Happy December! I hope you had a wonderful holiday with family, friends, and loved ones. This week we have a special edition; in addition to our normal writing on research, we’re featuring a call for study participants from the Center for Neuroscience and Regenerative Medicine and Concussion Alliance’s first-ever press release promoting our CME course. Read on to learn more!

This week's lead article, Depression app clinical trial: Center for Neuroscience and Regenerative Medicine recruiting Service Members & Veterans for Remote CBT Study, is in the Opportunities category.

In this newsletter: Special Feature: Opportunities, Therapies Currently Available, Therapies & Diagnostic Tools Under Research, Special Feature: Concussion Course, Youth, and CTE & Neurodegeneration Issues.

We appreciate the Concussion Alliance Interns and staff who created this edition:
Writers: Susan Klein, Lori Mae Yvette Calibuso Acob, Sravya Valiveti, Conor Gormally & Malayka Gormally

Editors: Conor Gormally and Malayka Gormally

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Special Feature: Opportunities

Service members and veterans with a history of mild traumatic brain injury (including concussion) and struggling with symptoms of depression may want to participate in a new clinical trial testing a cognitive behavioral therapy (CBT) app for depression tailored to the military community. Study participants will be provided with the CBT app and will work with the researchers remotely. The time commitment is 30–60 minutes per week for 16 weeks.

To learn more, read our blog post and the flyer, or contact the study team. Call or text 301.461.4322 or email CNRM-D@usuhs.edu.

Looking for youth study participants: researchers at Nationwide Children’s Hospital are “Looking for Youth Athletes Who Stopped Contact Sports After Concussion” to take “to complete a few short online surveys and a 30-min phone or video interview.”

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.

Therapies Currently Available

Advocating for improved provider training and multidisciplinary services for people experiencing persistent symptoms

There are an estimated 170,000 cases of concussion per year in Australia, according to an article in ABC News Australia. Yet, a lack of understanding among general practitioners and few multidisciplinary rehabilitation services is creating barriers for Australians with persistent post-concussion syndrome (PPCS) looking for appropriate care. Hayley Gleeson’s article expresses that clinicians need more and improved concussion education; patients suffer “because of a lack of understanding among general practitioners about how to manage patients with mild traumatic brain injury.”

The gap in concussion management training leaves clinicians inexperienced at managing patients with concussions. As a result, variable diagnoses and treatments may be advised that have the potential to prolong recovery and impair the quality of life of patients. Another reason people with concussions or PPCS struggle to find appropriate care is the absence of dedicated rehabilitation services. Gill Cowen, the Royal Australian College of General Practitioners spokesperson, points out that without clinics specializing in brain injury treatments, patients cannot seek adequate care. This lack of options is especially concerning for people without private health insurance.

Dr. Sarah Hellewell, a neuro-trauma expert at Curtin University, echoes this advocacy for more integrated care. In Australia, people suffering from PPCS are trying to figure out the pieces for themselves. However, there needs to be greater patient advocacy among general practitioners and the community. Thus, general practitioners need to become educated in diagnosing and treating concussions, and more infrastructures that specialize in brain injuries need to be established.

Therapies & Diagnostic Tools Under Research

A saliva test that measures MicroRNAs may predict risk for persistent symptoms in children and adolescents

Figuring out whether your child or adolescent is at risk for persistent symptoms following a concussion might be as simple as having them spit into a test tube within one week after the injury. That’s the promise of a study published in Frontiers in Public Health which identified 13 microRNA (microRNA) that were expressed at higher levels in those with persistent post-concussion symptoms compared with those who recovered within the standard timeframe.

In a press release, senior author Jingzhen Ginger Yang noted, “The diagnosis of concussion is based on self-report, and it can be difficult for children, especially those who are very young, to describe their symptoms following injury…Currently, there are no markers to objectively predict who is going to recover sooner or later. If physicians could identify children at risk for prolonged recovery, they may be able to intervene earlier, providing personalized concussion care, to improve patient recovery.”

Authors Katernine E. Miller et al. studied 60 youth ages 11-17 over 4 weeks following their concussion, collecting saliva for microRNA analysis at 1, 2, and 4 weeks post-injury and tracking symptoms with a daily checklist (Post-Concussion Symptom Scale-PCSS). Using this daily checklist, the researchers identified a group of 18 subjects who had persistent symptoms at one month. In the persistent symptoms cohort, 13 of 91 microRNA were expressed at higher levels than the standard recovery group. Three of these 13 microRNAs had been reported by other researchers to be persistently expressed in those with persistent post-concussive symptoms. However, we are still some ways off from being able to use this interesting clinical tool.

What exactly are the researchers measuring in saliva? Atif and Hicks have provided a comprehensive review that explains why microRNA might tell us something about brain injury. MicroRNAs “hook on” to RNA, telling the RNA to degrade or be stored (inactive) in the cell for a time. Since neural (brain) tissue is where most of the microRNAs in our body exist, cell injury and metabolic changes after a concussion might change microRNA concentration in body fluids. Because microRNAs can cross the blood-brain barrier, they can be measured in saliva.

Miller and colleagues cautioned about the preliminary nature of this exciting report. The subject sample was small, ethnically homogeneous (White), and included no control group. Subjects did not provide baseline assessments of their microRNA profile, and not all the participants contributed saliva for all three measurement intervals. This study also demonstrated that microRNA expression varied with age; older subjects with persistent symptoms had more subtle increases in microRNA expression than the younger ones who were still symptomatic. Whether overexpression of the three microRNAs found in this sample will be replicable may depend on factors such as sample timing and age. Though Miller and colleagues compared their findings to an open-source database to evaluate what intracellular processes might be controlled by the microRNAs they identified, the available data are too limited to target specific dysfunctional brain processes.

