The lead article this week, Brain Training software improves cognition in chronic TBI, is in the Therapies Currently Available category.

In this newsletter: Opportunities, Pathophysiology, Therapies Currently Available, Therapies & Diagnostic Tools Under Research, Veterans & Service Members, Mental Health, Youth, Women’s Health, and Culture.

We appreciate the Concussion Alliance Volunteers and staff who created this edition:
Writers: Sravya Valiveti, Minhong Kim, Claire Holmes, Shelly Seth, Josh Wu, Conor Gormally, & Malayka Gormally

Editors: Conor Gormally and Malayka Gormally

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Opportunities

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."

Tuesday, June 14, 12 noon PST: a free online class, Rhythm (drum) Circle, will be led by Megumi Azekawa, Neurologic Music Therapy Fellow. Hosted by the Brain Injury Alliance of WA State – you do not need to be a WA State resident to participate. Register in advance.

Thursday, June 23, 12 noon PST: a free online class, Muscle Tightness after TBI, will be facilitated by physicians from UW Medicine. Hosted by the Brain Injury Alliance of WA State – you do not need to be a WA State resident to participate. Register in advance.

Pathophysiology

Acute neck pain following sports-related concussions associated with more overall symptoms

Findings from a study published in Clinical Journal of Sports Medicine suggest that acute neck pain is a symptom of concern and prevalent following sports-related concussions (SRC) among high school athletes. Researchers found that “Those with neck pain reported significantly more symptoms overall, relative to their non–neck pain counterparts.” Authors Kelly Cheever et al. highlight the need for an additional screening that could potentially “identify comorbid cervical pathology.” They also suggest prospective studies to “access the benefit of cervical therapy in the early stages in SRC patients with neck pain to reduce the risk of persistent postconcussion symptoms.”

The authors recruited 401 high school athletes from the National Athletic Treatment, Injury and Outcomes Network (NATION) study who suffered SRC between the 2011-2019 academic years. They measured outcomes based on “prevalence of neck pain (yes/no) – along with 33 other commonly reported concussion symptoms, number of symptoms reported, mechanism of injury (contact with person/surface or object), sport type (contact/noncontact), and injury history (first time/repeated injury).”

Of the 401 athletes, 33.9% (138) reported acute neck pain following SRC. Factors such as neck pain, repeated injury, and female sex were significantly associated with a higher number of concussion symptoms reported in the acute phase. Additionally, those with SRC due to contact with a surface were significantly less likely to disclose neck pain status than those who suffered SRC due to contact with a person.

Therapies Currently Available

Brain training software found to improve cognitive function in a small group with chronic TBI

A pilot study found that auditory processing speed training improved objective and subjective measurements of cognitive function in a small group of patients with chronic TBI. Authors Hannah M. Lindsey et al. found that 40 hours of auditory-based ‘brain training’ – completed over 13 weeks – led to “significant improvements in standard cognitive tests of attention, memory, and executive function, as well as in standard measures of self-reported symptoms,” according to a GlobeNewswire press release. The study, published in NeuroRehabilitation, also included imaging; chronic TBI patients who completed the training showed increased functional connectivity in their default mode network (DMN), a key region associated with cognitive function and internal thought processes.

The authors assigned 11 participants with chronic TBI to a ‘brain training’ group and 7 participants to a ‘no intervention’ control group. The brain training group used auditory processing speed training exercises from BrainHQ, a brain-training company with activities developed by neuroscientists. According to the GlobeNewswire press release, this study builds on a body of research showing the efficacy of BrainHQ training with respect to improving cognition, decreasing brain fog, and more.

BrainHQ works with sports, education, and veterans organizations and is also available online to individuals for a subscription fee. Their website notes that “BrainHQ is now available as a free online resource at hundreds of libraries around the United States.”

Therapies & Diagnostic Tools Under Research

The NYR-BI02 drug could potentially be an oral treatment for concussion

The biotechnology company, Nyrada, reveals a promising drug that can orally treat concussions. As detailed in an article from The Market Herald, Nyrada’s drug candidate, NYR-BI02, builds upon its previous iteration, NYR-BI01. NYR-BI02 includes a superior pharmacokinetic profile, “meaning it is absorbed, metabolized, and cleared in a manner that supports oral dosing.”.

