We appreciate your patience with this newsletter. Last week we had multiple short-term health issues in our staff that made us unable to meet our usual publishing deadline. The next newsletter will be published on our regular schedule on Thursday, July 7th.

This is the first Newsletter of our Summer 2022 Education & Advocacy Internship! The synopses you’ll be reading this week were written by our fantastic cohort of interns as part of their program; we hope you enjoy!

The lead article this week, Preventing concussions when swimming and diving, is in the Education category.

In this newsletter: Opportunities, Education, Sports, Cannabis & Psychedelics, Pathophysiology, Diagnostics, Self Care, Therapies & Diagnostic Tools Under Research, Veterans & Service Members, Mental Health, Statistics, CTE & Neurodegeneration Issues.

We appreciate the Concussion Alliance Interns and staff who created this edition:
Writers: Aaron Banse, Amanda Cheney Zitting, Ania Hoang, Chad Foster, Elizabeth Zegarowicz, Fadhil Hussain, Kaori Hirano, Kira Kunzman, Padmini Konidena, Sarah Fink, & Shannon Glor.

Editors: Conor Gormally and Malayka Gormally

Do you find the Concussion Update helpful? If so, forward this to a friend and suggest they subscribe.

Opportunities

Wednesday, June 29th, 1:00 pm PST: A free online class, BE with Your Brain, Yoga!, will be facilitated by Maria Dalbotten, MA, LMHC, RYT. Hosted by the Brain Injury Alliance of Washington State. You did not need to be a WA State resident to add. Register in advance.

Be part of a study on brain health and head impacts from sport: The Head Impact and Trauma Surveillance Study (HITTS) is recruiting study participants who will take a fully online, annual survey. "Anyone age 40 or older who played soccer or tackle football at any level (youth, high school, college, or pro/elite) can enroll."

Education

Preventing concussions when swimming and diving

KITV Island Television reports that more people should be concerned about concussions before diving into the pool. Recent reports from the University of Hawaii (UH) have caused concern for competitive swimmers and divers. UH has seen a rise in the number of concussions in athletes, specifically in swimmers. This year there were three concussions, which may not seem like many, but the last time there was even one was in the 2018-2019 school year. UH reports that they will be keeping an eye on the number of swimming and diving concussions.

Diving injuries usually occur when a diver hits the water after over-rotating or not completing their dive correctly. When your body hits the water during a dive, your whole body weight – plus gravity – impacts your head and spine.

You don’t have to be a high diver to get a concussion in the pool. Swimmers most often get concussions from colliding headfirst with other swimmers or objects.

Knowing where the walls and bottom of the pool are is very important for those who swim and dive. Divers should go feet first to get a feel for the pool before jumping off headfirst or doing twists & turns to reduce the risk of concussions when diving. Goggles can help protect pool-goers while swimming, aiding their ability to see the bottom and sides of the pool – and other swimmers. When doing the backstroke, know your stroke count to prevent hitting your head on the pool at the end of the lane.

Other safety precautions include staying in water depths fitted to your swimming ability, swimming with a buddy, and always being able to see where you are going. Although many perceive swimming and diving as low-risk activities, it is still essential to be aware of preventive measures which can reduce the risk of concussions while swimming.

Sports

International soccer board renews trials of permanent concussion substitutions, delaying implementation of rule

The International Football Association Board (Ifab) announced they are extending existing trials of permanent concussion substitutes until 2023. Ifab has also decided against trialing temporary concussion substitutes, which would keep the number of players on the field even while concussion evaluations take place to theoretically reduce any sporting concerns around taking players off the field.

Those against permanent substitutions argue that players are more likely to be left on the field. With many concussion symptoms not showing up immediately and difficulty in making concussion assessments on the pitch, critics argue that temporary replacements could allow for concussion diagnosis, according to the article in the Guardian. In the article, Ifab CEO Lukas Brud did not rule out temporary substitutions but said that Ifab would wait to complete the permanent substitution trials before trying anything else.

Concerns rose from families of England players who have suffered from concussions and accused Ifab of disregarding the players’ health. The families addressed their concerns through an open letter to Ifab ahead of their annual meeting in Doha. This extension of the trials leaves players in upcoming tournaments, including domestic and major European and winter World Cup championships, at unnecessary risk.

Permanent substitutions are safer, as FA chief executive Mark Bullingham told the Guardian; in rugby union, with temporary concussion substitutes, 15% of the diagnoses were incorrectly given and allowed the player to come back on the pitch with a concussion.

