This week's lead article, 45% of concussion patients show brain injury symptoms at six months, is in the Statistics category.

A woman on the couch, she his holding her forehead and has a headache

In this newsletter: Opportunities, Sports, Cannabis, Veterans, Statistics, Youth, Women’s Health, and CTE & Neurodegeneration Issues.

We appreciate the Concussion Alliance interns, staff, and Leadership Team members who created this edition:
Writers: Nancy Cullen, Fadhil Hussain, Minhong Kim, Susan Klein, MD, PhD, Jemsy Mathew, and Sravya Valiveti.

Editor: Malayka Gormally

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Opportunities

a man lying in bed having trouble sleeping

Friday, May 12, 1 pm PST: a free webinar, Social Communication and Traumatic Brain Injury, Presented by Lyn Turkstra, PhD, CCC-SLP, and hosted by The Center on Brain Injury and Training. Register in advance.

Tuesday, May 16, 6 pm EST: a free webinar, Sleep Problems: Getting to Sleep and Staying Asleep, presented by Dr. Neal Parekh and hosted by the Canadian Concussion Centre. Register in advance.

We recommend the Concussion Corner podcast, hosted by Dr. Jessica Schwartz, PT, DPT, CSCS. All episodes are listed on ConcussionCorner.com, and the podcast is available on all podcast platforms.

Researchers are seeking participants for an NIH-funded (NCCIH) K23 research study at Massachusetts General Hospital and Harvard Medical School, aiming to develop and test a program to prevent persistent concussion symptoms for young adults. There is no cost for participating, no medication, and no travel. Want to learn more? See our 3/9/23 newsletter, or email MGHConcussionToolkit@partners.org.

Sports

New Research Does Not Find Headgear Prevents Concussions

helmets and a football sitting on a field

New research challenges the efficacy of headgear in concussion prevention. One study, published in Applied Sciences, studied how conventional padded helmets affect the cerebrospinal fluid (CSF)’s ability to protect the brain. CSF, the fluid surrounding the brain and spinal cord, provides a “cushioning effect” on the brain by acting as a malleable barrier between delicate brain tissue and the hard skull. But Faiz Syed et al. showed that this effect is diminished as the brain bounces back and forth within the skull. This finding adds to a growing body of evidence that wearing headgear in sports does not protect against concussion.

A second study, published in the Annals of Biomedical Engineering, studied the effect of padded helmet shell covers, like the Guardian Cap, in American football. While lab testing showed that using a soft padded helmet cover led to significant reductions in various acceleration and axonal injury metrics, those reductions were not reproduced in preliminary on-field testing. The lab results may have been promising, but more robust research needs to be done on the field in real-life scenarios to determine if the helmet covers are of any substantial benefit.

The study examining how helmets affect CSF used a geometric model of a human head with a conventional two-layer helmet: an outside hard shell with thicker deformable padding underneath. The researchers modeled the interaction between the brain and skull under conditions resembling low-speed (2 m/s) head-on collisions. When the head is impacted, the brain experiences an initial acceleration-deceleration event as it moves toward one side of the skull. During this event, the CSF provides a cushioning effect to the brain. But then, the brain bounces back toward the other side of the skull and oscillates back and forth before coming to a stop. The study showed that the CSF’s “ability to cushion decreases with each subsequent wave of back-and-forth oscillations. It requires sufficient time to settle down before offering maximum protection once again.” This counterintuitive finding reinforces current literature, outlined by Donna Lu in an article for The Guardian, that protective headgear does not prevent concussions. Prof. Alan Pearce, a neurophysiologist and concussion researcher at La Trobe University, explains, “A helmet can prevent a skull from fracturing, but it doesn’t stop the brain tissue from moving inside the skull – and that’s the issue.”

For the study examining padded helmet covers, researchers equipped three different helmet models with a Generation 2 Guardian Cap, then performed several laboratory impact tests. These tests showed overall reductions in peak angular acceleration, Diffuse Axonal Multi Axis General Evaluation (DAMAGE), and Head Acceleration Response Metric (HARM) in lower velocity collisions, such as those thought to lead to chronic traumatic encephalopathy (CTE). However, these results were not reflected in the preliminary on-field testing of 10 Stanford University linebackers during the 2019 and 2021 seasons. The sample size was limited, but the lack of positive on-field results demonstrates the need for more research before determining whether these padded shells are effective. In an article by Mandy Erickson for Stanford Medicine, the senior author of the study Dr. David Camarillo noted, “We need to do more and larger studies to see if the Guardian Cap has any impact, but I don’t think it’ll make a big difference for the kind of blows that don’t lead to concussion but happen frequently on the field.”

