07 May 2012

Alzforum thanks Sam Gandy, Soong Ho Kim, and Effie Mitsis at Mount Sinai School of Medicine for preparing this meeting summary, edited by Tom Fagan.

Increasingly, sports-related head injuries, which can lead to chronic traumatic encephalopathy, are seen as a major public health concern. As was evident at Clinical and Molecular Biology of Acute and Chronic Traumatic Encephalopathies, a Keystone symposium held 26 February-2 March 2012, scientists are beginning to get a better understanding of the forces involved in brain injuries and what kind of damage they create at the molecular, cellular, and organ level. As repeated blows to the head lead to physiological changes in the brain, questions to be addressed include, How do sub-concussive blows contribute to impairment, and how may that be detected? Several theories surround concussion biomechanics, such as rotational and pressure gradients (whiplash, head motion), and the frontal lobe is a critical region of interest in both biomechanics and CTE. In terms of football collisions, typical blows generating 50-100 times acceleration due to gravity result in delivery of 100-200 pounds of force to the helmet, head, and neck. If the player is braced for the hit, that force is higher. For example, the helmet-first collision documented in three NFL players (Everett, Stingley, and LeGrand) resulted in more than 5,000 pounds of force on the neck.

Thomas Talavage and his team at Purdue University, West Lafayette, Indiana, initiated a study in high school sports players using cognitive tests (impact), structural and functional MRI, MRS in the pre- and post-season, and adding head collision monitoring (HITS, X2Impact) in season. Using these techniques, the researchers found that temporal and spatial distributions of hits link to distinct functional outcomes (see slides). Head contacts typically seen in sports affect neurophysiology as indicated by fMRI and MRS (the metabolic changes are sport and gender dependent), and metabolic changes in asymptomatic football players are consistent with TBI. Therefore, Talavage and colleagues conclude that concussion represents a physical injury with functional consequences.

Jeffrey Barth, University of Virginia, Charlottesville, focused on mild TBI cases entering the TBI study at UVA in the 1980s (55 percent of a total of 1,248 cases). It was found early on in this study that nearly 34 percent of people with mild TBI had not returned to work more than three months post-injury. Studies by Barth of mild head injury at the UVA in the early 1980s, aided by The Wall Street Journal article that described mild TBI as the silent epidemic, gave impetus to the early characterization of diffuse axonal injury and the neurochemical mechanisms involved in mild TBI. The Sports as a Laboratory Assessment Model (SLAM), used to study of football players at UVA, was among the first that focused on sports concussion as a vehicle for clinical research (to be applied to the general population) and for sports medicine. Barth (see slides) showed differences in cognitive functions, such as attention and complex problem solving pre- and post-concussion, and an inability to benefit from the practice effect on neurocognitive testing. The natural recovery curve from these sports concussions was between three and 10 days. Acceleration-deceleration mTBI/concussion sideline assessments (Standardized Assessment of Concussion [SAC] for civilians; Military Acute Concussion Evaluation [MACE] for military) and brief computerized neuropsychological assessments evolved from this work.

Based upon these studies, several critical issues in sports-related concussion were identified as important in terms of outcome (see slides): 1) severity of the injury; 2) when is it safe to return to play; and 3) the effects of multiple, timing, and latency of concussions. It is important to strike a balance, when considering return-to-play issues, between what is known scientifically (evidence based) and what we observe and hope to eventually understand, said Barth. Several negative outcomes have been identified as associated with early return-to-play and multiple concussions and sub-concussive blows: 1) Second Impact syndrome; 2) CTE; 3) emotional disturbance (depression); and 4) acute and chronic cognitive deficits. Individual vulnerability is associated with recovery. Barth said there are several important findings in the concussion literature: Recovery from a single sports concussion usually takes three to 10 days; one sports concussion increases the risk for subsequent concussion; multiple concussions increase the severity and duration of cognitive deficits; and children appear to recover from concussion more slowly than adults. Barth concluded that the controversy and complexities of the concussion issue should be treated as a challenge to scientific and clinical skills.

Ann McKee, Boston University, summarized our current understanding of chronic traumatic encephalopathy (CTE). CTE is a neurodegenerative disorder characterized by tauopathy and TDP-43 proteinopathy, but no Aβ accumulation. Once triggered, CTE progresses slowly over decades and spreads through many brain structures. CTE is often found in the brains of professional sports players, military veterans, and young people who had multiple mTBIs. The symptoms of CTE are often insidious and begin in midlife with personality and behavioral changes in addition to memory impairment, said McKee (see slides). Theresa Currier Thomas, University of Kentucky, Lexington, reported that in a rat model of CTE, thrombospondin-1 (TSP1)-mediated synaptogenic events are ongoing at one month post-diffuse brain injury (midline fluid percussion injury: FPI). TSP1 gene expression increased 30-fold between days 5-7 post-injury, while synaptic gene expression (SYN and GAP43) initially decreased, then rebounded, over 28 days. This evidence of post-traumatic circuit reorganization is accompanied by late onset of sensory sensitivity, increase in evoked glutamate release and altered neuron morphology at 28 days post-injury in the thalamus of FPI rats (see slides).

This is Part 2 of a five-part series. See also Part 1, Part 3, Part 4, Part 5. Read a PDF of the entire series.

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References

News Citations

1. Keystone: Traumatic Brain Injury—Epidemiology and Characteristics 4 May 2012
2. Keystone: Metabolic and Axonal Dysfunction in Traumatic Brain Injury 8 May 2012
3. Keystone: TBI—Learning From Markers, Models, and Diseases 9 May 2012
4. Keystone: Diagnosis and Model Treatments for Traumatic Brain Injury 10 May 2012

Other Citations

1. slides

Further Reading

No Available Further Reading