Posts Tagged ‘TBI’

by Nicole Fisher

Friday evening The Lancet Neurology published a new study concluding that a handheld portable device and blood test could help detect real-time brain injuries, even if a CT scan does not. Findings from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study suggest that technology might be able to fill a significant gap in emergency departments, sport fields and battle fields. Within as little as 15 minutes, patients who might have otherwise gone undiagnosed can be identified.

Although concussions and brain injuries are still greatly misunderstood, each year 4.8 million people in the U.S. visit the emergency room to be evaluated for a brain injury, and 82% of those have a head CT scan performed to test for TBI. Further, according to the Defense and Veterans Brain Injury Center, more than 380,000 military members have sustained TBIs over the past 20 years. But the most troubling part of brain injury statistics is that previous research found half of concussions go undetected and undiagnosed. That’s millions a year.

One of the main reasons is that current tools are not capable of detecting all brain injuries. Thus, even for those who do suspect an injury, cognitive and neurological questionnaires and CT scans simply cannot do the job well enough. And in situations like those following an accident or during combat, missing a diagnosis or waiting days for one could have significant consequences. But new blood-based biomarkers are emerging as an important tool to detect TBI.

Unfortunately, the field of neuroscience – and brain injuries in particular – have gotten a lot of attention over the last decade, but with much of the literature and many claims going unsubstantiated, or unable to be validated and replicated. But the authors of this article claim that the large, prospective cohort design and dynamic partnerships of TRACK-TBI are what make these results different, important, and exciting.

The TRACK-TBI study is one of the largest concussion studies of its kind, having evolved from the largest and most comprehensive natural history study of TBI ever conducted in the U.S. Led by the University of California San Francisco (UCSF), funding for the study comes from the National Institute of Neurological Disorders and Stroke (NINDS) and the U.S. Department of Defense (DOD), through U.S. Army Medical Research and Materiel Command (USAMRMC) and U.S. Army Medical Materiel Development Activity (USAMMDA), as well as funding from philanthropic and private partners, like Abbott.

According to Geoffrey T. Manley, M.D., Ph.D., the principal investigator of TRACK-TBI and a neurosurgeon and professor of neurosurgery at UCSF, “We all have a unified, common goal to advance technologies that provide objective information about what’s happening to the brain. The brain and brain injury are extremely complex. So, this work and the results are really about the power of partnership.”

In 2014, the DOD and Abbott partnered to begin working on developing a portable blood test that helps assess concussions right at a person’s side. And the military continues to use Abbott’s current i-STAT system, a handheld blood analyzer that carries out a range of clinical tests. Building on this, with its involvement in TRACK-TBI, Abbott now has more than 120 scientists devoted to researching and developing the concussion assessment test for the next generation of i-STAT™ Alinity™ system.

A critical part of the TRACK-TBI research initiative is to evaluate the effectiveness of blood-based biomarkers to detect brain injury.Consequently, the goal of this collaboration is to have a blood test based on robust, proven data that can easily be utilized in the military, on the field, and in hospitals around the world. To do this, Abbott provided its newest blood test to TRACK-TBI for analysis, while being blinded throughout the study to which samples represented which subjects.

The study results looked at the new handheld blood test, which specifically measures two types of proteins – GFAP and UCH-L1 – that are released from the brain and into the blood when the brain is injured. Or, as Beth McQuiston, M.D., R.D., neurologist and medical director in diagnostics at Abbott puts it, “We have blood tests used in the hospital to detect injury throughout the body. For example, your heart, kidney and liver. Yet, we don’t have a blood test to detect injury in the brain. This research shows that a blood test has the potential to help doctors evaluate and treat patients suspected of brain injury quickly and accurately to get them back to better health. Our blood test in development could be the first point-of-care blood test for assessing concussions.”

Dr. Manley adds, “This study demonstrates that these blood-based biomarkers are more sensitive at detecting brain injury than a CT scan. Even when we found that the CT scan was negative, the research found that these blood proteins levels were elevated above both the healthy and orthopedic controls.” As part of the study, the diagnosis of brain injury was by an MRI scan. Importantly, even when the MRI scan was negative, this protein was elevated more than it was in the controls – suggesting that similar to CT scans, it may be more sensitive than MRI imaging. “And this research suggests,” says Manley, “that proteins have the potential to improve our ability to triage patients with traumatic brain injury.”