These two studies demonstrate that, despite evolving technology, modern headgear is still ineffective in preventing concussions or the development of CTE. The best form of prevention remains avoiding head injuries whenever possible and properly identifying and managing head injuries if they occur.

Cannabis

Marijuana in the medical toolbox – some cautions, especially for PTSD

It is hard to study marijuana (cannabis) in scientific trials because of its DEA classification as a Schedule I substance under the Controlled Substances Act. Ironically, what has resulted is a lack of good trials to see whether people’s anecdotal experience of “it really helps me” holds up over time. Even more challenging is evaluating a specific therapy (cannabis) for conditions like concussion, when multiple problems can occur because of the injury, such as sleep disorders, problems concentrating, and headache. How do you know whether the intervention is safe and effective? And similarly, for PTSD, which can be present with concussion, is cannabis effective?

Dr. Libby Stuyt, in an opinion for MedPage Today, summarized some research that suggests that cannabis is ineffective in treating PTSD, another multifaceted disorder. One study by LaFrance et al. (2020) found that subjects did experience short-term relief from cannabis use. However, they selected higher and higher doses over time, which called long-term efficacy into question. Regarding study findings in veteran populations, Stuyt notes that cannabis is not an effective PTSD treatment, can worsen PTSD symptoms, and may intensify psychiatric comorbidities such as depression and anxiety, suicidal ideation, and substance abuse disorders.

Stuyt, a board-certified addiction psychiatrist who treats dual-diagnosis adults (people with a mental disorder and a substance abuse problem), found that all the studies she reviewed relied on self-reporting for cannabis use, likely because of hurdles in funding research on restricted medications. In the LaFrance et al. study, Canadians with PTSD reported their experience with cannabis products by identifying what they used from a list of over 3000 entries on the Strainprint website. Subjects could “manually enter the strain name and cannabinoid content of the product” if it was not in the database. The dose was defined as the number of hits, not a concentration of THC, CBD, or other components.

Stuyt also described several studies carried out with military veterans, a group that does experience a lot of brain injury, though brain injury is not specifically addressed in these reports. Subjects were drawn from longitudinally-followed cohorts of veterans from the Northeast Program Evaluation Center NEPEC 1992-2011 (Wilkinson et al. 2015) and the National Health and Resilience in Veterans Study NHRVS 2011 (Hill et al. 2021) and NHRVS 2019-2020 (Hill et al. 2021a, 2021b, 2022). As in the LaFrance report, there is no information about the dose or composition of cannabis. Subjects were categorized as minor variations of the following: never-users, stoppers, starters, and continuing users. Over time, the measures of PTSD and comorbid mental health issues become more sophisticated, and the findings across these studies are robust. Inequity driven by race and ethnicity, educational attainment, income, and younger age are all associated with persistent PTSD, and these subgroups are those in which cannabis use is more frequent.

Further, PTSD does not respond long-term to cannabis and appears to intersect with psychiatric comorbidity (including substance use disorders). The researchers ask whether veterans are self-medicating to deal with disorders unresponsive to treatment. Depressingly, regular mental health support for these veterans still is below 50% in these cohorts.

Dr. Stuyt has called for the reclassification of marijuana in the DEA Schedules so that additional research can be carried out. She has observed that concentrations of THC (the component which produces euphoria) currently are much higher than in the 1980s. In contrast, the concentration of CBD in current products has remained relatively low. She continued, “we have no idea if the benefit comes from the THC or CBD or one of the other multiple cannabinoids present in marijuana, or a combination. And we have no idea how much is needed or how often.” Her concerns about this, as well as about the effect of these components on the developing brain, are well-taken.

The lesson for concussion management is clear. Multisystem assessment and support are the cornerstones of management for conditions like concussion and PTSD. Treatment “miracles,” medication and otherwise, need to be viewed with skepticism while rigorous evaluation of them continues. Continued work toward health equity is key and can only help recovery from these complex disorders.

