Optimizing acute mTBI care in the ED: how biomarkers, machine-learning, and psychosocial outcomes can help

Concussion Center faculty council members Dr. Fred Korley and Dr. Katharine Seagly, along with their co-principal investigator, Dr. Chris Fung from Michigan Medicine’s department of emergency medicine, and a team of other collaborators, secured funding support from the Joyce and Don Massey Family Foundation and the Department of Defense for two related projects that will close the current gap in the acute evaluation of mild traumatic brain injury (mTBI). Their work will develop an algorithm for clinical decision-making when managing patients presenting to the emergency department (ED) with a Glasgow Coma Scale (GCS) score of 15 – the mildest form of a traumatic brain injury.

The current standard of care requires a brain CT for most patients arriving in the ED with a known or suspected head injury. Most patients who present to the ED with a GCS of 15 have a negative head CT, but a small subset is positive for a traumatic intracranial hemorrhage (i.e., bleeding in the brain). Unfortunately, some of these patients, deteriorate rapidly after the initial scan. The planned algorithm would use blood-based biomarkers and patient histories, such as medical comorbidities and risk factors, to identify this subgroup of patients early to prevent subsequent acute decompensation.

Our goal is to develop a scientifically informed method for determining who needs which assessments and interventions in order to optimize both acute and long-term outcomes in patients with GCS 15 TBI. By doing so, we can prevent overutilization or underutilization of healthcare resources by sending patients down the right, personalized treatment path as early as possible.

Katharine Seagly, Assistant Professor
Department of Physical Medicine & Rehabilitation

Once discharged, all patients with initial GCS of 15 and blood-based biomarker data, including those with and without positive head CTs, are receiving follow-up from the study team at 2-week and 3-month time points, where functional, cognitive, psychosocial, and quality of life outcome measures are collected. These data will help determine patterns in who gets better in these domains and who does not. In addition, they will be added to the algorithm to best predict who will most benefit from more comprehensive rehabilitative care early on post-injury and who is likely to get better on their own.

“Our goal is to develop a scientifically informed method for determining who needs which assessments and interventions in order to optimize both acute and long-term outcomes in patients with GCS 15 TBI.” said Dr. Seagly, “By doing so, we can prevent overutilization or underutilization of healthcare resources by sending patients down the right, personalized treatment path as early as possible.”

Seagly is also the Director of Michigan Medicine’s Brain Injury Rehabilitation Program. One of the program’s focus areas is concussion management through a recovery group. The Concussion Recovery Group, developed by Seagly and led by a licensed clinical social worker, supports all mTBI patients across all injury mechanisms, though it requires a referral. Regardless of how one sustains a concussion, this 6-session group aims to educate patients through evidence-based, patient-centered interventions that can aid recovery and return to usual daily activities. Seagly plans to add a 1.5-hour concussion education session for patients with acute mTBI as an adjunct project for the current mTBI studies in the ED, supporting the patients’ short- and long-term post-discharge outcomes.

ATHINA (pronounced Athena), is the ancient Greek Goddess of wisdom and warfare. She reminds us of Concussion Center Faculty, Dr. Eleanna Varangis, as she gracefully shares her knowledge of magnetic resonance imaging (MRI) and won the tough battle of choosing a lab name, all while maintaining high functioning cognitive capacity for other tasks around the Center. Her victory resulted in the creation of the Assessing Traumatic Head Injury with Neurocognitive Approaches (ATHINA) Lab.

My lab’s mission is to understand what underlies differences in neurocognitive aging trajectories in individuals with a history of head impacts or concussions. I hope that by learning more about what factors may buffer against cognitive impairment in aging, we can begin to develop interventions to help people stay cognitively healthy for longer. “

Eleanna Varangis, PhD, Assistant Professor, School of Kinesiology

The ATHINA Lab aims to explore the effects of mild traumatic brain injury (mTBI) on neurocognitive outcomes across the adult lifespan. They will utilize functional and structural neuroimaging and cognitive assessments to capture multiple aspects of brain and cognitive health in samples of current and former athletes. Their goal is to gain a more complete understanding of how mTBI affects healthy brain aging trajectories and identify factors that may protect against or exacerbate any deviations from them.

