Brain Injury Professional - Best Practices in Concussion Management

BRAIN INJURY professional vol. 19 issue 1

Best Practices in Concussion Management

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vol. 19 issue 1

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Editor in Chief Message Guest Editor’s Message Technology Article Expert Interview

features

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Multidisciplinary Concussion Care: Delivering the Whole Pizza

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Persistent Post Traumatic Headache

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David L. Brody, MD, PhD

Angelica P Ahrens, MS, MBA • Alan F Finkel MD FAAN FAHS

Updating the American Congress of Rehabilitation Medicine (ACRM) Diagnostic Criteria for Mild Traumatic Brain Injury Noah D. Silverberg, PhD • Grant L. Iverson, PhD

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The CDC Guideline on the Diagnosis and Management of Pediatric Mild Traumatic Brain Injury: A Commentary on the Commentaries Adrian Svingos, PhD • Stacy Suskauer, MD

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Department of Defense 2021 Progressive Return to Activity: Update to Concussion Care Gary McKinney, DHSc

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Tech-Knowledgy: Advancing Concussion Care through the use of Modern Tech Dr. Amy Mathews • Dr. Kathleen Bell

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TBI Biomarkers: Emerging Evidence and Translational Pathway Michael McCrea, PhD, ABPP-CN • Geoff T. Manley, MD, PhD

IBIA would like to acknowledge the education grant from Abbott for this publication. They have had no influence on the content.

Brain Injury Professional is a membership benefit of the North American Brain Injury Society and the International Brain Injury Association

NORTH AMERICAN BRAIN INJURY SOCIETY CHAIRMAN Mariusz Ziejewski, PhD VICE CHAIR Debra Braunling-McMorrow, PhD IMMEDIATE PAST CHAIR Ronald C. Savage, EdD TREASURER Bruce H. Stern, Esq. SECRETARY Brian Greenwald, MD FAMILY LIAISON Skye MacQueen EXECUTIVE DIRECTOR/ADMINISTRATION Margaret J. Roberts EXECUTIVE DIRECTOR/OPERATIONS J. Charles Haynes, JD MARKETING MANAGER Megan Bell-Johnston BRAIN INJURY PROFESSIONAL PUBLISHER J. Charles Haynes, JD CO-EDITOR IN CHIEF Beth Slomine, PhD - USA CO-EDITOR IN CHIEF Nathan Zasler, MD - USA ASSOCIATE EDITOR Juan Arango-Lasprilla, PhD – Spain TECHNOLOGY EDITOR Stephen K. Trapp, PhD - USA EDITOR EMERITUS Debra Braunling-McMorrow, PhD - USA EDITOR EMERITUS Ronald C. Savage, EdD - USA DESIGN AND LAYOUT Kristin Odom ADVERTISING SALES Megan Bell-Johnston EDITORIAL ADVISORY BOARD Nada Andelic, MD - Norway Philippe Azouvi, MD, PhD - France Mark Bayley, MD - Canada Lucia Braga, PhD - Brazil Ross Bullock, MD, PhD - USA Fofi Constantinidou, PhD, CCC-SLP, CBIS - USA Gordana Devecerski, MD, PhD - Serbia Sung Ho Jang, MD - Republic of Korea Cindy Ivanhoe, MD - USA Inga Koerte, MD, PhD - USA Brad Kurowski, MD, MS - USA Jianan Li, MD, PhD - China Christine MacDonell, FACRM - USA Calixto Machado, MD, PhD - Cuba Barbara O’Connell, OTR, MBA - Ireland Lisandro Olmos, MD - Argentina Caroline Schnakers, PhD - USA Lynne Turner-Stokes, MD - England Olli Tenovuo, MD, PhD - Finland Asha Vas, PhD, OTR - USA Walter Videtta, MD – Argentina Thomas Watanabe, MD – USA Alan Weintraub, MD - USA Sabahat Wasti, MD - Abu Dhabi, UAE Gavin Williams, PhD, FACP - Australia Hal Wortzel, MD - USA Mariusz Ziejewski, PhD - USA EDITORIAL INQUIRIES Managing Editor Brain Injury Professional PO Box 131401, Houston, TX 77219-1401 Tel 713.526.6900 Email: mbell@hdipub.com Website: www.nabis.org ADVERTISING INQUIRIES Megan Bell-Johnston Brain Injury Professional HDI Publishers PO Box 131401, Houston, TX 77219-1401 Tel 713.526.6900 Email: mbell@internationalbrain.org NATIONAL OFFICE North American Brain Injury Society PO Box 1804, Alexandria, VA 22313 Tel 703.960.6500 / Fax 703.960.6603 Website: www.nabis.org ISSN 2375-5210 Brain Injury Professional is a quarterly publication published jointly by the North American Brain Injury Society and HDI Publishers. © 2022 NABIS/HDI Publishers. All rights reserved. No part of this publication may be reproduced in whole or in part in any way without the written permission from the publisher. For reprint requests, please contact, Managing Editor, Brain Injury Professional, PO Box 131401, Houston, TX 77219-1400, Tel 713.526.6900, Fax 713.526.7787, e-mail mbell@hdipub.com.

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from the

editor in chief

As Co-Editor-in-Chief, I am pleased the share with you this issue of Brain Injury Professional that focuses on best practices in the management of concussion. Drs Wesley Cole and Emma Gregory, the guest editors for this issue, are clinical researchers and experts in multidisciplinary concussion management. Dr. Cole is a researcher and neuropsychologist who provides and contributes to evidence-based multidisciplinary care for individuals following concussion. Dr. Gregory is a research scientist and Chief of Research Section at the U.S. Department of Defense’s Traumatic Brain Injury Center of Excellence.

Beth S. Slomine, PhD, ABPP

Editor Bio Beth S. Slomine, PhD, ABPP, is co-director of the Center for Brain Injury Recovery and director of neuropsychology training and neuropsychological rehabilitation services at Kennedy Krieger Institute. She is an Associate Professor of Psychiatry & Behavioral Sciences and Physical Medicine & Rehabilitation at Johns Hopkins University School of Medicine. She is a licensed psychologist, board certified clinical neuropsychologist, and board certified subspecialist in pediatric neuropsychology. Research interests include developing neurobehavioral assessment tools and understanding factors influencing outcome following pediatric neurological injury. Dr. Slomine has authored >70 peerreviewed manuscripts, numerous book chapters, and co-edited a textbook entitled Cognitive Rehabilitation for Pediatric Neurological Conditions.

In this issue, Cole and Gregory pulled together an all-star multidisciplinary group of leaders in concussion management. As reported by the guest editors in their column, there has been an explosion of concussion research over the last 20 years. Given the rapid pace at which new literature is published in this area, it is challenging for professionals to stay abreast of recent advances. This issue succinctly provides our readership important highlights from the latest clinical research in multidisciplinary concussion management.

The feature article, entitled “Multidisciplinary Concussion Care: Delivering the Whole Pizza,” written by Dr. David Brody, provides an overview of a model of multidisciplinary care and illustrates how to employ this model to address common problems after concussion, including sleep, post-traumatic headache, mood disorders, and cognitive concerns. Brody’s article sets the stage for the content that follows which includes many outstanding articles, each focusing on key and emerging topics in concussion management.

Other articles focus on a range of topics. Highlights includes a summary of the work of the Mild Traumatic Brain Injury Task Force of the American Congress of Rehabilitation Medicine, Brain Injury Special Interest Group to update the definition of mild traumatic brain injury. The final definition is expected in 2023 (authors, Silverberg and Iverson).

Brief updates of relevant hot topics areas include diagnosis, evaluation, and treatment of persistent post traumatic headache (authors, Ahrens and Finkel), Department of Defense guidelines for return to activity after concussion (author: McKinney), the Centers of Disease Control guideline on the diagnosis and management of pediatric mild traumatic brain injury (authors, Svingos and Suskauer), and a review of promising traumatic brain injury biomarkers (authors, McCrea and Manley). There are also two articles on technology. One focuses on potential uses of modern technology broadly (authors, Mathew and Bell) and a second, describes a specific technological application that may be useful for concussion care (authors, Cayias and Trapp). The issue concludes with an informative expert interview with Dr. Risa Nakase-Richardson on the long-term impact of traumatic brain injury and rehabilitation needs of service members, veterans, and their families.

Finally, mark your calendars the 2022 Joint Conference on Brain Injury organized by the North American Brain Injury Society (NABIS) and the International Pediatric Brain Injury Society (IPBIS). This multidisciplinary event will offer a broad and varied program spanning cutting-edge research to practical and applied techniques for improving outcomes for persons with brain injury. The Joint Conference on Brain Injury will take place September 21 - 24, 2022 in New York City. In addition, the 14th Biennial World Congress on Brain Injury will now take place in March 29-April 1, 2023, in Dublin, Ireland. The International Brain Injury Association (IBIA) World Congress is the largest gathering of international professionals working in the field of brain injury. For more information, go to https://www. internationalbrain.org/meetings-and-events/2022-joint-conference-on-brain-injury

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from the

guest editors

Wesley R. Cole, PhD • Emma Gregory, PhD

Wesley R. Cole, PhD

Editor Bios In 2009 Dr. Wesley Cole joined Womack Army Medical Center, Fort Bragg and served as a neuropsychologist and Research Lead for Fort Bragg’s Intrepid Spirit Center, a multidisciplinary program for brain injury. In May 2022 he will be a Research Associate Professor in the Matthew Gfeller Center in the Department of Exercise and Sport Science at UNC-Chapel Hill to support their ongoing concussion clinical research programs, including the newly established Transforming Health & Resilience in Veterans (THRIVE) Program for Veterans with brain injury. He has numerous publications related to brain injury and frequently serves as a reviewer for various journals.

