This week’s lead article, Brain white matter changes following repetitive head hits in a single sporting event, is in the Therapies & Diagnostic Tools Under Research category.

This summer, we are delighted to publish weekly newsletters written by our fantastic cohort of interns. You can learn more about the internship program here.

In this newsletter: Opportunities, Education, Diagnostics, Therapies & Diagnostic Tools Under Research, Mental Health, and CTE & Neurodegeneration Issues.

We appreciate the Concussion Alliance interns who created this edition:
Writers: Sneha Bansal, Ella Webster, Runa Katayama, Jeffrey Kong, and Kaitlyn Chen

Editors: Malayka Gormally and Conor Gormally

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

Opportunities

Action alert from the Brain Injury Association of America: the U.S. Congress may cut all of the CDC’s brain injury and concussion-specific programs, including HEADS UP and the National Concussion Surveillance System. Click here for an easy form to contact your representative.
The form will automatically send your message to your U.S. Representative. You can optionally customize your message by adding your representative’s name, which you can find here by inputting your zip code.

August 20, 4 pm EDT: A live webinar, Attention and Information Processing Speed Following Brain Injury – An Interdisciplinary Approach, presented by Tracy Graham, MSP, CCC-SLP, CBIS, Amanda Heys, OTR/L, and Tori Stramara, DPT, CBIS, and hosted by the Brain Injury Association of America. Free to patients, $50 for CE credit; register in advance.

Education

Replacing the term "subconcussive" to improve understanding of brain injuries

In a recent editorial published in the British Journal of Sports Medicine, a team of experts from Harvard University, Boston University, the Mayo Clinic, and the Concussion Legacy Foundation argue that the term “subconcussive” should be replaced by new terms when referring to head impacts and injuries, specifically subclinical head acceleration events (HAEs) and injuries, “as defined by clinical, biomarker and/or neuroimaging change.” The authors recommend using the more agnostic term “non-concussive” to describe HAEs that do not result in a diagnosed concussion. The term “subconcussive” is a misnomer, as data from helmets and mouthguards has revealed that “many HAEs are associated with greater head acceleration than impacts that result in a diagnosed concussion.”

The authors recommend using “subclinical TBI” instead of “subconcussive injury,” as some non-concussive impacts may still cause injury associated with changes in brain function, biomarkers, and imaging, even in the absence of symptoms. In this case, the term “subconcussive” is contradictory, as it implies no injury occurred. The authors reference studies that show “increasing biomarkers of neuroinflammation” after acute HAE exposure and other studies that show repetitive HAE over time may increase the risk of concussion. They point out that recent studies have also correlated long-term repetitive HAE exposure to neurodegenerative diseases.

Dr. Chris Nowinski, the lead author of the editorial and co-founder and CEO of the Concussion Legacy Foundation (CLF), discusses this issue in a CLF blog post: “Scientists have been referring to head impacts that don’t cause concussion symptoms as ‘subconcussive impacts,’ which implies they are less than concussions. This has even led to CTE experts saying CTE is caused by ‘small, repetitive impacts.’ But when it comes to the size of the hit, 10% of head impacts are more than [the level of HAE that has caused some] concussions. We recommend replacing ‘subconcussive’ with ‘non-concussive’ to better describe these impacts. After a head impact, a concussion was either diagnosed, or it wasn’t.”

By changing the terminology, the authors aim to add specificity and clarity to understanding non-concussive impacts and their potential for causing subclinical brain injury. This argument is an essential step in advancing the conversation around concussions and repetitive head impacts in sports.

See our newsletter synopsis on research concerning long-term repetitive HAE and CTE and our Neurodegenerative Disease resource concerning elevated risk for neurodegenerative disease in former professional Scottish soccer players.

