Posts tagged TBI
Articles and news from the latest research reports.
Second impact syndrome: A devastating injury to the young brain
Physicians at Indiana University School of Medicine and the Northwest Radiology Network (Indianapolis, Indiana) report the case of a 17-year-old high school football player with second impact syndrome (SIS). A rare and devastating traumatic brain injury, SIS occurs when a person, most often a teenager, sustains a second head injury before recovery from an earlier head injury is complete. To the best of the authors’ knowledge, this is the first reported case in which imaging studies were performed after both injuries, adding new knowledge of the event. Findings in this case are reported and discussed in “Second impact syndrome in football: new imaging and insights into a rare and devastating condition. Case report,” by Elizabeth Weinstein, M.D., and colleagues, published today online, ahead of print, in the Journal of Neurosurgery: Pediatrics.
MRIs Reveal Signs of Brain Injuries Not Seen in CT Scans
Hospital MRIs may be better at predicting long-term outcomes for people with mild traumatic brain injuries than CT scans, the standard technique for evaluating such injuries in the emergency room, according to a clinical trial led by researchers at UCSF and the San Francisco General Hospital and Trauma Center (SFGH).
Published this month in the journal Annals of Neurology, the study led by UCSF neuroradiologist Esther Yuh, MD, PhD, followed 135 people treated for mild traumatic brain injuries over the past two years at one of three urban hospitals with level-one trauma centers: SFGH, the University of Pittsburgh Medical Center and University Medical Center Brackenridge in Austin, Texas. The study was called the NIH-funded TRACK-TBI (Transforming Research and Clinical Knowledge in Traumatic Brain Injury).
All 135 patients with mild traumatic brain injuries received CT scans when they were first admitted, and all were given MRIs about a week later. Most of them (99) had no detectable signs of injury on a CT scan, but more than a quarter (27/99) who had a “normal” CT scans also had detectable spots on their MRI scans called “focal lesions,” which are signs of microscopic bleeding in the brain.
Spotting these focal lesions helped the doctors predict whether the patients were likely to suffer persistent neurological problems. About 15 percent of people who have mild traumatic brain injuries do suffer long-term neurological consequences, but doctors currently have no definitive way of predicting whether any one patient will or not.
“This work raises questions of how we’re currently managing patients via CT scan,” said the study’s senior author Geoff Manley, MD, PhD, the chief of neurosurgery at SFGH and vice-chair of the Department of Neurological Surgery at UCSF. “Having a normal CT scan doesn’t, in fact, say you’re normal,” he added.
Better Precision Tools Needed for Head Injuries
At least 1.7 million Americans seek medical attention every year for acute head injuries, and three-quarters of them have mild traumatic brain injuries – which generally do not involve skull fractures, comas or severe bleeding in the brain but have a variety of more mild symptoms, such as temporary loss of consciousness, vomiting or amnesia.
The U.S. Centers for Disease Control and Prevention estimates that far more mild traumatic brain injuries may occur each year in the United States but the true number is unknown because only injuries severe enough to bring someone to an emergency room are counted.
Most of those who do show up at emergency rooms are treated and released without being admitted to the hospital. In general, most people with mild traumatic brain injuries recover fully, but about one in six go on to develop persistent, sometimes permanent, disability.
The problem, Manley said, is that there is no way to tell which patients are going to have the poor long-term outcomes. Some socioeconomic indicators can help predict prolonged disability, but until now there were no proven imaging features, or blood tests for predicting how well or how fast a patient will recover. Nor is there a consensus on how to treat mild traumatic brain injuries.
“The treatment’s all over the place – if you’re getting treatment at all,” Manley said.
The new work is an important step toward defining a more quantitative way of assessing patients with mild traumatic brain injuries and developing more precision medical tools to detect, monitor and treat them, he added.
If doctors knew which patients were at risk of greater disabilities, they could be followed more closely. Being able to identify patients at risk of long-term consequences would also speed the development of new therapeutics because it would allow doctors to identify patients who would benefit the most from treatment and improve their ability to test potential new drugs in clinical trials.
Mammalian brain knows where it’s at
A new study in the journal Neuron suggests that the brain uses a different region than neuroscientists had thought to associate objects and locations in the space around an individual. Knowing where this fundamental process occurs could help treat disease and brain injury as well as inform basic understanding of how the brain supports memory and guides behavior.
“Understanding how and where context is represented in the brain is important,” said study senior author Rebecca Burwell, professor of psychology and neuroscience at Brown University. “Context, or the place in which events occur, is the hallmark of episodic memory, but context is more than a place or a location. This room, for example, has a window, furniture, and other objects. You walk into a room and all that information helps you remember what happened there.”
