Posts tagged TBI
Articles and news from the latest research reports.
Baylor Research Institute Studies Traumatic Brain Injury Rehab Outcomes
For patients recovering from a traumatic brain injury (TBI), the rehabilitation process – compensating for changes in functioning, adaptation and even community reintegration – can be challenging. Unfortunately, not all rehab programs are created equal, and with the differences comes a difference in outcomes, according to a first-of-its-kind study published in The Journal of Head Trauma Rehabilitation.
Collectively authored by Baylor researchers, the outcomes study (titled “Comparative Effectiveness of Traumatic Brain Injury Rehabilitation: Differential Outcomes Across TBI Model Systems Centers”), set out to identify if outcomes at the post-discharge and one-year points varied across 21 Traumatic Brain Injury Model System (TBIMS) centers. The Baylor Institute of Rehabilitation (BIR) was one of the centers studied.
At the study’s onset, researchers had an idea of what they might find, but their findings revealed the opposite.
“We expected that, after accounting for differences in patient characteristics and severity of injury, patient outcomes would be similar across centers,” said Marie Dahdah, PhD, investigator at the Baylor Institute for Rehabilitation. “They were not. There were significant variations, with a 25 percent to 45 percent difference between the best performing site and the site with the lowest outcomes at discharge.”
While differences in outcomes have long been reported in designated trauma centers (and for other specialties, including general and cardiac surgery, transplant and oncology), the study was the first piece of research to demonstrate that those differences exist in the rehabilitation context.
The team acknowledged that those variances could be attributed to institutional structures, resources and clinical practices, but that more research is needed to determine which of these factors is associated with optimum outcomes.
“In order to identify factors that contribute to variation in patient outcomes across centers, we are undertaking research that identifies different patient, injury and process-level factors associated with functional outcomes of patients,” Dr. Dahdah said. “Those factors can then be targeted to improve patient outcomes.”
In other phases of this study, these Baylor investigators (along with teams from three other TBIMS sites) are reviewing the quantity and frequency of various types of rehabilitation therapies used in inpatient TBI settings. The team will also study evidenced-based best practices for speech, occupational, physical and recreational therapy interventions, as well as neurocognitive and psychosocial interventions.
The results from those subsequent studies could help identify gaps between current practices and evidence-based best practices, with the aim of helping inform rehabilitation programs across the country and ensuring that all centers have the same opportunities for quality outcomes.
“I think I speak for my entire research team when I say that our involvement in this type of research comes out of our collective desire to improve quality of rehabilitation care, thereby enhancing outcomes following TBI,” Dr. Dahdah said. “My hope is that by synthesizing and disseminating what is known about effective evidence-based rehabilitation interventions, BIR as part of the North Texas TBIMS will be able to encourage changes necessary to help institutions, clinicians and therapists to provide the best quality TBI rehabilitation care to their patients.”
Of course, with the Baylor Institute of Rehabilitation being among the 21-center pool, one very obvious question remains. How did BIR’s outcomes compare with the other 20 centers?
“I cannot count for you the number of times I have been asked that question,” Dr. Dahdah said. “To ensure the integrity of our study, even our research team is blind to the identity of the centers.”
But despite how well even the strongest inpatient rehab centers perform in a comparative context, there is always room for improvement, especially with best-practice regimens.
“Our research has already started discussions within the TBI Model Systems research community,” Dr. Dahdah said. “We believe more research needs to be done to identify the key determinants of patient outcomes so that benchmarks for quality rehabilitation care can be derived for patients and their families.”
(Source: media.baylorhealth.com)
Concussion secrets unveiled in mice and people
There is more than meets the eye following even a mild traumatic brain injury. While the brain may appear to be intact, new findings reported in Nature suggest that the brain’s protective coverings may feel the brunt of the impact.
Using a newly developed mouse trauma model, senior author Dorian McGavern, Ph.D., scientist at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, watched specific cells mount an immune response to the injury and try to prevent more widespread damage. Notably, additional findings suggest a similar immune response may occur in patients with mild head injury.
In this study, researchers also discovered that certain molecules, when applied directly to the mouse skull, can bypass the brain’s protective barriers and enter the brain. The findings suggested that, in the mouse trauma model, one of those molecules may reduce effects of brain injury.