He received a Ph.D. in Clinical Psychology from the University of South Carolina and completed pre- and postdoctoral training at the Kennedy Krieger Institute.

He is a past Board member and Board chair for the Brain Injury Association of North Carolina.

Over the past 20 years the military conflicts in Iraq and Afghanistan and an increased awareness in athletics has resulted in an explosion of concussion research. There have been over 7 times as many scholarly articles published on concussion versus the prior 20 years (i.e., 1980-2000) as well as a significant increase in broader awareness from coverage of concussion in mainstream news and sports media, or popular media portrayals (e.g., the movie “Concussion” from 2015). Though there have been significant strides in the way we evaluate and manage concussion, we still have a lot to learn. In fact, as you’ll see in Silverberg and Iverson’s article, we’re still refining the definition of concussion.

The ever growing body of research and the remaining gaps in our knowledge make it difficult for even the most experienced concussion providers to stay “up-to-date” on best practices. Therefore, we sought out leaders in the field of concussion for this edition, to help bring you up to speed on current concussion best practices and the future of concussion research. The feature article by Brody provides an overview of the standard of care for concussion. He uses the clever analogy of making and delivering a pizza to discuss how patients require an individualized, yet comprehensive approach to their care (go ahead and give in to your inevitable craving and place your pizza order now). Finkel and Ahrens summarize best practices for the management of posttraumatic headache, often the most prevalent and persistent postconcussive symptom.

Articles by McKinney as well as Svingos and Suskauer review recent advances in clinical recommendations for military and pediatric populations, respectively. And in looking forward, Bell and Matthews discuss how technology can improve concussion care, and McCrea and Manley review the current state of diagnostic and prognostic objective biomarkers for concussion. Finally, we are delighted to present the expert interview of Dr. Risa Nakase-Richardson, conducted by Dr. Theresa Woo of the National Intrepid Center for Excellence. Dr. Nakase-Richardson is the Project Director for the VA healthcare systems arm of the DoD and VA’s “15-year TBI study.” Here she discusses current findings of that study and what we can expect in the future from this incredibly valuable research effort.

We appreciate the editors in chief for giving space to discussing current best practices in concussion care. We acknowledge this is not a comprehensive review of all topics related to concussion. Of note, we don’t venture into the long-term outcomes of concussion or repeated head traumas, including topics related to neurodegenerative disease (e.g., CTE); for more information on chronic conditions, we direct you to volume 16, issue 3 of Brain Injury Professional. Regardless, we hope the content helps advance your knowledge of concussion management and sets the stage for your continued learning, as the field will continue to advance at lightning speed.

The views expressed herein are those of the author(s) and do not necessarily reflect the official policy of the Department of the Army, Defense Health Agency, Department of Defense, or the US Government.

Emma Gregory, PhD

Dr. Emma Gregory, is the Research Branch Chief at the U.S. Department of Defense’s Traumatic Brain Injury Center of Excellence (TBICoE), formerly known as the Defense and Veterans Brain Injury Center (DVBIC). Dr. Gregory oversees a portfolio of clinical research studies across an 8-site network focused on traumatic brain injury (TBI); the portfolio seeks to advance TBI knowledge and state of the science through military-relevant, gap-driven, clinically translatable research. Dr. Gregory received her Ph.D. in Cognitive Science in 2010 from JHU. Dr. Gregory has co-authored over 20 peer-reviewed articles and serves as an ad hoc reviewer for various journals.

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Multidisciplinary Concussion Care: Delivering the Whole Pizza David L. Brody, MD, PhD

Some of the material in this article has been derived from Concussion Care Manual 2nd Edition (Oxford University Press 2018) with updates and modifications. USU Disclaimer Statement: The opinions and assertions expressed herein are those of Dr. David Brody and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense.

Introduction Recently, there has been intense interest in the topic of concussion in the medical community, lay press and general public, in large part due to the increased focus on contact sports and military activities.

However, most concussions (also called mild traumatic brain injuries) occur in the general public, including the fast-growing subset of fallrelated injuries in older adults. While most patients with concussion recover well on their own, the substantial number of patients that do not make a rapid recovery can benefit from a highly professional multidisciplinary care team. It is not realistic to expect a single type of treatment (e.g., a single medication or a single rehabilitative therapy) to solve everything. If you ordered a pizza and only got one slice, you’d be pretty disappointed. Coordinated multidisciplinary care represents “delivering the whole pizza.” In this article, I outline one view of the components and operation of a multidisciplinary concussion care team, recognizing that many approaches are possible. Much of the information below is outlined in greater detail in Concussion Care Manual: 2nd Edition 2018.

Many patients with concussion can be managed by their primary care providers with a brief period of rest followed by progressive return to activity. Early education is a cornerstone of recovery for these patients. However, the substantial number of patients who do not make a rapid and complete recovery after 1-3 weeks should be promptly referred to a concussion care specialist who will serve as a team leader of the multidisciplinary care team. The concussion care specialist is usually a physician, often a sports medicine doctor, pediatrician, neurologist, neurosurgeon, physiatrist, psychiatrist, family practice doctor, internist, or orthopedic surgeon. The medical specialty is less important than the level of expertise and ability to coordinate the appropriate multidisciplinary team. Furthermore, the team leader should be willing and able to provide clear and factual education to the patient and other involved people (e.g., family, caregivers, supervisors, and teachers). The team leader performs an overall evaluation that includes taking a history from the patient and collateral sources (e.g. family, friends, and co-workers), performing

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a focused physical examination, reviewing medical records, and discussing priorities of care in a patient-centered fashion. Often the team leader will lay out several options for how to proceed, including relatively conservative ‘wait and see’ approaches, stepwise approaches addressing one problem at a time, and aggressive approaches addressing multiple problems at the same time. The ‘right’ approach is not always obvious; it depends just as much on patient preference as physician guidance. At present, there is no scientific evidence that one approach is more effective than another.

The most common approach is stepwise, addressing one problem at a time. Which problem should the team leader address first?

Consider these three principles: 1.

Ask the patients what’s bothering them the most. Common concerns include headaches (Figure 1), sleep disturbances (Figure 2), mood disorder such as depression or anxiety (Figure 3), trouble with concentration or memory (Figure 4), balance or vestibular issues, as well as others. In our experience, the most frequent issue patients bring up is post-traumatic headaches.

Post-traumatic headaches, especially those with migraine-like features, can be markedly impairing. Try to deeply understand the patient’s life to figure out what matters most.

Figure 1. The "whole pizza" for co-existing sleep disorders in patients with concussion.

Figure 2. The "whole pizza" for post-traumatic headache.

2.

Ask the collateral sources what is causing the most problems in the patients’ lives. It may not be the same as the patients’ own main concern. For example, mood instability is often perceived by collateral sources more clearly than by patients themselves.

“He’s not the same person” is a common complaint.

Sometimes, the most disruptive problems following concussion are not immediately apparent to the patient.

3.

Look for the ‘top of the cascade’: one single problem that is the root cause of one or more additional problems. For example, sleep disruption can in turn worsen memory, attention, pain, mood disorders and many other symptoms. Major depression can impair virtually every aspect of life including energy, sleep, pain, attention, memory, etc. There isn’t always a single root cause, but an important goal of comprehensive care is to find and address it if present.

Once the decision has been made about how to proceed, it is time to call upon the multidisciplinary team and “make the pizza.”

The Multidisciplinary Team Figure 3. The "whole pizza" for co-existing mood disorders in patients with concussion.

The ‘toolbox’ available to the team leader includes five primary domains: diagnostics, pharmacotherapy, interventional and devicebased treatments, professional rehabilitative therapies, and lifestyle modifications. However, not every patient with concussion needs everything in the toolbox, just as not everyone needs every topping on their pizza. One of the most important roles of the team leader is to work with each patient to decide what the priorities of care should be. The stepwise approach noted above may represent building the pizza layer by layer.

1. Diagnostics: Diagnosis is mostly based on the patient’s history.

Many patients with concussion don’t need any additional diagnostic tests. See Concussion Care Manual, 2nd Edition, Chapters 3-4 for details.

•

Polysomnography (sleep study) is often the most useful diagnostic test. Sleep apnea is very common after concussion, and untreated sleep apnea makes it difficult to recover. We order a sleep study in nearly every patient with concussion who complains about fatigue or unrefreshing sleep.

•

Neuropsychological testing to objectively measure cognitive performance is useful when there is concern about cognitive function, usually attention and memory lapses. However, many patients do not have objective impairments and will not need neuropsychological testing. Subjective cognitive impairments correlate better with mood disorders than with objective cognitive performance. We order neuropsychological testing to assess for attention deficit when we are considering treatment with a stimulant, to help guide return-to-work/school decisions, and to plan cognitive rehabilitation when indicated.

•

Blood tests for brain injury have been approved in the acute setting for determining the need for a CT scan. However, they are not routinely used otherwise (see McCrea & Manley, this issue). Blood tests for other conditions such as hypothyroidism, vitamin B12 deficiency, anemia, liver and kidney disease can be helpful to identify co-morbidities that may be unrelated but can adversely influence recovery. Order routine blood tests in older adults and other at moderate to high risk of comorbidities.

Typically, patients with concussion do not need detailed endocrinological evaluations.

•

Brain imaging is not necessary for the diagnosis of concussion.

Most patients with concussion have normal brain imaging.

Figure 4. The "whole pizza" for co-existing cognitive concerns in patients with concussion.

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Scans are useful to assess for more serious injury (usually a CT scan performed in the emergency department) or, when there are red flags, to rule out other conditions such as cerebral sinus thrombosis, tumor, or hydrocephalus that may be contributing to symptoms. MRI can be useful for medicolegal reasons to help objectively document brain injury when it is not otherwise apparent. Most patients with concussion do not need additional brain imaging.