While there are still many research milestones for TRACK-TBI, the detection of TBI and identification of patients who need brain injury treatment and care could be a significant game changer – principally for emergency situations. Using only a few drops of blood, assessment of the brain could literally, change lives in a matter of minutes.

https://www.forbes.com/sites/nicolefisher/2019/08/24/study-finds-new-blood-test-could-help-detect-brain-injury-in-minutes/#3ea8cc4e3ac8

BY: JENNIFER BROWN

More than 200,000 U.S. soldiers serving in the Middle East have experienced a blast-related traumatic brain injury, making it a common health problem and concern for that population.

Traumatic brain injury (TBI) can have various harmful long-term neurological effects, including problems with vision, coordination, memory, mood, and thinking. According to the Centers for Disease Control and Prevention, TBI from a head injury is a leading cause of death and disability in the United States, and close to 5 million Americans—soldiers and non-soldiers alike—are currently living with a TBI-related disability. Current therapy for these patients involves supportive care and rehabilitation, but no treatments are available that can prevent the development of chronic neurological symptoms.

Researchers from the University of Iowa believe they may have identified a potential approach for preventing the development of neurological problems associated with TBI. Their research in mice suggests that protecting axons—the fiber-like projections that connect brain cells—prevents the long-term neuropsychiatric problems caused by blast-related traumatic brain injury.

In a recent study, the UI team led by Andrew Pieper, professor of psychiatry at the UI Carver College of Medicine, investigated whether early damage to axons—an event that is strongly associated with many forms of brain injury, including blast-related TBI—is simply a consequence of the injury or whether it is a driving cause of the subsequent neurological and psychiatric symptoms.

To answer that question, the researchers used mice with a genetic mutation that protects axons from some forms of damage. The mutation works by maintaining normal levels of an important energy metabolite known as nicotinamide adenine dinucleotide (NAD) in brain cells after injury.

When mice with the mutation experienced blast-mediated TBI, their axons were protected from damage, and they did not develop the vision problems, or the thinking and movement difficulties that were seen when mice without the mutation experienced blast-related TBI. The findings were published Oct. 11 in the online journal eNeuro.

“Our work strongly suggests that early axonal injury appears to be a critical driver of neurobehavioral complications after blast-TBI,” says Pieper, who also is a professor of neurology, radiation oncology, and a physician with the Iowa City Veterans Affairs Health Care System.

“Therefore, future therapeutic strategies targeted specifically at protecting or augmenting the health of axons may provide a uniquely beneficial approach for preventing these patients from developing neurologic symptoms after blast exposure.”

In confirming the critical relationship between axon degeneration and development of subsequent neurological complication, the new study builds on previous work from Pieper’s lab. The researchers also have discovered a series of neuroprotective compounds that appear to help axons survive the kind of early damage seen in TBI. These compounds activate a molecular pathway that preserves neuronal levels of NAD, the energy metabolite that has been shown to be critical to the health of axons. Pieper’s team previously demonstrated that these neuroprotective compounds block axonal degeneration and protect mice from harmful neurological effects of blast-TBI, even when the compound are given 24 to 36 hours after the blast injury.

In addition to Pieper, the research team included Terry Yin, Jaymie Voorhees, Rachel Genova, Kevin Davis, Ashley Madison, Jeremiah Britt, Coral Cinton, Latisha McDaniel, and Matthew Harper. Pieper also is a member of the Pappajohn Biomedical Institute at the UI.

https://now.uiowa.edu/2016/10/study-traumatic-brain-injury

New research published in the Canadian Medical Association Journal shows that even mild concussions sustained in ordinary community settings might be more detrimental than anyone anticipated; the long-term risk of suicide increases threefold in adults if they have experienced even one concussion. That risk increases by a third if the concussion is sustained on a weekend instead of a weekday—suggesting recreational concussions are riskier long-term than those sustained on the job.

