Acute and chronic changes in myelin following mild traumatic brain injury

May 01, 2018

Charlottesville, VA (May 1, 2018). Preliminary research using mcDESPOT magnetic resonance imaging shows changes in the myelin content of white matter in the brain following mild traumatic brain injury. Myelin changes are apparent at the time of injury and 3 months afterward. For more details, see the article, "Prospective study of myelin water fraction changes after mild traumatic brain injury in collegiate contact sports, by Heather S. Spader, MD, and colleagues, published today in the Journal of Neurosurgery.

According to the Centers for Disease Control and Prevention, an estimated 1.7 million people in the United States sustain a traumatic brain injury (TBI) each year, and about 75% of these TBIs are mild TBIs, which include concussions.

Despite the gentle modifier, "mild" TBIs can cause disabling symptoms (headaches, dizziness, nausea, difficulties with concentration, and others), which in some cases do not resolve for weeks, months, or longer. In some contact-sport athletes, repeated mild TBIs have been linked to chronic traumatic encephalopathy (CTE), a serious neurodegenerative disease that develops later in life and is responsible for severe personality and neurocognitive changes.

What motivated the authors of the present study is the need for better diagnostic and prognostic tools for mild TBI, particularly in people who face greater risks of receiving one or more injuries, such as athletes engaged in contact sports. Thus far, conventional neuroimaging studies have been unable to reveal changes in the brain immediately following concussion and other mild TBIs.

Spader and colleagues tested a specific magnetic resonance imaging (MRI) technique--multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT for short)--to see if they could find evidence of white matter changes in the brains of male college rugby and football players after mild TBI. White matter tracts (bundles of axons covered by myelin) are susceptible to primary injury from mechanical forces at the time of head injury and again to secondary injury from the swelling and chemical changes that naturally occur in the brain following head trauma.

The researchers assessed white matter changes by measuring the myelin water fraction (MWF)--the ratio of myelin-associated water to total water--in voxels on neuroimaging studies. Changes in the MWF represent changes in the amount of myelin, the white fatty substance that acts as a sheath covering the axons of neurons. The higher the MWF, the more myelin is present. When sufficient amounts of myelin are present and organized, the myelin sheath aids in the swift and accurate transmission of electrical impulses from the nerve cell body across the axon and on to other nerve cells, muscles, or glands. Damage, loss, or disorganization of myelin slows down or impedes this process.

Twenty-three male Brown University students participated in the study: 12 contact sport players (CSPs) who had sustained mild TBIs (one member of the rugby team and 11 football players) and 10 age-matched controls with no such injury (athletes from non-contact sport teams, specifically swimming, fencing, and cross-country).

The CSPs underwent mcDESPOT imaging at the time of diagnosis of mild TBI (within 72 hours after injury) and again 3 months afterward. The controls underwent an identical imaging session. One CSP had also sustained a mild TBI some time before the study commenced; none of the controls had ever sustained a mild TBI.

The researchers compared the MWF in the brains of CSPs at each of the two time points with the MWF in the brains of the control players, which served as an uninjured comparison. The researchers also compared the MWF in the brains of CSPs at diagnosis with the MWF measured at the 3-month follow-up examination.

Here are the pertinent findings: These findings are depicted on MWF maps, essentially anatomical masks of white matter over which colored areas show an increased or a decreased MWF.

The increased MWF after mild TBI found in this study demonstrates an active remyelination process after mild TBI. However, as the researchers point out, increased myelin alone is not necessarily a good thing. Animal studies have shown that remyelination following mild TBI may result in disorganized and therefore less functional myelin.

In a related investigation, the researchers compared MWF maps obtained in this study with PET scans obtained in patients suspected of having CTE. The researchers found that the sites of increased MWF in CSPs at both time points corresponded to sites of brain changes in patients suspected of having CTE.

The study is preliminary and no clear clinical ramifications of the MWF changes are apparent. The authors call for further studies in which a true baseline MWF can be determined in CSPs before injury occurs rather than relying on a surrogate baseline MWF from non-contact sport players. The researchers also point out the need for a larger study population. Nevertheless, they note: "this study provides a basis for additional studies aimed at understanding the underlying neuropathophysiology of the brain's recovery from [mild] TBI."

When asked about the study, Dr. Spader replied, "We were surprised by the finding of increased myelin in the contact sports players compared with non-contact sports players at baseline and 3 months after injury. Using the mcDESPOT sequence, we can see that there is a remyelination process after an injury. The next question, however, is to determine if the increased myelin leads to the formation of a type of scar tissue that can cause disorganized signaling in the brain and which can eventually lead to an increased susceptibility to neurodegenerative disorders such as dementia."
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Spader HS, Dean DC III, LaFrance WC Jr, Raukar NP, Cosgrove GR, Eyerly-Webb SA, Ellermeier A, Correia S, Deoni SCL, Rogg J: Prospective study of myelin water fraction changes after mild traumatic brain injury in collegiate contact sports. Journal of Neurosurgery published online, ahead of print, May 1, 2018; DOI: 10.3171/2017.12.JNS171597.

Dr. Spader is affiliated with Joe DiMaggio Children's Hospital and Dr. Eyerly-Webb with Memorial Healthcare System in Hollywood, Florida. Dr. Dean is affiliated with the University of Wisconsin-Madison. Drs. Raukar, Ellermeier, and Rogg are affiliated with Rhode Island Hospital. Dr. LaFrance is affiliated with Rhode Island Hospital and Dr. Deoni with Memorial Hospital of Rhode Island; both are also affiliated with Brown University. Dr. Correia is affiliated with Brown University as well as Providence VA Medical Center. Dr. Cosgrove is affiliated with Brigham and Women's Hospital, Harvard Medical School.

Disclosure: This study was funded by a grant from the Department of Diagnostic Imaging, Rhode Island Hospital, Providence, Rhode Island. This work was additionally supported in part by the National Institutes for Mental Health (K99MH110596 to DCD) and the Eunice Kennedy Shriver National Institute of Child Health & Human Development under the National Institutes of Health (T32HD007489 to DCD and U54HD090256 to the Waisman Center, University of Wisconsin-Madison).

For additional information, please contact: Ms. Jo Ann M. Eliason, Communications Manager, Journal of Neurosurgery Publishing Group, One Morton Drive, Suite 200, Charlottesville, VA 22903. Email: jaeliason@thejns.org; Phone: 434-982-1209.

For 74 years, the Journal of Neurosurgery has been recognized by neurosurgeons and other medical specialists the world over for its authoritative clinical articles, cutting-edge laboratory research papers, renowned case reports, expert technical notes, and more. Each article is rigorously peer reviewed. The Journal of Neurosurgery is published monthly by the JNS Publishing Group, the scholarly journal division of the American Association of Neurological Surgeons. Other peer-reviewed journals published by the JNS Publishing Group each month include Neurosurgical Focus, the Journal of Neurosurgery: Spine, and the Journal of Neurosurgery: Pediatrics. All four journals can be accessed at http://www.thejns.org.

Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 10,000 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system including the brain, spinal column, spinal cord, and peripheral nerves. For more information, visit http://www.AANS.org.

Journal of Neurosurgery Publishing Group

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