Although concussions are common, not much is known about the effects of this type of damage. As part of this study, Lawrence Latour, Ph.D., a scientist from NINDS and the Center for Neuroscience and Regenerative Medicine, examined individuals who had recently suffered a concussion but whose initial scans did not reveal any physical damage to brain tissue. After administering a commonly used dye during MRI scans, Latour and his colleagues saw it leaking into the meninges, the outer covers of the brain, in 49 percent of 142 patients with concussion.
To determine what happens following this mild type of injury, researchers in Dr. McGavern’s lab developed a new model of brain trauma in mice.
"In our mice, there was leakage from blood vessels right underneath the skull bone at the site of injury, similar to the type of effect we saw in almost half of our patients who had mild traumatic brain injury. We are using this mouse model to look at meningeal trauma and how that spreads more deeply into the brain over time," said Dr. McGavern.
Dr. McGavern and his colleagues also discovered that the intact skull bone was porous enough to allow small molecules to get through to the brain. They showed that smaller molecules reached the brain faster and to a greater extent than larger ones. “It was surprising to discover that all these protective barriers the brain has may not be concrete. You can get something to pass through them,” said Dr. McGavern.
The researchers found that applying glutathione (an antioxidant that is normally found in our cells) directly on the skull surface after brain injury reduced the amount of cell death by 67 percent. When the researchers applied glutathione three hours after injury, cell death was reduced by 51 percent. “This idea that we have a time window within which to work, potentially up to three hours, is exciting and may be clinically important,” said Dr. McGavern.
Glutathione works by decreasing levels of reactive oxygen species (ROS) molecules that damage cells. In this study, high levels of ROS were observed at the trauma site right after the physical brain injury occurred. The massive flood of ROS set up a sequence of events that led to cell death in the brain, but glutathione was able to prevent many of those effects.
In addition, using a powerful microscopic technique, the researchers filmed what was happening just beneath the skull surface within five minutes of injury. They captured never-before-seen details of how the brain responds to traumatic injury and how it mobilizes to defend itself.
Initially, they saw cell death in the meninges and at the glial limitans (a very thin barrier at the surface of the brain that is the last line of defense against dangerous molecules). Cell death in the underlying brain tissue did not occur until 9-12 hours after injury. “You have death in the lining first and then this penetrates into the brain tissue later. The goal of therapies for brain injury is to protect the brain tissue,” said Dr. McGavern.
Almost immediately after head injury, the glial limitans can break down and develop holes, providing a way for potentially harmful molecules to get into the brain. The researchers observed microglia (immune cells that act as first responders in the brain against dangerous substances) quickly moving up to the brain surface, plugging up the holes.
Findings from Dr. McGavern’s lab indicate that microglia do this in two ways. According to Dr. McGavern, “If the astrocytes, the cells that make up the glial limitans, are still there, microglia will come up to ‘caulk’ the barrier and plug up gaps between individual astrocytes. If an astrocyte dies, that results in a larger space in the glial limitans, so the microglia will change shape, expand into a fat jellyfish-like structure and try to plug up that hole. These reactions, which have never been seen before in living brains, help secure the barrier and prevent toxic substances from getting into the brain.”
Studies have suggested that immune responses in the brain can often lead to severe damage. Remarkably, the findings in this study show that the inflammatory response in a mild traumatic brain injury model is actually beneficial during the first 9-12 hours after injury.
Mild traumatic brain injuries are a growing public health concern. According to a report from the Centers of Disease Control and Prevention, in 2009 at least 2.4 million people suffered a traumatic brain injury and 75 percent of those injuries were mild. This study provides insight into the damage that occurs following head trauma and identifies potential therapeutic targets, such as antioxidants, for reducing the damaging effects.
Brain Still Injured from Concussion After Symptoms Fade
After a mild concussion, special brain scans show evidence of brain abnormalities four months later, when symptoms from the concussion have mostly dissipated, according to research published in the November 20, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“These results suggest that there are potentially two different modes of recovery for concussion, with the memory, thinking and behavioral symptoms improving more quickly than the physiological injuries in the brain,” said study author Andrew R. Mayer, PhD, of the Mind Research Network and University of New Mexico School of Medicine in Albuquerque.
Mayer further suggests that healing from concussions may be similar to other body ailments such as recovering from a burn. “During recovery, reported symptoms like pain are greatly reduced before the body is finished healing, when the tissue scabs. These finding may have important implications about when it is truly safe to resume physical activities that could produce a second concussion, potentially further injuring an already vulnerable brain.”