Veterans

Free services and healthcare for veterans and caregivers

A recent tweet by UCLA Health Operation Mend reminds veterans of free services and healthcare available to them.

“Are you, or is someone you know, a post-9/11 #Veteran and struggling psychologically or physically? With our free services for Veterans and their #Caregivers we can build a brighter future. Call 310-267-2110 to speak with us. We are available from 8 am - 4 pm Pacific Time.”

You can read more about Operation Mend on their website and on our Service Members and Veterans resource page (in the Warrior Care Network section.

Statistics

45% of concussion patients show brain injury symptoms at six months

A woman sitting on the couch holding her forehead (she has a headache) and taking medication

Researchers Rebecca Woodrow and Dr. Emmanuel Stamatakis, in an article published by the University of Cambridge, discuss the ramifications of their research published in BRAIN. The team found that a mild brain injury can create changes in coordination between different regions of the brain (thalamic hyperconnectivity) and that these changes were related to their findings that 45% of the study participants still had symptoms such as cognitive impairment, depression, and most commonly, headaches, poor concentration, and fatigue at six months post-injury. (We wrote about the study in our 4/20/23 newsletter.)

Woodrow states, "Despite there being no obvious structural damage to the brain in routine scans, we saw clear evidence that the thalamus – the brain's relay system – was hyperconnected. We might interpret this as the thalamus trying to over-compensate for any anticipated damage, and this appears to be at the root of some of the long-lasting symptoms that patients experience."

The recovery phase may vary significantly from one patient to the next. Dr. Stamatakis notes, "At present, we have no clear way of working out which of these patients will have a speedy recovery and which will take longer, and the combination of over-optimistic and imprecise prognoses means that some patients risk not receiving adequate care for their symptoms." He added that there has been a sharp rise in mild TBI cases worldwide, with falls in the aging population and road traffic collisions being the most common causes.

In their Europe-wide research project, about 108 patients with mild traumatic brain injury were recruited to CENTER-TBI, and patients' ongoing symptoms were monitored. The research team then compared the functional MRI scans taken from the 108 patients with a mild TBI with those of 76 healthy volunteers. They found that the concussion patients had clear abnormalities associated with a particular region known as the thalamus in the brain, which is responsible for integrating sensory information and relaying information to multiple areas of the brain. They stated that "Counter-intuitively, a concussion was associated with increased connectivity between the thalamus and the rest of the brain – in other words, the thalamus was trying to communicate more as a result of the injury – and the greater this connectivity, the poorer the prognosis for the patient."

The researchers also used positron emission tomography (PET scans measure the chemical composition of body tissues) to identify key neurotransmitters linked to specific long-term symptoms a patient might be experiencing. "For example, patients experiencing cognitive problems such as memory difficulties showed increased connectivity between the thalamus and areas of the brain rich in the neurotransmitter noradrenaline; patients experiencing emotional symptoms, such as depression or irritability, showed greater connectivity with areas of the brain rich in serotonin."

Dr. Stamatakis provided more insight into the future implications of these findings. He elaborated by saying that there are currently drugs available that target these key neurotransmitters in the brain and hopes that further research may not only allow them to predict a patient's prognosis but also aid in offering treatments that precisely target their symptoms.

Youth

The Difference in Recovery Time Between Adults and Adolescents, as well as Between Boys and Girls: One Girl’s Story

a teenage girl lying in be with an icepack on her forehead

Adolescents and adults recover from concussions differently; not only that, girls and boys recover differently, too. Journalist Batya Swift Yasgur tells the story of teenager Layla Blitzer in an article for WebMD that discusses differences in recovery timelines. Layla suffered a concussion last October when she was hit in the head with a field hockey ball at her high school game. She didn’t even know she had a concussion at first, as “even the referee said [to her], ‘You’re not throwing up, so you’re fine.’” She was diagnosed with her concussion shortly after, but she and her mother had a lot more to learn.

As Dr. David Wang describes, adults and adolescents have the same symptoms, but the severity and recovery times are quite different; symptoms are more severe for adolescents than adults or younger children. The consensus statement on concussion in sport (which will be updated in June 2023) states that normal recovery time is >10–14 days in adults and >4 weeks in children. Dr. Wang confirms this, saying that an adolescent regularly takes 3-4 weeks to recover, maybe even longer for teen girls. Puberty is one of the differences between adolescents and adults; plus, adolescents are not neurologically mature. The ongoing maturation in teens makes them more vulnerable to concussions. The difference between the genders is also true between adult men and women; research has identified several potential physiological reasons for female and male differences in concussion recovery. There is some hope for adolescents, though; a recent analysis found that physical therapy is an effective treatment.

