Traumatic Brain Injury Can Lead to Widespread Tissue Loss

By Judith Groch
TORONTO, March 4 -- A loss of brain tissue after a traumatic head injury may help explain the cognitive and emotional fallout that often follows the event, researchers here found.
In a study of mild to severe traumatic brain injury, the more severe the injury, the greater the tissue loss after a year, particularly white matter, Brian Levine, Ph.D., of the University of Toronto, and colleagues reported in the March 4 issue of Neurology.
The analysis, using high-resolution MRI, found a stepwise, dose-response relationship between loss of volume and brain injury, encompassing both frontal and posterior brain regions, the researchers said.
Notably, even patients with a mild injury had changes that could be reliably distinguished from the noninjured controls. The most reliable effects were in the frontal, temporal, and cingulated regions, although there were effects to varying degrees in nearly every brain region.
The patterns of diffuse tissue loss even in the absence of focal injury helped explain the well-known substantial handicap that patients have in the wake with a traumatic brain injury, particularly with concentration, working memory, organizing, planning, and mood changes, the researchers said.
To assess the relationship between regional brain volume changes and the severity of traumatic brain injury in patients with and without the focal lesions, the researchers recruited 69 chronic-phase traumatic brain-injury patients from consecutive hospital admissions to a large trauma center. Fifty-five of the patients (80%) were injured in a motor vehicle accident.
The patients, spanning the full range of severity, received high-resolution structural MRI a minimum of one year after the injury.
Analyzed with a technique that permitted template matching, the imaging technique detected tissue loss after a significant blow to the head that might otherwise evade detection by traditional qualitative radiological examination, the investigators said.
Multivariate statistical analyses assessed covariance patterns between volumes of gray matter, white matter, and sulcal/subdural and ventricular cerebrospinal fluid across 38 brain regions.
Severity of the brain injury was assessed by depth of coma or consciousness alteration at the time of injury. Some patients had minor injuries (13) while twenty-six had severe injuries including extended loss of consciousness.
Patients with diffuse and diffuse plus focal injury were analyzed both separately and together and compared with 12 age- and sex-matched non-injured controls. The controls had significantly more education than the injured groups.
All group differences in correlations for mild, moderate, and severe injury were reliably different from that of the non-injured group, and correlations for the moderate and severe injury groups were reliably different from that of the mild injury patients.
A spatially extensive pattern of volume loss varied along with injury severity, with particularly widespread effects in white matter volume and sulcal/subdural cerebrospinal fluid.
Focal lesions were associated with greater loss of volume in the left medial ventral frontal and posterior temporal regions, but volume loss included other regions and remained marked even when analyses were restricted to patients with diffuse injury.
Loss of white matter, also widespread, was greatest in the lateral superior frontal, superior parietal, posterior temporal, and posterior cingulated regions bilaterally, with a tendency toward greater volume loss in the right hemisphere.
However, the researchers noted that although white matter loss was greater, gray matter loss was nonetheless marked. In fact, Dr. Levine said, localized gray matter loss may have greater implications for specific behavioral changes than localized white matter loss.
Patterns of volumetric changes can differentiate the severity of levels of traumatic brain injury, even in mild injury. This form of brain injury causes a spatially extensive pattern of volume loss that reflects independent but overlapping contributions of focal and diffuse injury, the researchers said.
Although the sample size was large compared with previous studies, the size of the brain injury groups, particularly the mild group, was small. Also, the current study did not investigate the significance of tissue loss on behavior, a topic now being studied in this group of patients, the researchers said.
In addition, the researchers said, the MRI technique used, although well suited to patients with distorted brain anatomy, lacked the anatomic precision of manual tracing and the resolution of voxel-based methods. A fuller appreciation will require additional imaging technologies, such as functional neuroimaging and MR spectroscopy, the researchers concluded.
This study was supported by grants from the Canadian Institutes of Health Research and the NIH-National Institute of Child Health and Human Development.
The authors reported no conflicts of interest.

Primary source: NeurologySource reference:Levine B, et al "The Toronto traumatic brain injury study: Injury severity and quantified MRI" Neurology 2008; 70: 771-778.