There has been difficulty in obtaining medical information of players from so many countries, and the lack of data slowed down the process of the trials. Ifab has chosen to focus on the permanent concussion substitute option to deal with head injuries. According to an article in AP National Sports, Ifab ratified allowing 15 bench players (instead of 7) and 5 injury substitutes (instead of 3) at its Doha meeting.

Cannabis & Psychedelics

Maryland subsidizes psychedelics studies and potential “cost-free” access for veterans with trauma

Maryland passed a bill that creates a state fund to subsidize the study of, and “cost-free access” to alternative methods of trauma treatment for veterans, including “hyperbaric oxygen therapy and psychedelics including…MDMA, psilocybin, and ketamine.” This Post-Traumatic Stress Disorder and Traumatic Brain Injury Alternative Therapies Fund was created to address the needs of eligible veterans who have PTSD or traumatic brain injury.

Senate Bill 709 was proposed by Sen. Sarah Elfreth (D) and unanimously passed through both chambers. According to an article by Marijuana Moment, Gov. Larry Hogan (R) announced he will enact the measure without signing his name to the bill. The bill allocates $1,000,000 in Maryland’s 2024 annual budget to the fund.

While there has not been nearly enough research done yet to conclude that psychedelics will be the answer to treating the long-term and persistent effects of brain injury, the Maryland Department of Health is partnering with the Department of Veterans Affairs, John Hopkins University, and other medical organizations to determine the “effectiveness of and a method for improving access to alternative therapies for treating” PTSD and traumatic brain injury in veterans. On December 1, 2022, the Maryland Health Department will report its initial findings to the legislature.

Maryland is not the only state where this type of legislation is coming to fruition. Similar legislation has also been proposed in Colorado, Connecticut, Georgia, Maine, Utah, Missouri, Washington, Hawaii, Oklahoma, Rhode Island, Oregon, Pennsylvania, California, New Hampshire, and Texas. The various legislative proposals will work towards reform within the current laws and regulations concerning psychedelics, including; Psilocybin, Methylenedioxymethamphetamine (MDMA), and Ketamine for therapeutic purposes.

Pathophysiology

Study finds no association between cerebral microbleeds and white matter alterations when adjusting for TBI severity

A recent study from the Turku Brain Injury Center, published in Frontiers in Neurology, looked at the association between cerebral microbleeds (CMB) and white matter (WM) alterations. A CMB is a vascular injury, and WM alterations are axonal injuries, so this study aimed to learn how these two types of injuries are associated. (When CMBs occur in mild TBI, the injury is called a complicated mTBI).

The study findings suggest that CMB and WM alterations are both influenced by the severity of TBI but do not affect each other. While CMB “have a limited ability to serve” as an indication of WM damage, scientists should look to develop more sensitive methods of detecting microstructural WM alterations. Currently, scans commonly used in clinical settings cannot detect WM alterations.

The study involved 54 patients with TBIs, most of which were mild, selected from a total of 203 patients involved in the TBIcare project at Turku University Hospital. Researchers used an MRI alongside a grading system that categorized patients’ CMB into different severities. This grading system took into account where the bleeding took place and how much bleeding there was. Researchers also used diffusion tensor imaging (DTI) to analyze WM microstructural integrity. Lastly, patients were assessed on their injury severity using the Glasgow Coma Scale (GCS) and the duration they experienced post-traumatic amnesia (PTA).

Using GCS and PTA to control for TBI severity, the authors found no correlation between the level of CMB and DTI measures of WM alterations. Researchers Juho Dahl et al. conclude that “it is important to note that even though CMBs were associated with more severe injury, a patient with TBI and CMBs can recover with no long-term disability, as well as a patient with TBI without CMBs can show a poor outcome.”

Diagnostics

For optimal cognition assessment, study finds that subjective (self-reported) assessments should be paired with objective (neuropsychological battery)

One of the most contentious issues in concussion research and policy is the potential for long-term effects, including declining cognitive abilities. A study published in The Clinical Neuropsychologist examined former collegiate football players to investigate the “association between subjective self-report and objective performance-based cognition” and its “relationship to self-reported concussion history.”

After analyzing their results, Andrew M. Bryant et al. determined that “reliance on self-reported measures of cognitive functioning alone are insufficient when assessing functional status in former contact sport athletes.” Other influences of subjective cognition could be factors such as psychological distress, which include stress and unrelated sleep disturbances. The authors conclude that “a comprehensive evaluation involving both subjective and objective performance-based data is optimal.”

