Neural Injury in Adolescents With Concussion

This study utilizes multimodal brain imaging to obtain quantitative biomarkers of brain injury and to improve understanding of the biological basis of brain pathology in adolescents with concussion. Adolescents with a concussion will undergo neuroimaging and neuropsychology assessments acutely and four months after injury.

Study Overview

• Status: Completed
• Conditions: Mild Traumatic Brain Injury; Acute Brain Injury; Concussion, Mild
• Intervention / Treatment: Device: MEG; Device: MRI; Behavioral: Neuropsychology assessment

Detailed Description

Concussion is a highly prevalent condition in adolescence, but it remains a clinical diagnosis that largely relies on subjective patient report with no reliable objective biomarkers for diagnosis. Traditional clinical brain imaging has not been found useful for concussion as the pathology is generally not visible on conventional acute MRI or CT. The proposed study addresses this gap in concussion diagnosis and management by examining the sensitivity of magnetoencephalography (MEG) for identifying areas of brain injury through detection of abnormal neural activity (slowing) in adolescents with concussion compared to healthy controls. Adolescents with a concussion will complete neuroimaging (MEG and MRI) and neuropsychology assessments at two time points within ten days and then again 4 months post-injury. Healthy controls will complete neuroimaging and neuropsychology assessments at a single time point.

• Study Type: Observational
• Enrollment (Actual): 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adolescents with a recent concussion will be recruited from outpatient clinics in orthopedics and trauma surgery. Healthy controls will be obtained via volunteers and previous brain imaging research studies.

Description

Inclusion Criteria:

• Diagnosis of concussion and within 2 weeks of injury (case subjects)
• No history of diagnosed concussion (control subjects)

Exclusion Criteria:

• Head injury within 1 year of recent concussion (case subjects)
• History of neurologic, psychiatric, developmental or learning disorders (all subjects)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adolescents With Concussion; Adolescents with a concussion (n=120) will undergo neuroimaging (MEG and MRI) and neuropsychology assessments at two time points in the acute and chronic periods after injury, respectively. Brain imaging injury measures will be compared to a control normative database we will create. These brain measures will also be associated with cognitive and clinical outcomes.	Device: MEG; MEG is a non-invasive functional imaging technique that can measure slow-wave neural activity.; Device: MRI; MRI is a non-invasive imaging modality that provides measures of brain structure.; Behavioral: Neuropsychology assessment; A battery of tests will be administered by a neuropsychologist to evaluate the cognitive function of adolescents with concussion compared to healthy controls.
Adolescents Without Concussion; Age- and gender-matched healthy controls (n=160) will be recruited to establish a normative database of whole-brain slow-wave maps from MEG resting-state data as well as white-matter diffusion measures from MRI.	Device: MEG; MEG is a non-invasive functional imaging technique that can measure slow-wave neural activity.; Device: MRI; MRI is a non-invasive imaging modality that provides measures of brain structure.; Behavioral: Neuropsychology assessment; A battery of tests will be administered by a neuropsychologist to evaluate the cognitive function of adolescents with concussion compared to healthy controls.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in MEG Whole-Brain Slow-Wave Sensitivity between Controls and Concussion Patients	Whole-brain, resting-state slow-wave maps of whole brain activity will be obtained from the MEG imaging in both adolescents with a concussion and healthy controls. Control images will be analyzed to determine a whole brain z-score value that includes typically developing controls below the 95th percentile, the z-score threshold for this group). Z-score images for the adolescents with concussion will be obtained and the number of adolescents with concussion above this z-score threshold will be determined, and compared to the healthy controls. The sensitivity and specificity of this method determined.	Up to 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in MRI White-Matter Diffusion Measures between Controls and Concussion Patients	MRI diffusion data will be collected to examine associations between abnormal brain slowing and white matter damage in the adolescents with a concussion versus controls. Regions showing abnormal white matter diffusion will be comparing to normative control diffusion data.	Up to 2 months

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Christina L Master, MD, Children's Hospital of Philadelphia

Publications and helpful links

General Publications

• Huang MX, Theilmann RJ, Robb A, Angeles A, Nichols S, Drake A, D'Andrea J, Levy M, Holland M, Song T, Ge S, Hwang E, Yoo K, Cui L, Baker DG, Trauner D, Coimbra R, Lee RR. Integrated imaging approach with MEG and DTI to detect mild traumatic brain injury in military and civilian patients. J Neurotrauma. 2009 Aug;26(8):1213-26. doi: 10.1089/neu.2008.0672.
• Huang MX, Nichols S, Robb A, Angeles A, Drake A, Holland M, Asmussen S, D'Andrea J, Chun W, Levy M, Cui L, Song T, Baker DG, Hammer P, McLay R, Theilmann RJ, Coimbra R, Diwakar M, Boyd C, Neff J, Liu TT, Webb-Murphy J, Farinpour R, Cheung C, Harrington DL, Heister D, Lee RR. An automatic MEG low-frequency source imaging approach for detecting injuries in mild and moderate TBI patients with blast and non-blast causes. Neuroimage. 2012 Jul 16;61(4):1067-82. doi: 10.1016/j.neuroimage.2012.04.029. Epub 2012 Apr 20.
• Lewine JD, Davis JT, Bigler ED, Thoma R, Hill D, Funke M, Sloan JH, Hall S, Orrison WW. Objective documentation of traumatic brain injury subsequent to mild head trauma: multimodal brain imaging with MEG, SPECT, and MRI. J Head Trauma Rehabil. 2007 May-Jun;22(3):141-55. doi: 10.1097/01.HTR.0000271115.29954.27.
• Huang MX, Nichols S, Baker DG, Robb A, Angeles A, Yurgil KA, Drake A, Levy M, Song T, McLay R, Theilmann RJ, Diwakar M, Risbrough VB, Ji Z, Huang CW, Chang DG, Harrington DL, Muzzatti L, Canive JM, Christopher Edgar J, Chen YH, Lee RR. Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury. Neuroimage Clin. 2014 Jun 16;5:109-19. doi: 10.1016/j.nicl.2014.06.004. eCollection 2014.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 11, 2017
• Primary Completion (ACTUAL): June 1, 2018
• Study Completion (ACTUAL): June 1, 2018

Study Registration Dates

• First Submitted: December 29, 2016
• First Submitted That Met QC Criteria: January 4, 2017
• First Posted (ESTIMATE): January 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 24, 2018
• Last Update Submitted That Met QC Criteria: July 23, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Magnetic resonance imaging (MRI); Magnetoencephalography (MEG)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Brain Concussion
• Other Study ID Numbers: 16-013207

Plan for Individual participant data (IPD)

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