“The typical patient I see is a middle-aged adult, not an elite athlete,” says Donald Redelmeier, a senior scientist at the University of Toronto and one of the study’s lead authors. “And the usual circumstances for acquiring a concussion are not while playing football; it is when driving in traffic and getting into a crash, when missing a step and falling down a staircase, when getting overly ambitious about home repairs—the everyday activities of life.”

Redelmeier and his team wanted to examine the risks of the concussions acquired under those circumstances. They identified nearly a quarter of a million adults in Ontario who were diagnosed with a mild concussion over a timespan of 20 years—severe cases that resulted in hospital admission were excluded from the study—and tracked them for subsequent mortality due to suicide. It turned out that more than 660 suicides occurred among these patients, equivalent to 31 deaths per 100,000 patients annually—three times the population norm. On average, suicide occurred almost six years after the concussion. This risk was found to be independent of demographics or previous psychiatric conditions, and it increased with additional concussions.

For weekend concussions, the later suicide risk increased to four times the norm. Redelmeier and his fellow researchers had wondered whether the risk would differ between occupational and recreational concussions. They did not have information about how the concussions happened, so they used day of the week as a proxy. Although they do not know why weekend risk is indeed higher, they suspect it may be because on weekends medical staff may not be as available or accessible or people may not seek immediate care.

Although the underlying causes of the connection between concussion and suicide are not yet known, Redelmeier says that there were at least three potential explanations. A concussion may be a marker but not necessarily a mechanism of subsequent troubles—or, in other words, people who sustain concussions may already have baseline life imbalances that increase their risks for depression and suicide. “But we also looked at the subgroup of patients who had no past psychiatric history, no past problems, and we still found a significant increase in risk. So I don’t think that’s the entire story,” he notes. One of the more likely explanations, he says, is that concussion causes brain injury such as inflammation (as has been found in some studies) from which the patient may never fully recover. Indeed, a study conducted in 2014 found that sustaining a head injury leads to a greater risk of mental illness later in life. The other possibility is that some patients may not give themselves enough time to get better before returning to an ordinary schedule, leading to strain, frustration and disappointment—which, in turn, may result in depression and ultimately even suicide.

Lea Alhilali, a physician and researcher at the Barrow Neurological Institute who did not participate in this study, uses diffusion tensor imaging (an MRI technique) to measure the integrity of white matter in the brain. Her team has found similarities between white matter degeneration patterns in patients with concussion-related depression and noninjured patients with major depressive disorder—particularly in the nucleus accumbens, or the “reward center” of the brain. “It can be difficult to tease out what’s related to an injury and what’s related to the circumstances surrounding the trauma,” Alhilali says. “There could be PTSD, loss of job, orthopedic injuries that can all influence depression. But I do believe there’s probably an organic brain injury.”

Alhilali points to recent studies on chronic traumatic encephalopathy (CTE), a progressive degenerative brain disease associated with repeated head traumas. Often linked to dementia, depression, loss of impulse control and suicide, CTE was recently diagnosed in 87 of 91 deceased NFL players. Why, then, she says, should we not suspect that concussion causes other brain damage as well?

This new study may only represent the tip of the iceberg. “We’re only looking at the most extreme outcomes, at taking your own life,” Redelmeier says. “But for every person who dies from suicide, there are many others who attempt suicide, and hundreds more who think about it and thousands more who suffer from depression.”

More research needs to be done; this study was unable to take into account the exact circumstances under which the concussions were sustained. Redelmeier’s research examined only the records of adults who sought medical attention, it did not include more severe head injuries that required hospitalization or extensive emergency care. To that extent, his findings may have underestimated the magnitude of the absolute risks at hand.

Yet many people are not aware of these risks.