•

There is no routine role for other tests such as EEG, MEG, evoked potentials, eye tracking, pupillometry, optical coherence tomography, or ultrasound-based tests in concussion care at present; however, a great deal of research is going on in these domains and the field is moving fast.

2. Pharmacotherapy: Not every patient with concussion needs medication; sometimes less medications are better than more.

Patients with concussion can be at higher-than-average risk of adverse cognitive effects from anticholinergic and sedating medications. First, do no harm. That being said, some medications can be very helpful. Consult with a pharmacist for drug-drug interactions and with specialists (e.g., neurologists, psychiatrists) who have experience with these medications.

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•

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For post-traumatic headaches, many of which are similar to migraine, triptans (e.g., Imitrex), NSAIDs (e.g., ibuprofen), and acetaminophen are helpful for acute pain, and prophylactics (i.e., amitriptyline) are beneficial to reduce headache frequency in those with more than 2 headaches per week. A common prescription is amitriptyline starting at 25 mg each night for prophylaxis, and 50 mg of Imitrex used as soon as possible on onset of headache as an abortive. Nasal Imitrex can be helpful when an oral triptan isn’t effective. Topiramate starting at 25 mg twice per day is often a second line prophylactic in this context (see Finkel & Ahrens, this issue; Concussion Care Manual, Chapter 7).

For attention issues, direct stimulants such as methylphenidate (Ritalin) and mixed amphetamine salts (Adderall) are very helpful. However, these medications have serious risks and require careful monitoring by the provider. Concerns include hypertension, tachycardia, appetite suppression, anxiety, insomnia (when used late in the day), and rarely, hallucinations or seizures. This being said, the benefits of stimulants can outweigh these risks in many patients making them worthwhile. A typical starting prescription is methylphenidate 10 mg, taken each morning and each day at noon, 6 days per week (not 7), and 51 weeks per year (not 52). If this is well tolerated, methylphenidate can be titrated up to 0.3 mg/kg per dose (~20 mg for a 70-kg adult). Other medications such as acetylcholinesterase inhibitors, modafinil, amantadine, and atomoxetine are less consistently beneficial. See Concussion Care Manual, Chapter 9 for details.

For mood disorders, pharmacological treatments are similar to those used in patients without concussion. Common prescriptions include serotonin specific reuptake inhibitors such as fluoxetine and paroxetine for depression and anxiety, prazosin for PTSD-related nightmares, and mood stabilizing antiepileptics such as lamotrigine and oxcarbazepine for mood instability. Many of these medications have only modest benefit and are best used in combination with lifestyle modifications and cognitive behavioral therapy. Some other medications such as lithium, antipsychotics, and valproic acid can have substantial side effects in patients with concussion and are best used with caution. See below and Concussion Care Manual, Chapters 1012 for details.

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For sleep disorders such as insomnia, the first line treatments are not pharmacological but rather behavioral: cognitive behavioral therapy for insomnia should usually be the primary intervention. Nonetheless, common medications that can be used for short-term treatment include melatonin, trazodone, zolpidem (Ambien) and Eszopiclone (Lunesta).

It is generally best to avoid anticholinergic medications such as diphenhydramine (Benadryl), benzodiazepines such as diazepam (Valium), and antipsychotics like quetiapine (Seroquel) unless they are needed for other conditions. See below and Concussion Care Manual, Chapter 8, 16 and 17 for details.

3. Interventional and device-based treatments are preferred by many patients to avoid drug-drug interactions and having to take medication or do therapy every day.

•

Sleep apnea is best treated with a CPAP device or surgical procedure. Refer to a sleep specialist without delay.

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Post-traumatic migraine headaches can be effectively prevented with botulinum toxin injections in many patients with concussion.

•

Post-traumatic cervicogenic headaches may be treatable with occipital nerve blocks or radiofrequency ablation.

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Post-traumatic stress/hyperarousal can be treated with stellate ganglion blocks.

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Headaches and other pain conditions can be treated with various forms of acupuncture, though the scientific evidencebase for this family of treatments is still developing.

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Non-invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS) has been used to treat headaches and depression in the setting of concussion; this is the topic of several ongoing research studies. The risk of seizure, while elevated in patients with more severe traumatic brain injury, does not appear to be a concern in typical patients with concussion without other risk factors.

4. Professional rehabilitation often involves cognitive behavioral therapy, physical therapy, occupational therapy, speech therapy, and a rapidly expanding array of other services.

•

Cognitive behavioral therapy (for insomnia, mood dysregulation, and pain) can have a tremendous benefit in the setting of concussion and is supported by a strong scientific evidence base. Cognitive behavioral therapy for insomnia is considered the first line treatment for this condition, and cognitive behavioral therapy for mood dysregulation paired with pharmacotherapy is generally more effective than either treatment in isolation. Great progress has been made with telemedicine-based cognitive behavioral therapy, and smart-phone apps that provide key elements of cognitive behavioral therapy in a fully automated fashion (e.g., Somryst® for insomnia, which has been authorized by the FDA as a Prescription Digital Therapeutic). These options are often much more convenient and more widely available to patients with concussion than conventional in-person therapy.

•

Physical therapy can be very useful for treating balance disorders, vestibular dysfunction, and neck pain. Treating balance and vestibular disorders is important to prevent future injuries. Post-traumatic benign paroxysmal positional vertigo caused by damage to the peripheral vestibular apparatus can be quickly mitigated or even cured using repositioning maneuvers which are familiar to many physical therapists. [See Concussion Care Manual Chapter 14]

•

Occupational therapy often plays a key role in return-to-work, return-to-school, and return-to-activity progression and decision making. Ideally, occupational therapists may simulate key aspects of the patients’ work, school, or essential daily activity and then work with the patient to optimize function in these domains.

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Speech therapy in the setting of concussion may provide cognitive rehabilitation that can be beneficial even for subjective cognitive performance concerns, regardless of whether there are objective deficits detected on formal testing.

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A variety of professional rehabilitation services including art therapy, music therapy, animal-assisted therapy, driving rehabilitation, virtual reality-based therapy, and recreational therapy are sometimes available, and may be recommended at the discretion of the team leader when appropriate. At present, these services are not typically covered by insurance.

5. Lifestyle modification involves supervised changes in exercise, sleep patterns, alcohol and drug use, diet, and caffeine intake.

Often several members of the treatment team provide advice and coaching with regard to lifestyle modifications. Changes are often hard to make, and a bit of insight is required to understand how to best motivate each individual patient. Importantly, the members of the team should all be ‘on the same page’ with regard to lifestyle modification advice and coaching to avoid giving mixed messages.

•

Progressively increasing physical exercise is often very beneficial with regard to persistent mood, sleep, pain, and cognitive performance concerns after concussion. A typical goal is 30-60 minutes of moderately intense cardiovascular exercise 6 days per week.

The ‘toolbox’ available to the team leader includes five primary domains: diagnostics, pharmacotherapy, interventional and device-based treatments, professional rehabilitative therapies, and lifestyle modifications.

However, not every patient with concussion needs everything in the toolbox, just as not everyone needs every topping on their pizza. One of the most important roles of the team leader is to work with each patient to decide what the priorities of care should be. The stepwise approach noted above may represent building the pizza layer by layer.

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Moderate cardiovascular exercise means 65-80% of maximum heart rate; intense enough to sweat and breathe hard, but not so intense as to cause exhaustion. Often patients will need to work up to this goal gradually under the supervision of a physical therapist or trainer. This recommendation is related to, but distinct from, the symptom limited acute phase progressive return-to-activity exercise protocols discussed by McKinney in this issue.

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The team leader needs to impress upon the patient the importance of sleep for optimal recovery from concussion.

Many patients did not get optimal sleep even before their concussion for a wide variety of reasons. In some patients, sleep hygiene education is enough, but many require a full course of cognitive behavioral therapy for insomnia, a commitment to reliably using CPAP or other sleep apnea treatment devices, and a consistent resolution to appropriately prioritize sleep.

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After a concussion, alcohol and drug tolerance is often reduced and the adverse effects of these substances are often more pronounced. The team leader in conjunction with other members of the team should council patients about alcohol and drug use, often advising them to stop using alcohol and drugs entirely or substantially limit them to very modest quantities (e.g., 1-2 drinks at most in any 24-hour period). We often tell patients that our job is not to tell them what they want to hear, but to give them best medical advice, and that commonly means no drinking or drugs. A written note from a physician to this effect can help with peer pressure issues.

A referral for evidence-based addiction therapy should be provided when alcohol or drugs are a serious problem.

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Caffeine use after concussion requires a careful balance.

On one hand, moderate caffeine use can improve cognitive performance, mood, and some headache disorders. On the other hand, excessive caffeine can impair sleep, cause anxiety, and worsen headaches. We typically recommend moderate (e.g., 1-2 caffeinated drinks per day) and consistent (i.e., the same every day of the week) use of caffeine in those who have been using caffeine prior to concussion, with no caffeine later than 8 hours prior to bedtime (e.g., none after 2 pm for a 10 pm bedtime).

There is no strong evidence favoring any specific diet after concussion, but in general a healthy, well balanced diet is likely to improve exercise performance, sleep, and mood. Patients with post-traumatic migraine may be sensitive to certain foods, and these should be identified and avoided when possible.

We do not typically recommend any specific supplements, vitamins, or nutraceuticals as there is not enough scientific evidence at this time.

So with all these ‘toppings’ available for the pizza, how does the team leader decide what to do? It’s typically an ongoing dialogue with the patients and other relevant people. The team leader often spends a good amount of time explaining why certain things are not necessary, or at least not top priorities at the moment. This may require a bit of insight in order to understand the pre-conceived ideas that patients and others may have, based on media reports or additional sources of information. It is important to note that complex concussion patients may need to work with their teams for 6-12 months or longer to make an optimal recovery.