This longer recovery time affects many aspects of a teenager’s life, especially academically. Layla experienced this firsthand; she attempted to be in school three days after her concussion. However, it was too bright and overstimulating, so she stopped attending school after two weeks. Despite her school being supportive and having worked with a concussion specialist to reduce her workload and give her extra time on assessments and breaks, Layla fell behind in her schoolwork. Her school expected her to recover much sooner than she could. Falling behind and trying to catch up is stressful; Dr. Wang calls it “academic quicksand” because “it feels like the more the teenager struggles, the deeper they sink because the struggle itself can be so stressful.” But academics aren’t the only part affected; a teenager’s social life also becomes stressful. Layla isn’t able to out with her friends on the weekends, as she knows it’ll be too loud or bright. Another factor is that missing school and other social activities takes its toll on maturation.

Layla is doing better, though; she’s still recovering, but she’s also an intern at a nonprofit for women with concussions; she works as an advocate for other teens with concussions. Currently, she’s working with her league to require protective gear for field hockey and a more realistic back-to-school protocol. She believes that teachers “should be educated to expect that kids who have had a concussion may not be up to speed in work for some time. And they should know how to help a student successfully handle schoolwork again.”

Women’s Health

Differences in brain activity in males and females after a pediatric concussion

A recent journal article published in Scientific Reports found differences in resting-state functional brain activity in males and females after a pediatric concussion. Compared to controls, females with a concussion had differences in brain region connectivity in fifteen significant clusters. Compared to controls, males with a concussion had differences in brain region connectivity in only three significant clusters.

Authors Bhanu Sharma et al. examined 29 children who had sustained a concussion injury in the previous month and 361 controls. They compared medical image scans from both groups, taken one-month post-injury, using resting-state functional magnetic resonance imaging (rs-fMRI). Noting that nearly 30% of children develop long-term symptoms (typically defined as symptoms lasting longer than one month), the researchers suggest their study supports increasing evidence that males and females differ in recovery timelines.

The researchers found differences in females with concussions (compared to their healthy peers) that were not seen in males with concussions. They found that in females with a concussion, there was reduced connectivity between the “anterior cingulate cortex of the salience network and the thalamus and precuneus and the cingulate gyrus.” Furthermore, they observed increased connectivity between the “salience network seed and the cerebellum and the PCC and the thalamus, cuneal cortex and lateral occipital cortex left.” These scans were analyzed using “seed-based and region-of-interest” methods to investigate sex-based differences in the brain.

While reduced connectivity was observed in ten significant clusters and increased connectivity was observed in five significant clusters for females with concussions, only three significant clusters were observed in males with concussions. Ultimately, the authors conclude, “our study is the first to report that in pediatric concussion, there are rs-fMRI disturbances observed in females that are not present in the males.”

CTE & Neurodegeneration Issues

Protein TDP43: A potential biomarker to understand the long-term impact of concussions

A news story from the University of Michigan Concussion Center reports a strong connection between TDP43 (a protein essential for proper RNA processing and protein synthesis) and conditions such as chronic traumatic encephalopathy (CTE) and frontotemporal dementia (FTD).

The accumulation of abnormal protein deposits in our brains can lead to neurodegenerative diseases like Alzheimer’s and chronic traumatic encephalopathy (CTE). Sami Barmada, an associate professor in the university’s Neurology department, states that neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) specifically involve the build-up of the protein called TDP43. Barmada explains that TDP43 has also been observed to accumulate in individuals who have sustained numerous concussions (mTBIs) and developed dementia later in their life. “There’s a strong connection between TDP43, FTD, and the condition we now call CTE due to repetitive head injuries,” he says.

More research on the functions of TDP43 will illuminate what occurs in concussion-related injuries and help us discover other potential concussion biomarkers. Barmada is especially interested in examining the ‘similarities between age-related neurodegenerative disorders on the one hand and concussion/CTE on the other.’ He explains that a measure or biomarker would allow us to detect neurodegenerative diseases early and identify at-risk individuals. Such findings could be critical in improving concussion treatment and long-term management.