This week's lead article, Combined exercise and biofeedback more helpful than either alone, preliminary findings say, is in the Self-Care category.

In this newsletter: Opportunities, Cannabis & Psychedelics, Pathophysiology, Self-Care, Mental Health, Statistics, and CTE & Neurodegeneration Issues.

We appreciate the Concussion Alliance Interns and staff who created this edition:
Writers: Minhong Kim, Susan Klein, Sravya Valiveti, Kira Kunzman, and Malayka Gormally

Editors: Conor Gormally and Malayka Gormally

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Opportunities

In a new episode of the Concussion Corner podcast, Dr. Jessica Schwartz speaks with Dr. Anthony Kontos, Director of the UPMC Sports Medicine Concussion Program, about the interdisciplinary roles of concussion rehabilitation, clinical profiles, and their new Concussion Clinical Profiles Screening (CP Screen) Tool.

Tuesday, April 4, 6 pm EST: a free webinar, Drugs for Neuropsychiatric Symptoms of Concussion, presented by Dr. Abe Snaiderman and hosted by the Canadian Concussion Centre. Register in advance.

Thursday, April 13, 4 pm EST: a free webinar, The process and science underlying the new SCAT6 Tools, presented by Rubin Echemendia, PhD, and hosted by the University of Michigan Concussion Center. Dr. Echemendia will provide an in-depth overview of the SCAT6 for evaluating a suspected sports-related concussion for ages 13 years and older. Register in advance.

Researchers are seeking participants for an NIH-funded (NCCIH) K23 research study at Massachusetts General Hospital and Harvard Medical School, aiming to develop and test a program to prevent persistent concussion symptoms for young adults. There is no cost for participating, no medication, and no travel. Want to learn more? See our previous newsletter or email MGHConcussionToolkit@partners.org.

Cannabis & Psychedelics

Medical cannabis meaningfully impacts quality of life in those with chronic pain

A study by Martha Nicholas et al. found that medical cannabis decreased headaches and improved quality of life in patients with chronic pain. Headache disorders are a common cause of disability and reduced health-related quality of life globally. Growing evidence supports the use of cannabis-based medicinal products (CBMPs) for chronic pain; however, a paucity of research focuses explicitly on CBMPs’ efficacy and safety in headache disorders. This study, published in Expert Review of Neurotherapeutics, aimed “to assess changes in validated patient-reported outcome measures (PROMs) in patients with headaches prescribed CBMPs and investigate the clinical safety in this population.”

The associated changes in headache- and migraine-specific PROMs reached clinically significant thresholds. At all follow-up points, PGIC-1 scores reflected ‘a definite improvement’ that had made a ‘real and worthwhile difference,’ and PGIC-2 scores indicated a ‘good’ degree of change since beginning care at the clinic. While the authors emphasize ‘cautious’ interpretation of results, their findings indicate that CBMPs can meaningfully impact quality of life for people managing chronic pain.

Pathophysiology

Neck pain and stiffness associated with longer recovery

Is there such a thing as a “cervical spine disorder” after concussion? And do severe neck symptoms set up slower recovery? Oyekan and colleagues at Pittsburgh invite us to consider this association between neck problems and slower recovery in a study of 306 patients (average age 16, range 9-51) seen in their concussion clinic. The study, published in The Journal of Head Trauma Rehabilitation, found that neck pain and stiffness, and particularly severe symptoms, are associated with prolonged recovery in patients.

They used the CP Screening Tool to identify concussion subtypes (anxiety/mood, cognitive/fatigue, migraine, ocular, vestibular) and explored the relationship of neck symptoms to recovery. Across the whole group, 48% of patients reported neck pain, with those sustaining non-sports concussions more likely to report neck pain. Predictive factors for neck pain included a history of ADHD. Predictive factors for severe neck pain included older age, a history of motion sickness, a history of workers’ compensation action, and injury by motor vehicle accident or fall. Predictive signs for neck pain were higher scores on vestibular-ocular-motor testing and cognitive tests.

