Teaming up to Tackle Concussion

Teaming up to Tackle Concussion

On March 31, 2015, NINDS and the Foundation for the National Institutes of Health (FNIH) convened 39 scientists and clinicians as well as representatives from several organizations including the National Football League (NFL), National Hockey League, United States Olympic Committee, and other NIH Institutes for the Sports and Health Research Program (SHRP) Stakeholders Board Meeting. This meeting marked the first time SHRP stakeholders have been able to meet with grantees and hear about their research in concussion, traumatic brain injury, and chronic traumatic encephalopathy first hand. Launched in 2012, SHRP was made possible by a $30 million commitment from the NFL to develop an innovative public-private partnership to augment ongoing research on concussion, traumatic brain injury, and other sports injuries.

A concussion, or mild traumatic brain injury, is defined as an alteration in brain function or other evidence of brain pathology caused by an external force, such as a blow to the head. Although concussion is the most common type of Traumatic Brain Injury (TBI), scientists and clinicians do not fully understand what happens to the brain at the time of concussion. We do know, however, that TBI is a major global health problem. According to the Centers for Disease Control and Prevention (CDC), in 2010, TBIs accounted for about 2.2 million emergency department visits, 280,000 hospitalizations, and 50,000 deaths in the United States.1

TBI at a Glance

TBIs are rated by severity based on a scale of three categories: mild, moderate, and severe. Concussions are generally considered mild TBIs, where common symptoms include headache, dizziness, nausea, confusion, memory impairment, imbalance, and behavioral changes. Every year, between 1.6 million and 3.8 million sports-related concussions are estimated in the United States, particularly in youth athletes.2 Most concussive TBIs are mild, and people usually recover fully, however multiple concussions acquired over an athlete’s career may cause long-term cumulative impairment.3 Concussion is also a serious issue for members of the U.S. military, where it has been estimated that roughly 20% of deployed forces suffered a head injury in the wars in Iraq and Afghanistan, 83% of whom endured a mild, uncomplicated TBI or concussion. What is most alarming about these figures is that they likely largely underestimate the actual number of afflicted individuals, since many of those who suffer concussion never seek medical attention.

Department of Defense (DoD) Worldwide Numbers for TBI. More information can be found here: http://dvbic.dcoe.mil/sites/default/files/DoD-TBI-Worldwide-Totals-2000-2014-Q1-Q4-Feb23-2015.pdf

The Research on Getting Your Bell Rung

Following concussion, some people suffer from what is known as post-concussion syndrome, a disorder in which the symptoms of concussion like headaches and loss of memory may last for weeks or sometimes months after the injury. The NCAA-DOD Grand Alliance on Concussion Assessment, Research and Education (CARE) Consortium, well on its way to enroll tens of thousands of collegiate athletes, will bring data-driven answers to many of the most important questions about the effects of concussion (http://cdmrp.army.mil/phtbi/research_highlights/14consortium_oct_highlight.shtml).  To optimize the scientific value of their many studies, the NIH and DOD have established a data repository (https://fitbir.nih.gov) and strongly encourage the use of common data elements to enable comparisons between studies (http://www.commondataelements.ninds.nih.gov/tbi.aspx#tab=Data_Standards).

Studies suggest that athletes and military personnel are at greater risk for long-term impairment from concussion due to their probability of sustaining multiple injuries in rapid succession without adequate time for physiologic recovery in between injuries. The mystery of why a history of repetitive concussions increases one’s chances of having worsened and longer duration symptoms upon subsequent injury remains unsolved. The most devastating type of concussion is associated with repeated, hard blows to the head and is characterized by progressive degenerative disease in the brain, called chronic traumatic encephalopathy (CTE). Originally designated “Punch Drunk” syndrome because it was first described in boxers in the 1920s, in its end stage CTE causes dementia and severe brain atrophy with widespread aggregation of the tau protein. The theory behind the CTE pathology is that repeated concussions stress brain cells, resulting in abnormal tangles of tau protein that accumulate in neurons. Unfortunately, because the lack of objective tests, specific clinical symptomatology, CTE can only be detected at autopsy, meaning that individuals can only be diagnosed after death.

Normal Brain vs. Advanced CTE
Source: Boston University Center for the Study of Traumatic Encephalopathy

For many years, the NIH has supported research on sports concussions, including advanced brain imaging to improve diagnosis, studies with helmet monitors that measure physical forces during play, more sensitive pre- and post-concussion behavioral testing, and studies following the outcomes of a cohort of former professional football players. NIH funded $87 million of research on TBI in FY 2014, with NINDS contributing almost 60% of these funds. The Sports and Health Research Program (SHRP), made possible by a founding commitment from the NFL, supports high quality science in concussion, TBI, and CTE. In 2013 NIH chose to support eight projects that promise to answer some of the most fundamental problems on TBI, including the long-term effects of repeated head injuries and improving diagnosis of concussions. Through this research, as well as workshops that bring together scientists, clinicians, and government officials to identify strategies and next steps for future TBI research, SHRP has made it possible for NIH investigators to begin to unravel the complex neuropathology of TBI and develop new methods of detection, intervention, and rehabilitation in concussion research.

With support from SHRP, in April 2013, the NIH launched a major effort to define the pathologic characteristics of CTE. Two projects, funded for four years and $6 million each, are aimed at studying the neuropathology associated with CTE and the delayed effects of TBI. The groups are working to identify neuroimaging signatures of the neuropathology as a foundation for the development of in vivo diagnostic scanning technology. In February 2015, NINDS convened nine expert neuropathologists in Boston for the first consensus meeting to evaluate preliminary pathological consensus criteria for CTE. The summary of this workshop describes the required and supportive criteria for diagnosis of CTE as well as findings that are considered exclusionary to diagnosis. Importantly, the workshop investigators noted that to date, CTE pathology has only been found in individuals who are typically exposed to multiple episodes of brain trauma.

SHRP

SHRP is helping investigators get closer to answering important questions about the underlying mechanisms and long-term permanent effects of concussion for athletes, and to extend the impact of that research beyond the playing field to benefit the general population, including our service members. These studies promise to answer critical questions about the chronic effects of single versus repetitive injuries on the brain and how repetitive TBI relates to neurodegenerative disorders. Meanwhile, recent research from NIH-supported scientists at the University of California and University of Chicago shows that we are getting closer to being able to image CTE in living patients using radioactive tracers that label the tau protein.4

Together with our partners at the NIH and the NFL, NINDS is committed to research on the impact of concussion on the brain at all ages and in all people. We strive to develop strategies and interventions to mitigate the primary and secondary brain damage that occurs as a result of head trauma, to devise therapies that treat brain injury and improve long-term recovery of function, and to provide clinicians with better tools to identify injury at the earliest possible signs of damage. SHRP provides a critical driving force behind these efforts.

References:

1)   Centers for Disease Control and Prevention. Report to Congress on Traumatic Brain Injury in the United States: Epidemiology and Rehabilitation. Atlanta: National Center for Injury Prevention and Control; Division of Unintentional Injury Prevention, 2014.
2)   Giza and Kutcher. An introduction to sports concussions. Continuum (Minneap Minn) 2014; 20: 1545-51.
3)   Lehman EJ, Hein MJ, Baron SL, and Gersic CM. Neurodegenerative causes of death among retired National Football League players. Neurology 2012; 79(19): 1970-4.
4)   Barrio et al. In vivo characterization of chronic traumatic encephalopathy using [F-18] FDDNP PET brain imaging. PNAS 2015; 112(16): E2039-47.

Tuesday, June 2, 2015