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Future Perspectives: The need for evidencebased medicine.

Unfortunately, we do not yet have enough scientific evidence to indicate the optimal approaches to concussion care. Still, patients in concussion clinics in both the military and civilian sectors remain our greatest teachers, and much of this article is based on what my colleagues and I have learned from them. While we as a community have a great deal of ‘practice-based’ experience, there is a great need for improvement in the scientific evidence base. Steady progress is being made by focusing on specific individual symptoms and deficits, an approach that we have called “one bite at a time.”

There has been a “quiet revolution” in the field, with a substantial number of small to moderately-sized randomized controlled trials published in the last few years focused on various aspects of concussion care. However, there remains a tremendous need for more randomized controlled trials and other sources of high-quality evidence-based medicine in the domain of concussion.

Reference Brody, D. L. (2019). Concussion care manual: A practical guide (2nd ed.). Oxford University Press, USA.

Author Bio David L. Brody, MD, PhD, is a board-certified neurologist with both a research and a clinical specialization in TBI and neurodegenerative diseases. Dr. Brody joined the USUHS faculty in August of 2017.

Previously, Dr. Brody was the Norman J. Stupp Professor of Neurology at the Washington University School of Medicine in St. Louis. Dr. Brody was also the Washington University site director for the National Football League Neurological player care program.

He is the author of Concussion Care Manual: A Practical Approach published by Oxford University Press, and the recently appointed editor-in-chief of Journal of Neurotrauama. Dr. Brody earned a B.A. in Biological Sciences from Stanford University in 1992 and M.D. and Ph.D. from The Johns Hopkins School of Medicine in 2000. He completed his internship and neurology residency at Washington University.

Disclosures •

Royalties: Sales of Concussion Care Manual (Oxford University Press)

•

Honoraria: Mary Ann Liebert, Inc. Publisher of Journal of Neurotrauma for services as Editor-in-Chief.

•

Editorial Board Membership: Acta Neuropathologica

•

Research currently funded by NIH, Department of Defense.

•

Previous research funded by DARPA, National Football League, Cure Alzheimer’s Fund, Health South, Thrasher Foundation, BrightFocus, F-Prime & Burroughs Wellcome.

•

Consulting: Pfizer, Health Advances, Signum Nutralogix, Kypha, iPerian, Sage Therapeutics, St Louis Public Defenders Office, Avid Radiopharmaceuticals (Eli Lilly), Intellectual Ventures.

•

Equity: Inner Cosmos LLC

•

Conflicts of Interest: None

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BRAIN INJURY professional 13

Persistent Post Traumatic Headache Angelica P. Ahrens, MS, MBA Alan G. Finkel, MD, FAAN, FAHS

The most common sequala of concussion/mild Traumatic Brain Injury (mTBI) is new onset or worsened headache. Post Traumatic Headache is diagnosed as Persistent (pPTH) if present after three months.

Diagnosis The Centers for Disease Control and Prevention (CDC) estimate 2.8 million Americans experience TBI annually. In a survey of 3009 Americans, one-quarter had sustained concussion and one-third had persistent symptoms, with 80% seeking treatment1.

The estimated prevalence of pPTH is 15 – 35% at 5 years2,3, with 35% having multiple weekly headaches and 60% reporting migraine/probable migraine2. At eleven-years, 54% of Veterans with deployment-TBI had disabling headaches at least two days a week and 44% were near daily4.

The International Classification of Headache Disorders 3rd Edition5 classifies PTH by TBI severity: mild or moderate/severe. Acutely, headache characteristics are nonspecific. pPTH takes on features of migraine and other primary headaches. Worsening pre-existing headache is characteristic of secondary headache. The 7-day rule is a diagnostic criterion, requiring that headache occur within seven days of injury, regaining consciousness, or recovering the ability to report pain5; however, this rule has been challenged6 and may miss 20-50% of PTH. The most common phenotype of pPTH is migraine. Primary headache diagnosis is based upon an accepted group of symptoms and characteristics. Using a 4-point scale (none-mild-moderatesevere), migraine is defined by discrete attacks lasting 4–72 hours with and without aura. Aura is less common and is recognized as the sine qua non of migraine. TABLE 1 shows diagnostic criteria for pPTH.

Evaluation Taking the history is crucial in pPTH evaluation: time from injury, mechanisms, symptom severity, immediate effects including disorientation, post-traumatic amnesia (PTA), and loss of consciousness. The examiner must establish the phenomenology of headache: time course (intermittent or continuous), type and location of pain, and symptomatology, e.g., migraine associations of light and noise sensitivity. A brief neurologic examination should be performed with attention to the cranial nerves and long track signs.

Routine imaging/blood testing is not necessary. If indicated, MRI is best. CT scan should be used in the acute period to rule out blood.

Structural and functional changes7 include loss of cortical thickness8, cerebrovascular reactivity, and decreases in grey matter9. Tract changes in major cortical areas10, differences in connectivity11, and disruption in hypothalamic function connectivity12 have been described. In acute PTH, a recent publication observed iron deposition in areas of recognition and pain processing13. Clinical symptoms correlate with imaging changes14.

Veterans with deployment-related TBI have high-incidence migraine and chronic daily headache4. Migraine with aura (MWA) is the most common phenotype (41%4, 6% in our clinic-based study15). MWA is a potent predictor of pPTH16. The second most potent predictor is continuous or daily headache16. Seventy-five-percent of service members with TBI describe continuous headaches15. Perhaps most important is headache density/frequency. Using classification, we showed headache phenotypic diagnosis was not the determinant of outcomes15. Continuous duration, pain intensity, activities during headache, medication, history of headache and headache density predicted termination of military service.

Treatment To treat pPTH, we use primary headache phenotype. There are no successful controlled trials for any medication, treatment, or technique.

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Table 1. Diagnostic criteria for pPTH. Adapted from5.

Table 1. Diagnostic criteria for pPTH. Adapted from5.

5.2 Persistent headache attributed to traumatic injury to the head Headache of more than three months’ duration caused by traumatic injury to the head.

A. Any headache fulfilling criteria C and D B. Traumatic injury to the head1 has occurred C. Headache is reported to have developed within seven days after one of the following: 1. the injury to the head 2. regaining of consciousness following the injury to the head 3. discontinuation of medication(s) impairing ability to sense or report headache following the injury to the head D. Headache persists for >3 months after its onset E. Not better accounted for by another ICHD-3 diagnosis.

Defined as a structural or functional injury resulting from the action of external forces upon the head.

1

5.2.2 Persistent headache attributed to mild traumatic injury to the head A. Headache fulfilling criteria for 5.2 Persistent headache attributed to traumatic injury to the head B. Head injury fulfilling both of the following: 1. associated with none of the following:

Triptans in soldiers showed 70-75% improvement17.

Occipital nerve blocks help but without long-lasting effects18.

Preventive medications include valproate, topiramate, amitriptyline, and gabapentin.

Onabotulinum toxin has been utilized19, and showed improvements in soldiers20. A controlled study in Veterans also showed significant effectiveness21.

– loss of consciousness for >30 minutes – Glasgow Coma Scale (GCS) score <13 – post-traumatic amnesia lasting >24 hours2 – altered level of awareness for >24 hours – imaging evidence of a traumatic head injury such as skull fracture, intracranial hemorrhage and/or brain contusion 2. associated with one or more of the following symptoms and/or signs: – transient confusion, disorientation or impaired consciousness – loss of memory for events immediately before or after the head injury – two or more of the following symptoms suggestive of mild traumatic brain injury: – nausea – vomiting

– visual disturbances Calcitonin Gene Related – dizziness and/or vertigo Peptide (CGRP) and its receptor are targets of migraine therapy.

– gait and/or postural imbalance Erenumab and Fremanezumab – impaired memory and/or concentration. are effective in reduction of 2 Time between injury and resumption of normal continuous recall of events. headache days and migraine prevention, respectively, but the latter failed to reach its Pre-injury headache28,29, psychiatric comorbidities28, PTA30, sleep/ primary endpoint of improvement in moderate-to-severe headache fatigue30, headache severity27, neck stiffness31, symptoms in arms/ days. hands, dizziness/unsteadiness31, catastrophizing27, and pain modulation27 associate with outcome. This supports routine followNonpharmacologic treatments can help PTH. Multidisciplinary up, which is rare, with only <10% of neurotrauma centers scheduling treatments22 and lifestyle modification/cognitive behavioral therapy/ biofeedback showed dramatic changes in refractory pPTH23. a routine follow-up after discharge from the emergency room Improvements in headache intensity in pPTH were observed oneand a modest 54% after hospital admission32. In the long-term, psychiatric comorbidities, employment status31 and lower recovery week post-Transcranial Magnetic Stimulation but were not sustained expectations/catastrophizing27 were most impactful. at four-weeks24. Hyperbaric oxygen did not change pPTH25, nor did pulsed electromagnetic stimulation26.

Conclusion

Recovery appears dependent upon premorbid, peri- and post-injury characteristics and clinical markers. Females are more likely to demonstrate PTH and pPTH27.

pPTH is common after mTBI. Evaluation, diagnosis, and testing have shown promise. Evidence in support of a range of treatments is growing. Personalized paradigms of treatment are on the horizon.

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References 1. Hensley S. Poll: Nearly 1 In 4 Americans Reports Having Had A Concussion. NPR. https://www.npr. org/sections/health-shots/2016/05/31/479750268/poll-nearly-1-in-4-americans-report-having-had-aconcussion. Published May 31, 2016. Accessed November 12, 2021.