Redelmeier is adamant that people should take concussions seriously. “We need to do more research about prevention and recovery,” he says. “But let me at least articulate three things to do: One, give yourself permission to get some rest. Two, when you start to feel better, don’t try to come back with a vengeance. And three, even after you’re feeling better, after you’ve rested properly, don’t forget about it entirely. If you had an allergic reaction to penicillin 15 years ago, you’d want to mention that to your doctor and have it as a permanent part of your medical record. So, too, if you’ve had a concussion 15 years ago.”

http://www.scientificamerican.com/article/a-single-concussion-may-triple-the-long-term-risk-of-suicide1/


Over the past 15 years, more than 330,000 US soldiers have suffered a traumatic brain injury. Many were evacuated by air for further treatment. A new study has found evidence that such air evacuations may pose a significant added risk, potentially causing more damage to already injured brains.

Over the past 15 years, more than 330,000 U.S. soldiers have suffered a traumatic brain injury (TBI). It is one of the leading causes of death and disability connected to the country’s recent conflicts in Afghanistan and Iraq. Many of these patients were evacuated by air from these countries to Europe and the U.S. for further treatment. In general, these patients were flown quickly to hospitals outside the battle zone, where more extensive treatment was available.

But now a new study by researchers at the University of Maryland School of Medicine has found evidence that such air evacuations may pose a significant added risk, potentially causing more damage to already injured brains. The study is the first to suggest that air evacuation may be hazardous for TBI patients. The study was published in the Journal of Neurotrauma.

“This research shows that exposure to reduced barometric pressure, as occurs on military planes used for evacuation, substantially worsens neurological function and increases brain cell loss after experimental TBI — even when oxygen levels are kept in the normal range. It suggests that we need to carefully re-evaluate the cost-benefit of air transport in the first days after injury,” said lead researcher Alan Faden, MD, the David S. Brown Professor in Trauma in the Departments of Anesthesiology, Anatomy & Neurobiology, Neurology, and Neurosurgery, and director, Shock, Trauma and Anesthesiology Research Center (STAR) as well as the National Study Center for Trauma and Emergency Medical Services.

About a quarter of all injured soldiers evacuated from Afghanistan and Iraq have suffered head injuries.

Faden and his colleagues tested rats that were subjected to TBI, using a model that simulates key aspects of human brain injury. Animals were exposed to six hours of lowered air pressure, known as hypobaria, at levels that simulated conditions during transport; control animals were exposed to normal pressure. All the animals received extra oxygen to restore normal oxygen concentrations in the blood. In another study, animals received oxygen, either as in the first study or at much higher 100 percent concentration, which is often used during military air evacuations. On its own, low air pressure worsened long-term cognitive function and increased chronic brain inflammation and brain tissue loss. Pure oxygen further worsened outcomes.

Faden and his colleagues believe the findings raise concerns about the increased use of relatively early air evacuation, and suggest that this potential risk should be weighed against the benefits of improved care after evacuation. It may be necessary, he says, to change the current policy for TBI patients and delaying air evacuation in many cases.

In an accompanying editorial, Patrick Kochanek, MD, a leading expert on TBI and trauma care at the University of Pittsburgh, called the findings “highly novel and eye-opening,” and said that they could have “impactful clinical relevance for the field of traumatic brain injury in both military and civilian applications.”

Faden and colleagues believe that one of the mechanisms by which hypobaria worsens TBI is by increasing persistent brain inflammation after injury. They are currently examining how this process occurs and have tested treatments that can reduce the risks of air evacuation. Early results are promising. Scientists suspect that breathing pure oxygen could worsen TBI by increasing production of dangerous free radicals in the brain. After brain injury, these free radicals flood the site of injury, and pure oxygen may further boost these levels. Several recent studies from trauma centers, including from the R Adams Cowley Shock Trauma Center at the University of Maryland Medical Center, have found evidence that using 100 percent oxygen in trauma patients may be counterproductive.

Journal Reference:

Jacob W Skovira, Shruti V Kabadi, Junfang Wu, Zaorui Zhao, Joseph DuBose, Robert E Rosenthal, Gary Fiskum, Alan I Faden. Simulated Aeromedical Evacuation Exacerbates Experimental Brain Injury. Journal of Neurotrauma, 2015; DOI: 10.1089/neu.2015.4189

http://www.sciencedaily.com/releases/2015/11/151130110013.htm