Concussions

Concussions Linked to Higher Brain Iron

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Findings showed those with a history of concussions and headaches exhibited increased iron accumulation in the brain, correlating with the number of concussions and frequency of headaches. This study, supported by the U.S. Department of Defense and NIH, suggests iron accumulation could serve as a biomarker for concussion-related injuries, offering new insights into brain recovery processes.

Key Facts:

  1. Higher Iron Levels in Concussion Patients: Individuals with concussions and subsequent headaches showed greater iron accumulation in brain areas like the left occipital area and right cerebellum.
  2. Correlation with Concussion History: The extent of iron accumulation was linked to the number of concussions and headache frequency, highlighting potential long-term brain injury markers.
  3. Indirect Measure of Iron Burden: The study utilized an indirect method to assess iron levels, suggesting findings could reflect changes due to hemorrhage or tissue changes, not just iron.

Source: AAN

People who have headaches after experiencing concussions may also be more likely to have higher levels of iron in areas of the brain, which is a sign of injury to brain cells, according to a preliminary study released today, March 5, 2024, that will be presented at the American Academy of Neurology’s 76th Annual Meeting taking place April 13–18, 2024, in person in Denver and online.

“These results suggest that iron accumulation in the brain can be used as a biomarker for concussion and post-traumatic headache, which could potentially help us understand the underlying processes that occur with these conditions,” said study author Simona Nikolova, PhD, of the Mayo Clinic in Phoenix, Arizona, and a member of the American Academy of Neurology.

The study involved 60 people who had post-traumatic headache due to mild traumatic brain injury, or concussion. The injuries were due to a fall for 45% of the people, 30% were due to a motor vehicle accident and 12% were due to a fight.

Other causes were the head hitting against or by an object and sports injuries. A total of 46% of the people had one mild traumatic brain injury in their lifetime, 17% had two, 16% had three, 5% had four and 16% had five or more mild traumatic brain injuries.

The people with mild traumatic brain injuries were matched with 60 people who had not had concussions or post-traumatic headache.

All the participants had brain scans to look at iron levels in various areas of the brain, using an indirect measure for iron burden. For those with mild traumatic brain injuries, the scans were taken an average of 25 days after the injury.

The study found that compared to the people without concussion, those with a history of concussion and headaches had higher levels of iron accumulation in several areas of the brain, including the left occipital area, right cerebellum and right temporal lobe.

For example, in the left occipital area, those with concussion and headaches had more iron accumulation than those with no concussion or headaches.

Researchers also found that the more concussions people had over their lifetime and the more frequent their headaches were, the more likely they were to have higher levels of iron accumulation in certain areas of the brain. They also found that the more time that had passed since the concussion occurred, the more likely people were to have higher levels of iron accumulation in areas of the brain.

“Previous studies have shown that iron accumulation can affect how areas of the brain interact with each other,” Nikolova said. “This research may help us better understand how the brain responds and recovers from concussion.” 

Nikolova said that since the study used an indirect measure of iron burden, it’s possible that the change in that measure could be due to other factors such as hemorrhage or changes in tissue water rather than iron accumulation.

Repeated Concussions Can Thicken the Skull

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Summary: Repeat concussions thicken the structure of skull bones. Researchers theorize the thickening of the skull may occur as the body attempts to better protect the brain from subsequent damage.

Source: Monash University

New research has found that repeated concussions can thicken the structure of skull bones. Previous studies have shown damage to the brain following concussion, but have not looked at the brain’s protective covering.

A Monash-led study published in the journal Scientific Reports by Associate Professor Bridgette Semple from the Monash University’s Central Clinical School Department of Neuroscience, found that repeated concussions resulted in thicker, denser bones in the skull.

It is unclear whether this thickening of the skull is a good thing or a bad thing. In theory, a thicker skull is a stronger skull, suggesting that this may be the bone’s attempt to protect the brain from subsequent impacts.

