Learning & neurological disorders affect baseline testing (2/4/21 newsletter)

Feb 4

We would like to acknowledge our volunteers and leadership team members who wrote for this newsletter:

Writers: Malayka Gormally, Tori Gray, Mack Hancock, Micale Hunt, Julian Szieff, Rainey Tilley, Alex Whitis, and Josh Wu.

Editors: Conor Gormally and Malayka Gormally.

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Education

CATT concussion course educates medical professionals, improves care

A study published in the Journal of Sports Medicine investigated the 2018 relaunch of the Concussion Awareness Training Tool (CATT) for Medical Professionals, looking at the number of professionals who took the course and their assessments of the course's quality. This course, available in French and English, is "is an accredited program designed to provide medical professionals with the information they need to provide evidence-based care for their patients who have sustained a concussion."

The free, two-hour online course provides a "Learning Check'' at the end of the unit, consisting of several True/False questions and feedback regarding your answer. Concussion Alliance has assigned the course to our interns. CATT is a challenging yet accessible and helpful source of information for anyone interested in concussion care, including concussion patients and advocates.

Authors Shelina Babul et al. noted that page views for the course rose from 8,072 in 2018 to 9,382 in 2019. Of the eight-nine medical and healthcare professionals who completed the assessment, "85% of respondents reported learning new information about concussion; 73% reported changing the way they diagnose, treat, or manage concussion; and 71% reported recommending the CATT to colleagues." The study authors conclude that "CATT for medical professionals has demonstrated promise as a tool to promote knowledge translation practice and help fill the gap in concussion training and knowledge reported by medical and healthcare professionals."

Sports

Soccer competitions trial concussion substitutions in 2021

IFAB, soccer’s international governing body, for the first time is recommending a trial of concussion substitutions during games, according to an article in Reuters. The proposed change would allow for two additional permanent substitutions in addition to the three general substitutions already permitted. While this change has developed out of a long-term push from the medical field and concussion advocates, this new rule’s details are not in line with medical advice.

One of the biggest concerns surrounding concussions in sports is proper player evaluation. Concussion evaluation takes at least 10 minutes and requires a player’s removal from the field of play. The proposed rule changes do not mandate a complete concussion evaluation or explicitly state that a medical evaluation and a decision about substitution should occur on the field. In addition to the presence of coaches and fans, the game’s fast pace may place pressure on the referee and the medical staff to rush their assessment and risk endangering the players.

While these rules changes are insufficient to adequately protect players, the introduction of concussion substitutions will increase head injury awareness and allow teams to continue playing while their potentially injured players receive treatment. Check out our blog post on this topic for more information.

Cannabis & Psychedelics

100 mg/kg synthetic CBD induces antidepressant effects in mice through modulation of neurotransmitters in the hippocampus

Melkamu Alemu Abame et al. have found that chronic administration of CBD 100 mg/kg in rats produced antidepressant effects, while lower doses of CBD did not induce an effect. This study, published in Neuroscience Letters, investigated the threshold at which a CBD dose produces antidepressant effects and the resulting differences in essential proteins and neurotransmitters.

The study involved administering CBD to a sample of eighty 7-week-old male mice and subjecting them to a forced swim test (FST) to measure the antidepressant potential for the 10 mg/kg, 30 mg/kg, and 100 mg/kg dosage levels. They also examined the hippocampi to determine potential new or different protein/neurotransmitter production. The 100 mg/kg CBD group displayed significantly less immobility time (IT), indicating an antidepressant-like effect.

However, both the 30 mg/kg and 10 mg/kg exhibited no significant IT variance from the control group. They discovered no change in proteins or significant effect on protein levels. However, neurotransmitters, serotonin (5-HT) and noradrenaline (NA), significantly increased in the hippocampi (HPC) of the 100 mg/kg group. Furthermore, none of the treatments influenced any locomotor activity.