Mayer noted that standard brain scans such as CT or MRI would not pick up on these subtle changes in the brain. “Unfortunately, this can lead to the common misperception that any persistent symptoms are psychological.”
The study compared 50 people who had suffered a mild concussion to 50 healthy people of similar age and education. All the participants had tests of their memory and thinking skills and other symptoms such as anxiety and depression two weeks after the concussion, as well as brain scans. Four months after the concussion, 26 of the patients and 26 controls repeated the tests and scans.
The study found that two weeks after the injury the people who had concussions had more self-reported problems with memory and thinking skills, physical problems such as headaches and dizziness, and emotional problems such as depression and anxiety than people who had not had concussions. By four months after the injury, the symptoms were significantly reduced by up to 27 percent.
The people who had concussions also had evidence of abnormalities in the gray matter in the frontal cortex area of both sides of the brain, based on the diffusion tensor imaging scans. The increase equated to about 10 percent compared to the healthy people in the study. These abnormalities were still apparent four months after the concussion. In contrast, there was no evidence of cellular loss on scans.
Mayer said possible explanations for the brain abnormalities could be cytotoxic edema, which results from changes in where fluids are located in and around brain cells, or reactive gliosis, which is the change in glial cells’ shape in response to damage to the central nervous system.
Blood Test Accurately Diagnoses Concussion and Predicts Long Term Cognitive Disability
A new blood biomarker correctly predicted which concussion victims went on to have white matter tract structural damage and persistent cognitive dysfunction following a mild traumatic brain injury (mTBI). Researchers in the Perelman School of Medicine at the University of Pennsylvania, in conjunction with colleagues at Baylor College of Medicine, found that the blood levels of a protein called calpain-cleaved αII-spectrin N-terminal fragment (SNTF) were twice as high in a subset of patients following a traumatic injury. If validated in larger studies, this blood test could identify concussion patients at increased risk for persistent cognitive dysfunction or further brain damage and disability if returning to sports or military activities.
More than 1.5 million children and adults suffer concussions each year in the United States, and hundreds of thousands of military personal endure these mild traumatic brain injuries worldwide. Current tests are not capable of determining the extent of the injury or whether the injured person will be among the 15-30 percent who experience significant, persistent cognitive deficits, such as processing speed, working memory and the ability to switch or balance multiple thoughts.
"New tests that are fast, simple, and reliable are badly needed to predict who may experience long-term effects from concussions, and as new treatments are developed in the future, to identify who should be eligible for clinical trials or early interventions," said lead author Robert Siman, PhD, research professor of Neurosurgery at Penn. "Measuring the blood levels of SNTF on the day of a brain injury may help to identify the subset of concussed patients who are at risk of persistent disability."
In a study published yesterday in Frontiers in Neurology, Penn and Baylor researchers evaluated blood samples and diffusion tensor images from a subgroup of 38 participants in a larger study of mTBI with ages ranging from 15 to 25 years old. 17 had sustained a head injury caused by blunt trauma, acceleration or deceleration forces, 13 had an orthopaedic injury, and 8 were healthy, uninjured, demographically matched controls.
In taking neuropsychological and cognitive tests over the course of three months, results within the mTBI group varied considerably, with some patients performing as well as the healthy controls throughout, while others showed impairment initially that resolved by three months, and a third group with cognitive dysfunction persisting through three months. The nine patients who had abnormally high levels of SNTF (7 mTBI and 2 orthopaedic patients) also had significant white matter damage apparent in radiological imaging.
"The blood test identified SNTF in some of the orthopaedic injury patients as well, suggesting that these injuries could also lead to abnormalities in the brain, such as a concussion, that may have been overlooked with existing tests," said Douglas Smith, MD, director of the Penn Center for Brain Injury and Repair and professor of Neurosurgery. "SNTF as a marker is consistent with our earlier research showing that calcium is dumped into neurons following a traumatic brain injury, as SNTF is a marker for neurodegeneration driven by calcium overload."
The blood test given on the day of the mild traumatic brain injury showed 100 percent sensitivity to predict concussions leading to persisting cognitive problems, and 75 percent specificity to correctly rule out those without functionally harmful concussions. If validated in larger studies, a blood test measuring levels of SNTF could be helpful in diagnosing and predicting risk of long term consequences of concussion. The Penn and Baylor researchers hope to determine the robustness of these findings with a second larger study, and determine the best time after concussion to measure SNTF in the blood in order to predict persistent brain dysfunction. The team also wants to evaluate their blood test for identifying when repetitive concussions begin to cause brain damage and persistent disability.