Pinpointing where the brain puts together objects and places to form a context could also matter for treating traumatic brain injuries or neuropsychiatric diseases, such as schizophrenia and depression, that involve that part of the brain, said Burwell, who is also affiliated with the Brown Institute for Brain Science.
“We know that contextual representations are disrupted in mental disorders, particularly schizophrenia and depression,” Burwell said. “Individuals with these disorders have trouble using context to plan actions or choose appropriate behaviors.”
Researchers Find Evidence That Brain Compensates After Traumatic Injury
Researchers at Albert Einstein College of Medicine of Yeshiva University and Montefiore Medical Center have found that a special magnetic resonance imaging (MRI) technique may be able to predict which patients who have experienced concussions will improve. The results, which were presented at the annual meeting of the Radiological Society of North America (RSNA), suggest that, in some patients, the brain may change to compensate for the damage caused by the injury.
“This finding could lead to strategies for preventing and repairing the damage that accompanies traumatic brain injury,” said Michael Lipton, M.D., Ph.D., who led the study and is associate director of the Gruss Magnetic Resonance Research Center at Einstein and medical director of MRI services at Montefiore, the University Hospital and academic medical center for Einstein.
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“In a traumatic brain injury, it’s not one specific area that is affected but multiple areas of the brain which are interconnected by axons,” said Dr. Lipton, who is also associate professor of radiology, of psychiatry and behavioral sciences, and in the Dominick P. Purpura Department of Neuroscience at Einstein. “Abnormally low FA within white matter has been correlated with cognitive impairment in concussion patients. We believe that high FA is evidence not of axonal injury, but of brain changes that are occurring in response to the trauma.”
MRI shows brain disruption in patients with post-concussion syndrome
MRI shows changes in the brains of people with post-concussion syndrome (PCS), according to a new study published online in the journal Radiology. Researchers hope the results point the way to improved detection and treatment for the disorder.
PCS affects approximately 20 percent to 30 percent of people who suffer mild traumatic brain injury (MTBI)—defined by the World Health Organization as a traumatic event causing brief loss of consciousness and/or transient memory dysfunction or disorientation. Symptoms of PCS include headache, poor concentration and memory difficulty.
Conventional neuroimaging cannot distinguish which MTBI patients will develop PCS.
"Conventional imaging with CT or MRI is pretty much normal in MTBI patients, even though some go on to develop symptoms, including severe cognitive problems," said Yulin Ge, M.D., associate professor, Department of Radiology at the NYU School of Medicine in New York City. "We want to try to better understand why and how these symptoms arise."
Dr. Ge’s study used MRI to look at the brain during its resting state, or the state when it is not engaged in a specific task, such as when the mind wanders or while daydreaming. The resting state is thought to involve connections among a number of regions, with the default mode network (DMN) playing a particularly important role.
"Baseline DMN is very important for information processing and maintenance," Dr. Ge said.
Alterations in DMN have been found in several psychiatric disorders, including Alzheimer’s disease, autism and schizophrenia, but little is known about DMN connectivity changes in MTBI.
For the new study, Dr. Ge and colleagues used resting-state functional MRI to compare 23 MTBI patients who had post-traumatic symptoms within two months of the injury and 18 age-matched healthy controls. Resting state MRI detects distinct changes in baseline oxygen level fluctuations associated with brain functional networks between patients with MTBI and control patients.
The MRI results showed that communication and information integration in the brain were disrupted among key DMN structures after mild head injury, and that the brain tapped into different neural resources to compensate for the impaired function.
"We found decreased functional connectivity in the posterior network of the brain and increased connectivity in the anterior component, probably due to functional compensation in patients with PCS," Dr. Ge said. "The reduced posterior connectivity correlated positively with neurocognitive dysfunction."
Dr. Ge and the other researchers hope to recruit additional MTBI patients for further studies with an eye toward developing a biomarker to monitor disease progression and recovery as well as treatment effects.
"We want to do studies to look at the changes in the network over time and correlate these functional changes with structural changes in the brain," he said. "This could give us hints on treatments to bring back cognitive function."
(Source: medicalxpress.com)
Virtual Reality Could Spot Real-World Impairments
A virtual reality test being developed at UTSC might do a better job than pencil-and-paper tests of predicting whether a cognitive impairment will have real-world consequences.
The test developed by Konstantine Zakzanis, associate professor of psychology, and colleagues, uses a computer-game-like virtual world and asks volunteers to navigate their ways through tasks such as delivering packages or running errands around town.
“If we’re being asked to tell if people could do things like work, houseclean, and take care of their kids, we need to show that our tests predict performance in the real world,” says Zakzanis.
