The lead article this week, Will transcranial magnetic stimulation treatment improve post-concussion symptoms?, is in the Therapies & Diagnostic Tools Under Research category.

In this newsletter: Opportunities, Education, Self-Care, Therapies Currently Available, Therapies & Diagnostic Tools Under Research, Youth, Culture, & CTE & Neurodegeneration Issues.

We appreciate the Concussion Alliance Interns and staff who created this edition:
Writers: Fadhil Hussain, Susan Klein, Minhong Kim, Melissa Sodko, Lori Mae Yvette Calibuso Acob, Conor Gormally, and Malayka Gormally

Editors: Conor Gormally and Malayka Gormally

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Opportunities

Thursday, October 27, 10 am - 5:30p pm EST: A free virtual course, the 6th annual CTE Conference, will be hosted by the BU Alzheimer’s Disease Research Center. Speakers include Ann McKee, MD, and Robert Stern, PhD. For professionals, 7 CME credits are available for paid attendance. Register in advance.

Friday, October 28, 1 am PST: A free webinar, Trauma 101, will cover “neurological & academic impacts of trauma, trauma-responsive classroom strategies & interventions, and educator wellness.” Hosted by The Center on Brain Injury Research and Training.

Video recording now available: Investigating Risk for Chronic Traumatic Encephalopathy, presented by Jesse Mez, MD, MS. The presentation was live on October 12 and hosted by the Alzheimer’s Disease Research Center at Boston University.

Podcast episode now available: Dr. Julie Stamm gives a “Concussion Concerns” talk on the Athletic Training Chat podcast. Dr. Stamm is the author of The Brain on Youth Sports, and she has been a guest speaker for our internship program.

Thursday, November 3, 12:00 pm PST: A free online class, Memory and Attention Tools, covering “strategies for improving memory and attention following Brain Injury.” The class is presented by Dr. Del Piero and hosted by the Brain Injury Alliance of WA State. Register in advance; you do not need to be a WA state resident to attend.

Education

Lancet Neurology Commission on TBI findings: a leading cause of death and disability, 50% of mTBI patients aren’t recovered at 6 months, & more

A collection of over 80 authors, led by Andrew Maas, David Menon, and Geoffrey Manley, has published an update to the 2017 Lancet Neurology Commission on TBI, which “called for a concerted effort to tackle the global health problem posed by TBI.” The 2022 update, entitled Traumatic brain injury: progress and challenges in prevention, clinical care, and research, “presents new insights and challenges across a range of topics around TBI.” The authors present a table of key messages and recommendations that aptly summarize their findings, which we show below.

Key messages include “More than 90% of patients presenting to hospital with TBI have so-called mild TBI (GCS 13-15) but evidence to inform treatment of patients with mild TBI is scarce…Around 50% of patients with mild TBI presenting to hospital do not recover to pre-TBI levels of health and wellbeing by 6 months after injury.” The recommendation for this message is “Implement care pathways to ensure structured follow-up of patients with mild TBI, and stimulate research to identify patients with mild TBI at high risk for incomplete recovery, which would allow timely evaluation and treatment.”

Self-Care

A one-hour walk in nature creates healthy effects in brain regions associated with stress

A study published in Molecular Psychiatry found that a one-hour walk in nature produced decreased activity in the amygdala compared to a one-hour walk in an urban environment. These results provide evidence for the potential mental health benefits of exposure to nature for those living in an urban setting. Although not about concussion, the conclusion of authors Sonja Sudimac et al. might be relevant. The authors suggest that a walk in nature has health-producing “effects on stress-related brain regions, and consequently, it may act as a preventive measure against mental strain and potentially disease.”

The study evaluated 63 participants (median age 27). All participants completed a behavioral questionnaire and fMRI scanning procedure which included questions on rumination, the Fearful Faces Task (FFT), and Montreal Imagining Stress Task (MIST). According to anxiety.org, rumination is the “phenomenon of getting stuck thinking about the same negative things over and over.” Both the FFT and MIST test social stress.