2. Stacey A, Lucas S, Dikmen S, et al. Natural History of Headache Five Years after Traumatic Brain Injury. J Neurotrauma. 2017;34(8):1558-1564. doi:10.1089/neu.2016.4721 3. Cnossen MC, van der Naalt J, Spikman JM, et al. Prediction of Persistent Post-Concussion Symptoms after Mild Traumatic Brain Injury. J Neurotrauma. 2018;35(22):2691-2698. doi:10.1089/neu.2017.5486 4. Couch JR, Stewart KE. Headache Prevalence at 4–11 Years After Deployment-Related Traumatic Brain Injury in Veterans of Iraq and Afghanistan Wars and Comparison to Controls: A Matched Case-Controlled Study.

Headache J Head Face Pain. 2016;56(6):1004-1021. doi:10.1111/head.12837 5. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia Int J Headache. 2018;38(1):1-211. doi:10.1177/0333102417738202 6. Scher AI, Monteith TS. Epidemiology and classification of post-traumatic headache: what do we know and how do we move forward? Comment on Lucas et al., “Prevalence and characterization of headache following mild TBI.” Cephalalgia Int J Headache. 2014;34(2):83-85. doi:10.1177/0333102413499644 7. Schwedt TJ. Structural and Functional Brain Alterations in Post-traumatic Headache Attributed to Mild Traumatic Brain Injury: A Narrative Review. Front Neurol. 2019;10:615. doi:10.3389/fneur.2019.00615 8. Chong CD, Berisha V, Chiang CC, Ross K, Schwedt TJ. Less Cortical Thickness in Patients With Persistent Post-Traumatic Headache Compared With Healthy Controls: An MRI Study. Headache. 2018;58(1):53-61. doi:10.1111/head.13223 9. Burrowes SAB, Rhodes CS, Meeker TJ, Greenspan JD, Gullapalli RP, Seminowicz DA. Decreased grey matter volume in mTBI patients with post-traumatic headache compared to headache-free mTBI patients and healthy controls: a longitudinal MRI study. Brain Imaging Behav. 2020;14(5):1651-1659. doi:10.1007/s11682019-00095-7

24. Leung A, Metzger-Smith V, He Y, et al. Left Dorsolateral Prefrontal Cortex rTMS in Alleviating MTBI Related Headaches and Depressive Symptoms. Neuromodulation J Int Neuromodulation Soc. 2018;21(4):390-401. doi:10.1111/ner.12615 25. Skipper LD, Churchill S, Wilson SH, Deru K, Labutta RJ, Hart BB. Hyperbaric oxygen for persistent post-concussive symptoms: long-term follow-up. Undersea Hyperb Med J Undersea Hyperb Med Soc Inc. 2016;43(5):601-613.

26. Nelson DV, Esty ML. Neurotherapy for chronic headache following traumatic brain injury. Mil Med Res. 2015;2:22. doi:10.1186/s40779-015-0049-y 27. Naugle KM, Carey C, Evans E, Saxe J, Overman R, White FA. The role of deficient pain modulatory systems in the development of persistent post-traumatic headaches following mild traumatic brain injury: an exploratory longitudinal study. J Headache Pain. 2020;21(1):138. doi:10.1186/s10194-020-01207-1 28. Yue JK, Cnossen MC, Winkler EA, et al. Pre-injury Comorbidities Are Associated With Functional Impairment and Post-concussive Symptoms at 3- and 6-Months After Mild Traumatic Brain Injury: A TRACKTBI Study. Front Neurol. 2019;10:343. doi:10.3389/fneur.2019.00343 29. Sawyer K, Bell KR, Ehde DM, et al. Longitudinal Study of Headache Trajectories in the Year After Mild Traumatic Brain Injury: Relation to Posttraumatic Stress Disorder Symptoms. Arch Phys Med Rehabil.

2015;96(11):2000-2006. doi:10.1016/j.apmr.2015.07.006 30. Bomyea J, Lang AJ, Delano-Wood L, et al. Neuropsychiatric Predictors of Post-Injury Headache After MildModerate Traumatic Brain Injury in Veterans. Headache. 2016;56(4):699-710. doi:10.1111/head.12799 31. Varner C, Thompson C, de Wit K, Borgundvaag B, Houston R, McLeod S. Predictors of persistent concussion symptoms in adults with acute mild traumatic brain injury presenting to the emergency department. CJEM. 2021;23(3):365-373. doi:10.1007/s43678-020-00076-6 32. Foks KA, Cnossen MC, Dippel DWJ, et al. Management of Mild Traumatic Brain Injury at the Emergency Department and Hospital Admission in Europe: A Survey of 71 Neurotrauma Centers Participating in the CENTER-TBI Study. J Neurotrauma. 2017;34(17):2529-2535. doi:10.1089/neu.2016.4919

10. Chong CD, Peplinski J, Berisha V, Ross K, Schwedt TJ. Differences in fibertract profiles between patients with migraine and those with persistent post-traumatic headache. Cephalalgia Int J Headache.

2019;39(9):1121-1133. doi:10.1177/0333102418815650

Author Bios

11. Maleki N, Finkel A, Cai G, et al. Post-traumatic Headache and Mild Traumatic Brain Injury: Brain Networks and Connectivity. Curr Pain Headache Rep. 2021;25(3):20. doi:10.1007/s11916-020-00935-y

Angelica P. Ahrens, MS, MBA, is a PhD candidate in Microbiology and Cell Science at the University of Florida.

Her research is based in microbial underpinnings of mental health, chronic pain, and autoimmune disorders, with interest in prediction and education. She received her BS from Duke University in 2012 and trained in data analytics and microbiology at NSU Florida and UF, receiving an MBA and MS, respectively. She has presented at forums including National Academy for Neuropsychologists, International Neuropsychological Society, and Military Health System.

She has co-authored original research in refereed journals including Cell Reports, Nutrients, American Journal of Sports Medicine, and Concussion.

12. Lu L, Li F, Wang P, Chen H, Chen YC, Yin X. Altered hypothalamic functional connectivity in post-traumatic headache after mild traumatic brain injury. J Headache Pain. 2020;21(1):93. doi:10.1186/s10194-020-011649 13. Nikolova S, Schwedt TJ, Li J, et al. T2* reduction in patients with acute post-traumatic headache. Cephalalgia Int J Headache. Published online October 13, 2021:3331024211048509. doi:10.1177/03331024211048509 14. Chong CD, Berisha V, Ross K, Kahn M, Dumkrieger G, Schwedt TJ. Distinguishing persistent posttraumatic headache from migraine: Classification based on clinical symptoms and brain structural MRI data.

Cephalalgia Int J Headache. 2021;41(8):943-955. doi:10.1177/0333102421991819 15. Finkel AG, Yerry JA, Klaric JS, Ivins BJ, Scher A, Choi YS. Headache in military service members with a history of mild traumatic brain injury: A cohort study of diagnosis and classification. Cephalalgia Int J Headache. 2017;37(6):548-559. doi:10.1177/0333102416651285 16. Metti A, Schwab K, Finkel A, et al. Posttraumatic vs nontraumatic headaches: A phenotypic analysis in a military population. Neurology. 2020;94(11):e1137-e1146. doi:10.1212/WNL.0000000000008935 17. Scott BR, Uomoto JM, Barry ES. Impact of Pre-Existing Migraine and Other Co-Morbid or Co-Occurring Conditions on Presentation and Clinical Course Following Deployment-Related Concussion. Headache.

2020;60(3):526-541. doi:10.1111/head.13709 18. Larsen EL, Ashina H, Iljazi A, et al. Acute and preventive pharmacological treatment of post-traumatic headache: a systematic review. J Headache Pain. 2019;20(1):98. doi:10.1186/s10194-019-1051-7 19. Jia C, Lucchese S, Zhang F, Govindarajan R. The Role of Onabotulinum Toxin Type A in the Management of Chronic Non-migraine Headaches. Front Neurol. 2019;10:1009. doi:10.3389/fneur.2019.01009 20. Yerry JA, Kuehn D, Finkel AG. Onabotulinum toxin a for the treatment of headache in service members with a history of mild traumatic brain injury: a cohort study. Headache. 2015;55(3):395-406. doi:10.1111/ head.12495 21. Zirovich MD, Pangarkar SS, Manh C, et al. Botulinum Toxin Type A for the Treatment of Post-traumatic Headache: A Randomized, Placebo-Controlled, Cross-over Study. Mil Med. 2021;186(5-6):493-499. doi:10.1093/milmed/usaa391 22. Janak JC, Cooper DB, Bowles AO, et al. Completion of Multidisciplinary Treatment for Persistent Postconcussive Symptoms Is Associated With Reduced Symptom Burden. J Head Trauma Rehabil.

2017;32(1):1-15. doi:10.1097/HTR.0000000000000202 23. Baker VB, Eliasen KM, Hack NK. Lifestyle modifications as therapy for medication refractory posttraumatic headache (PTHA) in the military population of Okinawa. J Headache Pain. 2018;19(1):113. doi:10.1186/s10194-018-0943-2

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Alan G. Finkel, MD, FAAN, FAHS, is a neurologist and headache specialist at the Carolina Headache Institute in Durham, NC. He received his MD from SUNY at Buffalo and completed neurology and subspecialty training in pain medicine and headache medicine at UNC at Chapel Hill. His work has included pain management, medical and headache medicine education and from 2008 – 2019 his work with the TBI team at Ft Bragg/Intrepid Spirit included research and peer reviewed publication on Post Traumatic Headache. An active editor, reviewer for major journals he also attends and chairs sections at NIH and the DOD/CDMRP.