The CP Screening Tool does not classify “cervical spine disorder” as a separate diagnostic category, as Kontos et al. 2020 pointed out. The authors believe that neck problems after concussion are different from Whiplash Associated Disorder and, further, that early identification will guide rehabilitation of neck function and overall recovery. The authors caution that radicular signs (relating to an issue at the root of the spinal nerve) or failure to respond to rehabilitation requires a referral and further testing (e.g., imaging). Whether or not “cervical spine disorder” is a specific phenotype in concussion remains to be seen.

Self-Care

Combined exercise and biofeedback more helpful than either alone, preliminary findings say

According to a press release from the American Academy of Neurology, findings from a preliminary study released in Feb 2023 highlighted the benefits of biofeedback-guided breathing practice and aerobic exercise for patients experiencing slower recovery from concussion. The research team plans to present findings from this preliminary study at the upcoming American Academy of Neurology’s 75th Annual Meeting in Boston.

Slow recovery was described as concussion symptoms such as headache, dizziness, depression and mood disturbances, and cognitive problems associated with memory and concentration that were persistent for a month or longer. Results showed that patients experienced benefits from each therapy separately, but the combined intervention provided greater improvement in thinking, memory skills, depression, and mood.

Researchers compared the effectiveness of each intervention separately to a combination of the two and assessed how these therapies might impact patient outcomes and symptom severity. The study involved 30 teenagers who suffered concussions during sport and had been experiencing persistent symptoms for more than a month. Participants were assigned to one of three groups: exercise, biofeedback, or the combined intervention group, matched on age, gender, physical activity level, and body mass index.

For those in the exercise group, the criteria included following a regimen of three 20-minute workouts per week of low-intensity aerobic activity, gradually increasing intensity and duration. The biofeedback group practiced breathing techniques at a slow rate with a handheld biofeedback device for 20 minutes for four nights a week to train their breathing to match their heart rate, which “can help balance the autonomic nervous system and manage symptoms.” The combined intervention group incorporated both aerobic exercise and biofeedback breathing exercises.

The researchers evaluated key concussion symptoms such as heart rate variability, sleep, mood, thinking, and memory skills in all participant groups at the start of the study and after six weeks. They noted that all three groups reported improved sleep, mood, cognitive and autonomic function. However, those in the combined intervention group experienced greater benefits regarding their concussion symptoms compared to those in the standalone exercise or biofeedback groups. Quantitatively, those in the combined group experienced a two times greater reduction in symptom severity compared to participants in the exercise group and a 1.3 times greater reduction in symptom severity compared to participants in the biofeedback group.

The researchers also assessed participants’ mood and symptoms of depression. Those in the combined intervention group experienced a 1.2 times greater reduction in symptoms of depression compared to the exercise group and 1.3 times greater symptom reduction than those in the biofeedback group. The combined intervention group also reported a 1.4 times reduction in total mood disturbance compared to the exercise- or biofeedback-only intervention groups.

The combined intervention group reported greater improvement in domains of cognitive function, attention, and working memory–as well as larger improvements in heart rate variability.

The Researchers concluded that supplementing concussion therapies with interventions such as combined exercise and biofeedback-guided breathing techniques could help patients manage persistent concussion symptoms more effectively. Study author R. Davis Moore notes, “These therapies are inexpensive, easy to implement, and can be self-administered, making them feasible and accessible for everyone with persistent symptoms.” In the press release, Moore comments that “when someone has a concussion, it can affect the body’s autonomic nervous system, and it is increasingly clear that this underlies the inability to tolerate exercise, problems with thinking skills and mood issues in those with persisting symptoms.”

Heart rate variability is the variability of the time between heartbeats (not changes in heart rate, but almost-undetectable fluctuations between beats when heart rate is steady). Those who have experienced a TBI (including concussion) have been found to experience abnormalities in their heart rate variability for a brief period of time. The expectation has been that these changes would resolve and return to normal post-recovery. However, those with persistent concussion symptoms have been found to experience long-lasting changes associated with heart rate variability.

There is a need for further follow-up studies based on this preliminary data with larger cohort sizes. Current data is also limited due to the lack of a control group that received no intervention.