This experiment's data provide a new perspective on CBD's dosage results and add evidence to its antidepressant effect. However, this experiment's results vary from past experiments reporting that chronic administration of CBD 30 mg/kg and 10 mg/kg for 14 days decreased IT in FST. The next step would be to conduct more tests to determine a consistent administration of chronic CBD treatments for mice.

Diagnostics

Concussions damage lymph system in mice, VEGF-C protein may help fix “faulty pipes”

In a superbly written article for Knowable Magazine, Helen Santoro elaborates on "Emerging research [that] suggests that even mild hits to the head may damage the tiny lymphatic vessels that clear toxic chemicals and cellular debris from the brain." The study that Santoro discusses, by Ashley C. Bolte et al. and published in Nature Communications, found that "mild forms of brain trauma cause severe deficits" in the brain's lymphatic drainage system in mice. This damage was observable within hours, lasting at least one-month post-injury.

With clear explanations and helpful illustrations, Santoro explains the history of the recent discovery of a lymphatic system for the brain, how it works, and how even sub-concussive hits (in mice) appear to damage this system. The research may explain why repeated concussions, or multiple sub-concussive hits, may cause long-term symptoms and even make a person more prone to neurodegenerative diseases.

The authors also explored fixing these "faulty pipes." Previous studies have shown that a protein called vascular endothelial growth factor C, or VEGF-C, "increases the diameter of lymphatics tubes," helping them drain. Bolte et al. gave older mice a concussion and then introduced VEGF-C into their brains. These mice had fewer macrophages and microglia than the control group of older mice that did not receive VEGF-C after a concussion.

Macrophages and microglia act to remove "damaged cells and molecular debris and can cause damage if left unchecked," leading the authors to suggest that VEGF-C "fixes the faulty pipes that drain all of the bad things from our brain." This theory has not yet been researched in humans.

See our 9/17/20 newsletter (in the Diagnostics sections) for more information about the original study by Bolte et al.

Self-care

Winter conditions and activities increase the risk of concussion, TBI

An article from WKBN27, Ohio, cautioned about the greater risk of concussionsand TBIs in winter. As snow and ice cover our streets and slopes, everyone wants to get outside to ski, snowboard, and sled. However, the force and speed of barreling down hills and falling on icy patches may cause injuries that should be taken seriously. Dr. Brandon Weeks, an expert in rehabilitation, explains that he has seen thousands of concussions and TBIs during this time of year. With the intense storms and temperatures all over the country, knowing how to keep yourself and your family safe is critical.

In this article, experts emphasize taking precautions. Knowing symptoms of concussions can help identify a possible concussion. See our web page for a list of symptoms that warrant a trip to the Emergency room. If you suspect a concussion, get a medical evaluation within two days. Simple decisions like wearing a helmet, checking the weather and slope conditions, and checking after every hard fall can help diagnose concussions and keep people safe.

Therapies Currently Available

Photobiomodulation interview with Larry Carr, PhD – case-study patient turned pilot study consultant

In a new blog post, we interview Larry Carr, PhD, about his experience with light therapy (photobiomodulation) for his worsening CTE-like symptoms – resulting in the remission of those symptoms. Dr. Carr was one of Dr. Margaret Naeser’s two-case studies discussed in a previous blog post. December 2020 intern Josh Wu and Dr. Carr consider why this therapy is not more well known and what Dr. Carr would say to photobiomodulation skeptics.

Dr. Carr is a consultant for the five different light therapy pilot studies. In this interview, he describes these studies and their subject populations: former collision sports athletes, firefighters, women’s soccer players, and current football players.

To learn more about research into light therapy for concussions, particularly persistent post-concussion symptoms, see our photobiomodulation page.

Therapies Being Researched

Nanoparticles may help siRNA pass through the blood-brain barrier, increasing therapeutic potential

Published in Science Advances, Wen Li et al. present a method to increase small interfering RNA (siRNA) delivery to brain cells that relies on nanoparticles (NPs). siRNA can efficiently silence specific genes, offering the potential to reduce the level of signaling cascades associated with TBI secondary injury. However, a previous roadblock has been safely transporting siRNA across the blood-brain barrier (BBB).