Dr. Varangis, ATHINA Director, recently led a discussion on the “Fundamentals of MRI in mTBI Research” during the Concussion Center’s February Lunch & Learn. Center members may find it helpful to have a general idea of MRI research procedures and how it compares to other methods that capture brain structure and activity, such as computerized tomography (CT) and electroencephalogram (EEG).

During her presentation, Dr. Varangis outlined how increasingly high-resolution MRI images are used to generate incredibly detailed 3D images of the brain and surrounding tissue. Dr. Varangis also touched on the basics of structural and functional MRI (fMRI), the Haemodynamic Response Function, types of MRI scans, analysis of fMRI data, and how fMRI may be useful to gain a better understanding of the effects of mTBI and concussion on the brain and cognitive function.

“My lab’s mission is to understand what underlies differences in neurocognitive aging trajectories in individuals with a history of head impacts or concussions,” said Dr. Varangis, “I hope that by learning more about what factors may buffer against cognitive impairment in aging, we can begin to develop interventions to help people stay cognitively healthy for longer.”

If you have any questions about the ATHINA lab or MRI research, feel free to reach out to athinalab@umich.edu.

U-M Concussion Center post-doctoral fellow Landon Lempke, along with co-investigators Dr. Benjamin Brett from the Medical College of Wisconsin’s Departments of Neurosurgery and Neurology and Dr. Douglas Terry from the Vanderbilt University Medical Center’s Department of Neurological Surgery, received grant funding from the Eastern Athletic Trainers’ Association to lead a project addressing the current gap in concussion return to play assessments. The project will determine the reliability and validity of their novel cognitive-motor assessment battery called the Functional Assessment of Neurocognition in Sport (FANS) designed to emulate the demands of on-field sports.

“Our ultimate goal is to improve clinical decision-making and concussion healthcare, but in a stepwise fashion to ensure we do not put the proverbial cart before the horse, which would cause an undue burden on both patients and clinicians.”

Landon Lempke, PhD, Post-doctoral Research Fellow, U-M Concussion Center

Current concussion assessments have strong diagnostic accuracy and serve an important role in initial injury healthcare. However, their diagnostic strength decreases after the acute timeframe, and collective research indicates a return to pre-injury levels long before biomarker-based (e.g., functional magnetic resonance imaging or spectroscopy). Current assessments also do not reflect the on-field sports demands, as they only require static balancing or simple finger-movement for neurocognitive testing. Thus, the team believes current concussion assessments have limited ability to inform safe return-to-play decision-making and are not valid for this purpose.

Dr. Lempke and co-investigators, therefore, developed FANS to address the current gaps in concussion management. After a concussion, the FANS battery assesses verbal and visual memory, reaction time, processing speed, and cognitive-motor flexibility, commonly impaired with concussion. Traditional neurocognitive testing often assesses these same domains by using a computer and finger-movement input to respond. FANS differs starkly from traditional neurocognitive testing as participants respond during testing through full-body movements and athletic tasks to better emulate the on-field sport demands in a standardized manner.

“Our first step here is to determine whether FANS is both reliable and valid among healthy individuals without a concussion to ensure a psychometrically sound and appropriate assessment is possible before implementing into post-concussion evaluations,” said Dr. Lempke. “If FANS is reliable and valid, we will then have individuals experiencing a concussion complete FANS before returning to play and monitor them over time so that we can determine if FANS possesses augmentative clinical utility. Our ultimate goal is to improve clinical decision-making and concussion healthcare, but in a stepwise fashion to ensure we do not put the proverbial cart before the horse, which would cause an undue burden on both patients and clinicians.”

Concussion Center director Dr. Steve Broglio also leads the NeuroTrauma Research Lab with the School of Kinesiology, which focuses on conducting research to improve athlete health and safety related to concussion. We are excited to share some updates on the innovative work done by undergraduate students Carlin Pendell and Alvin Anand, both juniors with the College of LS&A majoring in Neuroscience who have been hard at work exploring a range of fascinating concussion-related topics.

“Students are the cornerstone of our University, Center, and lab. We are incredibly proud of the work they are doing and are excited to see the impact their research will have in the future.”

