The lead article this week, Researchers to trial concussion diagnostics and treatments for long COVID patients, is in the COVID category.

In this newsletter: Opportunities, Education, Sports, Cannabis & Psychedelics, Pathophysiology, Self-Care, Therapies & Diagnostic Tools Under Research, CTE & Neurodegeneration Issues, and COVID.

The application cycle for our Summer 2022 Education & Advocacy Internship is open! It runs June 13 – August 5 and is open to undergraduate students. Our program is remote and open to any students who are interested and able to attend our synchronous meetings. For more information about the program and how to apply, go to our Internship Program page.

We appreciate the Concussion Alliance Volunteers who created this edition:

Writers: Aaron Banse, Sravya Valiveti, Josh Wu, Shelly Seth, Minhong Kim, Sam Kanny, Conor Gormally, & Malayka Gormally

Editors: Conor Gormally and Malayka Gormally

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Opportunities

Tuesday, May 17, 1 pm PST: free online class, LoveYourBrain Yoga, will cover "breathing, meditation, gentle yoga poses, and guided community conversation." Provided by the LoveYourBrain organization and hosted by the Brain Injury Alliance of WA State. You do not need to be a WA state resident. Register in advance.

Thursday, May 19, 3 pm EST: a paid online webinar ($50), Life After TBI in a Remote World: How MHealth Can Support Individuals with TBI in Their Community. The speakers are Shannon Juengst, Ph.D., CRC and Amanda Rabinowitz, Ph.D. Registration closes at 11:59 pm EST, May 18.

Tuesday, May 24, 6 pm EST: free webinar, Patient Panel: Our Journey to Recovery. "Dr. Lesley Ruttan will interview people recovering from concussion." Hosted by the Canadian Concussion Centre. Register in advance.

Wednesday, May 25, 2 pm PST: free online class, Understanding Behaviors after Brain Injury. Hosted by the Brain Injury Alliance of WA state, not necessary to be a WA state resident. Register in advance.

Wednesday, May 25, 11 am EST: webinar, free to IBIA members and $25 for guests, Looking Beyond Our Own Backyards: The Role of Telemedicine in Providing Pediatric Concussion Care to Rural and Remote Communities. The speaker is Michael Ellis, MD, FRCS(C). Register in advance. Note, this webinar series is excellent and you can attend for free if you join the IBIA as a “Special Interest Group Member” for $75/year.

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

College athletes and service academy cadets with non-sports-related concussions have worse outcomes, more days lost to injury

Please see our blog post to read this synopsis.

Sports

Professional cyclist Lizzy Banks: “there’s not book on how you treat concussion”

Please see our blog post to read this synopsis.

Cannabis & Psychedelics

Wesana Health is developing psilocybin and CBD medication to treat symptoms of TBI

Life-science company Wesana Health currently has two provisional patents for medications combining psilocybin and cannabidiol (CBD) for “TBI-related symptoms, such as depression and anxiety, and non-TBI symptoms such as migraine,” according to an article in Benzinga. Wesana co-founder and CEO Daniel Carcillo was a former NHL player (and 2x Stanley Cup winner) who retired at age 30 due to Post-Concussion Syndrome (PCS) after enduring seven concussions during his career. At the Benzinga Psychedelic Capital Conference, he explained that he co-founded Wesana Health as part of a “personal journey” to find evidence-based treatments for his symptoms.

By using psilocybin and CBD in conjunction for six months, Carcillo saw a dramatic reduction in his brain abnormalities (as confirmed by his doctors) as well as a significant improvement in his symptoms. Under Wesana Health, Carcillo is currently developing two areas called “Care Development” and “Care Delivery” to collect information about these treatment plans to further personalize patient care protocols.

Wesana Health aims to integrate psilocybin and CBD treatments to help patients who have sustained a traumatic brain injury (TBI) or endure migraines. These medications increase neurogenesis (the process by which new neurons form in the brain), increase neuroplasticity (the brain’s ability to modify functions and connections in the brain), and reduce brain damage due to inflammation from trauma.

Currently, Wesana Health is in the process of obtaining a patent for their new drug, SANA-013, which would treat TBI-associated anxiety and migraines. By using third-party labs for testing, Wesana plans to start pre-clinical trials in the fall of 2022 and obtain approval from the FDA to move on to a phase 1B/2A study, which tests the safety, side effects, and best dosage for the drug.