But standard tests don’t do that very well, he says. Although tests that ask people to do things like solve math problems, sort cards, remember names, or judge the relative positions of lines in visual two dimensional space, can detect cognitive impairments caused by circumscribed lesions following a stroke or head injury, they’re not very good at predicting who will be able to function in the real world and who won’t.
That’s a problem for cognitively impaired people who might be denied insurance benefits or workers compensation based on tests that are insensitive to demonstrating their impairment. It is akin to having a broken arm with no x-ray to prove it.
Hunting neuron killers in Alzheimer’s and TBI
Sanford-Burnham researchers discovered that the protein appoptosin prompts neurons to commit suicide in several neurological conditions—giving them a new therapeutic target for Alzheimer’s disease and traumatic brain injury.
Dying neurons lead to cognitive impairment and memory loss in patients with neurodegenerative disorders–conditions like Alzheimer’s disease and traumatic brain injury. To better diagnose and treat these neurological conditions, scientists first need to better understand the underlying causes of neuronal death.
Enter Huaxi Xu, Ph.D., professor in Sanford-Burnham’s Del E. Webb Neuroscience, Aging, and Stem Cell Research Center. He and his team have been studying the protein appoptosin and its role in neurodegenerative disorders for the past several years. Appoptosin levels in the brain skyrocket in conditions like Alzheimer’s and stroke, and especially following traumatic brain injury.
Appoptosin is known for its role in helping the body make heme, the molecule that carries iron in our blood (think “hemoglobin,” which makes blood red). But what does heme have to do with dying brain cells? As Xu and his group explain in a paper they published recently in the Journal of Neuroscience, excess heme leads to the overproduction of reactive oxygen species, which include cell-damaging free radicals and peroxides, and triggers apoptosis, the carefully regulated process of cellular suicide. This means that more appoptosin and more heme cause neurons to die.
Not only did Xu and his team unravel this whole appoptosin-heme-neurodegeneration mechanism, but when they inhibited appoptosin in laboratory cell cultures, they noticed that the cells didn’t die. This finding suggests that appoptosin might make an interesting new therapeutic target for neurodegenerative disorders.
What’s next? Xu and colleagues are now probing appoptosin’s function in mouse models. They’re also looking for new therapies that target the protein.
“Since the upregulation of appoptosin is important for cell death in diseases such as Alzheimer’s, we’re now searching for small molecules that modulate appoptosin expression or activity. We’ll then determine whether these compounds may be potential drugs for Alzheimer’s or other neurodegenerative diseases,” Xu explains.
Putting a stop to runaway appoptosin won’t be easy, though. That’s because we still need the heme-building protein to operate at normal levels for our blood to carry iron. In a previous study, researchers found that a mutation in the gene that encodes appoptosin causes anemia. “Too much of anything is bad, but so is too little,” Xu says.
New therapies that target neurodegenerative disorders and traumatic brain injury are sorely needed. According to the CDC, approximately 1.7 million people sustain a traumatic brain injury each year. It’s an acute injury, but one that can also lead to long-term problems, causing epilepsy and increasing a person’s risk for Alzheimer’s and Parkinson’s diseases. Not only has traumatic brain injury become a worrisome problem in youth and professional sports in recent years, the Department of Defense calls traumatic brain injury “one of the signature injuries of troops wounded in Afghanistan and Iraq.”
(Source: beaker.sanfordburnham.org)
Battling back from a brain injury
Much of the recent attention on traumatic brain injury has focused on the increased risk of neurodegenerative diseases doctors think recurrent injuries may lead to. But transportation accidents and falls, particularly among the elderly, are leading causes of TBI, and one serious head injury can be devastating. Karl Weisgraber is a retired biochemist who worked on cardiovascular and Alzheimer’s research at the Gladstone Institutes in San Francisco. In October of last year, he was on a ladder doing work on the side of his house when he fell and smacked his head on a rock, suffering a severe traumatic brain injury. The 71-year-old Walnut Creek man spent three weeks in a coma and, through therapy, had to relearn how to walk, read and write. He is greatly appreciative of the staffs at San Francisco General and California Pacific Medical Center who worked with him, and of his wife, Judi.
A child who suffers a moderate or severe traumatic brain injury (TBI) may still have substantial functional disabilities and reduced quality of life 2 years after the injury. After those first 2 years, further improvement may be minimal. Better interventions are needed to prevent long-lasting consequences of TBI in children conclude the authors of a study published in Journal of Neurotrauma, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers.