“This is a bit of a conundrum,” Associate Professor Semple said. “As we know, repeated concussions can have negative consequences for brain structure and function. Regardless, concussion is never a good thing.”

The team hopes that the microstructural skull alterations caused by concussion are now considered by researchers in the field to better understand how concussions affect the whole body.

Concussion is a form of mild traumatic brain injury, and repeated concussions have been linked to long-term neurological consequences.

Most studies focus on understanding how these head injuries affect the brain and its function—but they largely ignore the overlying skull bones that protect the brain.

This shows a head with radiating circles around it
It is unclear whether this thickening of the skull is a good thing or a bad thing.

Although bones are considered a mostly structural component of the human body, bones are in fact active living tissues that can respond to applied mechanical forces.

Study collaborator Professor Melinda Fitzgerald, from Curtin University and the Perron Institute in Western Australia, has previously shown that repeated concussive impacts lead to subtle problems with memory, and evidence of brain damage.

In this new study, high-resolution neuroimaging and tissue staining techniques were used in a pre-clinical model, and revealed an increase in bone thickness and density, in close proximity to the site of injury.

“We have been ignoring the potential influence of the skull in how concussive impacts can affect the brain,” Associate Professor Semple said.

“These new findings highlight that the skull may be an important factor that affects the consequences of repeated concussions for individuals.”

Future studies are planned, with collaborator and bone expert Professor Natalie Sims from St Vincent’s Institute of Medical Research in Melbourne, to understand if a thickened skull resulting from repeated concussions alters the transmission of impact force through the skull and into the vulnerable brain tissue underneath.

Abstract

Localized, time-dependent responses of rat cranial bone to repeated mild traumatic brain injuries

While it is well-established that bone responds dynamically to mechanical loading, the effects of mild traumatic brain injury (mTBI) on cranial bone composition are unclear.

We hypothesized that repeated mTBI (rmTBI) would change the microstructure of cranial bones, without gross skull fractures.

To address this, young adult female Piebald Viral Glaxo rats received sham, 1×, 2× or 3× closed-head mTBIs delivered at 24 h intervals, using a weight-drop device custom-built for reproducible impact.

Skull bones were collected at 2 or 10 weeks after the final injury/sham procedure, imaged by micro computed tomography and analyzed at predetermined regions of interest. In the interparietal bone, proximal to the injury site, modest increases in bone thickness were observed at 2 weeks, particularly following 2× and 3× mTBI.

By 10 weeks, 2× mTBI induced a robust increase in the volume and thickness of the interparietal bone, alongside a corresponding decrease in the volume of marrow cavities in the diploë region. In contrast, neither parietal nor frontal skull samples were affected by rmTBI.

Our findings demonstrate time- and location-dependent effects of rmTBI on cranial bone structure, highlighting a need to consider microstructural alterations to cranial bone when assessing the consequences of rmTBI.

Concussions Drive Dementia Risk Decades Later

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A serious head injury may increase the risk for dementia even decades later, a new, large study suggests.

A traumatic injury to the brain — such as a concussion from a sports collision or a motor vehicle accident — is already associated with short-term risk of dementia. But the new research finds that, although the risk decreases over time, it still continues for many years.

“The main finding is the strong association between a previous traumatic brain injury and the risk of dementia,” said the study’s senior author, Peter Nordstrom.

“The association is stronger for more severe or multiple traumatic brain injuries, and the association persists for more than 30 years after the trauma,” added Nordstrom, a professor of geriatric medicine at Umea University in Sweden.

 This isn’t the first study to link traumatic brain injuries (TBIs) and later problems with memory and thinking. A number of studies have looked at professional athletes — such as football players, boxers and mixed martial arts fighters — and have found a connection to later serious brain troubles. These include dementia or chronic traumatic encephalopathy (CTE), a degenerative brain disease.

As with previous studies, this one can’t yet prove a cause-and-effect relationship or point to exactly how a TBI might trigger later dementia.

