Happy Halloween week! As the season turns and the pumpkins come out, we hope that you're all able to enjoy your Halloweekend in a less limited capacity than last year's. We have so much exciting news and research to share with you this week!

In this newsletter: Opportunities, Covid-19, Education, Sports, Cannabis, Diagnostics, Veterans & Service Members, Mental Health, Women’s Health, CTE & Neurodegeneration Issues, and Culture.

The lead article, NFL settles discrimination lawsuit, ending race-norming, is in the Culture category.

We appreciate the volunteers and leadership team members who created this edition:

Writers: Minhong Kim, Nox Zand, Conor Gormally, & Malayka Gormally

Editors: Conor Gormally and Malayka Gormally.

Do you find the Concussion Update helpful? If so, forward this to a friend and suggest they subscribe.

Opportunities

Casual Conversations every Thursday, 2 pm EST, presented by Brain Injury Professional and NABIS. A one-time registration is required to attend the free programs.

October 28, 2 pm EST: Pituitary hormone dysfunction after concussions presented by Dr. Tamara Wexler.

November 4, 2 pm EST: The Cross-section of Domestic Violence and TBI, presented by Nneka MacGregor.

Fall 2021: Love Your Brain is offering free, online interactive Mindset and combined Mindset & Yoga programs, starting this fall. They also have free in-person yoga classes starting soon in Colorado, Massachusetts, North Carolina, Utah, and Washington.

Hjärnskakningsguiden [The Concussion Guide] Nonprofit launches in Sweden with Concussion Alliance as a partner

The Concussion Guide is a “non-profit project from the Brain Injury Association Hjärnkraft” [Brain Power]. The Concussion Guide and Brain Injury Association Hjärnkraft share many values and perspectives with Concussion Alliance. The Concussion Guide’s creation was also driven by patient experience and the recognition that many providers (in Sweden in this case) do not properly treat and refer concussion patients. The Concussion Guide was built and developed by a team of patients, Hjärnkraft employees, and medical, physiotherapy, and law students. The guide is a web-based resource with information like ‘What is a Concussion,’ and succinct, well-made pages on these chronic symptoms: neck pain, vision dysfunction, vestibular dysfunction, emotional dysregulation, and autonomic nervous system dysfunction and cerebral blood flow changes. Critically, the site also contains a list of vetted care providers and multidisciplinary clinics in Sweden.

The Concussion Guide team reached out to Concussion Alliance in the early stages of developing their resources and has partnered with us in our shared mission to reduce the gap between research and care paradigms and ensure that patients know where to go to find the care that they need. Check them out at: hjarnskakningsguiden.se!

Covid-19

Demyelination lesions in the brain associated with COVID-19

By Marvin 101 - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2846763

In a narrative review from the Tabriz University of Medical Sciences, Zahra Shabani discusses COVID-19’s connection to the demyelination of neural cells, primarily in the brain. Demyelination refers to the process by which neurons’ myelin sheath, a protective layer of fatty tissue surrounding the axon, is eroded and stripped away. The myelin sheath is responsible for insulating the axon and maintaining the speed of electric conduction between neurons. Because of this, demyelination disrupts the essential function of a neuron’s ability to transmit information to surrounding neurons, with outcomes ranging from headaches to encephalitis.

Shabani discusses how certain symptoms of COVID-19, ranging from headaches to seizures, indicate that immunological dysfunction in infected individuals leads to demyelination. This mechanism is corroborated by previous studies involving cerebral and spinal MRIs of COVID-19 patients, with findings of demyelinating lesions after infection. This process is thought to be a result of a three-stage immunological host response to COVID-19. Shabani describes these stages as the initiation phase, amplification phase, and consummation phase. Demyelination occurs during the amplification phase of the disease as a result of cytokine storm, autoimmune response, and leukopenia (lowered white blood cell count) & lymphocytopenia (insufficiency of specific white blood cells called lymphocytes).

Education

New paper recommending changes to international consensus statement group

A paper authored by a group of “researchers, clinicians, humanists, advocates, and caregivers,” including Concussion Alliance Professional Advisory Board members Stephen Casper and Elizabeth Sandel, received international attention for calling for a paradigm shift in the authorship process of the upcoming 6th International Consensus Statement on Concussion in Sport. The authors advocate for a “public health and patient-centered” approach that they (and Concussion Alliance) believe has not been sufficiently present in the creation of the previous five statements. The article was published in the Journal of Law, Medicine, & Ethics.

The article argues that the consensus-building process has been exclusionary and dominated by individuals with close ties to sports organizations. For these and other reasons, the resulting statements “have promoted sports-friendly viewpoints that could be construed to pronounce concussions and repeated subconcussive impacts more benign, recoverable, transient, and reversible injuries than we consider reasonable.”

