years. Severe abuse of alcohol, prescription drugs and / or illegal drugs. Psychiatric morbidity or severe neurological disease that impedes participation in the treatment, i.e. Bipolar Disorder, autism, psychotic disorder (lifetime), multiple sclerosis etc.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| mTBI subjects<br>mTBI subjects with ongoing symptoms | Behavioral: Graded and behavevial theraphy<br>* Graded and behavevial theraphy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microstructural changes in the thalamus, corpus callosum and hippocampus between baseline and follow up, as measured by Diffusion kurtosis imaging (DKI) | MRI measurement | Baseline 2-6 month after mTBI with follow up 6 month after | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microstructural changes in the thalamus, corpus callosum and hippocampus from baseline to follow up, as measured by Diffusion tensor imaging (DTI) | MRI measurement | Baseline 2-6 month after mTBI with follow up 6 month after | 
| Change in post-concussion symptoms from baseline to follow up, as measured by Rivermead post-concussion questionnaire (RPQ) and headache (VAS scale) | Symptom score | Baseline 2-6 month after mTBI with follow up 6 month after | 
| Change in Cognitive performance from baseline to follow up, as measured by executive function, verbal and visual memory, processing speed, working memory, Visuospatial perception and construction | Cognitive test battery | Baseline 2-6 month after mTBI with follow up 6 month after |