The researchers administered 11 tests to the 57 football players (15 years after retirement from sport). Six tested their objective cognitive functioning, three tested their subjective cognitive functioning, and two tried other functioning such as sleep quality. Subjective cognition was measured using the Quality of Life in Neurological Disorders Cognitive Functioning-Short Form, which includes self-reported problems such as increasing forgetfulness, losing a train of thought, feeling overwhelmed making decisions or planning, and depression. Objective cognition was measured using the Neuropsychological Battery Form, which includes performance-based issues such as attention, comprehension, memory, and executive functions.

Their results suggest that other factors, such as distress, can influence subjective cognition – distress that may or may not be related to the effects of past contact sports. The study found that a greater “self-reported concussion history was inversely associated with subjective cognition” and that “Distress was significantly related to all metrics of subjective cognition.”

The study mentions other cognitive conditions, such as Parkinson’s patients and cancer patients who have undergone chemotherapy. Similar discrepancies in subjective vs. objective cognition are found in concussion patients. More broad research is needed about the most effective way to assess an effective method of analyzing the decline of cognitive abilities.

Self Care

Study Finds Gut Microbiome Impacts the Effectiveness of Different Dietary Patterns

Self-care for concussion entails psychological and physical considerations, including nutrition. A study in Cell Host and Microbiome discusses how the gut microbiome – the bacteria and archaea that live within the digestive tract – are linked to diet and chronic disease risk in a multidirectional way. Anissa M. Armet et al. assert that “virtually all chronic diseases have…been linked to the microbiome.” Although the study is not about concussion, it demonstrates the interconnectedness of health.

The study focuses on the interconnectedness of foods within traditional nutrition plans but includes restorative practices an individual can adopt into previous eating habits. Fermented foods that contain probiotics are full of live microorganisms that can positively increase the diversity of microbiota in the gut, ultimately reducing chronic disease risk and digestive tract inflammation.

Some microbiome restoration strategies focus solely on increasing the intake of fiber. However, “approaches focused solely on dietary fiber are unlikely to replenish lost microbial species.” Therefore, increasing the amount of fermented foods like yogurt, kimchi, sauerkraut, kombucha, and kefir can positively increase the diversity of bacterium within the gut microbiome. The New York Times articles “How Fermented Foods May Alter Your Microbiome and Improve Your Health” and “The Dos and Don’ts of Fermented Foods” provide further information about fermented foods and their impact on the gut microbiome.

The food you eat (processed vs. whole foods, for example) may directly impact you, such as a rush of sugar that is felt instantly, and may affect you in the long term, such as a high-sugar diet contributing to diabetes. In addition, the components of foods (such as phytochemicals and fibers in plants) impact the microbiome. A positive impact would be the promotion of a diverse microbiome. A negative impact could include a lack of diversity in the microbiome and the promotion of “metabolic abnormalities and low-grade inflammation,” as found in mice studies.

Armet, A. M., Deehan, E. C., O’Sullivan, A. F., Mota, J. F., Field, C. J., Prado, C. M., Lucey, A. J., & Walter, J. (2022). Rethinking healthy eating in light of the gut microbiome. *Cell Host Microbe*, 30(6), 764–785. https://doi.org/https://doi.org/10.1016/j.chom.2022.04.016

Nutritional components affect the microbiome both individually and by interacting with each other in different combinations based on a person’s diet, with highly variable implications for the microbiome. This interaction effect makes traditional nutritional plans, like the Mediterranean diet, so efficacious, as they include multiple positively synergistic nutritional components.

Regarding nutrition sources, “Low-fat diets are often rich in vegetables, fruits, whole grains, and plant-based proteins and therefore provide beneficial dietary components that alter microbiome metabolism.” Whole plant foods have phytochemicals (these account for the color, flavor, and smell) that, through fiber fermentation, create short-chain fatty acids. Increasing the production of these short-chain fatty acids has been linked to an enhanced gut barrier. Increased short-chain fatty acids reduce the intrusion of bacteria, thus decreasing an individual’s risk of chronic disease.

Aside from providing less nutritional value than whole-plant foods, “Processed foods can further contain food additives to enhance mouthfeel and shelf-life that affect gut microbiota.” These food additives “impaired gut barrier function and led to microbiota epithelial encroachment,” observed in inflammatory bowel disease and colitis. Although fermented foods can help restore the microbiome diversity in the gut, prioritizing whole-plant foods over processed foods will also help maintain a healthy gut microbiome while improving overall health.