(Source: uphs.upenn.edu)
Surgeons Find New Method to Reduce Risk of Blood Clots During Brain Traumas
Researchers from the University of Missouri School of Medicine have found that a new protocol that uses preventive blood-thinning medication in the treatment of patients with traumatic brain injuries reduces the risk of patients developing life-threatening blood clots without increasing the risk of bleeding inside the brain.
According to the Centers for Disease Control and Prevention, at least 1.7 million traumatic brain injuries occur each year. One of the most common complications associated with traumatic brain injuries is the risk of dangerous blood clots that can form in the circulatory system elsewhere in the body. For patients with traumatic injuries, the body forms blood clots which can break loose and travel to the lungs or other areas, causing dangerous complications.
"Our study found that treating traumatic brain-injured patients with an anticoagulant, or blood-thinning medication, is safe and decreases the risk of these dangerous clots," said N. Scott Litofsky, MD, chief of the MU School of Medicine’s Division of Neurological Surgery and director of neuro-oncology and radiosurgery at MU Health Care. "We found that patients treated with preventive blood thinners had a decreased risk of deep-vein blood clots and no increased risk of intracranial hemorrhaging."
In May 2009, Litofsky, along with study co-author Stephen Barnes, MD, acute care surgeon and chief of the MU Division of Acute Care Surgery, created a new protocol for treating head trauma patients in University Hospital’s Frank L. Mitchell Jr., M.D., Trauma Center using blood-thinning medications.
"One of the main challenges in treating patients with traumatic brain injuries is balancing the risk of intracranial bleeding with the risk of blood clots formed elsewhere in the body," Litofsky said.
In the study, the researchers compared the outcomes of 107 patients with traumatic brain injuries who were treated before the new protocol was put into place with the outcomes of 129 patients who were treated with the blood-thinning medication. Among the patients who did not receive blood thinners, six experienced deep-venous clotting, compared with zero instances of the condition in patients who received the medication. Among the patients who did not receive blood thinners, three patients experienced increased bleeding in the brain, compared with one patient who received the medication.
"Based on our results, we will continue to follow the new protocol in our trauma center, and we believe that other trauma centers would benefit from adopting a similar protocol in their practice," Litofsky said. "If we look at this issue across the country, we should hopefully see this complication occurring less often in brain-injured patients."
The study, “Safety and Efficacy of Early Thromboembolism Chemoprophylaxis After Intracranial Hemorrhage from Traumatic Brain Injury,” was published online Sept. 20 by the Journal of Neurosurgery, the journal for the American Association of Neurological Surgeons.
(Source: medicine.missouri.edu)
New Hope for Victims of Traumatic Brain Injury
Researchers from TAU demonstrate hyperbaric oxygen therapy significantly revives brain functions and life quality
Every year, nearly two million people in the United States suffer traumatic brain injury (TBI), the leading cause of brain damage and permanent disabilities that include motor dysfunction, psychological disorders, and memory loss. Current rehabilitation programs help patients but often achieve limited success.
Now Dr. Shai Efrati and Prof. Eshel Ben-Jacob of Tel Aviv University’s Sagol School of Neuroscience have proven that it is possible to repair brains and improve the quality of life for TBI victims, even years after the occurrence of the injury.
In an article published in PLoS ONE, Dr. Efrati, Prof. Ben Jacob, and their collaborators present evidence that hyperbaric oxygen therapy (HBOT) should repair chronically impaired brain functions and significantly improve the quality of life of mild TBI patients. The new findings challenge the often-dismissive stand of the US Food and Drug Administration, Centers for Disease Control and Prevention, and the medical community at large, and offer new hope where there was none.
The research trial
The trial included 56 participants who had suffered mild traumatic brain injury one to five years earlier and were still bothered by headaches, difficulty concentrating, irritability, and other cognitive impairments. The patients’ symptoms were no longer improving prior to the trial.
The participants were randomly divided into two groups. One received two months of HBOT treatment while the other, the control group, was not treated at all. The latter group then received two months of treatment following the first control period. The treatments, administered at the Institute of Hyperbaric Medicine at Assaf Harofeh Medical Center, headed by Dr. Efrati, consisted of 40 one-hour sessions, administered five times a week over two months, in a high pressure chamber, breathing 100% oxygen and experiencing a pressure of 1.5 atmospheres, the pressure experienced when diving under water to a depth of 5 meters. The patients’ brain functions and quality of life were then assessed by computerized evaluations and compared with single photon emission computed tomography (SPECT) scans.