Steve Broglio, PhD, Concussion Center Director

With an interest in examining how cognitive control is affected long after a concussion, Carlin Pendell, an undergraduate in LSA, has begun data collection for her senior honors thesis among the University of Michigan students to understand how they might be impacted. Though concussions result in neurological deficits acutely, it is unclear if persistent deficits may be experienced long after the injury. Cognitive control, the mental processes that allow us to regulate our actions to achieve a task, is crucial for every activity we engage in, including sports. The inability to perform to the best of one’s cognitive ability is detrimental to the success of many athletes. The implications of this study may reveal novel insights into the lingering effects of concussion and its potential impact on cognitive function after injury. Carlin’s work has been selected and supported by the LSA Honors Program. Center director Dr. Steve Broglio and members Dr. Landon Lempke and Adrian Boltz have been instrumental in supporting her project by sharing their research expertise. Her work will surely fill a critical literature gap and help Carlin along her future academic career path. We look forward to her continued hard work and dedication to addressing critical problems in the field.

Separately, Alvin Anand is conducting a systematic review and meta-analysis examining the effect of concussion on the onset of depression. He has been conducting a thorough review of existing literature on the topic, gathering data from various studies that examine depression incidence following concussion. He uses advanced statistical techniques to analyze the data and draw meaningful conclusions about the relationship between these two conditions. The findings from this research will inform the mental health field by demonstrating implications for the diagnosis, treatment, and prevention of depression in individuals who have suffered a concussion.

“Students are the cornerstone of our University, Center, and lab. We are incredibly proud of the work they are doing and are excited to see the impact their research will have in the future,” Broglio said. Stay tuned for more updates on their progress.

In recognition of National Athletic Training Month, the Concussion Center hosted a Concussion & Cocktails event featuring Jeremiah Freeman, the NeuroSport Athletic Trainer Clinical Specialist. As an experienced Athletic Trainer with Michigan Medicine since 2000, Jeremiah is an invaluable team member, providing at-the-elbow support for clinicians and student-athletes in concussion treatment and management.

“Research has shown the benefits of supervised exercise progression for our sports concussion athletes. Having a structured progression can help the athlete manage their recovery and progress their activity in a way that helps them recover more quickly.”

Jeremiah Freeman, NeuroSport Athletic Trainer Clinical Specialist

More than 20 center members, including colleagues from Emergency Medicine, Physical Medicine & Rehabilitation (PM&R), NeuroSport, Kinesiology, and Athletic Medicine, attended the event. Jeremiah demonstrated the concussion rehab protocol and shared clinically relevant information tips and resources for the audience.

*Jeremiah demonstrates medicine ball chops through a pre-recorded video.*

“Research has shown the benefits of supervised exercise progression for our sports concussion athletes. Having a structured progression can help the athlete manage their recovery and progress their activity in a way that helps them recover more quickly,” said Jeremiah.

Different clinical rehab protocols were introduced to the audience, including the aerobic progression (e.g., stationary bike, elliptical, treadmill), basic vestibular protocol (e.g., medicine ball toss and chops, hopping exercises), light impact progression (e.g., box drill), and agility/ sports-specific exercises such as the agility ladder and drills.

“I am very impressed with how Jeremiah presented the evidence-based practices supporting athletes during concussion recovery,” said Benjamin Wojtas, a strength and conditioning coach with PM&R, “I look forward to attending more in-person events like this in the future.”

*The “agility ladder” exercise demonstration*

Center member Dr. Andy Hashikawa, associate professor of emergency medicine, is organizing more Pop-up Safety Town events in underserved communities in Michigan this April and May. Pop-Up Safety Town is a pediatric injury prevention education program for young children and families. During these events, children (currently aged 3-5) and their families can tour the town to learn various injury prevention tips, including pedestrian safety, dog bite prevention, medication safety, and helmet safety. Upon entry, each child is given a “Pop-Up Safety Town Passport,” allowing them to receive stamps as they rotate through different stations every 15 minutes; children and families will receive free bike helmets fitted by trained volunteers, food, and children’s books upon completion of all activities.