The authors argue for the addition of voices and perspectives, both professional and patient/caregiver, to the consensus statement process, both in creating the statement itself and in a proposed rigorous peer review process following its completion. They also argue for additional vetting and transparency around potential conflicts of interest in the guideline-creators, along with the publication of non-anonymous votes of agreement/disagreement for each section and subsection of the statement.

Concussion Alliance has recently joined Repercussion Group, the international working group associated with the publication of this paper, and fully endorses its proposals in both spirit and detail. The International Consensus Statement is, for better or for worse, THE document that informs guidelines, regulations, and policies around the world. Given the stakes set by the authority of the consensus group, the upcoming consensus statement (to be authored in October 2022) should be held to a higher standard of medicine, research, and ethics than has historically been the case.

Sports

50 former professional rugby players launch a class-action lawsuit against the Rugby Football League

News broke yesterday (Wednesday, 10/27/21) that Rylands Legal will represent 50 former players in an upcoming class-action lawsuit against the Rugby Football League, the governing body of the sport in England. Rylands Legal is also representing 175 former rugby players in a separate suit. According to an article in The Sydney Morning Herald, the lawsuit stems from the players’ claims that “RFL failed in its duty of care to introduce and enforce rules regarding the assessment, diagnosis, and treatment of actual or suspected concussive and sub-concussive injuries.”

The players involved range in age from 20s-50s; many have already begun to experience or have been diagnosed with neurological and cognitive deficits. Bobbie Goulding, who played professionally for 17 years at multiple high-profile clubs, has been diagnosed with early-onset dementia and probable CTE at 49 and is one of the players leading the charge to change the paradigm surrounding accountability and player care in rugby. According to the Herald article, many of the players involved are not motivated primarily by any monetary gain from the lawsuit but by a desire to see the game they love made safer for those who still play and will play in the future.

Cannabis & Psychedelics

Headache and migraine may respond to treatment with medical cannabis

Though not specific to concussion, a literature review by Soujan Poudel et al. argues that "medical cannabis use decreases migraine duration and frequency and headaches of unknown origin. Patients suffering from migraines and related conditions may benefit from medical cannabis therapy due to its convenience and efficacy."

Published in the journal Cureus, this review included 34 studies published between 1987-2020 that met review criteria. The authors found that the included articles tended to address three primary questions: "(i) Is medical cannabis effective on headaches and migraines? (ii) What forms of medical cannabis do people prefer? (iii) What is an ideal dose for the 'preferred form?" The paper goes on to summarize various study findings. For example, a survey study by Cutler et al. (2019) found that for inhaled cannabis usage, "results demonstrated that headaches were reduced by 47.3% and migraines by 49.6%." Baron et al. (2018) found that using "19% THC or THC+ 9% CBD," at a 200 mg dose, "effectively reduced the intensity of migraine pain by 55%." Another study (Leroux et al.) found that for cluster headaches, medical cannabis had a "modest effect in 1/4 of all patients, and eliminated an attack in 1/8 of patients."

While each study had its own limitations worthy of consideration, the authors' conclusions are noteworthy, "Despite mixed findings regarding the effectiveness of medical cannabis on both headaches and migraines, there is a consensus for the indication of medical marijuana therapy when first, and second-line treatment fails."

Diagnostics

Near point of convergence is associated with greater somatic symptoms in adolescent concussion patients

A study by Dr. Gregory A.Walker et al., published in Vision Research, found that receded near point of convergence (NPC) is associated with greater somatic symptoms in adolescent concussion patients. (Somatic symptoms are related to the body, such as headaches, and distinct from mind-related symptoms, such as cognitive dysfunction or mental health disorders.)

NPC measures the distance from the bridge of a person’s nose to where both eyes can focus without having double vision. The authors determined patients with NPC greater than 6 cm to have receded NPC. Out of 123 adolescent concussion patients, 77 had receded NPC, and 46 had normal NPC. “The group who went on to experience persistent symptoms had a significantly greater NPC break point at initial evaluation than those without persistent symptoms.”

Patients with receded NPC were consistently associated with a higher degree of somatic symptoms, as multiple data analyses confirmed the statistical significance. While other patient characteristics such as cognitive symptom severity and postural stability were also associated with receded NPC, their statistical significance was not as strong.

Veterans & Service Members

Navy will review dishonorable discharge for veterans with TBI, PTSD

In a significant win for Navy veterans with TBI, PTSD, military sexual trauma, and other mental and behavioral conditions who received a less than honorable discharge, the Navy has agreed to review these discharges, following the settlement of a class-action lawsuit. Honorable discharge is necessary to access certain benefits, such as “educational and health care benefits and eligibility for many job training and financial assistance programs,” according to an article in NavyTimes.

The Navy will evaluate discharge status differently depending on the date of discharge. Those discharge-status-upgrade decisions from March 2, 2012, through to the settlement date will be automatically reviewed. Veterans whose discharge decisions occurred between October 7, 2001, and March 2, 2012, are eligible to reapply for an honorable discharge. The Navy will allow veterans to request an appearance via video-teleconference for the hearing. Veterans wishing to learn more can contact The Yale Veterans Legal Services Clinic, which won the settlement, manker.settlement@yale.edu, or call (203) 364-4588. See the Twitter account for the Yale Vets clinic or the Naval Discharge Review Board web page for additional information.

Clinical Trial for veterans and active-duty military members with Insomnia

A current study is enrolling service members and veterans to test the efficacy of an online Cognitive Behavioral Therapy app for insomnia (SHUTi), customized specifically for military members. The study is totally online and remote; contact the study team by emailing cnrm-ecbti@usuhs.edu or call or text (301)456-5474 to learn more.

Mental Health

Male veterans with blast TBI show astroglial scarring compared to civilians post-mortem

A post-mortem case series by Shively et al., funded by the Department of Defense and published in Lancet Neurology, found cerebral differences between male veterans with blast-related TBIs and male civilians without exposure to blasts. The authors compared the brains of veterans with chronic blast exposure, acute blast exposure, or chronic impact brain injury with the brains of civilians with exposure to opiates, a TBI, or no TBI. The five veterans with chronic blast exposure were diagnosed with posttraumatic stress disorder before death, and all five of these cases exhibited “prominent astroglial scarring.” “Researchers believe the unique scarring that the study found could account for the mental health conditions that are diagnosed more frequently among service members who have suffered mild TBIs or been exposed to blast concussions,” according to an article in Defence Visual Information Distribution Service (DVIDS). “In other words, the ‘invisible wounds’ - as TBI is frequently called - might not be invisible anymore.”

Shively et al. found that the astroglial scarring in those with chronic blast exposure was specifically at various boundaries between brain parenchyma and fluids and at junctions between grey and white matter. Astroglial cells, also known as astrocytes, outnumber neurons at a ratio of 5:1. Astroglial cells are responsible for supporting the axons of neurons along with synapses. Additionally, astrocytes play a role in controlling the flow of the blood-brain barrier.

Women’s Health

24 months post-concussion, pregnancy rate is 76% lower

The first study to assess the "impact of concussions on women's future pregnancy outcomes" was published in the Journal of Head Trauma Rehabilitation. Twenty-four months post-injury, the pregnancy incident rate of a cohort of women who sustained a concussion was 76% lower than the comparison cohort of extremity-injured women. Additionally, the concussed women who experienced "menstrual and/or sexual dysfunction" six weeks post-injury had a pregnancy incidence rate that was 84% less than the extremity injury group. The researchers Martina Anto-Ocrah et al. note that "Our study potentially serves as a clarion call to understand the long-term reproductive effects of female concussions."

This longitudinal cohort study involved collecting data from the charts of the study participants: 245 reproductive-age women (ages 18-45 years), including 102 concussed and 143 extremity-injured study participants. The comparison time points were within seven days of the injury, six weeks post-injury (including an "evaluation of self-reported postinjury menstrual and sexual changes"), and 24 months post-injury.The authors theorize that the lowered pregnancy incidence could be related to HPG (hypothalamic-pituitary-gonadal axis) dysregulation and suggest additional studies to elucidate "the biological plausibility of our hypothesis." They pose the question, "would this concussion effect on pregnancy rates be even more significant if these patients were followed 'for 3, 5, or 10 years post-injury, as has been shown in NFL studies?"' The NFL studies found low testosterone, erectile dysfunction, and hypogonadism two decades after concussion exposure, which demonstrates that concussion-induced changes to the HPG feedback loop...can (i) span decades and (ii) have prolonged effects on patients' reproductive level."

For context, the researchers note that infertility affects 13 million in the U.S. and "has been associated with poor mental health, relations discord, and poor quality of life." Also, "concussions have been associated with physical and psychosocial challenges, which may impact the feasibility or even desirability of pregnancy." Postconcussive syndrome "may complicate return to normal activities such as working and maintaining relationships with family and friends for months or years. Even those without significant complaints at the time of injury have been shown to develop secondary complaints and functional limitations as late as 1-year post-injury."

CTE & Neurodegeneration Issues

Concussion history-cognitive function relationship may change with age in Rugby Players

The BRAIN study attempted to determine the relationship between concussion history and cognitive function in a sample of former high-level rugby players from before a professional rugby league was established (the amateur era). The study was authored by Valentina Gallo and published in Alzheimer’s & Dementia, and supported by the Rugby Football Union (RFU) and the Drake Foundation. The study assessed 146 elite rugby union players from the amateur era, all aged over 50.

