Head injury

FDA clears lab blood test for evaluating concussion

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The FDA has cleared Abbott’s laboratory blood test for concussion, making it the first commercially available test of its kind, according to a company press release.

The Alinity i traumatic brain injury test measures two serum biomarkers that are closely associated with brain injury and provides results in 18 minutes. Those with a negative test would be able to avoid a CT scan and may be able to reduce their time waiting at a hospital, the release stated. The test can be used for adult patients within 12 hours of suspected injury.

FDA clears Abbott’s lab-based blood test to evaluate for concussion. Image Adobe Stock
FDA clears Abbott’s lab-based blood test to evaluate for concussion. Image: Adobe Stock

Because misdiagnosis of or undiagnosed TBI can exacerbate its short- and long-term effects, “providing tools that can objectively aid in the evaluation of a TBI or concussion is essential to giving people the answers and treatment they need,” the company said.

“People sometimes minimize a hit to the head, thinking it’s no big deal,” Beth McQuiston, MD, medical director in Abbott’s diagnostics business, said in the release. “Others wonder if a visit to the doctor or emergency room for a possible concussion will provide them with meaningful answers or care. Now that this test will be widely available in labs across the country, medical centers will be able to offer an objective blood test that can aid in concussion assessment. That’s great news for both doctors and people who are trying to find out if they have suffered a traumatic brain injury.”

According to Abbott, the Alinity i TBI test has a 96.7% sensitivity and complements the company’s i-STAT TBI plasma test, a rapid blood test for concussion previously cleared by the FDA in 2021.

FDA Okays Marketing of First Cognitive Testing Devices for Patients With Head Injury

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Two medical devices for evaluating symptoms and cognitive function after a head injury have received marketing permission, according to an announcement today from the US Food and Drug Administration (FDA).

The computerized Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) system and ImPACT Pediatric are both manufactured by the ImPACT Applications company.

The first product was created for individuals aged 12 to 59 years who have sustained a head trauma. Using a desktop or laptop computer, licensed clinicians use specialized software to assess a patient’s cognitive skills, such as working memory, attention span, nonverbal problem solving, and reaction time. The results are then matched to a control-group database or, if possible, a patient’s own previous scores.

The child-specific ImPACT Pediatric works the same way but is for patients aged 5 to 11 years — and works only on an iPad. It has a game-like design and takes about 10 to 15 minutes to complete.

These are the first medical devices with this indication to receive marketing allowance, noted the FDA in a press release.

“These devices provide a useful new tool to aid in the evaluation of patients experiencing possible signs of a concussion, but clinicians should not rely on these tests alone to rule out a concussion or determine whether an injured player should return to a game,” Carlos Peña, PhD, director of the FDA’s Division of Neurological and Physical Medicine Devices at the Center for Devices and Radiological Health, said in the same release.

In fact, the manufacturer calls these products “concussion management tools” on their website and reports that there are currently 17,000 cases in their normative database.
The FDA used its de novo classification process to review the new testing systems. This type of process is for evaluating first-of-its-kind, low-to-moderate-risk medical devices.

After examining more than 250 peer-reviewed articles submitted by ImPACT Applications, the FDA found that there was “valid scientific evidence to support the safety and effectiveness” of these products.

Inducing Deep Sleep after Head Injury May Protect the Brain

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A new study in rats could one day benefit people suffering neurological conditions associated with the buildup of unwanted proteins in the brain, including traumatic brain injury and Alzheimer’s

Last week a senior National Football League official acknowledged for the first time the link between head injuries in professional football and a degenerative brain disease called chronic traumatic encephalopathy. The admission—which has been compared with Big Tobacco’s 1997 disclosure that smoking causes cancer—comes at a time when the dangers of less severe traumatic brain injuries (TBIs), including concussions, have also been making headlines.

Scientists do not yet understand the biological mechanisms underlying the detrimental effects of TBI—and as a result, effective treatments remain elusive. In fact, how to deal with even a mild concussion is the subject of debate: Some doctors prescribe rest for several weeks whereas others claim this may have negative consequences and urge patients to stay active.

Now it turns out that the type of rest patients get may be key. In a study on rats published this week in The Journal of Neuroscience a team of researchers at University Hospital Zurich (UHZ) found that enhancing the slow-wave cycle of sleep after a traumatic head injury preserves brain function and minimizes damage to axons, the long projections from neurons that send signals to other cells in the brain.

Previous research has shown that TBIs cause axonal damage as well as the buildup of neurotoxic molecular waste products that result from injury. In the new study the researchers examined two different methods of inducing a slow-wave sleep state—the deepest sleep stage characterized by low-frequency, high-amplitude waves. During this stage, the brain clears out protein buildup, leading the researchers to question whether it could help treat rats that had suffered a brain injury.

The team first dealt a blow to the prefrontal cortex in 25 rats. They then divided the animals into three groups, treating the first group with sodium oxybate, a drug used to produce slow-wave brain function in people suffering from narcolepsy. (The exact mechanism for this drug’s effect is unclear but the prevalent hypothesis is that sodium oxybate improves daytime vigilance by inducing deep sleep when people rest.) In the second group the researchers restricted sleep by gently handling the rats—keeping them awake for long periods of time. Previous research has shown that after sleep deprivation, slow-wave activity increases during a period of “rebound sleep.” Meanwhile, the third group received a placebo injection.