After completing the questionnaires, the participants were randomly assigned to take a 60-minute walk in a natural environment (the Grunewald Forest in Berlin) or an urban environment (a busy street within a city center in Berlin). Upon completing the walk, the participants returned to the lab to complete the questionnaires and fMRI tasks again, along with one additional social stress task called the Social-Evaluative Threat task (SET).

The results showed decreased bilateral amygdala activity for both tests in the nature-walk group but no change in the urban-walk group. Additionally, participants in the nature-walk group reported that they enjoyed the walk more than the urban-walk group. Sudimac told PsyPost, “The results suggest that spending more time in nature might increase the amygdala’s threshold for activation, leading to reduced amygdala activity during stress. This means that exposure to nature could potentially buffer the negative impact of urban living and lower the risk of mental disorders among city dwellers.”

The study is “the first study to demonstrate the causal effects of acute exposure to a natural vs. urban environment on stress-related brain regions.” The results confirm the importance of accessible green space within urban areas and for those who live in urban environments to find time to spend in natural settings when they can.

Therapies Currently Available

Israeli researchers find first evidence of oxygen treatment for pediatric persistent symptoms

Researchers at Shamir Medical Center in Israel demonstrated that hyperbaric oxygen therapy (HBOT) relieved symptoms in children experiencing persistent post-concussion symptoms (PPCS), particularly in the cognitive and behavioral domains. The study by Amir Hadanny et al., published in Scientific Reports, is the first randomized sham-controlled clinical trial to evaluate the effect of HBOT in pediatric patients suffering from PPCS.

HBOT involves patients breathing in pure oxygen in a pressurized environment. This therapy increases oxygenation to the body’s tissues, promotes the formation of new blood vessels, and encourages the growth of stem cells. Hadanny et al. assert that HBOT has “beneficial effects… in adults with chronic TBI and PPCS,” referencing several studies (a 2013 study, 2017 study, 2018 study, and others).

[Concussion Alliance is cautious of the evidence for HBOT’s efficacy, but we wrote about an interesting 2020 HBOT study in the Therapies section of a 2020 newsletter.] HBOT had not been studied in the pediatric population prior to the Hadanny et al. study.

From December 1st, 2017, to November 1st, 2021, the researchers followed twenty-five children ages eight to fifteen suffering from PPCS after a mild traumatic brain injury. Participants were randomized into the hyperbaric oxygen group (n=15) and the sham-controlled group (n=10). After 60 sessions spanning over three months, Hadanny and his team found that the HBOT group experienced a significant improvement in their cognitive and behavioral functions. In particular, researchers observed recovery in emotional and psychosocial development, memory, planning/organizational skills, and attention. Hadanny et al. also observed significant improvement in the brain microstructure, coinciding with the aforementioned improved brain performance.

The main challenge of this study was recruitment because many parents were reluctant for their children to enter a sham-controlled study. As a result, the sample size was limited, and the results may not be generalizable to a larger population. The researchers suggest further study to “characterize the children who can benefit the most,” and to optimize HBOT protocols. These suggestions align with the 2020 study that recommended further research to standardize HBOT protocols, including the specific HBOT pressure and the exposure time and frequency of the therapy.

Therapies & Diagnostic Tools Under Research

Will transcranial magnetic stimulation treatment may improve post-concussion symptoms?

UCLA Health has received a $3 million Department of Defense grant to study how transcranial magnetic stimulation (TMS) may improve chronic post-concussion symptoms (PPCS). TMS is currently FDA-approved for “some psychiatric conditions and certain types of migraine headaches.” The study will investigate whether brief sessions of TMS will modulate an overly rigid brain circuit in the brain of patients with PPCS, thus reducing fear avoidance and promoting a gradual return to activities.