Diagnostics

Patient symptom report remains the most accurate method of sport concussion assessment

In a case-control study published in JAMA Network, Kimberly G. Harmon et al. found that an athlete’s symptom report is more accurate for concussion diagnosis than the Standardized Assessment of Concussion (SAC), a cognitive evaluation commonly used as part of the Sports Concussion Assessment Tool (SCAT). The SCAT is used for evaluation in sports and encompasses both the subjective symptom report and the SAC, which screens for signs of cognitive dysfunction commonly seen in concussion patients. Researchers analyzed the components of SCAT-5 baseline results and post-injury SCAT-5 for 92 NCAA athletes who suffered a concussion while playing their sport. Many of the studied athletes had inconsistent SAC scores while a concussion was present, highlighting the importance of the symptom report.

When a concussion was suspected, athletes were screened with the SCAT-5 within 48 hours, including the SAC––using a 10-word list to test memory and recall introduced in the SCAT-5 after criticisms of previous versions’ 5-word list. If a concussion was confirmed, a control athlete underwent the same tests. Each concussed athlete was matched to a non-injured control athlete of the same gender, age, sport, and a baseline SCAT-5 score within 2 points. Researchers found that SAC had poor diagnostic utility regarding sensitivity and specificity even using the 10-word list, whereas reported symptoms were more accurate in both sensitivity and specificity. Concerningly, 45% of athletes with a concussion scored at or above their baseline SAC (within normal limits), despite a score below baseline indicating concussion. Although a score at or above baseline SAC may be inconclusive, the fact that the SAC did not identify almost half of the concussions highlights the importance of the symptom report and the lack of accuracy of the SAC cognitive examination. The study authors add that in addition to the symptom report (typically an increase in symptoms), “other objective indicators of concussion such as visual signs and vestibulo-ocular or balance abnormalities” are an important part of concussion diagnosis. One of the limitations of the study noted by the authors is that the variance between sets of 10-word lists used for the SAC was not monitored, despite a previous study showing that these lists varied in difficulty.

In areview article by Sophie Dorey with The Daily, Harmon expresses the importance of a rounded approach, “The takeaway is if you get hit in the head and you have a headache, you’re dizzy, and you don’t feel right — that’s a concussion even if you do normally on the [SAC],” Harmon said. “You have to look at the big picture.” Harmon emphasizes the continuous use of a multimodal approach to concussion diagnosis for athletes.

Therapies & Diagnostic Tools Under Research

Brain white matter changes following repetitive head hits in a single sporting event

In an observational cohort study published by the Journal of Neurotrauma, researchers found that after a single collegiate football game, which involves repetitive head hits (RHHs), changes to glial fibrillary acidic protein (GFAP) correlated with head impact exposure and reduced brain white matter integrity in 30 Division III college football players two days later.

Bazarian et al. identified correlations between GFAP elevations in blood samples and the “number of hits, total linear acceleration, and total rotational acceleration captured by helmet impact sensors” and reduced white matter integrity two days later. Diffusion tensor imaging (DTI) showed a decline in fractional anisotropy (FA) in the fornix and corpus callosum, two key brain regions associated with cognition and information transfer between brain regions. (FA measures the level of water diffusion in the brain as a proxy for white matter integrity.) Researchers theorize that GFAP “may be a biologically relevant indicator of the brain’s acute response to non-concussive head impacts during a single sporting event.”

The rotational forces from head impacts physically strain and activate astrocytes, a type of brain cell that performs essential metabolic and neuroprotective functions. The strained and activated astrocytes release GFAP and swell, limiting water movement between the axons. This astrocyte activation and swelling contribute to the lowering of FA, indicating a possible relationship between head impact exposure and reductions in white matter integrity.

Focusing on a single Division III National Collegiate Athletic Association football game, the research team took blood samples from 30 football players at the University of Rochester. The researchers took blood samples at three different time points: immediately before the game, immediately after the game, and 45 minutes after the game. They performed DTI and had athletes complete a symptoms checklist 24 hours before the game and 48 hours after the game. Additionally, helmet and body exertion impact sensors were used to monitor the athletes during the game.