Therapies & Diagnostic Tools Under Research

Interleukin-2 indirectly decreases inflammation in the brain due to traumatic brain injury in mice

A recent study published in Nature found a potential new treatment option for traumatic brain injury (TBI). Lidia Yshii et al. found that Interleukin-2 (IL-2) increases regulatory T cells, decreasing inflammation in the brain. Regulatory T cells are the body’s natural response to inflammation in the brain. A TBI can cause significant inflammation in the brain, often contributing to long-term symptoms.

The authors designed a gene-delivery delivery system to deliver the protein IL-2 across the relatively impervious blood-brain barrier, which has previously been a challenge for the delivery of medications. The controlled release is restricted to the central immune system (solely within the brain), so it does not impact the rest of the body through the peripheral immune system. The study was done with mice given moderate TBIs and validates “gene delivery as effective protection against neuroinflammation.”

In an article in Genetic Engineering and Biotechnology News, Dr. Adrian Liston explained, “Unfortunately, there are very few of these regulatory T cells in the brain, so they are overwhelmed by the inflammation following an injury. We sought to design a new therapeutic to boost the population of regulatory T cells in the brain so that they could manage inflammation and reduce the damage caused by traumatic injury.”

To test IL-2’s effectiveness, researchers split male mice into two groups: the control did not receive IL-2 supplements; the second group did. They gave each group a moderate TBI and examined MRI images of the brain 14 days later. The authors found a significant difference in lesion size and number of regulatory T cells between the two groups, with smaller lesions and more regulatory T cells in the IL-2 group. These findings suggest that increased regulatory T cells are correlated with smaller lesions and less inflammation.

This IL-2 treatment is essential, according to Dr. Liston, who says, “with tens of millions of people affected every year, and few treatment options, this has real potential to help people in need.” While the study found that the treatment can decrease moderate TBI symptoms in mice, clinical trials are necessary to determine if the same effect is seen in patients.

Veterans & Service Members

Blunted ‘fight or flight’ response in military members with more blast, combat exposure

A study published in Stress and Health investigated how different levels of combat exposure influenced stress response, specifically the activation of the sympathetic nervous system – or the 'fight or flight' response. In response to maximal effort exercise, military members with more exposure to combat showed "blunted" electrodermal activity (EDA) compared to those with less exposure to combat. EDA is a measure of electrical skin conductance that can estimate central sympathetic activation.

A blunted EDA in response to maximal effort exercise may signify that the sympathetic nervous system is not working as well as it should in those with more combat and blast exposure. For this study, Marcus K. Taylor et al. studied 51 US Navy Explosive Ordnance Disposal (EOD) personnel members, "a group of specialized military operators with expertise in explosives, diving, and parachuting."

Study participants completed a graded exercise test to determine if combat exposure affects the EDA response to exercise stress. The researchers measured electrodermal activity continuously as the military men worked their way up to their maximal effort, then walked and sat to recover. Those with low combat exposure and no blast exposure showed a steep linear increase in EDA through maximum effort that leveled off during recovery. Those with more exposure to combat and blasts saw EDA level off or even decline before reaching maximal effort.

These results reflect a "dampened sympathetic nervous system response" in military members who have been in more combat and blast situations. Further research could help determine how military members can more optimally regulate stress and preserve performance.

Mental Health

Psychological factors influence symptom provocation when testing activity, cognition, balance

A study published in The Journal of Head Trauma Rehabilitation finds that psychological factors may influence symptom provocation tests. The study findings suggest additional caution in interpreting these provocation test results, as incomplete recovery may not be the only cause for “symptom provocation test failure” (the test eliciting an increase in symptoms).

Some symptoms, such as fatigue and headache, are found in both post-concussion symptoms and psychological factors, making it essential to understand the impact of psychological factors on symptom provocation tests. This study expands on previous research, which has suggested that physical and mental activity intolerance during cardiovascular, cognitive, and vestibular/ocular tests may be influenced by factors other than concussion, such as anxiety.

Study authors Alex R. Terpstra et al. examined 79 participants who experienced a concussion between 1 and 12 months before the study began. All participants self-reported at least three post-concussion symptoms as moderate to severe. The study examined the effect of psychological variables on symptom provocation in cardiovascular, cognitive, and vestibular/ocular tests. The psychological variables include anxiety history, current anxiety, somatization (physical symptoms caused by a mental state), catastrophizing (magnification of seriousness/consequences of symptoms), and fear-avoidance behaviors (avoidance of behaviors that could affect symptoms).