While most patients recover from concussions, some develop chronic post-concussion symptoms–such as headaches, dizziness, fatigue, and anxiety. Dr. Kevin Bickart, a neurologist at UCLA and the principal investigator of the DoD grant, says that a “potential cause of post-concussion symptoms is fear avoidance, where patients refrain from activities or situations that could trigger symptoms.”

Patients who partake in initially symptom-triggering activities such as exercising, viewing a computer screen, and facing bright light can gradually increase their tolerance to such activities. However, patients who avoid symptom-triggering situations can become even more sensitive to these activities.

To help patients confront their fear avoidance, UCLA researchers will use one- to two-minute sessions of TMS to target a brain circuit involving the amygdala and the prefrontal cortex. Dr. Bickart’s preliminary work suggests that MRIs “are able to detect a blood flow pattern,” demonstrating a rigid connection between the amygdala and the prefrontal cortex in patients with post-concussion symptoms. Because the amygdala is a region of the brain that regulates emotions, its rigid connection with the prefrontal cortex may “prevent the brain from eliminating fears and resolving symptoms.”

By using transcranial magnetic stimulation, the researchers hope to reduce amygdala-to-prefrontal connectivity and thereby help concussion patients resolve their fear avoidance. Dr. Bickart concludes that transcranial magnetic stimulation treatment could “help patients reintegrate normal activities into everyday life, which would build tolerance and improve symptoms,” resulting in better outcomes for concussion patients.

Youth

Delay in seeking specialty care among several risk factors for prolonged recovery in youth

How do you know how long it will take young patients to recover from a concussion? What factors put youth at greater risk for slower recovery? Researchers from Nationwide Children’s Hospital (Ohio) recently explored the “natural history” of concussion in nearly 5000 patients (ages 10-18) seen in their sports medicine concussion clinic over a 7-year period. Steven Cuff et al. documented pre-injury factors and injury symptoms to see which might predict whether symptoms would decrease quickly, hang on a little longer than the 3-4 week expected recovery time (prolonged recovery), or continue beyond 90 days (extended recovery).

The take-home messages from the study, published in the British Journal of Sports Medicine, are compelling. Cuff and colleagues reinforce the need for thoughtful multi-system assessment and management of symptoms as quickly as possible after a concussion. Each week that comprehensive management is delayed increases the risk for prolonged or extended symptoms, so coordination of care between early assessors and specialty providers is essential. Factors predicting prolonged and extended recovery times include a prior history of concussion(s), a “higher initial [concussion] symptom score,” delayed initial visit to a specialist, older age, and a history of an anxiety disorder or ADHD.

The authors included youth with a concussion diagnosis verified by a physician within 90 days of the event and had documentation of symptom resolution at the time of clinic discharge. Clinical outcome was based on Post Concussion Symptom Scale (PCSS) score. The authors defined prolonged recovery as a PCSS score greater than zero after 28 days and extended recovery as a PCSS score greater than zero more than 90 days after concussion. The group was split into those less than 15 years old and those 15 years or older to evaluate the impact of several factors on prolonged or extended recovery in different age groups. The factors studied were age, prior concussion(s), headache history, psychiatric history (attention, mood, learning, or anxiety disorders), gender, ethnicity (collapsed into white and non-white), and injury characteristics (sport/non-sport, participation after injury, loss of consciousness, amnesia).

Interestingly, the risk of experiencing prolonged or delayed recovery increased with each week of delay of the initial visit to the specialty clinic. Those with faster recovery were seen in a sports medicine concussion clinic within the first week of their injury. Those seen in a specialty clinic within a month of their head injury recovered within 7 weeks. The authors noted, “delay in seeking specialty care was associated with a 75-242% increase in prolonged recovery… and a 90% risk for extended recovery, for those with a first visit more than 4 weeks after injury.”

