The science of traumatic brain injury, rewired
Over 300,000 traumatic brain injuries are reported each year, though actual numbers are potentially tens of thousands more as data reflects cases presented to hospitals only.
They range from people with concussions (classed as ‘mild’ brain injury) to people who spend days, or weeks in a coma and require long-term rehabilitation and support.
Despite advancements in medicine, in severe cases of brain injury there’s a 30-40% mortality rate, with no effective treatments to counter damage to the brain.
While around 90% of brain injuries are ‘mild’, or concussion, this term can be misleading as for around 50% of people with mild brain injuries, their symptoms will persist. Their symptoms may include headache, dizziness, irritability, depression and memory impairment, making it difficult to resume their normal life.
For people across the spectrum of mild to severe traumatic brain injury, there are significant costs in terms of medical expenses, lost productivity and need for personal and family support, with costs estimated between $2.5m and $4.8m per person over their lifetime.
Broad spectrum thinking
Sarah Hellewell, Senior Research Fellow at Curtin Medical Research Institute and the Perron Institute, has a career focus on traumatic brain injury. She says the science of traumatic brain injury is being reframed from outdated classification based on a few metrics of injury to consider a broader clinically informed ‘spectrum’ that accommodates a wide range of factors — symptoms, medical history, personal factors such as resilience and social support, alongside biomarkers derived from blood and imaging (MRI and CT).
Her research incorporates both clinical and basic science programs spanning the spectrum of brain injury severity, enabling her to rapidly identify clinical problems patients face and investigate these in depth in the laboratory to determine vulnerability to poor recovery and develop personalised treatments. This work combines analysis and modelling of injury responses directly in the brain with measures of biomarkers in blood, cognitive assessments and other factors which may influence recovery.
While concussions from sports receive much of the spotlight they only account for 15-16% of TBI, with the majority of injuries occurring due to falls, road traffic accidents, workplace accidents, assaults and increasingly many in family and DV settings.
Persisting post-concussion symptoms
Up to 50% of the population will continue to have symptoms long after the concussion, with symptoms remaining for months, years or even decades.
Dr Hellewell is a lead researcher on the Australian mild traumatic brain injury study (AUS-mTBI) at Curtin University, a national project that aims to predict long term outcomes from concussion.
She says the goal of this study is to identify early markers that will let doctors know what a concussed person’s recovery trajectory may look like, in order to identify and provide appropriate support for people who need it.
“Ultimately, this work aims to reduce the rates of persisting post-concussion symptoms in the Australian community,” Dr Hellwell explains.
She also leads studies aiming to prevent or reduce persisting symptoms after concussion using non-invasive brain imaging to guide personalised treatment and improve both the underlying brain dysfunction and the symptoms people experience.
“Everyone’s’ brain responds differently to brain injury, and there are many factors which can affect recovery like age, sex and previous medical history. We are also just starting to understand that things like resilience (ability to bounce back from adversity) and social or family support can be very influential in recovery.”
“We want to find out whether these factors can change the brain’s structure and function … we are using tools like MRI, cognitive tests, blood and saliva biomarkers to see how these factors influence symptoms and change brain function as well.”
Developing and testing personalised treatments
Instead of a ‘one-size-fits-all’ approach, Dr Hellewell’s research takes these individual factors into account to develop and test personalised treatments. Her initial findings suggest that targeting these individual responses in treatments specific to each person’s unique injury can support brain recovery and improve persistent symptoms.
Australian research
In traumatic brain injury cases, it is unknown will recover, who will not, and who will develop persistent symptoms. The national AUS-mTBI study being led by Curtin University hopes to change that.
This mobile phone app and online data collection program includes participants recruited up to 14 days after a suspected concussion. Participants can track their symptoms, and are followed for up to 12 months or until symptoms resolve. This study, built into the HeadCheck app, features guided recovery for people with concussion tailored to their symptoms, to help them get back to work, school and sports.
“It’s not uncommon for people with symptoms such as headaches to find themselves at the doctor and unable to answer questions such as the frequency and severity of symptoms… this app will serve as a practical tool for tracking symptoms by providing personalised graphs of symptoms over time. This data could help doctors to provide more accurate, personalised support for those who need it,” says Dr Hellewell.
5,000 people are being recruited Australia-wide.
The AUS-mTBI study also includes in-person data collection from post-concussion cases (up to 26 hours after people present at emergency departments in West Australian, Queensland and Victorian hospitals), with participants undergoing MRI scans and blood tests alongside assessments of their injury and demographic profiles.
Like the mobile app, this arm of the study follows participant recovery over 12 months to determine whether biological and personal factors can predict recovery.
AUS-mTBI Regstry
To extend the use of the data collected from the hospital sites beyond the project’s lifespan it will be stored in a dedicated registry to be linked to other health data from medical records. This information can then be combined in order to understand the long-term consequences of concussion.
Dr Hellewell says this will “allow us to gain a comprehensive understanding of how concussion affects various aspects of health for Australians in the years and decades following injury, and uncover associations with future health that have not been previously understood”.
This approach could lead to improved health outcomes post-concussion on a national scale.
Promising blood biomarker distinguishing concussion from non-concussion
Dr Hellewell says that even the diagnosis of concussion is challenging, with no clear markers or tests to determine what is happening in the brain. Her research is trialling several promising blood biomarkers which may be able to provide more accurate data on brain pathology, delineating people who have biological evidence of concussion from those with a more minor injury which does not cause changes in the brain. These promising markers reflect changes in the brain’s white matter tracts, as well as those from astrocytes — supporting cells which respond to injury.
“In a research setting, we can now accurately diagnose concussion from non-concussion by assessing these markers in blood tests. Combinations of these markers can also now be used to guide clinical management, with levels now being used in some hospitals to decide whether someone should have a CT scan. By measuring concentrations of the markers GFAP and UCH-L1 in the blood within 16-24 hours, we can see specific changes in the blood profile which may indicate that someone has a brain bleed or skull fracture, factors that are known to contribute to poor recovery. Using these markers in combination can help doctors limit CT scans to those who need them, avoiding unnecessary exposure to radiation for those who don’t.”
“Very promising markers for sports concussion”
The development of blood biomarkers is a very active area of research, with particular uses in contact sports such as Australian football and rugby, where players are at risk of repeated injuries.
The goal of this research is to use blood biomarkers to help confirm concussion on the sideline, with potential for repeated assessments to be used to inform brain recovery and help guide decisions on return to play.