How much can traumatic brain injuries (TBIs) vary in severity?
Traumatic brain injury is a very heterogeneous disease. The college football player who sustains blows to the head and has headache and memory problems that last 1-2 weeks and resolves completely; the military veteran who is exposed to blast injuries and has headaches, difficulties with attention and concentrating on tasks, and suicidal thoughts; the driver in a motor vehicle crash who sustained injuries to the head and is now in a coma all have traumatic brain injuries but of varying severity.
Some traumatic brain injury patients have bleeding in their brain and increased intracranial pressure, needing surgery to correct these problems. Others have no evidence of bleeding in their brain but have significant damage to brain cells.
The severity of traumatic brain injury is currently crudely classified as mild, moderate or severe. However, often patients referred to as mild have debilitating symptoms that are not “mild”. Additionally, there are patients currently classified as moderate or severe who regain their pre-injury functional status whereas others don’t.
What causes the symptoms of TBIs?
TBI symptoms are typically caused by a number of different underlining injuries including:
- Damage death to brain cells;
- Death of brain cells;
- Disintegration of parts of the brain circuitry;
- Bleeding in the brain;
- Problems with brain cells forming connections with each other;
- Inflammation in the brain after traumatic injury;
- Increased pressure in the brain; among others.
How are TBIs currently diagnosed?
TBI is currently diagnosed in patients through a careful understanding of how the injury occurred, a patient’s symptoms, a physical exam including a neurologic exam and findings from a head CT scan.
In what ways are CT scans limited in the detection of TBIs?
Head CT scans are excellent at determining whether there is bleeding in the brain and whether there are signs of increased pressure in the brain. However they are silent when it comes to determining whether there are damaged brain cells, disintegrated brain circuits, and inflammation in the brain, among others.
Can damage to brain cells occur without bleeding?
Please can you outline your recent research into potentially using a blood test to diagnose TBI and determine its severity? What proteins did you measure?
We measured brain derived neurotrophic factor (BDNF) in blood samples obtained within 24 hours of injury from patients presenting to 2 different emergency departments with findings consistent with traumatic brain injury.
We also measured BDNF in emergency department patients who did not have any trauma within 1 week of coming to the emergency department.
We noticed that BDNF values were lower in traumatic brain injury patients compared to those without traumatic brain injury.
We then performed a validation study in which we measured BDNF in blood samples obtained within 24 hours of injury from patients presenting to 3 different emergency departments with traumatic brain injury who were enrolled in another study.
These patients were followed for up to 6 months after injury to determine how well they had recovered from their injuries. We then examined whether BDNF values were associated with how well patients recovered from their injuries.
What were your main findings?
We found that BDNF values were lower in traumatic brain injury cases than in those without traumatic brain injury.
We also found that among those with traumatic brain injury, the ones with the lowest BDNF values had four times the odds of having incomplete recovery at 6 months compared to traumatic brain injury patients with higher BDNF values.
Why do you think brain-derived neurotrophic factor (BDNF) was so successful at predicting outcomes?
This is partly because BDNF is produced predominantly in the brain. Its expression is also governed by brain activity, which presumably is decreased during the acute phase of trauma. It is likely that a severe reduction in brain activity, as evidenced by a lower BDNF value, predicts poor outcome.
What are the main advantages of being able to predict prognosis early on?
It provides clinicians with a more accurate information for counselling patients on what their expected course is.
It also allows them to identify those who will need additional and more intensive treatments.
Finally as new drugs are being tested for traumatic brain injury, it allows researchers to better identify the best candidates for clinical trials, increasing the chance that these trials will be successful.
What further research is needed to understand why brain injuries are associated with lower levels of BDNF in the blood?
We need to understand how quickly BDNF levels fall during brain trauma. We also need to better understand the factors that are associated with BDNF expression in trauma and whether blood BDNF values are reflective of brain BDNF values.
Where can readers find more information?
Either on Pubmed: http://www.ncbi.nlm.nih.gov/pubmed/26159676
Or on the website of the Journal of Neurotrauma: http://online.liebertpub.com/doi/10.1089/neu.2015.3949
About Dr Korley
Frederick Korley M.D., Ph.D. is an Assistant Professor of Emergency Medicine at the Johns Hopkins University School of Medicine. He completed his medical school education and residency training in emergency medicine at the Northwestern University Feinberg School of Medicine. Dr. Korley was appointed Chief Resident during his final year of residency training. He joined the Johns Hopkins faculty in 2007 as the inaugural recipient of Robert E. Meyerhoff Endowed Professorship. He subsequently completed a doctoral degree in clinical investigation at the Johns Hopkins University Bloomberg School of Public Health with election to Phi Beta Kappa.
Dr. Korley's research activities involve translation of novel diagnostics to inform clinically rational, timely, and cost-effective diagnosis of cardiac and brain injury in the emergency department. The goal of his traumatic brain injury work is to improve the acute care diagnosis, risk-stratification and treatment of TBI by identifying distinct molecular subtypes of TBI that will allow for targeted treatment and improved outcomes. The central hypothesis of this work is that a data-driven, multi-disciplinary approach utilizing novel methods (proteomics, genomics, connectomics, advanced imaging) for characterizing patient and injury characteristics, will enable a precise and personalized approach to delivering the right treatment to the right TBI patient at the right time. He is an inventor on a patent for a panel of novel traumatic brain injury biomarkers.
Dr. Korley is the recipient of numerous clinical and research awards including: The Johns Hopkins Clinical Scholars Award (2010 – 2012), Department of Emergency Medicine Teacher of the Year Award (2010), Department of Emergency Medicine Attending of the Year Award (2011), Johns Hopkins Clinician Scientist Award (2012 – 2014) and the Harold Amos Medical Faculty Development Award sponsored by the Robert Wood Johnson Foundation (2015 – 2019).