A prior history of concussion and high PCSS symptom score increased the risk of both prolonged (>28 days) and extended (>90 days) recovery from symptoms. Female sex, attention disorder diagnosis, and history of anterograde amnesia also predicted prolonged recovery. Other factors were more predictive of extended recovery, including older patients and those with an anxiety disorder). Non-white patients were less likely than those in the white group to report slowed recovery in the first 28 days but had the same risk for extended recovery.

Patients with a history of headaches were less likely to experience either prolonged or extended recovery than those who did not have that history. Explanations for this observation are intriguing, with the possibility that individuals with a headache history know how to manage it more effectively than those without it. This observation may reinforce prior observations that effective headache control is vital to concussion management.

How do you know how long it will take young patients to recover from a concussion? What factors put youth at greater risk for slower recovery? Researchers from Nationwide Children’s Hospital (Ohio) recently explored the “natural history” of concussion in nearly 5000 patients (ages 10-18) seen in their sports medicine concussion clinic over a 7-year period. Steven Cuff et al. documented pre-injury factors and injury symptoms to see which might predict whether symptoms would decrease quickly, hang on a little longer than the 3-4 week expected recovery time (prolonged recovery), or continue beyond 90 days (extended recovery).

The take-home messages from the study, published in the British Journal of Sports Medicine, are compelling. Cuff and colleagues reinforce the need for thoughtful multi-system assessment and management of symptoms as quickly as possible after a concussion. Each week that comprehensive management is delayed increases the risk for prolonged or extended symptoms, so coordination of care between early assessors and specialty providers is essential. Factors predicting prolonged and extended recovery times include a prior history of concussion(s), a “higher initial [concussion] symptom score,” delayed initial visit to a specialist, older age, and a history of an anxiety disorder or ADHD.

The authors included youth with a concussion diagnosis verified by a physician within 90 days of the event and had documentation of symptom resolution at the time of clinic discharge. Clinical outcome was based on Post Concussion Symptom Scale (PCSS) score. The authors defined prolonged recovery as a PCSS score greater than zero after 28 days and extended recovery as a PCSS score greater than zero more than 90 days after concussion. The group was split into those less than 15 years old and those 15 years or older to evaluate the impact of several factors on prolonged or extended recovery in different age groups. The factors studied were age, prior concussion(s), headache history, psychiatric history (attention, mood, learning, or anxiety disorders), gender, ethnicity (collapsed into white and non-white), and injury characteristics (sport/non-sport, participation after injury, loss of consciousness, amnesia).

Interestingly, the risk of experiencing prolonged or delayed recovery increased with each week of delay of the initial visit to the specialty clinic. Those with faster recovery were seen in a sports medicine concussion clinic within the first week of their injury. Those seen in a specialty clinic within a month of their head injury recovered within 7 weeks. The authors noted, “delay in seeking specialty care was associated with a 75-242% increase in prolonged recovery… and a 90% risk for extended recovery, for those with a first visit more than 4 weeks after injury.”

A prior history of concussion and high PCSS symptom score increased the risk of both prolonged (>28 days) and extended (>90 days) recovery from symptoms. Female sex, attention disorder diagnosis, and history of anterograde amnesia also predicted prolonged recovery. Other factors were more predictive of extended recovery, including older patients and those with an anxiety disorder. Non-white patients were less likely than those in the white group to report slowed recovery in the first 28 days but had the same risk for extended recovery.

Patients with a history of headaches were less likely to experience either prolonged or extended recovery than those who did not have that history. Explanations for this observation are intriguing, with the possibility that individuals with a headache history know how to manage it more effectively than those without it. This observation may reinforce prior observations that effective headache control is vital to concussion management.

Culture

Failure of NFL concussion protocol again in the spotlight

A glaring public spotlight on concussion and the NFL concussion protocol flared over the last two weeks, resulting in a change to the NFL concussion protocol–as explained in this 3-minute Good Morning America video. Miami Dolphins quarterback Tua Tagovaivola took a hard hit in the first half of a September 25 game. After falling backward and hitting his head, he got up and showed an evident lack of balance (to the degree that he had to be supported by teammates), shaking his head “to clear the cobwebs”–a known concussion sign. The team initially announced that Tua had a concussion.

