What's All The Fuss?

Concussion (mTBI) and in the broader sense Traumatic Brain Injury (TBI), directly impacts millions of people yearly worldwide, and indirectly in even greater numbers. The current publicity around the issue is predominantly in and around sport (chiefly NFL in the US but moving 'rapidly' through sporting codes worldwide). However, most realistically, it is a minute-to-minute proposition within all Emergency Departments (ED) worldwide.  

Currently, diagnosis of TBI is made by subjective interpretation of physical symptoms and self-reporting of other symptoms. A combination of the Glasgow Coma Scale (GCS) score along with clinical variables such as pupillary reaction and computed tomography scan (CT) brain findings are utilized by most clinicians, but are estimated to be accurate only 37% of the time. 1, 2. Researchers are investigating other less invasive and specific modalities. Leading this quest are biological biomarkers.  

Glia has invested its efforts in nucleic acid based markers that have been shown to be extremely sensitive and specific. Most excitingly, they hold undeniable promise for prognosis (Return to Play, Work, School, Duty), the ultimate ‘golden egg’ in this burgeoning space.  

As a whole, medicine is pushing more into the ‘brain space’. Recognition of psychological conditions; depression, anxiety, etc and solid moves to confront pathological conditions; Alzheimer’s, Parkinson’s and the like, are constructing rock solid foundations for TBI diagnostics to be developed and marketed.  

Practicality suggests that not only is a blood based pathology test required to help overcome the burden both socially and financially TBI is having, but more logically, a Point of Care (PoC) test is also required at the ‘front line’ to assist with diagnosis and triage to minimize the proven on going effects and maximise recovery.

image46

The Problem

Globally, TBI is the leading cause of death and disability in children and adults and is involved in nearly half of all trauma deaths. In Australia, Europe and the United States, the estimated annual incidence of TBI requiring hospitalisation is 100 per 100 000 population, with 80%–90% of cases categorised as mild TBI (mTBI). In the US it affects more than 3.5 million people each year alone.3.

Annual hospital presentations for sport related concussions between the ages of 0-19 in the US are reported to be 175,000.4. Of these, up to 15% most likely continue to be asymptomatic resulting in performance decline for a prolonged period of time (2 years) following their last concussion, a finding which is highly important for future discussion about current RTP guidelines and reducing the risk of re-injury in this and indeed all age groups. Evidence also suggests that TBI may be a risk factor for the later development of neurodegenerative disorders, including Alzheimer's disease.5-11. 

The impact of TBI is significant, and includes the personal burden endured by survivors and their families, as well as the substantial economic toll on society.12.

We and others argue that the use of biomarkers is a useful and important approach to comprehensively assess brain function following concussion.13.

The Cost

Globally, traumatic brain injury (TBI) is the leading cause of death and disability in children and adults and is involved in nearly half of all trauma deaths. For some young adults in the US, the annual incidence of emergency department presentations for TBI is reportedly as high as 760 per 100 000 population. In Australia, one report estimated the direct hospital costs for all TBI in the 2004–05 financial year at $184 million.14.

According to the US Centers for Disease Control and Prevention (CDC), the economic cost of TBI in the United States in 2010, including direct and indirect medical costs, was estimated at $76.5 billion.15.

References

1. Perel P, Wasserberg J, Ravi RR, Shakur H, Edwards P, Roberts I (2007) Prognosis following head injury: a survey of doctors from developing and developed countries. J Eval Clin Pract 13:464-465. doi:10.1111/j.1365-2753.2006.00713.x
2. Rosenfeld JV, Maas AI, Bragge P, Morganti-Kossmann MC, Manley GT, Gruen RL (2012) Early management of severe traumatic brain injury. Lancet 380:1088-1098. doi:10.1016/S0140-6736(12)60864-2
3.V.G. Coronado, L.C. McGuire, K. Sarmiento, J. Bell, M.R. Lionbarger, C.D. Jones, A.I. Geller, N. Khoury, and L. Xu (2012). Trends in traumatic brain injury in the U.S. and the public health response: 1995–2009. J Safety Res.
4. Faul M, Xu L, Wald MM, Coronado VG. Centers for Disease Control and Prevention. Traumatic brain injury in the United States. GA, USA.
5. C.A. Molgaard, E.P. Stanford, D.J. Morton, L.A. Ryden, K.R. Schubert, and A.L. Golbeck (1990). Epidemiology of head trauma and neurocognitive impairment in a multi-ethnic population. Neuroepidemiology 9, 233–242.
6. J.A. Mortimer, L.R. French, J.T. Hutton, and L.M. Schuman (1985). Head injury as a risk factor for Alzheimer's disease. Neurology 35, 264–267.
7. J.A. Mortimer, C.M. van Duijn, V. Chandra, L. Fratiglioni, A.B. Graves, A. Heyman, A.F. Jorm, E. Kokmen, K. Kondo, W.A. Rocca, and et al. (1991). Head trauma as a risk factor for Alzheimer's disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int. J. Epidemiol. 20, Suppl 2, S28–S35.
8. E.S. O'Meara, W.A. Kukull, L. Sheppard, J.D. Bowen, W.C. McCormick, L. Teri, M. Pfanschmidt, J.D. Thompson, G.D. Schellenberg, and E.B. Larson (1997). Head injury and risk of Alzheimer's disease by apolipoprotein E genotype. Am. J. Epidemiol. 146, 373–384.
9. Z. Guo, L.A. Cupples, A. Kurz, S.H. Auerbach, L. Volicer, H. Chui, R.C. Green, A.D. Sadovnick, R. Duara, C. DeCarli, K. Johnson, R.C. Go, J.H. Growdon, J.L. Haines, W.A. Kukull, and L.A. Farrer (2000). Head injury and the risk of AD in the MIRAGE study. Neurology 54, 1316–1323.           
10. B.L. Plassman, R.J. Havlik, D.C. Steffens, M.J. Helms, T.N. Newman, D. Drosdick, C. Phillips, B.A. Gau, K.A. Welsh-Bohmer, J.R. Burke, J.M. Guralnik, and J.C. Breitner (2000). Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias. Neurology 55, 1158–1166.
      

11. V.E. Johnson, W. Stewart, and D.H. Smith (2012). Widespread tau and amyloid‐beta pathology many years after a single traumatic brain injury in humans. Brain Pathol. 22, 142–149.                    12. P. Corso, E. Finkelstein, T. Miller, I. Fiebelkorn, and E. Zaloshnja (2006). Incidence and lifetime costs of injuries in the United States. Inj. Prev. 12, 212–218.                                                 
13. Marc Dalecki, et al. Concussion May 12, 2016.

​14. Caroline F Finch, Angela J Clapperton and Paul McCrory. Increasing incidence of hospitalisation for sport-related concussion in Victoria, Australia. Med J Aust 2013; 198 (8): 427-430.

​15. CDC. Severe traumatic brain injury. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/TraumaticBrainInjury/severe.html. Accessed: Jul 14, 2015.