There is currently no FDA-approved medication for concussion. An oral drug that alleviates secondary brain injury could be a revolutionary solution as concussions could immediately be treated “in the field immediately after a concussion injury.” The term secondary brain injury refers to “changes that evolve over a period of hours to days after the primary brain injury. It includes an entire series of steps or stages of cellular, chemical, tissue, or blood vessel changes in the brain that contribute to further destruction of brain tissue (John Hopkins Medicine).”

A white paper published by Nyrada notes that “NYR-BI02 readily crosses the blood-brain-barrier, providing assurance that it should reach therapeutic levels in the brain.”

The NYR-BI02 drug candidate would provide a different treatment method for people who aren’t comfortable with an intravenous infusion, though NYR-BI02 aims to offer intravenous administration. Nyrada plans on running Phase 1 human studies in Australia in the latter half of this year.

Veterans & Service Members

Supplement offers promise for veterans with TBI and sleep issues

In a pilot study, researchers Jonathan E Elliot et al. found that supplementation with “branched chain amino acids (BCAA: leucine, isoleucine, and valine)” improved sleep and insomnia symptoms in a group of veterans with TBI. Compared to two control groups, the participants who took BCAA for 21 days reported improved insomnia symptoms, took less time to fall asleep, and woke up less during the night.

The study, published in Frontiers in Systems Neuroscience, tested the feasibility and safety of BCAA supplementation after promising results in rodent models. In addition to the promising results, the authors report that “BCAA were well-tolerated with few side effects and no adverse events.” Their next step is a larger, randomized clinical trial to further evaluate BCAA’s promise as an intervention for TBI patients struggling with their sleep.

For more information about branched chain amino acids, we suggest this Healthline article, although it does not address sleep and insomnia.

Mental Health

Women and people of color at higher risk for depressive symptoms after mTBI

A study published in Journal of Neuropsychiatry found that women and people of color were “at higher risk for clinically significant postconcussive symptoms and incomplete functional recovery” within the first six months of recovery. Authors Durga Roy et al. found that these two factors (postconcussive symptoms and incomplete functional recovery) were associated with “depressive symptom development and poor outcomes after mTBI.”

Researchers evaluated 217 patients who had sustained an mTBI for the first time and divided them into subgroups based on their onset/presence of depressive symptoms: new onset of depressive symptoms, recurrent depressive symptoms, prior history of depression only (without experiencing depressive symptoms at six months post-injury), and never depressed. The authors analyzed patients’ clinical and demographic data and the presence of postconcussive symptoms to determine if specific populations developed depressive symptoms post-injury.

Of the study participants, 11% of the sample developed new-onset depressive symptoms, and 12% experienced recurrent depressive symptoms. Among these groups, women and people of color were more likely to experience these levels of depressive symptoms. They were also at a higher risk for enduring clinically significant postconcussive symptoms and an “incomplete functional recovery” 6 months post-injury.

The researchers note that these depressive symptoms may form after enduring postconcussive symptoms and a lack of proper recovery and emphasize the importance of clinical treatment for these symptoms in order to mitigate depressive symptoms.

Youth

Adolescents with mTBI need age-specific rehabilitation for changing self-identity post-injury

Researchers investigated identity formation in adolescents with a mild to severe TBI, focusing on gaps in research regarding clinical treatment for post-TBI adolescents who have symptoms of changing self-identity. The review, published in Neuropsychological Rehabilitation, concludes that adolescents (age 13-18) are a unique population and should be treated differently than post-TBI adults or younger children when it comes to symptoms of changing identity. Identity is a complex idea that begins to form in adolescence based on biopsychosocial factors at the time. Identity formation can be “derailed by TBI, and complicated further by identity reconstruction post-TBI.”