This study did, however, look at a very large number of people from the general population in Sweden. It began with more than 3.3 million people aged 50 or older in 2005.

From that group, the researchers found more than 164,000 people who had brain injuries serious enough for them to seek care at an emergency department from 1964 through 2012, Nordstrom said.

The investigators also looked at more than 136,000 people who were diagnosed with dementia during the study follow-up period.

The researchers matched each of the people in those two groups with two healthy people to serve as a control group.

A third group consisted of almost 47,000 siblings pairs, of which only one sibling had experienced a serious head injury.

During the first year after a head injury, the risk of dementia was about four- to sixfold higher. The risk dropped quickly, but never returned to normal. Even 30 years after the brain injury, the odds of dementia were 25 percent higher, the findings showed.

In some cases, it’s possible that dementia developed first and contributed to the head injury, the researchers suggested.

Dr. Daniel Kaufer is director of the memory disorders program at the University of North Carolina at Chapel Hill. He said, “This study clearly illustrates that TBI is something we need to pay attention to and track.” Kaufer was not involved with the new study.

“People are really starting to pay attention to TBI and aren’t taking it lightly,” Kaufer added.

“It’s not only about short-term consequences anymore — like whether Gronk can play in the Super Bowl this weekend,” he said, referring to the New England Patriots tight end Rob Gronkowski, who recently suffered a concussion. “It’s concern about the long-term risk of developing cognitive symptoms,” Kaufer explained.

Just as doctors follow high blood pressure and high cholesterol, they need to track brain injury in a more systematic way, Kaufer said.

Dr. Ajay Misra, chairman of neurosciences at NYU Winthrop Hospital in Mineola, N.Y., said this study is important largely because of its size, and that it confirms what people knew intuitively.

But he noted the jury is still out on whether this relationship is causal.

While research continues, the experts suggested taking steps to avoid TBI whenever possible. Some people might choose to stop playing contact sports, or not allow their child to play. “I think we’ll see more of that,” Kaufer said.

The most important thing to remember, however, is to protect your head. That can often be accomplished by wearing a helmet when participating in activities such as riding a motorcycle or a bicycle, he said.

 

Stem Cell Therapy for Concussions: Is It for Real?

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‘We haven’t even begun to study this’

Earlier this week, MedPage Today received an email from someone representing plastic surgeon Joel Singer, MD, of Park Avenue Stem Cell in New York City. According to the email, Singer is “treating unnamed NFL players for brain injuries that came as a result of repeated concussions.” The email went on to suggest that Singer uses autologous fat-derived mesenchymal stem cells for these procedures. Singer’s website also invites athletes to “learn about the benefits of Stem Cell Therapy for the treatment of Concussions and other medical conditions.”

This being an application of stem cell therapy we had not heard of before, we asked Michael De Georgia, MD, a neurologist and critical care specialist at University Hospitals Cleveland Medical Center, for his views on such treatments for brain injuries. In this video, he explains that stem cell treatments have shown promise in early studies for certain conditions, but there is currently no evidence that stem cell infusions have any benefit in the context of concussion.

Following is a transcript of De Georgia’s remarks:

Well, there’s obviously a lot of optimism about stem cells in the treatment of brain injury, including ischemic stroke and traumatic brain injury, mainly because of its pluripotential nature. There have been hundreds of preclinical animal studies showing in general the beneficial effects of stem cells, including the reduction of infarct volume.

But the translation of those preclinical studies to a reliable and consistent therapy that improves the outcomes has been more challenging. There have been a handful of randomized trials, none of which have really panned out, even for ischemic stroke. There has been a little more research done in ischemic heart disease. There have been dozens of randomized trials, some of which have shown a benefit in terms of heart function. But even in those two conditions of ischemic heart disease and ischemic stroke, there have not been any large, randomized, double-blind controlled trials that have shown that consistent benefit. For concussions, there have been especially no clinical trials for this. While there is reason to believe that stem cell therapy may be beneficial, I think it’s way too early to jump to the conclusion that it is beneficial for patients.