Dr. Hashikawa needs more volunteers for upcoming events. These events will provide educational opportunities for pre-schoolers living in low-resource neighborhoods. Volunteers will be working with injury experts and Michigan Medicine physicians to run educational stations for medication safety, pedestrian safety, electrical safety, firearm safety, and animal safety, etc. Your help and enthusiasm are much appreciated! For more information or additional questions, email pop.up.safetytown@umich.edu

Perry Head Start

550 Perry Ave, Ypsilanti, MI 48197

Thursday, April 13, 2023, 3:30 PM – 5:30 PM

Addison Elementary

219 N Comstock St, Addison, MI 49220

Saturday, April 22, 11:00 AM – 2:00 PM

Martin Luther King Jr Center

1107 Adrian, Jackson, MI 49203

Friday, May 5, 12:00 PM – 5:00 PM *Time may be adjusted within this window*

Lincoln Early Childhood Center at Model Elementary School

8850 Whittaker Rd, Ypsilanti, MI 48197

Wednesday, May 10, 5:30 PM – 7:30 PM

Carmen-Ainsworth Middle School

1409 Maple Rd., Flint, MI 48507

Friday, June 9, 10:00 AM – 12:00 PM

Video: Jarrett Irons, Concussion Center’s advisory board member and former U-M football co-captain in the 1990s, shared his father’s story and the reasons why he believes and supports the center’s mission. (Credit: Michigan News, Laura Bailey & Jeremy Marble)

Jarrett Irons, a name familiar to many who watched Michigan football in the late 1990s, was the team’s co-captain and named consecutively the Roger Zatkoff best linebacker in 1995 and 1996. As we celebrate black history month, we would also like to take this opportunity to honor Jarrett, whose serving heart has inspired many of us to continue pursuing neurological science relentlessly through research, clinical care, outreach, and public engagement.

The Concussion Center was first connected with Jarrett in early 2022, shortly after his family moved to Michigan from Chicago. We met with Jarrett in a popular brunch restaurant in downtown Detroit, which he now calls home. After listening to the story about how the Concussion Center was founded and our mission for the future, Jarrett raised his hand to join our advisory board, where he now provides guidance and wise counsel to leadership as someone who has personal experience with a concussion and knows why brain health matters.

Sports-related injuries are not foreign to the Irons family. Many family members, including his brother, cousins, and father, played collegiate or professional football. When we first met Jarrett, he mentioned the family’s suspicion of the link between his dad’s repetitive head injuries to the cognitive impairment before his passing. As concussion research and neurological science are evolving, we know we must do more studies to understand the correlation fully.

In the fall of 2022, Concussion Center members launched the “U-M Alumni Neurological Health Study.” This survey, once completed, will be U-M’s first population-based study investigating key long-term neurological outcomes in former male and female athletes, as well as the broader U-M alumni community age spectrum. As a former collegiate and professional athlete, Jarrett was one of the first to complete the survey and helped promote the study among fellow alums without hesitation. He shared his stories, vision, and pride in being an integral part of the Concussion Center with U-M’s Michigan News team. A local media, Detroit News, later shared these stories with an even wider audience.

“I just want to help” is a motto that reminds us of Jarrett, and this all-American linebacker is now a true concussion champion for the center.

Curious about what Jarrett has to say? Check out:

Michigan News: “Brain health, concussions, and sports: is there a long-term connection?”
Detroit News: “UM to study sports concussions, brain health of alumni.”
Video Interview: “Jarrett Irons – Former UM football player Jarrett Irons talks about the decline in health and death of his father, former NFL player Gerald Irons.

Jarrett Irons visiting the Alumni Center in May 2022 — Jarrett Irons visiting Alumni Center in May 2022. “For those who leave Michigan, but for whom Michigan never leaves.”

The Concussion Center is honored to host an internationally renowned neuropsychologist, Dr. Ruben Echemendia from the University Orthopedics Center in Pennsylvania, at our April 2023’s Speaker Series. Dr. Echemendia specializes in sports-related concussions and has been involved in various large-scale national studies, including the “NFL-LONG: Neurologic Function across the Lifespan: A Prospective, LONGitudinal, and Translational Study for Former National Football League Players.” He was also part of the international group that spearheaded the consensus statement on concussions in sports.