Lisa Kakonge et al. reviewed studies of identity in adolescents with TBI and then mapped “the evidence onto a biopsychosocial framework for rehabilitation.” The study authors used 11 articles narrowed by many criteria and “applied Gracey et al.’s Y-shaped process model for rehabilitation to capture what literature revealed about” treatment for this symptom in adolescents. In identifying the necessity of rehabilitation specific to adolescents, the authors note that, during adolescence, identity formation, socialization, and participation are very important and can be impacted by TBI and cause conflict between pre-TBI and post-TBI self-identity. Future research could include speaking to clinicians directly about how adolescents are treated and providing support for making rehabilitation targeted toward adolescents.

Limitations of this article come about in studies that had non-adolescent participants, and the investigators not accounting for other confounding variables.

Women’s Health

Women face poorer long-term concussion outcomes compared to men

A study published in PLOS One focusing on sex differences in concussion outcomes eight years after the initial injury found that “women reported more post-concussive symptoms, higher levels of anxiety, and a greater impact of their health on work productivity than men.” Authors Nicola Jayne Starkey et al. concluded that assessing concussion history, particularly in women, can help identify patients at the greatest risk of poor long-term outcomes, facilitating early treatment and intervention.

Starkey et al. recruited 151 adults who sustained concussions between 2010 and 2011 to examine their lives eight years later. These adults were at least 16 years old at the time of injury and at least 24 years old for the follow-up assessment. In addition, the study recruited 151 age and sex-matched adults with no history of concussion.

Female concussion patients were at higher risk of poor outcomes than males. “Over twice as many females with mTBI met PCS [post concussion syndrome] cut-offs compared to any other group.” Compared to male concussion patients and female controls, female concussion patients obtained the highest scores on the post-traumatic stress disorder (PTSD) scale and “reported that their health had the greatest impact on time-related work demands.” Female concussion patients “reported more post-concussive symptoms, higher levels of anxiety and a greater impact of their health on work productivity than men.”

“Almost two-thirds of the study participants “had experienced a prior TBI.” Female concussion patients with a history of more than one concussion had the “greatest symptom burden and were most likely to have symptoms of clinical significance.” Strikingly, “Twice the proportion of women with repetitive mTBI exceeded the clinical cut-offs for post-concussive, anxiety, and PTSD symptoms compared with males with repetitive TBI or women with a single TBI.”

Culture

How my dryer gave me a concussion - we highly recommend this Washington Post article

How my dryer door gave me a concussion, published in the Washington Post, is the best first-person perspective piece about concussion that we’ve ever read. Journalist Melanie D.G. Kaplan, a 2021-22 MIT Knight Science Journalism Fellow, starts by explaining that “as I sorted laundry on the floor in front of my stacked washer and dryer, the dryer door silently swung open to a 90-degree angle. I stood up quickly and whacked my head square into the metal door.” Her concussion symptoms persisted for a year.

Why do we love this article? First, Kaplan brings attention to how concussions can, and do, occur from freak accidents that can happen to anyone – concussions are not just from sports. She mentions populations more vulnerable to concussions, such as children, the elderly, and survivors of intimate partner violence. (The ubiquity of concussions and the impossibility of preventing all concussions are driving factors behind Concussion Alliance’s emphasis on appropriate concussion management and treatment.)

Kaplan went on a fact-finding mission, both for her recovery and her article. She interviewed leading professionals affiliated with the Brain Injury Research Center (Mount Sinai, NY), the Concussion and Traumatic Brain Injury Clinic at George Washington University School of Medicine and Health Sciences, and the Concussion Assessment, Research and Education (CARE) Consortium.

Kaplan imparts crucial information in an easily readable and approachable manner. Most surprising, the info is entirely accurate, something we rarely see in first-person or even in many news stories. She imparts what the professionals (including her physical therapist) have told her regarding concussion management and recovery timelines, associated mental health issues, self-care, and rehabilitation interventions.

She conveys that concussion care is a new science with many unknowns. Yet, Kaplan gives the readers accurate information about treatments available, plus tips for self-care in the section “How to treat your injured noggin.” Because Kaplan weaves her newfound knowledge into the arch of her story, it’s easy to relate to and remember.