Most of the research [on therapies in general] has focused on traumatic brain injury, again, in terms of animals models and clinical trials. There is a whole range of studies, mainly clinical studies, looking at how to diagnose concussions and how to translate some of what we know about traumatic brain injury, more serious traumatic brain injury, into more minor brain injuries like concussions. But to date, there is not a foolproof, simple treatment for concussion, other than rest, which is what we advise our patients.

As a physician scientist, we’re always open to new ideas and to looking at different ways of using innovative therapies. Having said that, we need to be very cautious about claims and promises to patients who may be under the assumption or the belief that this therapy has been showed to be effective, and it hasn’t. So as long as studies are being done in a carefully controlled way, under an institutional review board (IRB), ethically approved way, then I think this type of stem cell research is fine and appropriate. What we need to be careful about is the application of these non-proven therapies to patients under the guise of a proven therapy, which it is not yet.

I think that we’re all open to new ideas and innovative therapies, but we’re not quite there yet in terms of the science to advocate stem cell therapy really for anything yet. We’re probably closest for ischemic heart disease. For ischemic stroke, we’re not quite there yet. For traumatic brain injury, we’re not there yet. For concussions, all bets are off. We haven’t even begun to study this, really.

Concussions at Altitude: No Longer Worth Investigating?

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Can a single meta-analysis of three retrospective studies really close the case on a controversial topic? Two researchers believe they have done just that for the risk of concussion for athletes in contact sports at higher altitude.
Gerald Zavorsky, PhD, of Georgia State University in Atlanta, and James Smoliga, DVM, PhD, of High Point University in High Point, N.C., said their review provides conclusive evidence that playing football at a higher elevation isn’t protective against concussion — and that other researchers shouldn’t waste any more time on the question.

“We firmly believe epidemiologic data are already sufficient to indicate that this is an issue that should not be examined further,” they wrote in a research letter in JAMA Neurology.
They noted that any additional research “will simply divert resources from more clinically effective research aimed at identifying modifiable risk factors for concussion, developing scientifically sound technologies that improve athlete safety, and improving acute and long-term management of sport-related head injuries.”
The potential biological mechanism? If higher altitude increases cerebral blood flow, it may lead to a slight brain swelling that creates a tighter fit between the brain and the skull, which prevents the brain from sloshing around, and potentially reducing concussions.
But Zavorsky and Smoliga say that mechanism “is not scientifically sound.”
In their meta-analysis, they found similar ranges in concussion rates at sea level (0.07% to 0.45%) and at higher altitudes of about 650 ft and above (0.06% to 0.50%), leading to no difference in relative risk of concussion in a random effects model.

However, not everyone is convinced that these findings are the last word. Four concussion experts from the University of Florida in Gainesville — Steven DeKosky, MD, Russell Bauer, MD, Mike Jaffee, MD, and Breton Asken — reviewed the research letter, and said that while the statistics were solid, there were several issues that limit the conclusions that can be drawn.
Only three studies met their inclusion criteria, which is too small a number “to ‘close the book’ on any scientific question, the large number of hits [included] notwithstanding,” DeKosky said, speaking on behalf of the foursome, none of whom were involved in the meta-analysis.
And all three were retrospective studies, which carry several caveats that prevent researchers from drawing firm conclusions. In this case, for instance, that includes variables such as “differences in acclimatization to the altitude by the visiting team and if it had an effect, and effects on autoregulation that might be different in low-altitude versus high-altitude players,” DeKosky said.
“The idea that three retrospective studies answers all the questions to the point where there is not more work to be done is, I think, a risky conclusion to an otherwise methodologically well-performed study,” he told MedPage Today. “Prospective studies, especially noting differences in the high-altitude acclimated versus the low-altitude dwelling visiting team, would be helpful in trying to determine actual risks.”