On Thursday, April 13, 2023, Dr. Echemendia will present: “The process and science underlying the new SCAT6 Tools”, where he will provide an in-depth overview of the SCAT6 for evaluating a suspected sports-related concussion and how this standardized tool can be used on patients who are 13 years and older.

Situated on the corner of Glen Avenue and East Huron Street in Ann Arbor is the Biomedical Science Research Building, sometimes nicknamed “the Pringle,” which is home to nearly 240 state-of-the-art research facilities, including Dr. Sami Barmada’s lab.

Sami Barmada is the Angela Dobson Welch and Lyndon Welch Research Professor and an associate professor in the Department of Neurology. He also oversees the University of Michigan’s Brain Bank. Overlooking the university’s medical campus from his fourth-floor office, Barmada actively engages in neurodegenerative disease research focused on a nervous system disease called Amyotrophic Lateral Sclerosis (ALS) and frontotemporal dementia (FTD).

Abnormal protein deposits and accumulations in our brains could cause diseases like Alzheimer’s and chronic traumatic encephalopathy (CTE). One of the proteins that Barmada is studying is TDP43, an essential element responsible for different aspects of RNA processing, including splicing, translation, and transport. When the TDP43 protein is not located correctly in the brain, the cells will not be able to survive due to interrupted RNA processing, which then causes neurodegenerative diseases such as ALS and FTD.

In addition to age-related degenerations, TDP43 also builds up in patients who sustained numerous mild traumatic brain injuries (concussions) and have developed dementia later in life. “There’s a strong connection between TDP43, FTD, and the condition we now call CTE due to repetitive head injuries,” said Barmada. “Why does this happen to TDP43? What does this have to do with the development of symptoms, and what can we do to stop it?”

For Barmada, seeing the changes at the molecular level for age-related neurodegenerative diseases, such as ALS and FTD, has allowed him to understand these conditions further. Additionally, examining the functions of TDP43 might shed some light on what happens in concussion-related injuries when this protein is “not in the right place,” Barmada said. It could also reveal other potential concussion biomarkers and lead to understanding the mechanisms of disease that potentially cause CTE. Together with collaborators at the University of Michigan, he is currently looking at different proteins and RNA molecules that can show changes in TDP43 function or localization in patients before symptoms develop. Consistent with the Concussion Center’s research mission to understand and promote long-term brain health, Barmada notes critical findings that could be equally influential for concussion treatment and long-term management.

A challenge for Barmada is figuring out who is most at risk for developing neurodegenerative problems later in life.

“Somebody has a concussion, and then 20 years later, they develop dementia. What happened during those 20 years?” asked Barmada. “Having some measure or biomarker that we could detect would give us a leg up on not just identifying who’s at risk, but acting early enough to reverse it,” he added.

As director of the Michigan Brain Bank, Barmada sees many opportunities to work with the U-M Concussion Center on concussion-related research.

“We want to look at the similarities between age-related neurodegenerative disorders on the one hand and concussion/CTE on the other. We also want to provide resources to other investigators who want to study the same problem,” he said.

The U-M Biosciences Initiative recognized Barmada’s work by selecting him as one of the Mid-career Biosciences Faculty Achievement Recognition (MbioFAR) Award recipients. The MbioFAR, established in 2021, recognizes exceptional mid-career faculty in sciences and provides discretionary funds to encourage innovative, high-risk research.

He was one of six U-M research scientists to receive the award.

While Barmada’s lab has previously built prospective imaging systems for brain cells and neurons, there have been limitations in what they can measure due to technical difficulties such as low microscope resolution. He is excited about the possibility of conducting more robust assessments with the Biosciences Initiative’s support.

“Their support feeds right into what we’re doing. It opens doors,” he said. “There are many exciting, risky things we’ve wanted to do for years but haven’t had the chance. This is our chance.”

Somebody has a concussion, and then 20 years later, they develop dementia. What happened during those 20 years? Having some measure or biomarker that we could detect would give us a leg up on not just identifying who’s at risk, but acting early enough to reverse it.”