Updating the American Congress of Rehabilitation Medicine (ACRM) Diagnostic Criteria for Mild Traumatic Brain Injury Noah D. Silverberg, PhD • Grant L. Iverson, PhD

Since the American Congress of Rehabilitation Medicine (ACRM) published diagnostic criteria for mild traumatic brain injury (mTBI) in 19931, many other operational definitions of mTBI have been proposed but not one has reached universal acceptance.

One systematic review found that 38 different definitions of mTBI were used across 299 studies.2 Many of these definitions differ on fundamentals, such as whether subjective symptoms alone can qualify someone for a diagnosis of mTBI and whether people with trauma-related neuroimaging findings should be excluded.

Variability between definitions of mTBI has likely hampered not only research but also equitable access to clinical care.

Delphi voting. The Working Group’s final product will be a peerreviewed position paper, targeted for early 2023.

In 2019, the Mild TBI Task Force of the ACRM Brain Injury Special Interest Group set out to update the 1993 definition. The aim was to create a definition that could be applied universally across civilian trauma, military, and sport settings, in children and adults, and that leveraged scientific developments from the past 25 years, such as blood biomarkers (see McCrea, this issue).

We assembled a Working Group within the Task Force and an international, interdisciplinary expert panel. An initial survey of the expert panel3 in spring 2019 revealed encouraging levels of agreement on certain diagnostic issues but a diversity of opinions on other matters, such as terminology (whether the terms mTBI and concussion were synonymous) and the timing of symptom onset. The expert panel also rated the diagnostic importance of various clinical signs, symptoms, test findings, and contextual factors, which the Working Group considered alongside findings from rapid evidence reviews to draft a new mTBI definition.

The revised ACRM definition of mTBI will be imperfect, reflecting the limitations and gaps in the research literature that serves as its basis. It will also require future updating to accommodate the changing science. Nevertheless, we hope its adoption will improve the consistency and accuracy of mTBI diagnoses in research and clinical settings for some years.

The Working Group launched a web-based Delphi consensus process in October 2020. Expert panel members rated their agreement with a series of evidence statements and a preliminary mTBI definition. The evidence statements (e.g., “Impairment on standardized balance testing within the first 24 hours post injury is associated with a clinical diagnosis of mild TBI.”) were presented with a narrative synthesis of available evidence, supported by a reference list. Each was related to a potential change to the 1993 ACRM case definition (e.g., incorporating balance test findings into the diagnostic criteria).

Based on feedback from the expert panel, including agreement ratings and qualitative comments, the Working Group revised the evidence statements and mTBI definition and sent them back to the expert panel members for a second round of Delphi voting in June 2021. In this round, agreement exceeded our prespecified thresholds for all items (i.e., at least 80% agree without reservations or with minor reservations). The Working Group is now preparing the consensus mTBI definition for stakeholder and public input. Any further revisions to the definition will be presented to the expert panel for an additional round of

The penultimate version of the updated definition differs from the 1993 version in several important ways. For example, it offers a probabilistic diagnostic approach. Observed clinical signs (e.g., difficulty answering orientation questions on acute assessment) are weighted more strongly than subjective symptoms (e.g., feeling dazed). Another new feature of the definition will likely be to incorporate clinical examination findings such as cognitive, balance, and oculomotor impairments.

References 1. Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation.

Definition of mild traumatic brain injury. J Head Trauma Rehabil. 1993;8:86-87.

2. Kristman VL, Borg J, Godbolt AK, et al. Methodological issues and research recommendations for prognosis after mild traumatic brain injury: results of the international collaboration on mild traumatic brain injury prognosis. Arch Phys Med Rehabil. 2014;95(3 Suppl):S265-77. doi:10.1016/j. apmr.2013.04.026 3. Silverberg ND, Iverson GL, Arciniegas DB, et al. Expert panel survey to update the American Congress of Rehabilitation Medicine definition of mild traumatic brain injury. Arch Phys Med Rehabil.

2021;102(1):P76-86. doi:10.1016/j.apmr.2020.08.022

Author Bios Noah D. Silverberg, PhD, leads a clinical research program focused on concussion outcomes and treatment at the University of British Columbia in Vancouver, Canada. He is a board-certified neuropsychologist (ABPP-CN) with 12 years of experience caring for civilians, athletes, and military service members with concussion and other forms of brain injury. He has contributed to multiple clinical practice guidelines for concussion and serves as Chair of the American Congress of Rehabilitation Medicine Brain Injury Special Group Task Force on Mild Traumatic Brain Injury.

Grant L. Iverson, PhD, is a Professor in the Department of Physical Medicine and Rehabilitation at Harvard Medical School. He is a clinician scientist, with more than 500 published articles and book chapters. He has a long-standing research interest in outcome from sport-related concussion and mild traumatic brain injury, and he is a leading proponent of a biopsychosocial model for conceptualizing both good and poor outcome from this injury.

He served as a consensus panel member for the 3rd, 4th, and 5th International Conferences on Concussion in Sport. He is a past President of the National Academy of Neuropsychology.

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The CDC Guideline on the Diagnosis and Management of Pediatric Mild Traumatic Brain Injury: A Commentary on the Commentaries Adrian Svingos, PhD • Stacy Suskauer, MD

The United States Centers for Disease Control and Prevention (CDC) Guideline for diagnosis and management of pediatric mild traumatic brain injury (mTBI) was published in 2018, representing the first U.S.-based evidence-based guideline for this purpose which was inclusive of all etiologies and severity of mTBI.1 The purpose of this article is to provide a brief background on the Guideline, an overview of commentaries that have been published in response to the Guideline (i.e., how the Guideline has been received), and a discussion of next steps relevant to future guideline development and ongoing implementation/dissemination efforts.

Why and how was the Guideline developed?

Education is a cornerstone of mTBI management as misinformation or lack of appropriate psychoeducation early in the recovery process can translate to prolonged absenteeism, worsening of symptoms, and increased risk of secondary injury. In the context of pediatric mTBI, families look to healthcare providers for important decisions regarding return to activities such as school and sports.

However, a survey conducted in 2014 demonstrated that less than half of pediatric providers seeing mTBI patients within 12 months felt prepared to make these decisions.2 In addition, relatively few providers reported use of standard tools or assessments to guide mTBI evaluation and management, highlighting the need for more robust dissemination of best practices and practical resources for providers evaluating and treating children with mTBI. The Guideline was developed using a rigorous process informed by the American Academy of Neurology classification scheme and Grading of Recommendations Assessment Development and Evaluation method which involve identification of answerable clinical questions, systematic review/ classification of the evidence, and formation and grading of recommendations.3 The CDC National Center for Injury Prevention and Control’s Board of Scientific counselors group established a workgroup of individuals from various training backgrounds and areas of expertise in pediatric brain injury that worked together to identify clinical questions and

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conduct a systemic review of the literature which formed the basis of the Guideline.4 At least 13 disciplines were represented in the workgroup, with the most individuals coming from the disciplines of neuropsychology (9), neurosurgery (8), or emergency medicine/ critical care (7).

Clinical questions covered a range of topics including those related to assessment/diagnosis (“do specific tools, compared with a reference standard, assist in accurately diagnosing mTBI?”), prognosis (“which factors identify patients at increased risk of longterm sequelae?”), and management (“which treatments improve mTBI-associated outcomes”). The review covered studies published over a 25-year period (1990-2015), with over 37,000 abstracts screened and over 2,900 articles fully reviewed.

The Guideline provides 19 sets of recommendations related to diagnosis, prognosis, and management/treatment, covering important topics that guide clinical decision-making. Each recommendation has an associated level of obligation based on supporting evidence identified during the literature review process. Some key takeaways from the Guideline include the recommendation that children not be routinely neuroimaged and the recommendation that children gradually return to activities after a brief period of physical and cognitive rest (i.e., 2-3 days).1

How has the Guideline been received?

Perhaps most strikingly, there have been over a dozen commentaries on the CDC guideline published in different peer reviewed journals since the Guideline was first presented in JAMA Pediatrics.5–17 Each commentary provides insight as to key takeaways and implications of the Guideline for a given provider or researcher group. Figure 2 illustrates the different discipline groups that have published commentaries as well as the journals (i.e., target audience for dissemination) in which these commentaries were published, highlighting the broad reach of the Guideline.

Figure 1. Authors of the 2018 CDC Guideline on Diagnosis and Management of mTBI Among Children by Discipline/ Expertise Area

Figure 2. Identified Commentaries Focused on the 2018 CDC Guideline on Diagnosis and Management of mTBI Among Children by Discipline/ Expertise Area

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Education is a cornerstone of mTBI management as misinformation or lack of appropriate psychoeducation early in the recovery process can translate to prolonged absenteeism, worsening of symptoms, and increased risk of secondary injury. In the context of pediatric mTBI, families look to healthcare providers for important decisions regarding return to activities such as school and sports. However, a survey conducted in 2014 demonstrated that less than half of pediatric providers seeing mTBI patients within 12 months felt prepared to make these decisions.2

Although each commentary has a different focus, common themes emerge which provide insight as to how the Guideline has been received and some important considerations across provider groups.

