Understanding Traumatic Brain Injury

09 March 2018
Posted by Shuhan He.

Traumatic Brain Injury, also known as TBI, is often similar to other injuries with the main difference that TBI has severe lifelong consequences for the individual and it can be triggered by any unfortunate event such as a car accident, a sports accident or during any other situation where a strong blow to the head is delivered...

The most important organ in the human body, the brain, is contained inside the skull and it is also suspended within a substance called cerebrospinal fluid, which acts as a protector against impacts. When an injury occurs, the blow can either penetrate the cranium or it causes the brain to crash against the inside of the skull, damaging brain cells and tearing arteries and veins that provide them with blood supply.

People with a TBI can experience symptoms such as headaches, nausea and vomiting. But after those initial manifestations, a string of events will begin to unfold leading to further damage; this succeeding stage is usually called the secondary injury. Cells that have been injured by the initial impact begin to release toxic substances that can harm other surrounding cells. This is why it is important to seek medical assistance as soon as possible, since although this collateral damage may take a few weeks to develop, it can occur within minutes of an injury being sustained, if an accident is sufficiently severe.

Part of the problem is that the brain is not good at repairing itself, so the consequences of traumatic brain injury are often long lasting or even permanent. Some of the long-term issues related to this injury include psychiatric disorders, such as anxiety and depression, physical problems, and other, more subtle cognitive changes.

Current treatment issues

Because TBI is so common and has the potential to inflict such a great impact on the quality of life of a head injury victim, various experimental drugs have been developed over the years in an to attempt to manage the condition. These treatments were born out of efforts to control both the original injury as well as the secondary injury. Nevertheless, despite some encouraging results from preclinical through to Phase II trials, none of these therapies have come to clinical fruition yet.

In fact, over thirty controlled trials have been conducted for potential TBI treatments, and despite a few promising outcomes they have all failed to find a successful treatment. Some of the recent attempts that have failed include brain and body cooling (hypothermia), progesterone, dexanabinol, and citicoline.

One of the biggest challenges in developing successful treatments for conditions like TBI is that animals are very different from the human patients they are intended to model. Human patients present with a wide spectrum of injuries, so each case is unique. In addition, human patients often present with comorbidities, which means there are also other medical conditions besides their brain trauma. These comorbidities can involve wounds on different regions of the body, oxygen deprivation, and additional chronic conditions like diabetes. Also, drug doses designed for animals might not be right for a human, and the timing of medication might also need to be adjusted for human use. All of these factors are a far cry from a well-controlled, highly stereotyped animal experiment.

Another possible reason for these failures is that scientists may not be making the right measurements for assessing recovery. Clinical trials for TBI normally limit themselves to assessing survival and death rates, and there is also the Glasgow Coma Scale (GCS), which measures changes in the level of consciousness. These instruments can tell doctors if the patients survived or not, but precious information such as whether tasks of day to day living, general functioning and well-being have changed in the weeks or months following the initial insult are not captured.

Clinical examinations designed to assess new TBI treatments should be incorporating these measurements and they need to be adequately sensitive to detect subtle and small differences between patients.

Innovative evaluation systems as a potential solution

Thankfully, new methods and tools like these are now being developed, meaning doctors and other healthcare professionals can better evaluate their patients’ day-to-day functioning and quality of life after TBI. Most of these tests are also using up-to-date mobile technologies and computer-based testing.

One of these tools is the NIH Toolbox, a collection of testing tools designed by the National Institutes of Health (NIH) to evaluate patients’ psychological health, reasoning abilities, motor function, and other relevant information. These assessments include both objective measures and self-reported measures.

Another recent NIH creation is the Patient-Reported Outcomes Measurement Information System (PROMIS), a system of self-reported measures that can cover different health areas such as mental health, physical health, and social well-being. This assessment tool has been developed to test patients on a wide range of diseases, and it has been designed by taking individuals from the general population.

An aspect of PROMIS is the use of Computerized Adaptive Testing (CAT). The questions directed in the evaluation will be automatically adjusted or adapted for each individual based on their answers to previous questions. The PROMIS adaptive system creates a profile for each patient that weighs them across nine health domains.

NIH has also introduced the Neuro-Quality of Life assessment (Neuro-QoL), which is similar to the PROMIS system but specific for neurological conditions. A similar system known as the TBI-QoL is currently under development. The TBI-QoL is an improvement of the Neuro-QoL because it has been specifically calibrated employing TBI patients, rather than random individuals from the general population.

The Experience Sampling Method (ESM) is also a new method that might be useful for the assessment of behavioral and cognitive issues that TBI patients often have. ESM requires patients to send specific information about their symptoms while in their everyday environments. As an example, a patient suffering from depression could report moment to moment how they are feeling during their normal daily activities. Recent studies have found that a mobile application integrated with ESM is useful for the long-term monitoring of TBI patients. Researchers have also been developing new methods for delivering these tests to the patients. Some of these include auto-enrollment, geofencing, and the integration of patient analysis into hospital electronic systems.

If we take a step back from the bedside and go to the laboratory, better mazes for mice are part of a solution I am personally tackling. Researchers use mazes to test an animal’s mental functions, such as memory and attention. During much of the last 100 years, mazes forced rodents to solve complex puzzles to explore their cognition. Today’s mazes have become much simpler, mostly for ease of use, but with the trade-off that we are able to learn less and cannot probe the subtleties of cognition or issues like inability to walk or remember basic traits. However, because researchers increasingly want to look at lots of animals in each experiment and to collect as many behavioral traits as possible, increasing complexity and automation has become a necessity in lock-step with each other. Newer mazes that are complex, driven by artificial intelligence, and run themselves hold the key to better understanding the subtle effects of a drug or disease.

By integrating these new assessments and tests and new findings from the laboratory, clinical trials should be more successful at finding the effects new treatments may have on the patients. Much the same as how the microscope enabled researchers to have a deeper perception of the world, having better quality of life tools with smartphone applications can change the way we comprehend patients with TBI. As a result, these tests may expand the number of positive results in clinical trials, propelling the advance of the much required new medications for the huge number of people suffering from TBI.


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