Researchers engineered five NP types using surface coatings previously shown to aid in trans-BBB drug delivery. Preliminary experiments determined which type of surface coating optimized cellular uptake, gene silencing efficiency, and BBB penetration in healthy mice, studying the most promising NP in a mouse model of TBI. Two hours post-injury, nine mice received an injection of either free siRNA (control) or NPs loaded with siRNA. Four hours later, brain imaging indicated that NP-siRNA significantly increased the accumulation of siRNA in the brain. This experiment yielded similar results when performed two weeks post-injury.

Researchers also demonstrated that the siRNA retains gene silencing capabilities in vivo. They designed siRNA to lower tau expression (a protein associated with TBI-induced neurodegeneration). TBI mice received treatment injections on days 0 & 1 or days 14 & 15. After 72 hours, mice receiving NP-siRNA showed significantly reduced tau cortical expression compared to mice who received only siRNA, only NP, or control injections.

Future studies should investigate a broader range of NP coating densities. Others could repeat the tau knockdown experiment on multiple genes or include a behavioral evaluation in the protocol.

Veterans and Service Members

Telemedicine appointments helpful in managing PTSD, create more avenues for rural care

An NPR segment focused on a veteran’s positive experience managing his PTSD with telemedicine care since the beginning of the pandemic. Although many doctors and health insurance companies were hesitant to provide telehealth services, the pandemic forced the rapid transition to virtual healthcare visits. Veteran Ron Loporto, who suffers from PTSD, transitioned from in-person appointments to telemedicine appointments with his VA psychologist, Dr. Robin Lipke. Despite the loss of physical presence in the same room, Dr. Lipke states that “her patients began opening up in a different way when she connected to them in their homes.”

In addition, telemedicine opens up another pathway for rural communities to receive healthcare without significant transportation barriers. In terms of concussion healthcare, telemedicine may provide better access to specialty concussion care.

Mental Health

Concussed athletes more likely to report depression, anxiety symptoms than athletes with an orthopedic injury

According to an article published in Archives of Clinical Neuropsychology, elite athletes who sustain concussions are more likely to report anxiety and depression than their counterparts who have suffered an orthopedic injury. The study, which required mental health screening evaluations at the start of the season, recruited 198 players from the Canadian Football League and Canadian varsity football teams. Players who sustained injuries were screened three additional times: 24-48 hours after the injury, when they were asymptomatic, and one month after they returned to play.

Authors Martin Mrazik, Dhiren Naidu, and Carley Hoyle found that individuals who had a history of one or more concussions reported “significant changes in symptoms of anxiety and depression over time." Anxiety-related symptoms increased above baseline between time of injury and 24-48 hours after injury, decreasing beyond that time frame. Depressive symptoms increased significantly above baseline “between 24-48 hours post-injury and 1-month post-return to play.” Healthy controls and players who suffered an orthopedic injury did not experience these changes.

A concussion history even made a difference in baseline testing, where “players who had a history of 1 or more concussions reported a greater number of anxiety and depression symptoms in comparison to players who did not have a history of concussion.”

Statistics

Pain response 1-2 weeks after a concussion may predict persistent post-traumatic headache

Researchers Kelly Naugle et al. published a study in The Journal of Headache and Pain examining if pain response at 1-2 weeks after mTBI would predict if patients developed persistent Post Traumatic Headaches (PTH) at four months. The authors examined pain response and headaches using tests of pressure pain thresholds, neurological pain responses, depression scores, and psychological pain factors. They found that those who developed PTH had increased neurological pain response, depression survey scores, and psychological pain factor scores 1-2 weeks after their concussion.

These researchers suggest that changes in how the body interprets and the mind processes pain are involved in the increased risk for PTH and PTH continuation. This study is limited by a small sample size of 44 but provides evidence that further research is needed to examine the connection between pain response and chronic headaches. The authors point out that there is currently “no specific pharmacological therapy … for persistent PTH”. If you would like to learn more about headaches and their treatment, please reference our new Headaches page.

