The new blood test for traumatic brain injury and what it may mean for athlete welfareDr Ben Koh, Dr Alan Pearce
Issues of traumatic brain injuries (TBI) in sports gained much public interest in 2011 when the former American football player Ray Easterling led a class action case against the National Football League (NFL) over the game’s handling of concussion. In Australia, Newcastle Knights rugby league player James McManus is currently in legal proceedings against his former club over the management of his multiple TBIs suffered during several games and during training.1 His case is expected to be heard in the New South Wales Supreme Court in March 2018.
Unlike the Easterling case that seemed to have focused on the NFL allegedly concealing the dangers of TBI, McManus’ case is expected to deal with issues of a club’s duty of care to its players pursuant to the Civil Liability Act (NSW).2 The court in McManus’ will likely look at issues of possible absence or maintenance of a safe system of work for employed rugby league players and the foreseeability of risks associated with a failure to conform to a proper and safe system of work. The legal analysis will involve scientific evidence from epidemiologists and sports medicine experts concerning what was known in the general sporting community and the rugby league community about the failure to properly treat TBI in 2015 when the alleged breaches occurred.
The NRL has made significant strides in the management of TBI since 2015. Its latest guideline for the management of concussion issued on 23rd November 2017 is based on the Consensus Statement produced following the 5th International Conference on Concussion in Sport, held in Berlin in October 2016.3 But since that consensus statement, the scientific knowledge and clinical assessment of concussion has continued to advance. As such the duty of care owed by clubs to their players, what risk is foreseeable and what precautions a reasonable club needs to take, and the burden of taking precautions to avoid the risk of harm are continuing to change.
One such scientific advancement is the U.S. Food and Drug Administration’s (FDA) recent approval of the first blood test (the Banyan Brain Trauma Indicator, BBTI) to evaluate concussion.4 A theme that runs through both the Easterling and McManus cases is the courts’ retrospective look at the diagnosis of a concussion or sub-concussion when it occurred. A sub-concussion is where there are no signs or symptoms but where long-term neurodegenerative conditions such as Chronic Traumatic Encephalopathy is possible.5 The question raised by the approval of the new test is whether the BBTI will assist the courts in future cases: will what be deemed reasonable and foreseeable change because of the BBTI? Furthermore, will the BBTI influence how insurers that cover injuries in sports do their risk assessments, do sports risk management policies need to be updated?
To address these issues, this article will:
First look at head injuries and what constitutes a concussion and TBI. It will discuss some of the limitations of imaging and bedside/on-field neurocognitive clinical testing and some of the practical considerations for the clinicians in the sports field and in the emergency hospital setting.
Then, it will consider how the BBTI works and what its potential clinical impact and limitations would be.
Finally, it will examine whether the BBTI influences the club’s duty of care towards its players and in shaping sports risk management policies.
What is a TBI?
A TBI results following a violent blow or force to the head, or by a hit to the body that causes the head and brain to move rapidly back and forth. This sudden movement can cause the brain to bounce around or twist in the skull, creating chemical changes in the brain and sometimes stretching and damaging brain cells. TBIs are graded as mild, moderate, or severe depending on the level of consciousness assessed using the Glasgow coma scale (GCS) score determined at the time of injury.6
The detection of athletes with moderate to severe TBI do not often present with much difficulty even for the non-medical sporting staff. These athletes may display florid signs ranging from having trouble standing up or walking, to having a seizure, to being in an unconscious unresponsive comatose state. The difficulty usually arises with the mild cases of TBI (mTBI).
Often, the term mTBI is used interchangeably with concussion; but some have preferred to classify concussion as a subset of mTBI.7 The distinction in concussion is the lack of noticeable intracranial trauma that can be detected on conventional neuroimaging.8 It is believed that in a concussion, neuropathological changes occur, but the acute clinical signs and symptoms largely reflect a functional disturbance9 rather than a structural injury and, as such, no abnormality is seen on standard structural neuroimaging studies.10
Individuals who experience a mTBI may appear confused or have a blank expression or blunted affect during the acute event. There may also be some delayed response to simple questioning and this may lead to an emotional lability as the athlete attempts to cope with their confusion. Many athletes with mTBI also complain of headache, dizziness and seeing stars, blurry vision, or double vision. These symptoms and signs often have a rapid onset, are short-lived and resolves spontaneously. However, in some cases, signs and symptoms evolve over a number of minutes to hours. In some further cases symptoms may be prolonged.
Unlike TBI, there is at present no classification to quantify the severity of concussion injury. A standardised concussion severity classification first developed in 1997 was abolished by the American Association of Neurology in 201311 in favour of individual assessment and on a case by case approach to diagnosis and recovery.
Head injuries in contact sport are very common.12 Not all hits to the head result in a TBI or concussion. There is currently no on-field test that can totally exclude a concussion. The diagnosis of a concussion is ultimately a clinical judgment made by a medical professional.