Persuasive confirmation
In both groups, the hyperbaric oxygen therapy sessions led to significant improvements in tests of cognitive function and quality of life. No significant improvements occurred by the end of the period of non-treatment in the control group. Analysis of brain imaging showed significantly increased neuronal activity after a two-month period of HBOT treatment compared to the control periods of non-treatment.
"What makes the results even more persuasive is the remarkable agreement between the cognitive function restoration and the changes in brain functionality as detected by the SPECT scans," explained Prof. Ben-Jacob. "The results demonstrate that neuroplasticity can be activated for months and years after acute brain injury."
"But most important, patients experienced improvements such as memory restoration and renewed use of language," Dr. Efrati said. "These changes can make a world of difference in daily life, helping patients regain their independence, go to work, and integrate back into society."
The regeneration process following brain injury involves complex processes, such as building new blood vessels and rebuilding connections between neurons, and requires much energy.
"This is where HBOT treatment can help," said Dr. Efrati. "The elevated oxygen levels during treatment supply the necessary energy for facilitating the healing process."
The findings offer new hope for millions of traumatic brain injury patients, including thousands of veterans wounded in action in Iraq and Afghanistan. The researchers call for additional larger scale, multi-center clinical studies to further confirm the findings and determine the most effective and personalized treatment protocols. But since the hyperbaric oxygen therapy is the only treatment proven to heal TBI patients, the researchers say that the medical community and the US Armed Forces should permit the victims of TBI benefit from the new hope right now, rather than waiting until additional studies are completed.
(Source: aftau.org)
Study Examines Amyloid Deposition in Patients with Traumatic Brain Injury
Patients with traumatic brain injury (TBI) had increased deposits of β-Amyloid (Αβ) plaques, a hallmark of Alzheimer Disease (AD), in some areas of their brains in a study by Young T. Hong, Ph.D., of the University of Cambridge, England, and colleagues.
There may be epidemiological or pathophysiological (changes because of injury) links between TBI and AD, and Αβ plaques are found in as many as 30 percent of patients who die in the acute phase after a TBI. The plaques appear within hours of the injury and can occur in patients of all ages, according to the study background.
Researchers used imaging and brain tissue acquired during autopsies to examine Αβ deposition in patients with TBI. Researchers performed positron emission tomography (PET) imaging using carbon 11-labeled Pittsburgh Compound B ([11C]PIB), a marker of brain amyloid deposition, in 15 participants with a TBI and 11 healthy patients. Autopsy-acquired brain tissue was obtained from 16 people who had a TBI, as well as seven patients with a nonneurological cause of death.
The study’s findings indicate that patients with TBI showed increases in [11C]PIB binding, which may be a marker of Αβ plaque in some areas of the brain.
“The use of ([11C]PIB PET for amyloid imaging following TBI provides us with the potential for understanding the pathophysiology of TBI, for characterizing the mechanistic drivers of disease progression or suboptimal recovery in the subacute phase of TBI, for identifying patients at high risk of accelerated AD, and for evaluating the potential of antiamyloid therapies,” the authors conclude.
(Source: media.jamanetwork.com)
Stem cells linked to cognitive gain after brain injury in preclinical study
A stem cell therapy previously shown to reduce inflammation in the critical time window after traumatic brain injury also promotes lasting cognitive improvement, according to preclinical research led by Charles Cox, M.D., at The University of Texas Health Science Center at Houston (UTHealth) Medical School.
The research was published in today’s issue of STEM CELLS Translational Medicine.
Cellular damage in the brain after traumatic injury can cause severe, ongoing neurological impairment and inflammation. Few pharmaceutical options exist to treat the problem. About half of patients with severe head injuries need surgery to remove or repair ruptured blood vessels or bruised brain tissue.
A stem cell treatment known as multipotent adult progenitor cell (MAPC) therapy has been found to reduce inflammation in mice immediately after traumatic brain injury, but no one had been able to gauge its usefulness over time.
The research team led by Cox, the Children’s Fund, Inc. Distinguished Professor of Pediatric Surgery at the UTHealth Medical School, injected two groups of brain-injured mice with MAPCs two hours after the mice were injured and again 24 hours later. One group received a dose of 2 million cells per kilogram and the other a dose five times stronger.