Pathophysiology

Concussion increases the risk of hypertension, diabetes, ischemic stroke several years after injury

A study by Saef Izzy et al. published in JAMA Network Open found that mild, moderate, and severe traumatic brain injury (TBI) were all associated with a higher risk of “chronic cardiovascular, endocrine, and neurological [and psychiatric] comorbidities” in patients without previous baseline diagnoses of comorbidities.

The researchers analyzed 4,351 patients with mild TBI, 4,351 patients with moderate to severe TBI, and 4,351 patients without TBI matched for age, sex, and race distributions. Compared to individuals not exposed to brain injury, mTBI patients were at 2.5 times the risk for hypertension, 1.9 times higher risk for diabetes, and 2.2 times the “risk of ischemic stroke or transient ischemic attack.” These comorbidities “emerged within a median of 3.49 years after injury.”

Strikingly, the risk of these comorbidities for mTBI patients was even higher in younger patients aged 18 to 40 years compared to unexposed individuals. In this group, hypertension risk increased by a factor of 5.9, hyperlipidemia risk by a factor of 2.3, and diabetes risk by a factor of 4.6.

These results suggest that increasing screening for “chronic multisystem diseases, particularly cardiometabolic diseases,” would benefit TBI patients, as they have a higher risk of developing chronic comorbidities.

However, it is important to note that some authors disclosed conflicts of interest with the pharmaceutical industry.

Self Care

Man with persistent post-concussion symptoms finds peace and a new life photographing owls

We love this story, published in the Star Tribune, about a former athlete, challenged by persistent post-concussion symptoms (PPCS) and a mini-stroke, who found healing and a whole new life via walks in the woods that led to photographing owls. His commitment to this project led to volunteer work at environmental centers, where he tags owls and teaches classes. Witchger’s new skill has led to gigs photographing music concerts and his recovery has allowed him to return to his teaching career.

After quitting soccer, Witchger lost his friend group and his primary motivator, and this story is a reminder that loss of identity is a common theme with PPCS. Witchger found a new community and a new way to be physically active; social support and physical activity promote recovery. Also, there is considerable research (though not much that is concussion-specific) about the healing value of emerging oneself in the arts or nature.

“And after that [final concussion] happened, none of that seemed to matter in any way to me anymore. I just started paying more attention to what was around me,” says Andy Witchger. “‘It was really peaceful, and it just opened these whole new worlds,” he said. “I realized I had this hole in my life to fill, because sports had been my life. I started hiking, I started fly-fishing, and during that time I started birding more and more.’” Witchger added,” ‘I love teaching, I love the outdoors, and then just the fact that I got to be outside after what had been such a crisis for me, it kind of saved me.’”

Here’s another lovely quote from Witchger. “‘But they [these new activities] all just kind of filled this empty space in my life that existed. They’ve probably been my biggest sources of joy. When you deal with a traumatic brain injury, your energy levels disappear, your desire to be social disappears. I’m an introvert to begin with, so there was almost nothing else to get me out of the house and to make me feel like I was involved in society other than that research or going to take pictures.

That really got me through some dark times, because another side effect of a traumatic brain injury is depression and anxiety. So, physical activity is going to help you. And then just those amazing experiences that you get seeing a new species, hiking a new trail, seeing a band playing an amazing set — all of those things give you that jolt that you need to carry you on to the next thing.”

To read more about the beneficial effect of natural environments for people with concussion symptoms, see the Self-care section in this newsletter. To read more about the arts, see the ‘Dancing Well’ section of this blog post.

Therapies & Diagnostic Tools Under Research

Promising Phase I clinical trials for concussion medication

Odyssey Group International, Inc, a company dedicated to developing life-saving medical solutions, announced positive results “from the first group of patients” in its Phase I clinical trial for PRV-002, a novel concussion drug, according to a press release. “A phase I clinical trial tests the safety, side effects, best dose, and timing of a new treatment” (Wikipedia), while a Phase II clinical trial is an initial assessment of the effectiveness of a medication. There is currently no official FDA-approved medication available for managing concussion care.

The first group of patients, a cohort of five healthy subjects, was administered a single drug dose. Initial data showed that the drug was well-tolerated and safe, with no serious adverse events reported. The ongoing clinical trial has 48 healthy subjects enrolled. The company states that “Based on our animal data and after reviewing our initial Phase I trial safety reports, we are optimistic that PRV-002 will be a safe option for the treatment of concussion.”