The psychological factors studied were associated with greater symptom increases during the Vestibular/Ocular Motor Screening for Concussions test (VOMS). Among participants with relatively high scores on the psychological variables, symptoms worsened more during the VOMS test than among those with lower scores. This association was not found in the cardiovascular (BCBT) or cognitive ability (NIHTB-CB) tests. The study notes that “participants who were too symptomatic to take the BCBT scored higher on measures of anxiety and catastrophizing than participants who took and failed the BCBT.” Further study is required to determine any impact of psychological factors on symptom provocation in cardiovascular and cognitive testing.

One fundamental limitation is that “psychological factors were strongly associated with pretest ratings of symptoms severity.” Participants who scored the highest on psychological factors were more likely to rate their symptoms at “near-ceiling levels” at the beginning of the study, limiting the ability of their scores to increase during the tests. Because the study measured variation from initial to post-test symptom results, starting with a higher symptom level leaves less ability to detect changes in these symptoms.

The authors also note that “the influence of psychological factors on symptom provocation testing may be more detectable in individuals who are not already highly symptomatic before provocation testing begins.” The authors point to this limitation as a potential explanation for not finding the association between pre-injury anxiety diagnosis and symptom provocation testing found in prior research.

Statistics

Insufficient Sleep Leads to Greater Risk of Sports-Related Concussions in Athletes

A study in the Journal of Athletic Training found that sleeping a sufficient amount is beneficial for reducing the risk of a sports-related concussion (SRC). Riegler et al. investigated the effects of an insufficient amount of sleep (≤5.78 hours) compared to a sufficient amount of sleep (>7.07 hours) in a group of 614 student-athletes.

Alarmingly, athletes deemed “insufficient sleepers” were almost twice as likely (15.69%) to sustain an SRC as compared to the athletes who received sufficient sleep (8.79%). Furthermore, the authors performed an additional symptom assessment of 592 student-athletes (qualifying participants taken from the first study). Out of those diagnosed with SRC, insufficient sleepers experienced “symptom clusters” (multiple symptoms in the affective, cognitive, physical, or sleep domains) and headaches to a greater extent than sufficient sleepers.

Researchers suggest several reasons for the profound impact of lack of sleep on physical performance, including “more dangerous playing behavior, reduced attention or reaction time.” These speculations build on prior research, including a study published in the Asian Journal of Sports Medicine by Taheri and Arabameri (2012), which stated that “cognitive functions such as reaction time are more vulnerable to be affected by sleep deprivation.”

With physical and cognitive abilities essential to playing sports impaired, it is not surprising that sleep deprivation creates conditions with an increased likelihood of sustaining a sports-related concussion. Reigler et al. concluded that “sleep may be an important target for primary intervention…to reduce risk of SRC.”

CTE & Neurodegeneration Issues

Arguing for a public-health approach to CTE education and risk management

In a perspective article in Frontiers in Neurology, Michael E. Buckland et al. argue that the assessment of evidence linking repetitive head injury (RHI) and chronic traumatic encephalopathy (CTE) should be shifted away from a scientific research framework to a public health framework. They argue that the research framework, as it is currently used by “professional bodies that oversee risk management,” requires evidence and a causal burden of proof that is impossible to get, rather than recognizing existing evidence of the relationship between RHI and CTE.

Research often assesses evidence through the Oxford “Levels of Evidence” approach. Randomized controlled trials (RCTs), graded as the highest level of evidence, cannot be conducted with CTE research because CTE is a life-threatening neurodegenerative disease that can only be diagnosed after death; RCTs are “simply infeasible with CTE, from both a practical and ethical perspective.” Because of these limitations, evidence is categorized as “low level” regardless of the exhibited association between RHI and CTE.

Public health frameworks review evidence prioritizing public education and risk reduction. The ambiguities associated with disease do not “negate the important causal association” in a public health framework. This framework encourages more recognition and research of CTE but also acknowledges that the uncertainties associated with RHI and CTE don’t invalidate the clear risks of repetitive head injury on long-term neurological health.

In an article published by The Age, concussion expert Alan Pearce suggests that CTE should be recognized as an occupational disease by the Australian (Rules) Football League (AFL), as “it would mean they can’t attribute it (CTE) to other reasons.” Acknowledging the association between RHI and CTE will lead to more research, potentially revealing mitigation strategies and a better understanding of the disease.

Shifting how research related to CTE is assessed will allow researchers to mitigate a “preventable environmental disease” that has devastating ramifications for those with likely CTE and their families. Treating CTE through a public health framework will allow for better knowledge translation to the public and professional athletes alike (even as some aspects remain unclear) instead of outright dismissal because of a “lack of evidence.”