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

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

Study Overview

• Status: Completed
• Conditions: Brain Concussion
• Intervention / Treatment: Behavioral: Graded and behavevial theraphy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 44

Contacts and Locations

Study Locations

• Denmark
  • Hammel, Denmark, 8450
    • Region Hospital Hammel Neurocenter

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Mild traumatic brain injury subjects with ongoing symptoms 2-6 months after trauma

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
mTBI subjects; mTBI subjects with ongoing symptoms	Behavioral: Graded and behavevial theraphy; Graded and behavevial theraphy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital; Regionshospitalet Hammel Neurocenter
• Investigators: Principal Investigator: Jørgen F Nielsen, Professor, Hammel Neurocenter - Universitetsklinik for Neurorehabilitering, Aarhus Universi

Publications and helpful links

General Publications

• Trillingsgaard Naess-Schmidt E, Udby Blicher J, Moller Thastum M, Ulrikka Rask C, Wulff Svendsen S, Schroder A, Hogh Tuborgh A, Ostergaard L, Sangill R, Lund T, Norhoj Jespersen S, Roer Pedersen A, Hansen B, Fristed Eskildsen S, Feldbaek Nielsen J. Microstructural changes in the brain after long-term post-concussion symptoms: A randomized trial. J Neurosci Res. 2021 Mar;99(3):872-886. doi: 10.1002/jnr.24773. Epub 2020 Dec 15.

Helpful Links

• Hammel Neurorehabilitation Centre and University Research Clinic, Aarhus University
• The Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital
• Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: January 19, 2015
• First Submitted That Met QC Criteria: January 26, 2015
• First Posted (Estimate): January 30, 2015

Study Record Updates

• Last Update Posted (Actual): May 24, 2018
• Last Update Submitted That Met QC Criteria: May 22, 2018
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Brain Injuries, Traumatic; Brain Concussion
• Other Study ID Numbers: 1-10-72-139-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO