This week's lead article, Even a single concussion can lead to the emergence of a new mental health disorder in adolescents, is in the Mental Health category.

In this newsletter: Opportunities, Sports, Pathophysiology, Mental Health, Statistics, Women’s Health, Culture, and CTE and Neurodegeneration Issues.

We appreciate the Concussion Alliance interns, staff, and Leadership Team members who created this edition:
Writers: Susan Klein, Josh Wu, Nancy Cullen, Sravya Valiveti, Kira Kunzman, and Ian Scott.

Editors: Conor Gormally and Malayka Gormally

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Opportunities

photo of three college students at a table studying

Researchers at the University of Maine are recruiting for online research studies. They are looking for caregivers of children with and without brain injury (including concussion) and college students (ages 18-22) with and without brain injury (including concussion) to complete online research surveys.

More information can be found at umaine.edu/bearlab/ongoing-research or by contacting Jessica Riccardi at jessica.riccardi@maine.edu. Please note that some research surveys can be directly accessed through the website, while others require screening questions that will be asked via email when you contact the researcher.

Sports

The 6th Consensus on Concussion in Sport has been published

Yesterday the Concussion in Sport Group released their Consensus statement on concussion in sport: the 6th International Conference on Concussion in Sport–Amsterdam, October 2022. This highly anticipated 6th consensus statement, delayed two years due to the COVID-19 pandemic, updates and expands upon the 5th International Consensus Statement on Concussion in Sport from the 2016 Consensus Conference in Berlin.

While we recommend reading the entire document for those interested (it is reasonably accessible), we want to provide a few highlights from our first read-through. The 6th Consensus provides in-depth and improved guidance on early physical activity as rehabilitation and referral for other rehabilitation–including cervicovestibular referral for headaches, neck pain, or dizziness that persist beyond ten days. For sport, the Consensus Statement recommends disallowing bodychecking and implementing mouth guards in adolescent ice hockey and neuromuscular training warm-up programs for rugby. This new Consensus makes more of an effort to recognize its limitations, the limited diversity of the panel, and its need to include more stakeholder voices in future documents. However, the Consensus does not clarify how it manages stated conflicts of interest, does not deeply discuss risk reduction (other than the above sport recommendations), and takes an increasingly controversial 'need more research' approach regarding long-term risks (more on that below).

While the 6th Consensus includes a number of positive changes, journalistic analyses, such as this Science Insider article by Meredith Wadman, point out that this consensus statement does not include a definitive position on the long-term risk of repetitive concussions on the development of cognitive deficits and neurodegenerative disease later in life. This decision runs counter to the increasing number of governmental organizations acknowledging this link, including the National Institutes of Health updating its official statement on CTE causation to include ("in-part") repeated traumatic brain injuries on the eve of the 6th Consensus Conference last October.

Additionally, despite anticipation from stakeholders and clinicians, the panel did not reach a consensus (>80% of voters) on including the Vestibular Ocular Motor Screening (VOMS) as 'optional/recommended' in the Sport Concussion Assessment Tool 6 (SCAT-6). The VOMS is a prominent screening tool for vision and vestibular (balance) issues developed by the University of Pittsburgh Medical Center and widely used (including being promoted by the Children's Hospital of Philadelphia). Vision issues are common after concussion, and the lack of mention of vision therapy or inclusion of VOMS on the SCAT-6 may be a barrier to care. However, the 6th Consensus Statement does recommend the VOMS in their new Sports Concussion Office Assessment Tool (SCOAT-6), designed to help healthcare providers' office assessment of patients in the subacute phase.

Concussion Alliance plans to address this new international paradigm in greater depth sometime this summer. For professionals interested in discussing the implications and limitations of the 6th Consensus, please contact us.

Pathophysiology

Explaining how neuroendocrine dysfunction after all-severity TBI affects recovery

An article by Stefanie N. Howell, PhD, for Psychiatric Times, discusses how many long-lasting symptoms of all-severity TBI are linked to TBI-induced neuroendocrine dysregulation, including hypervigilance, fatigue, disturbed affect, and problems with memory and attention. Dr. Howell notes that patients with mild TBI (concussion) should “be offered an assessment” if they are experiencing symptoms potentially related to neuroendocrine dysfunction but that neuroendocrine dysfunction is more frequent in moderate and severe TBIs.

Many times after a TBI, a part of your brain located above the brainstem, the diencephalon, is affected. There are two main parts of the diencephalon: the pituitary gland and the hypothalamus. These two primary structures create a type of feedback loop––the hypothalamus sends signals to the pituitary gland, which then proceeds to distribute hormones throughout the body. When this network, called the hypothalamic-pituitary system, is disrupted, people experience effects on their mood, memory, metabolism, energy, and reproduction.

Neuroendocrine disruption post-TBI has been coined “posttraumatic hypopituitarism,” or PTHP, and the symptoms arising from this disruption have been observed to surface up to a year after the injury. The authors highlighted four different signaling pathways, or “axes,” that the hypothalamic-pituitary system is involved in: the somatotropic axis, gonadal axis, adrenal axis, and thyroid axis. Keep in mind that the descriptions and statistics below are for all-severity TBI, primarily moderate and severe TBI, as opposed to mild TBI or concussion.

Dysregulation of the somatotropic axis creates various dysfunctions, most prominently, growth hormone deficiency (GHD), with more than 45% of chronic TBI patients with severe deficiency. Growth hormone (GH) receptors have been identified on most types of cells, so a deficiency of GH will affect nearly all tissues and organs. Additionally, patients with GHD often experience decreased bone density and muscle mass, fatigue, and impairments in attention and memory.

Dysregulation of the gonadal axis affects the release of gonadotropin growth hormone (GnRH), which is often associated with low levels of testosterone in men and low levels of estradiol in women. In men, this symptom will present right after injury and persists in 37% of male patients with a TBI. In women, up to 46% of female patients experience a complete cessation of menstruation, and up to 65% report irregular cycles.

Thirdly, the adrenal axis is linked to our stress response, starting with the corticotropin–releasing hormone (CRH), which then triggers the release of adrenocorticotropic hormone (ACTH), leading to the adrenal gland releasing cortisol. Cortisol helps us deal with stress, such as increased heart rate. Hypersensitivity to this signaling pathway has been observed post-TBI and has been linked to irritability, depression, anxiety, and mood swings, among other symptoms.

Finally, the improper regulation of the thyroid axis has detrimental effects on glucose metabolism and brain glucose, essential for high-level cognitive processing. Although impaired function is less common than the other three axes, this signaling pathway interacts with cortisol and gonadal hormones, showing that a disruption in one axis is likely to affect another. The dysregulation of this axis is linked with mood and energy levels.

Mental Health

A “must read”: even a single concussion can lead to the emergence of a new mental health disorder in adolescents

Even a single concussion can lead to the emergence of a new mental health disorder over the next 4-7 yrs (for females) or 9-10 yrs (for males). A stunning report utilizing the interlocking databases of the Manitoba Center for Health Policy, and published in The Journal of Pediatrics, suggests that adolescents who have had a single concussion face this risk.

Researchers Kelly Russel et al. mined the Interlocking databases in the Manitoba Center for Health Policy to identify a subset of 1.16M youth ages 10-18 living in Manitoba in 2003. They found 2082 Manitoba youth who had their “first life-time physician-diagnosed concussion” between 2000 and 2005. (The researchers appear not to have tracked whether members of this cohort sustained additional concussions.) The study authors then used a case-control design to match them by age and zip code (a way to match their economic status) to 10,500 controls with “no physician-diagnosed concussion during their lifetime.”

For one study component, the researchers compared “Baseline characteristics of adolescents with and without a previous concussion.” One finding was that adolescents with a concussion were more likely to have a “maternal history of mental health disorder” than the control group.

For a second component of the study, they evaluated these cohorts’ health and sociodemographic challenges over the follow-up period of 11–16 years. They found that the prevalence of mental health disorders in those with a concussion was significantly higher than in the controls.

They were more likely to have certain types of mental health disorders (such as psychosis and mood disorders) and experience substance abuse. Females were more likely to have ADHD as the identified mental health disorder. Although there were more males with concussion in this cohort, females were more likely to be given prescription medications to treat disorders.

Social and environmental stressors also emerged in the concussion cohort. In the follow-up period, the concussion cohort was more likely to experience child protective services contact and in-home assessments and more likely than their unconcussed counterparts to appear in an interlocking crime database (as a victim, witness, or accused person).

Despite some limitations (omission of data from indigenous populations in Manitoba, lack of documentation of mechanism of injury, duration of symptoms, or time to recovery, possibility of missing undocumented concussion in controls), this study adds valuable insight into how individuals should be supported after concussion. It underscores the need to monitor and support those who have even mild head injuries for the emergence of long-term sequelae. It also invites mitigation of factors that may place adolescents with concussion at higher risk for social and environmental challenges.

Statistics

Walking the dog and a growing concern about concussions

A new study by Ridge Maxon et al. has shed light on a concerning trend in the world of pet ownership. Over a span of almost two decades, data reveals that more than 422,000 adults in the United States sought emergency room treatment for injuries sustained while walking their leashed dogs. This study, published in Medicine & Science in Sports & Exercise, emphasizes the need for dog owners, especially women and individuals between 40 and 64 years old, to be aware of the potential risks associated with this seemingly harmless activity.

The study highlighted a surge in dog-related injuries from 2001 to 2020, with finger fractures, shoulder sprains, strains, and traumatic brain injuries, including concussions and “nonconcussive internal head injuries” such as hematoma, among the top diagnoses from leash-related incidents, according to a press release from John Hopkins Medicine. Startlingly, over this time period, the annual incidence of injuries from “leash-dependent dog walking” increased “more than four-fold.” Of those injured, 75% were women, and 47% were 40 to 64. In an article by Lindsey Bever for The Washington Post, an emergency medicine expert, Dr. Michael Levine, confirmed that these incidents occur more frequently than one might imagine.

The study emphasizes the need for dog owners to take precautions to minimize the risks associated with walking their pets. The Washington Post article has tips for making dog walking safer, such as using front-attaching harnesses to avoid those unexpected tugs, opting for shorter leashes, and steering clear of retractable leashes (which have a knack for causing trouble for both dogs and humans.). Additionally, it seems that training holds the key to leash success. Karen B. London, a professional dog trainer, emphasizes the importance of teaching dogs to walk nicely on a leash.

With a bit of training, dog walking mishaps can be reduced, and the joys of dog ownership need not be forsaken, especially for older adults. While our four-legged companions bring immeasurable joy, they also come with the risk of concussions and other injuries. Stay vigilant, train those pups, and minimize the risk of head injuries.

Women’s Health

Cognitive deficits (related to TBI) in IPV survivors compared to those who have not experienced violence

A study in The Clinical Neuropsychologist sought to determine the occurrence of traumatic brain injury (TBI) in a group of 50 intimate partner violence (IPV) survivors and to discover the types of changes in their cognitive abilities due to TBIs. Applying the HELPS brain injury screening tool, researchers found that 95% of the IPV group had a possible brain injury. When CDC criteria were used, 60% of the IPV group was identified as possibly having a brain injury. Another significant finding by Sarah A. Raskin et al. was that memory and executive functioning were lower in the IPV group than in the comparison groups. Those IPV survivors who had experienced non-fatal strangulation (NFS) were most affected; they had higher cognitive deficits than IPV survivors who had not experiences NFS.

This research is vital because it brings awareness to doctors, domestic violence shelter workers, and, hopefully, survivors about the need for TBI assessment when survivors try to get help. This research also shows some of the negative impacts of women in IPV situations with an untreated TBI, as “Deficits in memory and executive functioning can impede a survivor’s ability to effectively create and implement a safety plan or react effectively in a fast-moving situation.”

Raskin and their colleagues researched three groups: a cohort of 50 women who experienced IPV, 35 women who experienced sexual assault (SA) but did not experience a hit to the head or strangulation, and 50 women who experienced neither IPV nor SA. Researchers assessed their attention, executive functioning, and memory with neurocognitive assessments, as well as questionnaires that asked them about their emotions, symptoms of anxiety, depression, post-traumatic stress disorder (PTSD), and their traumatic experiences to identify possible TBIs and their demographics. A participant was identified with impaired cognitive abilities if their score was two standard deviations below the standard range of previously published normative data. The overall findings were a significant statistical difference between the three groups on the tests that involved memory and executive functioning, particularly between the IPV survivors and those who had not experienced either kind of violence. However, there was no statistical difference between the groups on the tests that examined attention. There also were significant differences between the groups on measures of depression and PTSD symptoms.

While there has been this significant interest in TBIs for IPV survivors, much research needs to be done. It is imperative to make TBI assessments available even to women still in dangerous situations and find ways to help them out of these situations – as they might not be able to do so as quickly on their own.

Culture

Elevated head trauma rates in refugees and asylum seekers

A 2023 systematic review published in Neurology highlights that refugees and asylum seekers are more vulnerable to head trauma and, due to the absence of a validated screening tool specific to traumatic brain injury in place, they are often at higher risk of complications from head trauma.

Head trauma within displaced populations may occur due to adverse circumstances such as trauma, war, interpersonal violence endured, or other complex factors, which may increase their exposure to head injuries during the process of resettlement and seeking refuge.

The study authors, Altaf Saadi et al., analyzed peer-reviewed original research to assess the global prevalence of head trauma and examined additional data related to severity, mechanism of injury, other trauma exposures, and comorbidities. Data was collected from prior studies where patients were mainly seen in hospitals/clinics or refugee camps. Most studies were conducted in the US, followed in prevalence by studies carried out in the Middle East and Latin America. The pooled mean age of the study participants was 29, and they were disproportionately men.

According to findings from this current study, the most frequent mechanism of injury and cause of head trauma was direct impact through blows to the head or physical violence. Additionally, based on findings from prior studies, the research team noticed significant inconsistencies in how TBI severity was assessed across these studies; hospital-based samples identified more moderate to severe head injuries than assessments performed in refugee camps. The research team notes, “There was significant variation among studies in how head trauma was defined and ascertained, with no study utilizing a validated screening tool specific to traumatic brain injury (TBI).”

They also note that mental health comorbidities were documented more frequently than physical health comorbidities.

This study brought key relevant findings to the fore concerning the susceptibility of refugees and asylum seekers to head trauma. The study team also recognized the lack of studies that utilized a systematic approach to traumatic brain injury screening within this vulnerable population. Overall, the study team concludes that increased awareness and attention to challenges surrounding head trauma in this at-risk population could pave the way to addressing risk and optimizing equitable care.

CTE and Neurodegeneration Issues

Impaired cognitive and behavioral functioning correlated with low levels of myelin proteins and associated with football-related repetitive head impacts

A study published in Brain Communications explores the association between the manifestation of cognitive symptoms as well as impulsivity (from clinical documentation) and the levels of immunoassays for myelin-associated glycoprotein (MAG) and proteolipid protein 1 (PLP) in brains donated by those exposed to American football-related repetitive head impacts (RHI). Michael L Alosco et al. found a correlation between low levels of these proteins and more years of football play and younger age of first exposure to football. The MAG and PLP proteins “contribute to the structure, function, and maintenance of myelin,” therefore helping to regulate brain cell connections.

This study examined the biochemical measurements of MAG and PLP in the brain tissue of 205 male brain donors (mean age = 67.17) with histories of playing football. Researchers found that “more years of football play was associated with lower PLP concentrations,” and participants who played for more than 11 years had “lower MAG and PLP concentrations.” Additionally, “younger age of first exposure to football was associated with lower PLP concentrations.” This research is also relevant for studying the neurodegenerative disease chronic traumatic encephalopathy (CTE), as lower PLP levels were associated with more severe CTE.

In brain donors 50 years or older, lower levels of MAG and PLP were associated with higher scores on the Functional Activities Questionaire, meaning worse impairment in activities of daily living. Lower MAG levels in brain donors were associated with higher (worse) scores on the Barratt Impulsiveness Scale. In an article published in Boston University’s research news site The Brink, Dr. Thor Stein explains that for “Young folks playing at an early age, their connections might be particularly susceptible to damage...If you started at a younger age, you were more likely to have less of these white matter–associated proteins decades later in life.”