The players’ average career length was 15.8 years, and 80% reported at least one rugby-related concussion. Players were asked “questions on rugby playing career, occupation, lifestyle factors, cognitive ability, and self-reported history of concussion.” Researchers utilized the BRAIN-Q tool to analyze concussion history, which “entails a 3-stage process: defining concussion, creating a visual timeline with life events, and establishing detailed characteristics for each reported concussion.” Players then completed the Preclinical Alzheimer Cognitive Composite (PACC) to test for cognitive function and memory. The researchers used career length as a proxy for subconcussive impacts as they could not expect players to report them accurately.

While the authors found no significant correlation between cognitive function and concussion history in the sample as a whole, “the association of high [3+] concussion and PACC… showed a steep decline starting from about age 75 years.” By 80 years, having three or more concussions was associated with a cognitive function level of about one full standard deviation below the median level for that age group.

According to an article in The Guardian, the RFU co-signed a press release focusing on the “no overall link” interpretation and is currently working on a study with the “Advanced Brain Health clinic and Premiership Rugby” to look at these effects on professional-era players. The RFU has taken the stance that any firm conclusions should be based on this upcoming research, “given the differences between the amateur and professional eras.”

In contrast, the Drake Foundation press release about the BRAIN study marks its results as “profoundly alarming,” according to the Guardian article. The Drake Foundation points out that the current professional era rugby is actually likely more dangerous than the amateur era, with their Drake Biomarker study finding “that almost one in four players studied had abnormal changes to their brain structure, and one in two had unexpected reductions in white matter volume.”

Culture

NFL settles discrimination lawsuit, ending race-norming

In a high-profile lawsuit in 2015, former football players reached a class action settlement with the NFL regarding concussions. After receiving their settlements from the NFL, 2 Black players, Kevin Henry and Najeh Davenport, realized that they had received significantly less than their white counterparts. The NFL’s rationale for this was that Black players’ dementia was less significant than white players since Black players purportedly had a baseline lower cognitive function than white players.

Two years and a discrimination lawsuit later, the NFL will eliminate race-based evaluations of players’ dementia claims, pending court approval.

Former evaluations required that Black players’ cognitive decline hit a lower threshold than white players. Because of this, Black former NFL players will be eligible for re-evaluation using race-neutral metrics that do not place them at an automatic disadvantage, according to an article in the New York Times. These new eligibilities extend past dementia, as former NFL players with ALS and CTE will also be paid under this new settlement.

Fantastic essay on the history of stigma and malingering in TBI patients

In an exquisitely penned essay, Concussion Alliance Advisory Board Member Stephen Casper sheds light on the complex historical, social, sporting, medical, and legal trends and paradigms that have generated stigma and distrust around brain injury patients since the mid 19th century. The essay was published in the Journal of Law, Medicine & Ethics.

Casper shows, with historical examples, how the early industrial era in the UK and United States generated and perpetuated harmful views about poverty and perceived deficiencies in laborer work ethics. These systems and perspectives placed poverty, and all of its causes and effects, within the reductive and harmful bucket of ‘moral failings.’

He then describes the role of medical practitioners, whose diagnoses fundamentally indicate whether or not they think their patients’ claims are legitimate, and members of the legal system, who view disability litigation through the lens of fault and perceived loss of value. Casper illustrates how medical and legal practitioners furthered these class-, character-, and context-based judgments of the legitimacy of patients’ injuries.

Drawing the narrative forward, Casper examines how gender roles have negatively impacted TBI diagnosis and treatment. He also speaks to how expectations around TBI both within and outside of sport have created a feedback loop that perpetuates invisibility, invalidation, and stigma for TBI patients. In his conclusion, Casper refers to his article pushing for a restructuring of the International Consensus In Sport Group’s process for the upcoming Consensus Statement on Concussion in Sport (written about in our Education section of this newsletter).

Concussion Alliance highly recommends reading the entirety of this essay. While they did not fit within the structure of this synopsis, we’ve included two critical quotes below:

“Structural competency in brain injury research requires recognizing that these long histories of courtroom battles, cultural concern about fakers, shirkers, and effeminacy, and economic resentments created through the compensability of workplace injuries, place large burdens on TBI patients to prove their own clinical and legal legitimacy. Many of them end up trapped in two ways. They are either too injured to address the burden and cannot. Or they possess the personal wherewithal or support structures to call attention to their difficulties but by so doing make experts question whether they are as bad as they report. In this area of clinical care and law, working at the least to make these social contexts and social pathologies structured in the clinical and legal system

visible for all is good social medicine, not least because it invites clinicians particularly to question their own assumptions about what sick people might have to do in order to survive in a society with scant resources dedicated to chronic patients daily needs and support.”