A review of these observations suggests it is too early to conclude that changes in the expression of one microRNA or a few microRNAs correspond clearly with specific clinical outcomes after concussion. However, Concussion Alliance agrees with these researchers that matching systematic clinical observations with this non-invasive lab test merits continued exploration.

Special Feature: Concussion Couse Press Release

Concussion Alliance addresses the need for concussion training for primary care providers

An article in ABC News Australia (covered in this newsletter, in Therapies) discusses a lack of concussion training among primary care providers that hinders recovery for concussion patients, particularly those with persistent symptoms; this problem exists in many countries, including the U.S. To address this lack of training, Concussion Alliance has published a press release (picked up by AP News) to increase awareness of our continuing medical education course (CME), A Patient-Centered Approach to Concussion Care for Emergency Medicine and Primary Care Physicians.

Our free, one-credit-hour CME and non-physician webinar has a unique format that combines perspectives from brain injury medicine physiatrist Elizabeth Sandel, MD, and persistent post-concussion symptom patient Conor Gormally. The course provides critical information and insights for healthcare providers, coaches, athletes, patients, and parents. Viewers will find up-to-date information on concussion research, best practices, specialty care referrals, and tools for evaluating and treating patients with acute and chronic symptoms, including a discussion of the prevalence of mental health disorders following a concussion.

Pediatric Neurologist Susan Klein, MD, has this to say about the CME: “This compelling AMA Category 1 free CME juxtaposes Dr. Elizabeth Sandel, an expert physiatrist in concussion care, with Conor Gormally, an articulate young man who shares his personal journey and perspectives on rehabilitation from concussion, including a critical perspective on mental health considerations post-injury. It’s the closest thing to the ‘live patient Grand Rounds experience’ in the post-COVID space and keeps the pacing of the hour fresh.”

Youth

Socioeconomic and racial disparities in referrals, pediatric adherence to provider recommendations

A study published in the Journal of Head Trauma Rehabilitation highlighted disparities in pediatric concussion patients' adherence to "providers' follow-up recommendations and continued care until doctors cleared them to return to full activity." Fairuz N. Mohammed, MPH, et al. identified race and socioeconomic factors that play a role in these disparities in adherence and receiving a referral to specialty care.

Researchers found that "non-Hispanic Black and publicly insured/self-pay patients are less likely to adhere to follow-up recommendations than non-Hispanic White and privately insured patients, respectively."

The study also found differences in those referred to specialty care, noting that "non-Hispanic Black patients and publicly insured/self-pay patients were more likely to receive a referral than their non-Hispanic White peers and privately insured patients."

The authors assessed the medical records of 755 Children's Hospital of Philadelphia (CHOP) primary care clinic patients aged 5 to 18 who presented with complaints of a concussion between September 26, 2019, and December 31, 2019.

In a CHOP press release, study author Daniel J. Corwin noted that "This study provides us with a basis to explore the individual- and system-level barriers that may prevent adherence to care, which ultimately will inform how we provide targeted approaches and establish more equitable care to reduce disparities among pediatric concussion patients."

CHOP announced it had received a four-year CDC grant for the Minds Matter Concussion Program to "identify additional disparities in concussion outcomes." The goal is to bridge gaps in care by facilitating accurate concussion diagnosis and management while identifying and providing support to those who need a specialist referral.

"Researchers plan to analyze electronic health records of patients seen within the CHOP network and evaluate the implementation of primary-care based interventions in urban and suburban practices. The study will analyze school re-entry data after concussion from the BrainSTEPS program of the Pennsylvania Departments of Health and Education, while also leveraging partnerships with urban schools and sports programs to improve education and access to concussion care."

CTE & Neurodegeneration Issues

First jury to rule on NCAA’s liability for the death of a former player finds the NCAA not responsible

The trial of the wrongful death lawsuit against the NCAA that we reported on in our last newsletter has ended, with the jury finding that the NCAA was not liable for the death of former USC Football Player Matthew Gee. According to an article in Front Office Sports, the jury determined that the NCAA did not fail to “take reasonable precautions around concussions and educate players on the dangers of repeated head collisions” during the course of Gee’s playing career (1988-92).

This lawsuit, the first of its kind to go before a jury, questioned the role of a major sporting organization in mitigating the risk of long-term neurodegenerative disease for one of its players. As a result, this jury decision will set a precedent in future legal battles regarding organizations like the NCAA’s level of responsibility for the long-term effects of repetitive impacts and concussions.

According to a Reuters article, the NCAA argued that Gee’s premature death was due to a substance abuse problem and had no connection to his college football career. Gee’s autopsy revealed he suffered from hypertension, which likely triggered his heart attack, combined with cocaine and alcohol toxicity. However, brain tissue analysis showed that Gee had been suffering from the progressive neurodegenerative disease CTE, which contributed to his sudden cognitive decline in the years leading up to his death.

Regardless, the LA jury ruled in favor of the NCAA’s argument, with the organization afterward issuing the following statement: “The NCAA bore no responsibility for Mr. Gee’s tragic death, and furthermore, the case was not supported by medical science linking Mr. Gee’s death to his college football career.”