After four months, the mice receiving the stronger dose not only continued to have less inflammation—they also made significant gains in cognitive function. A laboratory examination of the rodents’ brains confirmed that those receiving the higher dose of MAPCs had better brain function than those receiving the lower dose.
“Based on our data, we saw improved spatial learning, improved motor deficits and fewer active antibodies in the mice that were given the stronger concentration of MAPCs,” Cox said.
The study indicates that intravenous injection of MAPCs may in the future become a viable treatment for people with traumatic brain injury, he said.
(Source: uthouston.edu)
Traumatic Brain Injury Research Advances with $18.8M NIH Award
The National Institutes of Health is awarding $18.8 million over five years to support worldwide research on concussion and traumatic brain injury.
The NIH award, part of one of the largest international research collaborations ever coordinated by funding agencies, will be administered through UC San Francisco.
The award supports a team of U.S. researchers at more than 20 institutions throughout the country who are participating in the International Traumatic Brain Injury (InTBIR) Initiative, a collaborative effort of the European Commission, the Canadian Institutes of Health Research (CIHR), the National Institutes of Health (NIH) and the U.S. Department of Defense (DOD).
Although the potential long-term harms due to concussions and blows to the head have gained more attention recently – due in part to media coverage of the experiences of athletes and of soldiers returning from the Middle East – traumatic brain injuries, or TBI, that results from automobile crashes or other common accidents impacts many more people.
Many of those who are affected by TBI are never diagnosed, according to UCSF neurosurgeon Geoffrey Manley, MD, PhD, a principal investigator for the grant who will serve as the U.S. research team’s primary liaison to the NIH, and the chief of neurosurgery at the UCSF-affiliated San Francisco General Hospital, a Level-1 trauma center. SFGH was the first medical center in the nation to achieve certification from the Joint Commission for the treatment of TBI.
The U.S. Centers for Disease Control and Prevention estimates that 2 percent of the U.S. population now lives with TBI-caused disabilities, at an annual cost of about $77 billion.
“Each year in the United States, at least 1.7 million people seek medical attention for TBI,” Manley said. “It is a contributing factor in a third of all injury-related deaths.”
In the work funded by the NIH grant – which also is supported by contributions from the private sector and from the nonprofit One Mind for Research – the researchers aim to refine and improve diagnosis and treatment of TBI, which often has insidious health effects, but which frequently is undiagnosed, misdiagnosed, inadequately understood and undertreated, according to Manley.
New Approach to Lead to Patient-Specific Treatments
“After three decades of failed clinical trials, a new approach is needed,” Manley said. “We expect that our approach will permit researchers to better characterize and stratify patients, will allow meaningful comparisons of treatments and outcomes, and will improve the next generation of clinical trials. The work will advance our understanding of TBI and lead to more effective, patient-specific treatments.”
Since 2009, Manley and Pratik Mukherjee, MD, PhD, a professor of radiology and biomedical imaging at UCSF, have helped lay the groundwork for the continuing TBI research by leading the NIH-funded TRACK-TBI project, through which they and their research collaborators have demonstrated the value of gathering common data across research sites, including a standardized approach to imaging, clinical data, bio-specimens, and tracking outcomes.
Already, TRACK-TBI researchers have made progress toward more useful classification and prognosis of TBI.
Earlier this year, they reported that cases of concussion, or TBI that are classified as “mild” by standard criteria but that show abnormalities on early magnetic resonance imaging (MRI) scans, are much more likely to have worse outcomes three months after the scan in comparison to cases in which scans reveal no abnormalities. Furthermore, the researchers found that elevated blood levels of a protein released during brain injury was associated with the likelihood of an abnormal CT scan.
The new NIH award funds a continuation and expansion of TRACK-TBI. Among the goals is the creation of a widely accessible, comprehensive “TBI information commons” to integrate clinical, imaging, proteomic, genomic and outcome biomarkers from subjects across the age and injury spectra. Another goal is to establish the value of biomarkers that will improve classification of TBI and better optimize selection and assignment of patients for clinical trials.
The researchers also aim to evaluate measures to assess patient outcomes across all phases of recovery and at all levels of TBI severity, to determine which tests, treatments, and services are effective and appropriate – depending on the nature of TBI in particular patients.