For example, several commentaries attempt to place the CDC Guideline recommendations in context of discipline-specific position statements, consensus papers, or standard practices. A commentary published in the Journal of Athletic Training highlights how the Guideline may supplement the current National Athletic Trainers’ Association position statement as well as the “Berlin Guidelines” (Concussion in Sport Group, 2016).5 Several commentaries also provide practical guidance for clinicians in terms of how to best implement the guidelines and provide resources that are linked to specific recommendations or groups of recommendations. For example, the recommendation that children with mTBI should not undergo routine neuroimaging is presented in conjunction with the citation for the Pediatric Emergency Care Applied Research Network (PECARN) decision rules in order to support implementation of that specific recommendation. For the recommendation to provide accurate information about prognosis (i.e., that the large majority of children will recover by 1-3 months) the practical resource listed is the CDC Heads up handout, “Caring for Your Child’s Concussion.”5,6 Across commentaries there also appears to be an attempt to highlight the unique contributions afforded by specialty providers in terms of implementation and/or dissemination. For example, two commentaries published in American Journal of SpeechLanguage Pathology call attention to the unique contributions that can be made by speech language pathologists in terms of bridging care gaps and advocating for young students.14,15 A commentary focused on important considerations for neurosurgeons emphasizes

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advocacy and the extent to which neurosurgeons may be in a unique position as community educators and leaders to best support implementation of the Guideline and optimization of patient outcomes.9 The commentaries also align in terms of discussion of future directions and a general need for ongoing work in the area of pediatric mTBI to address various gaps. The systematic review paper which informed the current CDC Guideline identified several areas for continued work including the need for long-term outcome studies extending into adulthood and the need for refinement of cognitive testing and symptom scales for use in across injury contexts and with younger populations (i.e., children less than 13 years of age).4 A commentary focused on neuroimaging modalities as they relate to the 2018 CDC Guideline highlights significant variability in the imaging literature and calls for continued collaboration among investigators and practitioners in order to avoid compounding variability inherent to the developing brain.8

Where do we go from here?

In order to help inform future evidence-based guidelines, investigators must make an effort to utilize common data elements and reporting conventions (e.g., 95% confidence intervals should be reported) and consider other study design factors that impact quality and usability of data for this purpose. Suskauer and colleagues published a commentary on this topic which summarizes limitations in the evidence identified during the development of the 2018 Guideline.7 Importantly, practical recommendations are presented in tables, based on study type, to help researchers quickly identify critical reporting elements and aspects of study design to improve strength of resulting evidence.

Since the Guideline has been published, qualitative research has emerged which helps clarify ongoing needs in terms of dissemination and clinical implementation. A special report from the CDC published in 2018 used qualitative methods to identify preferred avenues for dissemination of the CDC Guideline among healthcare providers. Preferred methods identified by the study group included partnership with medical societies/organizations, integration of the Guideline within electronic health records, mobile applications, or other online platforms, and dissemination via healthcare system leadership and provision of continuing medical education opportunities.18 More recently, Daugherty and colleagues published data from a qualitative study focused on characterization of rural health care provider experiences in implementing the Guideline.19 Key themes identified across interviews with rural PCPs included the need for quickly accessible implementation tools that can be customized by visit type (i.e., initial visit, follow-up visit) and integrated within the electronic health record system.

In summary, the Guideline and related works demonstrate the broad representation of disciplines interested and involved in caring for children with concussion. Pediatric brain injury professionals must work to continue supporting dissemination and implementation of the Guideline, including in less-resourced geographic areas. Further, collaborative efforts and strong leadership are needed to optimize growth in the evidence base prioritizing good data stewardship to inform future guideline development.

References 1. Lumba-Brown A, Yeates KO, Sarmiento K, et al. Centers for Disease Control and Prevention Guideline on the Diagnosis and Management of Mild Traumatic Brain Injury among Children. JAMA Pediatr.

2018;172(11):1-13. doi:10.1001/jamapediatrics.2018.2853 2. Sarmiento K, Donnell Z, Hoffman R, Tennant B. Healthcare providers’ attitudes and behaviours related to paediatric mild traumatic brain injury: results from the 2014 DocStyles survey. 2018;32(7):889-893. doi:10.1 080/02699052.2018.1466197

3. Neurology) A (American A of. Clinical Practice Guideline Process Manual, 2011 Ed.; 2011.

4. Lumba-Brown A, Yeates KO, Sarmiento K, et al. Diagnosis and Management of Mild Traumatic Brain Injury in Children: A Systematic Review. JAMA Pediatr. 2018;172(11). doi:10.1001/jamapediatrics.2018.2847 5. Register-Mihalik JK, Sarmiento K, Vander Vegt CB, Guskiewicz KM. Considerations for athletic trainers: A review of guidance on mild traumatic brain injury among children from the centers for Disease Control and Prevention and the National Athletic Trainers’ Association. J Athl Train. 2019;54(1):12-20. doi:10.4085/10626050-451-18 6. Sarmiento K, Gioia GA, Kirkwood MW, Wade SL, Yeates KO. A commentary for neuropsychologists on CDC’s guideline on the diagnosis and management of mild traumatic brain injury among children. Clin Neuropsychol. 2020;34(2):259-277. doi:10.1080/13854046.2019.1660806 7. Suskauer SJ, Yeates KO, Sarmiento K, et al. Strengthening the Evidence Base: Recommendations for Future Research Identified Through the Development of CDC’s Pediatric Mild TBI Guideline. J Head Trauma Rehabil.

2019;34(4):215-223. doi:10.1097/HTR.0000000000000455 8. Fong AK, Allen MD, Waltzman D, et al. Neuroimaging in Pediatric Patients with Mild Traumatic Brain Injury: Relating the Current 2018 Centers for Disease Control Guideline and the Potential of Advanced Neuroimaging Modalities for Research and Clinical Biomarker Development. J Neurotrauma. 2021;38(1):4452. doi:10.1089/neu.2020.7100 9. Timmons SD, Waltzman D, Duhaime A, Spinks TJ, Sarmiento K. Considerations for neurosurgeons: recommendations from the CDC Pediatric Mild Traumatic Brain Injury Guideline. J Neurosurg.

2019;131(3):979-983. doi:10.3171/2019.3.JNS183339 10. Sarmiento K, Waltzman D, Lumba-Brown A, Yeates KO, Putukian M, Herring S. CDC Guideline on Mild Traumatic Brain Injury in Children: Important Practice Takeaways for Sports Medicine Providers. Clin J Sport Med. 2020;30(6):612-615. doi:10.1097/JSM.0000000000000704 11. Iaccarino MA, Paganoni S, Zafonte R. Evidence-based physiatry: The center for disease control guideline on pediatric mild traumatic brain injury and the expanded role of physiatry. Am J Phys Med Rehabil.

2019;98(1):84-85. doi:10.1097/PHM.0000000000001073 12. Choe MC, Gregory AJ, Haegerich TM. What pediatricians need to know about the CDC guideline on the diagnosis and management of mTBI. Front Pediatr. 2018;6(September):1-4. doi:10.3389/fped.2018.00249 13. Weissman B, Joseph M, Gronseth G, Sarmiento K, Giza CC. CDC’s guideline on pediatric mild traumatic brain injury: Recommendations for neurologists. Neurol Clin Pract. 2019;9(3):241-249. doi:10.1212/ CPJ.0000000000000624 14. Brown J, O’Brien K, Knollman-Porter K, Wallace T. The Speech-Language Pathologists’ Role in Mild Traumatic Brain Injury for Middle and High School–Age Children: Viewpoints on Guidelines From the Centers for Disease Control and Prevention. Am J Speech-Language Pathol. 2019;28(3):1363-1370. doi:10.1044/2019_AJSLP-18-0296 15. Lundine JP, Ciccia AH, Brown J. The Speech-Language Pathologists’ Role in Mild Traumatic Brain Injury for Early Childhood–, Preschool–, and Elementary School–Age Children: Viewpoints on Guidelines From the Centers for Disease Control and Prevention. Am J Speech-Language Pathol. 2019;28(3):1371-1376. doi:10.1044/2019_AJSLP-18-0295 16. McAvoy K, Haarbauer‐Krupa J. What Schools Need to Know about the Centers for Disease Control and Prevention’s Guideline on Diagnosis/Management of Mild Traumatic Brain Injury in Children—A Commentary. J Sch Health. 2019;89(12):941-944. doi:10.1111/josh.12834 17. Hang B (Tho). Updates in Concussion Care: New Data, New Guidelines. Clin Pediatr Emerg Med. 2019;20(1):71-80. doi:10.1016/j.cpem.2019.03.005

18. Donnell Z, Hoffman R, Myers G, Sarmiento K. Seeking to improve care for young patients: Development of tools to support the implementation of the CDC Pediatric mTBI Guideline. J Safety Res. 2018;67:203-209. doi:10.1016/j.jsr.2018.09.006 19. Daugherty J, Waltzman D, Popat S, Groenendaal AH, Cherney M, Knudson A. Rural Primary Care Providers’ Experience and Usage of Clinical Recommendations in the CDC Pediatric Mild Traumatic Brain Injury Guideline: A Qualitative Study. J Rural Heal. 2021;37(3):487-494. doi:10.1111/jrh.12530

Author Bios Adrian Svingos, PhD, is a postdoctoral research/ neuropsychology fellow at the Kennedy Krieger Institute Brain Injury Clinical Research Center and Johns Hopkins University School of Medicine. She completed her PhD and predoctoral internship at the University of Florida, Department of Clinical and Health Psychology (Clinical Neuropsychology). Her research interests broadly pertain to the prognostication of traumatic brain injury outcomes and the identification of risk and resiliency factors associated with recovery trajectories.

Stacy Suskauer, MD, earned undergraduate and medical degrees from Duke University. She completed residencies in Pediatrics and Physical Medicine & Rehabilitation at Cincinnati Children’s Hospital Medical Center and the University of Cincinnati. Dr. Suskauer completed a Pediatric Rehabilitation Brain Injury Research fellowship at Kennedy Krieger Institute and Johns Hopkins School of Medicine and is currently an Associate Professor at those institutions. Dr. Suskauer directs clinical and research programs for youth concussion and was an Invited Expert and Subgroup Leader on CDC expert panel for developing clinical guidance for the acute diagnosis and management of mild traumatic brain injury among children and adolescents.