Mental Health

Moderate or vigorous exercise is as good or slightly better than medication or psychotherapy for depression, anxiety, and psychological distress

Ben Singh et al. found that physical activity had positive effects on depression, anxiety, and psychological distress “comparable to or slightly greater” than that of medication or psychotherapy, according to an article in Healio that quoted the study authors. Their study, published in the British Journal of Sports Medicine, was an umbrella review of 97 systematic reviews of randomized control trials in 128,119 people with anxiety, depression, or psychological distress. They recommend that when managing patients with these conditions, structured exercise interventions should be a “mainstay approach.” (The study was not concerning concussion, but we believe that it will be useful to our readers.)

Moderate to vigorous physical activity was more effective in decreasing depression and anxiety than lower-intensity physical activity. The authors suggest that lower-intensity exercise may not be sufficient to produce the hormonal, neurologic, and antiinflammatory changes associated with reduced depression and anxiety.

Surprisingly, “smaller weekly duration interventions demonstrated larger effects than higher weekly duration.” The researchers suggest it’s likely easier to comply with doing a shorter duration of exercise each week, whereas adhering to longer bouts of exercise per week may be burdensome and so may negatively affect the psychological benefits of the exercise.

The magnitude of the effect of physical exercise varied among clinical populations; the authors surmise that those populations with above-average depression and anxiety and lower physical activity may benefit more. Resistance exercise had “the largest effects on depression,” while mind-body oriented activities such as yoga “were most effective for reducing anxiety.” One limitation of the review is that the bulk of the evidence addressed depression, with fewer systematic reviews (less evidence) concerning anxiety and psychological distress.

Singh and colleagues conclude that public health guidelines would include recommendations for “multimodal, moderate and vigorous” physical activity.

Statistics

“Football exposure might accelerate age-related cognitive declines” in former NFL players

A study by Roger W. Strong et al. found that retired NFL players “who reported experiencing concussion symptoms during their careers scored worse on assessments of episodic memory, sustained attention, processing speed and vocabulary,” according to a press release e from Mass General Brigham. Utilizing data from the Football Players Health Study at Harvard University, this study, published in Archives of Clinical Neuropsychology, concluded that this population’s performance on cognitive assessments was associated with the players recalled concussion symptoms.

A total of 353 former professional football players, who had retired an average of 29 years ago, participated in online neuropsychological tests and reported recollected concussion symptoms (following a blow to the head during practice or play), number of diagnosed concussions, length of professional career play, and age of first exposure to football. The researchers compared these former players’ performances to the performances of a sample of 5,089 male nonplayer participants.

While the researchers found a statistically significant association between former players’ performance on cognitive tasks and recalled football concussion symptoms, it was not associated with the number of diagnosed concussions, years of play, or the age of first exposure. This study suggests that “football exposure might accelerate age-related cognitive declines” and underlines the importance of focusing on symptoms instead of solely diagnoses within concussion research.

CTE & Neurodegeneration Issues

Swedish professional soccer players have a higher risk of neurodegenerative disease

A recent cohort study published in The Lancet Public Health found that Swedish professional soccer players had a significantly increased risk of neurodegenerative disease compared to the general population.

Authors Peter Ueda et al. examined 6,007 male soccer players who had played at least one game in Allsvenskan, the top division of Swedish soccer. The authors matched the players with 56,168 general population controls based on sex, age, and region of residence.

They found that 8.9% of the soccer players and 6.2% of the control group were diagnosed with neurodegenerative disease. The researchers concluded that “male football players in the Swedish top division had a 1.5-fold increased risk of neurodegenerative disease compared with population controls.” Specifically, this risk was increased for Alzheimer’s disease and different dementias but not for other types of neurodegenerative disease.

Moreover, the researchers note that this increased risk for neurodegenerative disease was observed for outfield players and not for goalkeepers. In fact, outfield players had a significantly increased risk of neurodegenerative disease compared to goalkeepers. Dr. Ueda says that “in contrast to outfield players, goalkeepers rarely head the ball… although other factors that differ by football player position could also affect this difference, the finding lends support to the hypothesis that heading the ball may increase the risk of dementia.”

Ultimately, Dr. Ueda emphasizes that this study shows an association between dementia and elite soccer, not a cause-and-effect relationship. Further research is needed to determine whether the study’s findings can be generalized to female and youth soccer players, as well as contemporary soccer players, given that “most players who had neurodegenerative disease events in our study played elite football during the mid-20th century.”