Sami Barmada, MD, PhD

After spending years as an athletic trainer supporting student-athletes, Dr. Allyssa Memmini developed a passion for helping students return to their classrooms safely, with minimal disruption to their learning, while including professional insights from a multidisciplinary team.

Concussion Center and Kinesiology alum (PhD ’22), Dr. Allyssa Memmini discussed her return to classroom protocol that supports post-secondary students after sustaining a concussion. During her first year as a graduate student instructor, she recalled one of her undergraduate students suffered a concussion during her first year of teaching. Due to the lack of resources supporting students beyond K-12 education settings, it was challenging for Dr. Memmini to gather medical documentation and student-support resources to guide the student, even though she was actively involved in concussion-related research. According to Memmini, now an assistant professor of Athletic Training at the University of New Mexico College of Education & Human Sciences, much of the return-to-learn research focuses on the younger populations. The unmet need of post-secondary students, regardless of their athletic history, drove her to develop a return-to-learn (RTL) protocol specifically for this population as part of her dissertation work.

Essentially, this guideline is a model to help students, their multi-disciplinary team (i.e., anyone who advocates for the student), and instructors develop an individualized plan for returning the student to the classroom after sustaining a concussion. This return-to-learn protocol, designed with post-secondary students in mind, was published recently in the Sports Medicine journal article “Achieving Consensus Through a Modified Delphi Technique to Create the Post-concussion Collegiate Return-to-Learn Protocol.” In addition to involving different stakeholders in the plan, Memmini advanced the return-to-learn guidelines to incorporate specific recommendations for university students.

“This [guideline] is very similar to the return-to-sport progression in such that if a student reports increasing symptoms, they either need to communicate that to their instructor and figure out if they need additional academic support or return to a prior stage because they may be experiencing too much too soon,” explained Memmini.

“We need to understand, through more qualitative work, some of the barriers university students face as they recover from concussion and how that might differ across race, the gender spectrum, LGTBQ students, and other underrepresented groups on campus.”

Allyssa Memmini, PhD, LAT, ATC

The first stage encourages students to undertake in-person activities with a light cognitive load, such as going to the cafeteria or socializing with friends. Memmini also recommends that students develop individualized guidelines specific to their coursework with their instructors and multi-disciplinary team.

During the second stage, the students are encouraged to reengage in course-related activities and work with their instructors to discuss alternative options for coursework, quizzes, and tests.

“We would prefer they engage in course-related activity as early as possible rather than have excused absences because those can build up over time and cause additional stress and anxiety, which we know can prolong some of those recoveries,” said Memmini.

By the third stage, Memmini recommends attending an entire class in their learning environment. She pointed out that additional recommendations could include alternative options for note-taking during class lectures or working with instructors on scaffolding the remainder of the course assignments.

Finally, students should be able to attend a whole week of class within their learning environment, whether in a remote or physical classroom. They should also be relying less on academic support and checking in with their multi-disciplinary team to see whether they are on track to complete the semester and if support is still warranted.

“What’s important in the fourth stage is that we encourage them (students) to seek medical care and to make it clear if they’re not recovering within two-to-four weeks, they may have some more lingering symptoms that may need to be addressed by a medical team and require further evaluation,” said Memmini.

She also knew it was essential to include information on how students could advocate for themselves“. When working with young adults, they are no longer supervised by a parent or legal guardian. So, it’s up to them to advocate for themselves,” said Memmini.

Before developing the protocol, Memmini conducted a qualitative study to help her understand some of the challenges students and faculty faced when a student was returning to the classroom after a concussion. She then used the four-step return to school progression from the 2016 Consensus statement on concussion in sports as her baseline, gathering input and recommendations from clinicians, academic staff, and concussion researchers on what should be included. She later published those research findings in the Journal of Head Trauma Rehabilitation article “Recommendations for Medical Discharge Documentation and Academic Supports for University Students Recovering From Concussion.”

Despite the comprehensive return-to-learn protocol, Memmini acknowledged the challenges, including the students’ discomfort with approaching instructors, especially in the higher education setting.

“We need to understand, through more qualitative work, some of the barriers and challenges our students face as they recover from concussion and how that might differ across race, the gender spectrum, LGTBQ students, and other underrepresented groups on campus,” she said.