Developing tools to measure neurological responses to RHHs could lead to the creation of effective and personalized strategies at the individual level. Further research is needed to validate the findings with a larger sample size.

Mental Health

Moderate to vigorous exercise during post-concussion recovery reduces anxiety levels in teens.

In a study published in Medicine & Science in Sports & Exercise, Katherine Smulligan et al. found that engaging in moderate-to-vigorous physical activity (MVPA) during post-concussion recovery can reduce anxiety levels in teens and have other beneficial effects. This experiment looked at the impact of physical exercise on post-concussion recovery among 48 adolescents aged 13 through 18. According to study coauthor David Howell in an article in Science Daily, teens who regularly participate in high-intensity sports and are advised to rest in a dark room post-concussion may “have trouble sleeping because of that activity modification.” Integrating MVPA into recovery can promote better sleep, thus contributing to recovery. In addition, integrating MVPA into their concussion recovery routine can help with mental health.

Researchers used data from a broader study to study a cohort of 48 participants (27 females and 21 males aged 13–18) who visited a sports medicine clinic within two weeks of sustaining a concussion. Each participant rated their concussion symptoms and anxiety levels on a PROMIS anxiety scale at their first meeting with the physician and at their one-week follow-up. At their initial visit, participants were given a device to monitor their physical exercise levels over the week and did not receive specific instructions or recommendations for physical activity levels.

The authors found that higher MVPA values early after concussions correlated with lower anxiety levels among the teens in the study. On average, each hour of MVPA during the week was associated with a 5-point decrease in PROMIS anxiety scores (which range from 7-35). These significant findings suggest that moderate to vigorous physical activity can be an effective part of post-concussion rehabilitation and can mitigate the anxiety that many adolescents experience after a concussion. Even though pre-existing anxiety issues can affect anxiety levels post-concussion, engaging in MVPA can still improve post-concussion anxiety symptoms.

CTE & Neurodegeneration

Study finds long-term neurodegeneration in all severities of TBI

Trigger warning: This synopsis discusses traumatic brain injury (TBI), neurodegeneration, and cognitive impairments. It includes details about the long-term effects of TBIs, brain volume loss, and related medical conditions. If these topics are distressing or triggering, please proceed with caution.

A study published in Alzheimer’s & Dementia found that neurodegeneration is “progressive and continues for many years after mild head trauma without signs of brain injury on conventional MRI.” The study included 143 mild, moderate, and severe TBI patients and 43 controls, with participants tested at various intervals from 30 days to 5 years after their injury. Data was collected using blood tests, MRIs, and cognitive tests over a 9-year period. All severities of TBIs experienced the same amount of brain volume loss but in different brain regions; mild TBI was associated with atrophy in gray matter, while moderate to severe TBIs were associated with atrophy in subcortical gray matter or white matter.

On a more optimistic note, both mild and moderate to severe TBI patients showed cognitive improvement after their concussion, although those with more severe TBIs performed slightly worse. The study authors explain that “the relationship between cognitive performance and neurodegeneration after TBI is complex, and suggests two distinct processes, in which there is an interaction between them early on, followed by a divergence in the years after injury.” In other words, there are opportunities for cognitive improvement despite neurodegeneration.

In addition, they found that serum NfL and GFAP, neuronal proteins, and initial TAI (traumatic axonal injury) can serve as biomarkers of neurodegeneration in patients with TBI. These biomarkers offer the potential for noninvasive detection of elevated risk of neurodegeneration immediately after a TBI, as well as tracking neurodegeneration over time, post-TBI. The study authors suggest that biomarkers can also be used in research to evaluate the effects of therapies on post-concussion symptoms or research into other neurodegenerative diseases.

Limitations of this study include missing data at certain time points, fewer MRI scans for controls to evaluate age-related brain atrophy, and a slightly imbalanced proportion of TBI severities.