In addition to Manley and Mukherjee, principal investigators for the newly funded project include Claudia Robertson, MD, Baylor College of Medicine; Joseph Giacino, PhD, Harvard University; Ramon Diaz-Arrastia, MD, PhD, Uniformed Services University of the Health Sciences; David Okonkwo, MD, PhD, University of Pittsburgh; and Nancy Temkin, PhD, University of Washington. Each of these leading experts has worked in the TBI field for two decades or more.
“The principal investigators bring expertise in neurosurgery, neurology, neuroradiology, critical care medicine, rehabilitation medicine, neuropsychology and biostatistics, all of which are essential and do not reside in any single individual,” Manley said.
International Funding and Collaboration
TRACK-TBI clinical enrollment sites throughout the United States will enroll 3,000 patients across the spectrum of mild to severe brain injuries. Clinical, imaging, proteomic, genomic and clinical outcome databases will be linked into a shared platform that will promote a model for collaboration among scientists within InTBIR and elsewhere.
In addition to the U.S. award, the European Commission, the executive body of the European Union, has awarded €35.2 million to fund the Collaborative European NeuroTrauma Effectiveness-TBI (CENTER-TBI) consortium, also part of the InTBIR. This project will collect data in over 5,000 patients across Europe, where 38 scientific institutes and more than 60 hospitals will participate.
In Canada, CIHR and its national partners also have made a multimillion dollar investment in TBI research, the details of which will be formally announced in the near future.
The InTBIR Scientific Advisory Committee met in Vancouver, British Columbia, on Oct. 17-18, and awardees from all three jurisdictions (EU, USA, Canada) now are aligning efforts to share resources and collaborate on strategies for achieving the InTBIR goals.
Brain scans show unusual activity in retired American football players
A new study has discovered profound abnormalities in brain activity in a group of retired American football players
Although the former players in the study were not diagnosed with any neurological condition, brain imaging tests revealed unusual activity that correlated with how many times they had left the field with a head injury during their careers.
Previous research has found that former American football players experience higher rates of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. The new findings, published in Scientific Reports, suggest that players also face a risk of subtle neurological deficits that don’t show up on normal clinical tests.
Hidden problems
The study involved 13 former National Football League (NFL) professionals who believed they were suffering from neurological problems affecting their everyday lives as a consequence of their careers.
The former players and 60 healthy volunteers were given a test that involved rearranging coloured balls in a series of tubes in as few steps as possible. Their brain activity was measured using functional magnetic resonance imaging (fMRI) while they did the test.
The NFL group performed worse on the test than the healthy volunteers, but the difference was modest. More strikingly, the scans showed unusual patterns of brain activity in the frontal lobe. The difference between the two groups was so marked that a computer programme learned to distinguish NFL alumni and controls at close to 90 per cent accuracy based just on their frontal lobe activation patterns.
“The NFL alumni showed some of the most pronounced abnormalities in brain activity that I have ever seen, and I have processed a lot of patient data sets in the past,” said Dr Adam Hampshire, lead author of the study, from the Department of Medicine at Imperial College London.
The frontal lobe is responsible for executive functions: higher-order brain activity that regulates other cognitive processes. The researchers think the differences seen in this study reflect deficits in executive function that might affect the person’s ability to plan and organise their everyday lives.
“The critical fact is that the level of brain abnormality correlates strongly with the measure of head impacts of great enough severity to warrant being taken out of play. This means that it is highly likely that damage caused by blows to the head accumulate towards an executive impairment in later life.”
Early detection
Dr Hampshire and his colleagues at the University of Western Ontario, Canada suggest that fMRI could be used to reveal potential neurological problems in American football players that aren’t picked up by standard clinical tests. Brain imaging results could be useful to retired players who are negotiating compensation for neurological problems that may be related to their careers. Players could also be scanned each season to detect problems early.
The findings also highlight the inadequacy of standard cognitive tests for detecting certain types of behavioural deficit.
“Researchers have put a lot of time into developing tests to pick up on executive dysfunction, but none of them work at all well. It’s not unusual for an individual who has had a blow to the head to perform relatively well on a neuropsychological testing battery, and then go on to struggle in everyday life.
“The results tell us something very interesting about the human brain, which is that after damage, it can work harder and bring extra areas on line in order to cope with cognitive tasks. It is likely that in more complicated real world scenarios, this plasticity is insufficient and consequently, the executive impairment is no longer masked. In this respect, the results are also of relevance to other patients who suffer from multiple head injuries.
“Of course, this is a relatively preliminary study. We really need to test more players and to track players across seasons using brain imaging.”