After being examined by the team physician and the unaffiliated neurotrauma consultant, Tua returned to the game for the second half, with the team announcing that his gross motor instability was due to a back injury found on an earlier exam. In response, the NFL Players Association immediately started an investigation to determine why the team returned Tua to the second half of the game. Public concern mounted the next few days about Tua playing in the upcoming Thursday game, with Concussion Legacy Foundation CEO Dr. Chris Nowinski tweeting, “If Tua takes the field tonight, it’s a massive step back for #concussion care in the NFL.”

After a brutal hit in the Thursday (9/29) game against the Cincinnati Bengals, Tua fell to the ground, hitting his head. Tua’s hands were splayed out and rigidly held in an abnormal position referred to as a “fencing posture,” a sign of serious neurological damage. He was put on a backboard and rushed to the hospital. When Tua was released from the hospital and allowed to travel home with the team, his coach, in a press conference, “expressed relief ‘that he didn’t have anything more serious than a concussion,’” leading to further accusations of insensitivity and lack of information.

Ultimately the NFL and the NFLPA agreed to a change in the NFL concussion protocol. The original protocol listed gross motor instability as a No Go, meaning a player cannot return to the game. However, a protocol loophole allowed the team to return the player to the game if the gross motor instability was attributed to a non-neurological issue like Tua’s previously-identified back injury. Brian Sutterer, MD, explains this NFL protocol loophole in a 9-minute video. In the new protocol, ataxia replaces the term gross motor instability and covers “abnormality of balance/stability, motor coordination, or dysfunctional speech).” The new NFL concussion protocol lists ataxia as one of the signs or symptoms for which a player “may not return to participation (practice or play) on the same day under any circumstances.”

CTE & Neurodegeneration Issues

Drastic changes are needed in rugby as study finds players are 15 times more likely to develop motor neuron disease

Researchers William Stewart et al. are calling for dramatic changes in rugby to reduce repetitive head impacts and the significant risk of neurodegenerative disease, according to an article in the Guardian. This call for changes comes on the heels of a retrospective cohort study led by Emma R Russell and William Stewart, finding that Scottish international rugby players' risk of motor neuron disease (MND) is 15 times higher than that of the general population. The study, published in BMJ Journals, found double the risks of dementia and three times the risk of Parkinson's. The authors conclude that "strategies to reduce exposure to head impacts and head injuries in sport should be promoted."

The study compared 412 male Scottish former international rugby union players born between 1900 and 1990 to 1236 general population members matched by age, sex, and area socioeconomic status. The two groups were identified by national electronic health records on death certifications, hospital admissions, and dispensed prescriptions. Deaths recorded were found in 121 (29%) former rugby players and 381 (31%) of the comparison group.

Neurodegenerative disease diagnosis was twice as high, occurring in 47 former rugby players (11.5%), compared to 67 in the control group (5.5%). Risk of diagnosis for dementia was just over twice as high (2.17), three times as high for Parkinson's (3.04), and 15 times as high for motor neuron disease (MND)/amyotrophic lateral sclerosis (ALS) (15.17). The players' position(s) on the field did not contribute to the risks.

Researchers are recommending ongoing development and promotion of strategies to reduce exposure to head impact and injuries. Consultant on the study, neuropathologist Dr. William Stewart, an honorary professor at the University of Glasgow, said to The Guardian, "I think this stimulus to them is to really pick up their heels and start making pretty dramatic changes as quickly as possible to try and reduce risk – they should talk about restricting competitions and seasons."

Concerning women's rugby, Stewart said, "We need to find out what's happening in the female game. We know the risks are higher for females than males for brain injury concussion in sport." More research is needed on youth, female, and non-elite athlete rugby players.