The decision of whether to allow a player to continue to play after a hit to the head is a balance of the health of the athlete versus the economic interests of the player and the club (where there is a mere hit in the head but with no TBI/concussion). This clinical decision making occurs on two main occasions: during the acute on-field instance (when the game is still in play) and during the off-field time when deciding if (and when) an athlete can return to training or participate in the game.
Return to play examination and decisions by the clinician is difficult as this varies with the individual athlete. New scientific evidence seems to indicate that while an individual’s symptoms have abated, this may not be indicative of complete brain healing. Electrophysiological studies have shown that brain physiology may not return to baseline levels despite symptom resolution.13
The return-to-play decision is often complicated by the lack of truthful reporting by athletes. It has been shown that athletes down play their mTBI and concussion symptoms by a factor of 6 to10 times.14 This underreporting may result from athletes’ lack of knowledge about the injury,15 desire to return to competition more quickly,16 athletes fear of removal from a game or losing their position on the team, or an ingrained cultural attitude in sports of not wanting to be seen as weak, letting the team mates down, or playing through a concussion as a "badge of honour".17
Athletes are also known to actively underperform at baseline neurocognitive testing with a strategy to purposefully perform poorly (e.g. “tank” or “sandbag” the baseline), so that post-concussion performance would compare more favourably with baseline performance.18 This thus affects the accuracy of return-to-play decisions when comparing an athlete’s pre-concussion and post-concussion neurocognitive functioning in determining when the athlete has recovered. When post-concussion test performance is close to or better than baseline test performance and the athlete is (self-reported as) asymptomatic with physical exertion, clinical recovery is assumed to have been achieved and the athlete is deemed safe to return to play.
Given the limitations of establishing a diagnosis and assessing the severity of a concussion, the availability of an objective biological marker would greatly improve the accuracy of the decision-making process.
Biomarker of concussion – the BBTI
An ideal biomarker test for concussion in sports would be one where: the test can be conducted at the point-of-care (i.e. in the field where the sports concussion occurs); samples for the biomarker is easily accessible (e.g. using tears, saliva or blood); the biomarker is detected soon after a concussion occurs; and the test has a high negative predictive value (i.e. a negative result accurately determines that a concussion has not occurred).
Blood tests of several clinical biomarkers of injury to the brain to analyse mTBI and predict clinical outcomes are currently in the research pipeline.19 Many biomarkers (e.g. S100-B, ubiquitin C-terminal hydrolase L1, UCH-L1, and glial fibrillary acidic proteins, GFAP) have shown promise in correlating to the GCS scores and neuroimaging findings.20
Whilst the ideal biomarker test for concussion is not yet available, one biomarker test (the BBTI), was recently approved by the FDA21 for clinical use. The FDA has positioned the BBTI as a new quick testing option to help reduce need for CT scans and radiation exposure for patients with TBI.
The BBTI measures specifically UCH-L1 and GFAP within 12 hours of a brain injury. Following a brain injury, elevated levels of these two brain proteins can help predict which individuals may have an intracranial lesion visible by clinical neuroimaging and those who may not. The test results are available within four hours. The BBTI can predict the presence of intracranial lesions on a CT scan in 97.5% of cases and those who did not have an intracranial lesion on a CT scan in 99.6% of cases. Being able to predict if a person has a low probability of intracranial lesions would be extremely useful in clinical decision-making.
While the BBTI is a significant step forward in clinical care, it is not a concussion test per se. At this stage, it simply determines whether the individual requires further clinical neuroimaging to detect observable structural damage in the brain. Crucially, a negative test does not mean that a sub-concussion did not take place.
Policy Making and Practical Duty of Care in Sport
Contact sports by its very nature predisposes athletes to head injuries. Until the day comes where the courts and communities determine that there is no social utility in a contact sport that creates the risk, the focus remains on ensuring that a club or sporting code takes reasonable steps to avoid the risk. This means a greater attention in ensuring trained staff to detect TBI when it occurs and confirming full recovery of the player before allowing return to play.
Unfortunately, the diagnosis and assessment of concussion at present largely remains a clinical one. Whilst there are various neurocognitive tools to help assess athletes with a mTBI without neuroimaging findings (i.e. a concussion), these tools have its limitations and are subject to inaccuracies from patient factors. The new biomarker has the potential in triaging athletes with head injuries, but it is not yet an effective negative predictive tool. As such its introduction into the clinical arsenal is not likely to drastically influence the standard of care a reasonable club or sporting code must take nor the underwriting risk for players’ insurance coverage. Volenti non fit iniuria ("to the willing comes no injury")?
1† McManus v Knights Rugby League Pty Ltd  NSWSC 1101.