Based on results from preclinical studies, the Odyssey Group notes that PRV-002 “has demonstrated equivalent, if not superior, neuroprotective effects compared to related neurosteroids.” PRV-002 has also been “shown to reduce behavioral pathological symptoms associated with concussion in animal models, such as memory impairment, anxiety, and motor/sensory performance.” PRV-002 is a synthetic drug; its structure allows it to easily cross the blood-brain barrier to eliminate swelling, oxidative stress, and inflammation – while improving circulation in the brain.

This clinical trial is being conducted at a Clinical Research Organization, Nucleus Network. Enrollment of healthy human subjects for the Phase I clinical trial included a comprehensive health screening process. Health measurements were collected from each patient after receiving a single dose of PRV-002; these data points included vital signs, ECG, spirometry, nasal examination, a questionnaire, and a sleepiness scale.

The Phase I clinical trial is ongoing and additional results will be reported when more data becomes available. Odyssey Health plans to present its findings to FDA and is currently awaiting FDA review. Odyssey Health has also created a military advisory board. Following the FDA review, they plan to initiate their Phase II clinical trial in the U.S., starting with the military population.

CTE & Neurodegeneration Issues

In former NFL players, adverse childhood experiences associated with poor mental health outcomes and dementia

Researchers Andrea Roberts et al. investigated the association of 10 adverse childhood experiences (ACEs) with neuropsychiatric outcomes among former National Football League (NFL) players. The study sourced data on 1,755 players from the Football Player’s Health Study at Harvard University.

Findings from the cross-sectional study published in JAMA Network Open suggest that “childhood family dysfunction may be a risk factor for dementia symptoms and poor neuropsychiatric health in adulthood among former professional football players.” These findings indicate that ACEs should be further studied as a possible indicator for persons at high risk of concussions among professional football players and other populations.

Adverse childhood experiences are defined as childhood abuse and other indicators of family dysfunctions. This study measured ACEs as the following experiences in the first 18 years of life: physical abuse, sexual abuse by an adult or person aged five or older, emotional abuse, emotional neglect, physical neglect, intimate partner violence, household member imprisoned, a household member with mental illness, household member who abused alcohol or drugs, and parents ever separated or divorced. These experiences occurring during childhood or adolescence can increase the likelihood of adults having low self-esteem, engaging in risk-taking behaviors, being more aggressive, and harming themselves. These impacts can also translate over to professional football players being more likely to be more aggressive and disregard their safety, which can lead to a higher risk of concussion.

A Neurology Advisor article about the study notes “concussion symptoms were linked in dose-dependent fashion with ACEs,” and that “compared with those who did not experience ACEs, individuals who experienced at least 4 ACEs had a 48% higher chance of positive dementia screening and a higher risk of all neuropsychiatric outcomes except anxiety.”

This is also an issue of racial and economic disparities. “ACEs were linked with childhood socioeconomic status (SES),” and “Black players more frequently had experienced more ACEs compared with White individuals.”

Only one other study has investigated the association between childhood abuse and family dysfunction with dementia. Both that previous study and this study indicate that ACEs increase the odds of developing dementia. These results suggest that clinicians and trainers involved in concussion management should consider treatment for psychological trauma in addition to treatment for physical injury to improve neurobehavioral outcomes.

COVID

Researchers to trial concussion diagnostics and treatments for Long COVID patients

University of Denver (UD) researchers are recruiting 50 Long COVID patients and 50 controls for a study investigating how Long COVID impacts vestibular ocular and neurocognitive systems, according to an article by Jon Stone published on the university’s website. The researchers will work with High Definition Physical Therapy, a Denver-based sports injury and concussion rehabilitation clinic, to trial the efficacy of therapies the clinic uses with concussion patients for treating Long COVID.

According to a vestibular physical therapist from the clinic: “We had patients coming in for concussive treatment that were getting better, but after they had COVID, their symptoms were regressing back to how they presented at the start of their concussion.” A UD researcher also notes that “COVID infection looks like a brain injury; it has the same metabolic and inflammatory signatures.”

According to the UD article, another of the researchers on the team is recruiting for another study investigating the impact of a history of both COVID infection and concussion on blood biomarker levels, compared to just one or neither. “We want to know what is it about this virus that is causing these long-term neurological effects and try to figure out what things we can do to blunt that… We have formulated a hypothesis that folks who have had a history of concussion or traumatic brain injury probably are predisposed to having more severe or chronic neurological effects post-COVID.” These studies aim to better understand the impact of COVID infection and Long COVID on systems in the brain, and to use research from concussion and COVID to improve treatment models for both conditions.