The researchers used electroencephalography, a method for recording electrical activity in the brain, to confirm that they had successfully enhanced slow-wave sleep in the rats in the first two groups. They then assessed the rats’ cognition based on the animals’ ability to recognize a novel object, and found that both groups of rats receiving the enhanced sleep treatments performed better on the object-recognition tests than the untreated rats. The deep sleeping rats also showed less memory impairment.

The team then tested for brain damage in the cortex and hippocampus by staining the rats’ brains for amyloid precursor protein, a biomarker used to detect axonal injury. The rats whose sleep had been modulated had significantly reduced levels of the protein—nearly 80 percent less, as compared with the control group. The team concluded that immediate treatment with slow-wave sleep—using both a physiological and pharmacological method—had helped preserve brain function and prevent axonal damage in rats suffering from a TBI.

The findings are promising but many questions need to be answered before they can be translated to possible human treatments. For one, determining an underlying mechanism for the effects the researchers observed requires further research. “These results could have something to do with enhancing the clearance of metabolites,” says Marta Morawska, a PhD candidate in neurology at UHZ and one of the study’s authors. “Or it could be preventing further accumulation of these metabolites. More studies are needed to untangle this.”

The researchers plan on tackling this distinction in future research. They are also collaborating with other institutions to find another nonsurgical technique for further improving slow-wave sleep—one that would not depend on sleep deprivation or sodium oxybate. (The compound, although used off-label for several disorders such as cluster headaches and fibromyalgia, is not used for trauma patients because it can also induce a sleeplike state during which patients cannot be neurologically monitored.) “[We’re working based on] the increasingly confirmed hypothesis that slow-wave activity is in fact essential for clearing the brain of waste products, including amyloids,” Morawska says.

Uzma Samadani, a neurosurgeon at the Hennepin County Medical Center in Minneapolis, who is not affiliated with this study and is taking a different approach to researching treatment for TBI patients, says Morawska’s findings are interesting but maintains that we must remain cognizant of the research’s limitations. “The study is an interesting one, supporting the idea that sleep modulation may be important for recovery from brain injury,” she says. “But I’d caution overinterpretation of the study’s importance. Often in neuroscience studies in rodents do not translate to humans.” In particular, rats’ metabolic rates and sleep patterns, including the proportion of time spent in slow-wave sleep, differ significantly from those of humans.

Morawska agrees. “I’d like to highlight that this is not a cure,” she says. “It needs to be developed more for use in clinical practice.” Even so, she has high hopes for the possibilities her team’s findings may open up, given more research directed at humans. “We strongly believe that this study will stimulate human research in this direction, and that inducing slow-wave sleep will prove beneficial for human trauma patients,” she says. “It could be used as a noninvasive treatment in pretty much any disease that’s primarily due to protein or metabolite accumulation, including Alzheimer’s disease.”

Researchers film early concussion damage, describe brain’s response to injury.

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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  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 .

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 . 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  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 ,” 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 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 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.

Nonsurgical treatment of chronic subdural hematoma with tranexamic acid.

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Clinical article

Chronic subdural hematoma (CSDH) is a common condition after head trauma. It can often be successfully treated surgically by inserting a bur hole and draining the liquefied hematoma. However, to the best of the authors’ knowledge, for nonemergency cases not requiring surgery, no reports have indicated the best approach for preventing hematoma enlargement or resolving it completely. The authors hypothesized that hyperfibrinolysis plays a major role in liquefaction of the hematoma. Therefore, they evaluated the ability of an antifibrinolytic drug, tranexamic acid, to completely resolve CSDH compared with bur hole surgery alone.

METHODS

From 2007 to 2011, a total of 21 patients with CSDH seen consecutively at Kuki General Hospital, Japan, were given 750 mg of tranexamic acid orally every day. Patients were identified by a retrospective records review, which collected data on the volume of the hematoma (based on radiographic measurements) and any complications. Follow-up for each patient consisted of CT or MRI every 21 days from diagnosis to resolution of the CSDH.

RESULTS

Of the 21 patients, 3 with early stages of CSDH were treated by bur hole surgery before receiving medical therapy. The median duration of clinical and radiographic follow-up was 58 days (range 28–137 days). Before tranexamic acid therapy was initiated, the median hematoma volume for the 21 patients was 58.5 ml (range 7.5–223.2 ml); for the 18 patients who had not undergone surgery, the median hematoma volume was 55.6 ml (range 7.5–140.5 ml). After therapy, the median volume for all 21 patients was 3.7 ml (range 0–22.1 ml). No hematomas recurred or progressed.

CONCLUSIONS

Chronic subdural hematoma can be treated with tranexamic acid without concomitant surgery. Tranexamic acid might simultaneously inhibit the fibrinolytic and inflammatory (kinin-kallikrein) systems, which might consequently resolve CSDH. This medical therapy could prevent the early stages of CSDH that can occur after head trauma and the recurrence of CSDH after surgery.

Source: JNS