2† Civil Liability Act 2002 (NSW). https://www8.austlii.edu.au/cgi-bin/viewdb/au/legis/nsw/consol_act/cla2002161/ (last accessed 28 Feb 2018)
3†NRL, 'The Management of Concussion In Rugby League ', https://playnrl.com/media/2604/the-management-of-concussion-in-rugby-league-final.pdf. (last accessed 25 Feb 2018).
4†U.S. Food and Drug Administration, 'FDA authorizes marketing of first blood test to aid in the evaluation of concussion in adults', fda.gov, 14 Feb 2018, last accessed 1 March 2018, <https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm596531.htm>..
5† Chad A. Tagge et al, 'Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model' (2018) 141(2) Brain 422.
6† Ghajar J, 'Traumatic brain injury' (2000) 356 The Lancet 923.
7† Finch CF, Clapperton AJ and McCrory P, 'Increasing incidence of hospitalisation for sport-related concussion in Victoria, Australia' (2013) 198 Med J Aust 427; McCrory P et al, 'Consensus statement on concussion in sport—the 5th international conference on concussion in sport held in Berlin, October 2016' (2017) 51 Br J Sports Med 838.
8† McCrory P et al, above n
9†Christopher C Giza and David A Hovda, 'The neurometabolic cascade of concussion' (2001) 36(3) Journal of Athletic Training 228.
10† S. Dimou and J. Lagopoulos, 'Toward objective markers of concussion in sport: a review of white matter and neurometabolic changes in the brain after sports-related concussion' (2013/11/26) (2014) 31(5) Journal of Neurotrauma 413.
11† Christopher C Giza et al, 'Summary of evidence-based guideline update: Evaluation and management of concussion in sports Report of the Guideline Development Subcommittee of the American Academy of Neurology' (2013) 80(24) Neurology 2250.
12† JM Hootman, R Dick and J Agel, 'Epidemiology of collegiate injuries for 15 sports: summary and recommendations for injury prevention initiatives' (2007) 42(2) Journal of athletic training 311; CM Baugh et al, 'Frequency of head-impact–related outcomes by position in NCAA Division I collegiate football players' (2015) 32(5) Journal of neurotrauma 314; RC Cantu, 'Head injuries in sport.' (1996) 30 British Journal of Sports Medicine 289; J Heshka and K Lines, '"One Ding to Rule Them All": A Proposed New Approach to Regulating Brain Injuries in Sport' (2012) 3(4) International Journal of Sport & Society 141.
13† BP Major, MA Rogers and AJ Pearce, 'Using transcranial magnetic stimulation to quantify electrophysiological changes following concussive brain injury: A systematic review' (2015) 42(4) Clinical and Experimental Pharmacology and Physiology 394.
14† Finch CF, Clapperton AJ and P, above n
15† Michael McCrea et al, 'Unreported concussion in high school football players: implications for prevention' (2004) 14(1) Clin J Sport Med. 13; Johna K Register-Mihalik et al, 'Knowledge, attitude, and concussion-reporting behaviors among high school athletes: a preliminary study' (2013) 48(5) J Athl Train. 645.
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17†AJ Pearce, N Aimers and L Parrington, 'Assessment of high velocity head impacts using transcranial magnetic stimulation in Australian national ice hockey players. A multiple-case study' (2017)(50) 50th Winter Conference on Brain Research 199.
18† P Schatz, RS Moser, GS Solomon, SD Ott, R Karpf J Athl Train. 2012 May-Jun; 47(3): 289–296.
19†Biswadev Mitra et al, 'Plasma micro-RNA biomarkers for diagnosis and prognosis after traumatic brain injury: A pilot study' (2017) 38 Journal of Clinical Neuroscience 37; Brendan OʼConnell et al, 'Use of Blood Biomarkers in the Assessment of Sports-Related Concussion-A Systematic Review in the Context of Their Biological Significance' (In Press) Clinical journal of sport medicine: official journal of the Canadian Academy of Sport Medicine.
20†Eric Mercier et al, 'Predictive value of neuron-specific enolase for prognosis in patients with moderate or severe traumatic brain injury: a systematic review and meta-analysis' (2016) 4(3) CMAJ open E371; Linda Papa et al, 'Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury' (2016) 73(5) JAMA neurology 551.
21†U.S. Food and Drug Administration, above n
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- Tags: Athlete Welfare | Concussion | National Football League (NFL) | Traumatic brain injuries (TBI) | United Kingdom (UK) | United States of America (USA) | U_S_ Food and Drug Administration’s (FDA) Banyan Brain Trauma Indicator (BBTI)
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About the Author
Dr Ben Koh is a medical doctor with a Masters in Sports Medicine and a Masters in Psychology and has clinical and educational training in surgery, sports medicine, emergency medicine and critical care.
Dr Alan Pearce is an Associate Professor in the School of Allied Health at La Trobe University and a Senior Research Fellow in the Melbourne School of Health Sciences, The University of Melbourne.