Youth

Neurological disorders increase the rate of invalid ImPACT baseline tests

A study in the Journal of the International Neuropsychological Society found higher than normal rates of invalid baseline test results in athletes who report neurodevelopmental disorders (ND), including ADHD, autism, learning disorders, and special education status. The ImPACT test is a commonly used tool that measures an athlete’s baseline reflexes and memory in order to help determine when a player can safely return to their sport. After sustaining a concussion, an individual’s score must equal their baseline in order to be cleared to return to play.

Despite the wide-usage of the ImPACT test, embedded indicators that determine the validity of scores may be influenced by the presence of ND in athletes. ImPACT validity indicators were analyzed in a sample of 33,772 high school athletes with or without self-reported ND. The authors found that “significantly more invalid ImPACT baselines for athletes with an ND diagnosis or special education history (between 9.7% and 54.3%)” compared to an overall rate of 7.1%. These findings suggest the ImPACT test may not accurately capture baselines and readiness for play in ND athletes.

Women's Health

Understanding traumatic brain injury in females Pt. 2

We covered the new study by Dr. Eve Valera et al., published in the Journal of Head Trauma Rehabilitation, in our previous edition (in the Women's Health section). This week we will be focusing on the paper’s recommendations. The study outlines both the limitations in female-specific TBI research and the path forward for a better research field. The authors found that “despite the growing number of studies examining a range of factors related to TBI, there remains relatively little research on females or sex and gender differences.”

The recommendations to address this research gap fall into three categories: sex-specific biological research, improved sex-differences data analysis, and cultural shifts in the research design process. While considering sex-specific biological research, the authors recommend increased hormonal assessment, expanded reproductive stage research, sex-specific diagnostic criteria, and increased examination of how sex-specific developmental stages interact with TBI

In terms of data analysis, their recommendations focus on improving sex-differences comparisons by including female participants in trials and including a sex-difference analysis in trials if possible. Lastly, the cultural shifts recommended include focusing on a life-course perspective of TBI and encouraging collaboration "between TBI and experts in sex differences research."

Culture

Nascar driver discusses his concussion history

Dale Earnhart Jr., one of the most famous Nascar drivers of all time, discusses his concussion and recovery process in this interview with Graham Bensingeron YouTube.

“Now, I tell my story to let people know they don’t have to silently walk it off. I tell it to my racing friends who confess they’ve also been suffering in secret and to many others who’ve never raced a lap. I will always wonder how many more races I could have won or how much longer I could have raced if not for my stubbornness. Don’t make the mistakes I made. Help is out there. You just have to ask.” - Dale Earnhart Jr.

If you’d like to know more about his story, please read the article about his journey in Sportscasting.

CTE and Neurodegeneration

Severe case of CTE found in former Australian pro footballer

“He knew something was wrong with his brain’: Shane Tuck had severe CTE,” is the title of an article about the late Australian footballer in The Age. Tuck played for the Australian Football League (AFL), a hybrid of rugby and soccer, and Australia’s most popular sport. After retiring, Tuck had a short boxing career and then developed common CTE-like symptoms, including problems with cognition and memory, as well as abnormal mood and behavior. He struggled with mental health, committing suicide at age 38, after which his family donated his brain to the Australian Sports Brain Bank.

Only four brains of AFL players have been donated to the Australian Sports Brain Bank; most CTE diagnoses come from brain banks in the United States. Of the AFL brains donated, three have been diagnosed with CTE. Tuck, while the youngest case, was the most severe of the three.

CTE is likely caused by the sub-concussive blows that athletes playing physical sports face for so many years of their life. “It’s fine if you get one or two, but if you get 10,000, you’re a risk,” says neuropathologist and professor Michael Buckland, one of the brain bank’s founders. “We’re very conscious of trying not to sound too alarmist. We don’t want to give the impression to all those ex-footy players out there that they need to be really, really worried. The information we want to push is that it is an occupational risk and a public health concern.”