Frederick Rivara and colleagues from University of Washington, Seattle, and Mary Bridge Children’s Hospital, Tacoma, WA, and Children’s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, PA, describe the functional and quality of life outcomes of children who experienced a moderate or severe TBI when they were 0-17 years of age. In the article “Persistence of Disability 24 to 36 Months after Pediatric Traumatic Brain Injury: A Cohort Study” they follow up on a previous report that found improvement in some areas of functioning for up to 24 months. In this expanded study, the authors showed no significant improvement in the children’s ability to function, participate in activities, or in their quality of life between 24 and 36 months post-injury, and they suggest that a plateau is reached in the recovery.
"This important communication by Rivara and colleagues reinforces the concept that pediatric traumatic brain injury is associated with significant enduring morbidity, with recovery plateauing over time," says John T. Povlishock, PhD, Editor-in-Chief of Journal of Neurotrauma and Professor, VCU Neuroscience Center, Medical College of Virginia, Richmond. “This finding also reinforces emerging thought that pediatric traumatic brain injury must be viewed in another context, rather than the current perception that the course of such injury parallels that found in the adult population.”
How a Single Brain Trauma May Lead to Alzheimer’s Disease
ScienceDaily (July 24, 2012) — A study, performed in mice and utilizing post-mortem samples of brains from patients with Alzheimer’s disease, found that a single event of a moderate-to-severe traumatic brain injury (TBI) can disrupt proteins that regulate an enzyme associated with Alzheimer’s. The paper, published in The Journal of Neuroscience, identifies the complex mechanisms that result in a rapid and robust post-injury elevation of the enzyme, BACE1, in the brain. These results may lead to the development of a drug treatment that targets this mechanism to slow the progression of Alzheimer’s disease.
"A moderate-to-severe TBI, or head trauma, is one of the strongest environmental risk factors for Alzheimer’s disease. A serious TBI can lead to a dysfunction in the regulation of the enzyme BACE1. Elevations of this enzyme cause elevated levels of amyloid-beta, the key component of brain plaques associated with senility and Alzheimer’s disease," said first author Kendall Walker, PhD, postdoctoral associate in the department of neuroscience at Tufts University School of Medicine (TUSM).
Building on her previous work, neuroscientist Giuseppina Tesco, MD, PhD, of Tufts University School of Medicine (TUSM), led a research team that first used an in vivo model to determine how a single episode of TBI could alter the brain. In the acute phase (first two days) following injury, levels of two intracellular trafficking proteins (GGA1 and GGA3) were reduced, and an elevation of BACE1 enzyme level was observed.
Next, in an analysis of post-mortem brain samples from patients with Alzheimer’s disease, the researchers found that GGA1 and GGA3 levels were reduced while BACE1 levels were elevated in the brains of Alzheimer’s disease patients compared to the brains of people without Alzheimer’s disease, suggesting a possible inverse association.
In an additional experiment using a mouse strain genetically modified to express the reduced level of GGA3 that was observed in the brains of Alzheimer’s disease patients, the team found that one week following traumatic brain injury, BACE1 and amyloid-beta levels remained elevated even when GGA1 levels had returned to normal. The research suggests that reduced levels of GGA3 were solely responsible for the increase in BACE 1 levels and therefore the sustained amyloid-beta production observed in the sub-acute phase, or seven days, after injury.
"When the proteins are at normal levels, they work as a clean-up crew for the brain by regulating the removal of BACE1 enzymes and facilitating their transport to lysosomes within brain cells, an area of the cell that breaks down and removes excess cellular material. BACE1 enzyme levels may be stabilized when levels of the two proteins are low, likely caused by an interruption in the natural disposal process of the enzyme," said Tesco, assistant professor of neuroscience at Tufts School of Medicine and member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.
"We found that GGA1 and GGA3 act synergistically to regulate BACE1 post-injury. The identification of this interaction may provide a drug target to therapeutically regulate the BACE1 enzyme and reduce the deposition of amyloid-beta in Alzheimer’s patients," she continued. "Our next steps are to confirm these findings in post-mortem brain samples from patients with moderate-to-severe traumatic brain injuries."
Moderate-to-severe TBIs are caused most often by traumas, such as severe falls or motor vehicle accidents, that result in a loss of consciousness. Not all traumas to the head result in a TBI. According to the Centers for Disease Control and Prevention, each year 1.7 million people sustain a TBI. Concussions, the mildest form of a TBI, account for about 75% of all TBIs. Studies have linked repeated head trauma to brain disease and some previous studies have linked single events of brain trauma to brain disease, such as Alzheimer’s. Alzheimer’s disease currently affects as many as 5.1 million Americans and is the most common cause of dementia in adults age 65 and over.
Source: Science Daily