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Department of Defense 2021 Progressive Return to Activity: Update to Concussion Care Gary McKinney, DHSc

Introduction and Background The Traumatic Brain Injury Center of Excellence (TBICoE)’s evaluation of the 2014 DVBIC Progressive Return to Activity (PRA) Clinical Recommendation Tool study, found that concussion/ mild Traumatic Brain Injury (mTBI) patients cared for by PRAtrained providers reported greater overall symptom reduction at one week, one month, and three months, and expedited recovery as compared to patients treated by non-trained-PRA providers.1 Building on these findings and others, the 2021 Progressive Return to Activity after Acute Concussion/mTBI Clinical Recommendation is an evidence-based return to activity protocol for use by primary care managers (PCMs) and mTBI clinic providers in the U.S. Military Health System.1

Progressive Return to Activity The PRA is a six-stage approach that begins after performing the Military Acute Concussion Evaluation 2 (MACE 2)2 and a diagnosis of concussion. Stage 1 of the PRA starts with relative (not bed) rest, with subsequent stages 2-5 allowing service members (SMs) to gradually increase physical and cognitive activities throughout the process, as symptoms resolve. The PRA includes instructions for progressing, where symptom provocation (same, better, worse, or new) is assessed before advancing to the next stage. In addition, during Stages 2–5, SMs should continue to use rest guidelines between more strenuous activities, or if they exhibit any new or worsening symptoms. Stage 6 is return to unrestricted activities.3 If symptoms worsen during an activity, the SM should follow the guidelines for relative rest until the exacerbation resolves, and then return to the previously tolerated stage for the remainder of the day. After 24 hours in Stage 5 without new or worsening symptoms, the SM should follow up with their PCM for return to duty screening. Before returning to full duty, the SM should pass the physical and cognitive screenings to ensure mission readiness.

The revised 2021 PRA has several significant changes, outlined below: •

The 2021 PRA combined several clinical tools into a single concussion care pathway to allow providers to smoothly transition from initiation of point of injury assessment to managing recovery across the continuum of care.

•

Rather than requiring daily completion of a full concussion symptom questionnaire, individuals simply answer if their symptoms are the same, better, or worse. Questionnaires are completed with providers at follow-up visits.

•

Activity restrictions and recommendations now include more military relevant tasks.

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•

The term “relative rest” replaced “rest” in the first stage of the PRA to reflect recent research showing that complete rest may prolong recovery.

•

Clarified activity recommendations and simplified restrictions for each PRA stage outlined in the Patient and Leadership Guide (PLG). The PLG provides more militaryspecific activities that a service member should do, or abstain from, during each progressive-recovery stage.

Summary The PRA is a standardized approach for returning to activity safely and progressively following a concussion. Major updates to the 2021 PRA have streamlined the tool and concussion care, encouraged early injury self-reporting, and defined relative rest.

References 1. Ettenhofer, M., Remigio-Baker, R., Bailie, J., Cole, W., & Gregory, E. (2020). Best practices for progressive return to activity after concussion: Lessons learned from a prospective study of US Military service members. Neurotrauma Reports 1(1). https://doi.org/10.1089/neur.2020.0023 2. Military Acute Concussion Evaluation 2 (MACE 2). Retrieved from https://www.health.mil/AboutMHS/OASDHA/Defense-Health-Agency/Research-and-Development/Traumatic-Brain-Injury-Center-ofExcellence/Provider-Resources 3. Traumatic Brain Injury Center of Excellence.(2021). Progressive Return to Activity Following Acute Concussion/Mild Traumatic Brain Injury. Retrieved from https://health.mil/Reference-Center/ Publications/2021/02/23/Progressive-Return-to-Activity-Following-Concussion-Mild-TBI-Guidance-forthe-Primary-Care-Manager

Author Bio Gary McKinney, DHSc, is a clinical researcher and Chief of Clinical Practice and Clinical Recommendations (CP/CR) with the Defense Health Agency Traumatic Brain Injury Center of Excellence (TBICoE) under the Department of Defense. He has also served in roles as Interim Director for Clinical Affairs Branch, managing and overseeing CP/CR, Surveillance, and the Office of Outcomes and Assessments. He received his bachelor’s degree in Sports and Health Science with a concentration in Sport Management from Barton County College, Great Bend Kansas. He completed training for Emergency Trauma at the Army Medical Department Center and Schools San Antonio, Texas. He holds a Masters in Heath Science and a Doctorate in Health Science and Global Health from A.T. Still University School of Osteopathic Medicine.

His role at TBICoE is the development of clinical guidelines and recommendations for assessment, diagnosis, and treatment of TBI in service members and veterans. He is lead clinical researcher and program manager for developing and updating acute concussion assessment and management tools and treatment recommendations. He retired from active duty in the Army after 23 years as a Health Care Specialist and Emergency Medical Technician. He is a member of the American Congress of Rehabilitation Medicine (ACRM), American College of Sports Medicine (ACSM), ReMed Community Advisory Board and Brain Injury Association of Maryland (BIAMD). Gary is also a member of The Order of Military Medical Merit (O2M3) society. He has authored or co-authored numerous peer reviewed publications

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Tech-Knowledgy: Advancing Concussion Care through the use of Modern Tech Amy Mathews • Kathleen Bell The use of technology in caring for patients with concussion is burgeoning, showing promise for education, assessment, and intervention. For assessment, healthcare providers, as well as non-medical personnel such as coaches, use applications to measure balance and ocular parameters in suspected concussion. Smart phone applications for symptom surveillance allow tracking of mood, pain, sleep, headaches, and heart rate.

Information from these applications may be useful for both patients and providers, if shared by the patient, to help target interventions.1 There are also “gamified” symptom applications, using interactive games for reporting, promoting engagement and health management in pediatric or adolescent populations.2 Neuropsychological virtual reality (VR) assessments simulate real-life scenarios to assess cognitive domains, and may have improved generalizability compared with computerized or pencil-and-paper modalities.3 Wearable devices are on the rise in consumer markets. These bands, rings, garments and patches with sensors allow monitoring of movement, sleep, sweat, and cardiorespiratory function. This consumer technology is moving toward personalization and real-time feedback to users.4 From a management standpoint, emerging technologies can facilitate patient engagement and increase care access through telehealth, smart phone applications, and virtual reality.

Telehealth has shown high rates of satisfaction, compliance, and ease of access to care, but limits physical examination, may pose technical difficulties, and may be difficult to use for those with cognitive deficits.5 Smart phone applications may provide strategies for users to manage individual symptoms. For example, device prompts may support impaired task initiation and memory for activities such as exercising, completing work tasks, or completing personal care.6 Cognitive and mood symptoms may benefit from applications to prompt deep breathing, cognitive behavioral techniques, meditation, and cognitive exercises. Training in immersive virtual reality environments can provide therapy experiences that are not immediately available or feasible in the “real world” and may improve compliance to recommended therapies by making exercises more enjoyable.7 The use of technology is not without potential risks. Concerns have been raised about the legal liability of non-medical providers using commercially available applications or devices for assessment.1 Additionally, although options for symptom tracking and surveillance are growing, the utility of tracking symptoms on long-term outcomes is still unknown, linkage with electronic medical records is mostly unavailable, and concerns for screen overuse persist1 The use of novel technologies or repurposing of existing technologies for new therapeutic purposes is an important part of concussion assessment and management.

Providers and patients should remain up-to-date on new technologies that may improve outcomes while being vigilant for misdirected application of these devices and apps.

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References 1. Kwan V, Bihelek N, Anderson V, Yeates K. A Review of Smartphone Applications for Persons With Traumatic Brain Injury: What Is Available and What Is the Evidence? J Head Trauma Rehabil.

2019;34(2):E45-E51.

2. Worthen-Chaudhari L, McGonigal J, Logan K, Bockbrader MA, Yeates KO, Mysiw WJ. Reducing concussion symptoms among teenage youth: Evaluation of a mobile health app. Brain Inj. 2017;31(10):1279-1286.

3. Santos FV, Yamaguchi F, Buckley TA, Caccese JB. Virtual reality in concussion management: from lab to clinic. J Clin Transl Res. 2020;5(4):148-154.

4. Peake JM, Kerr G, Sullivan JP. A Critical Review of Consumer Wearables, Mobile Applications, and Equipment for Providing Biofeedback, Monitoring Stress, and Sleep in Physically Active Populations.

Front Physiol. 2018;9:743.

5. Subbarao BS, Stokke J, Martin SJ. Telerehabilitation in Acquired Brain Injury. Phys Med Rehabil Clin N Am. 2021;32(2):223-238.

6. Jamieson M, Jack R, O’Neill B, et al. Technology to encourage meaningful activities following brain injury. Disabil Rehabil Assist Technol. 2020;15(4):453-466.

7. Aida J, Chau B, Dunn J. Immersive virtual reality in traumatic brain injury rehabilitation: A literature review. NeuroRehabilitation. 2018;42(4):441-448.

Author Bios Dr. Amy Mathews is currently an assistant professor in the Department of Physical Medicine and Rehabilitation at the University of Texas Southwestern Medical Center. Her clinical interests include care of patients with concussion and spasticity management.

Dr. Kathleen Bell is the Chair of the Department of Physical Medicine and Rehabilitation (PM&R) at UT Southwestern Medical. Her research interests include concussion, sleep disorders after TBI, and exercise/ autonomic nervous system after concussion. She has been funded or an investigator on grants from NIH, NIDILRR, the Department of Defense, PCORI, and the CDC since 1998. Dr. Bell is currently a Past-President of the American Academy of Physical Medicine and Rehabilitation, the CoDirector of the Texas Institute for Brain Injury and Repair, an investigator for the North Texas Concussion Registry (CON-TEX) and co-PI for the North Texas TBI Model System.

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TBI Biomarkers: Emerging Evidence and Translational Pathway Michael A. McCrea, PhD Geoffrey T. Manley, MD, PhD

Biomarkers in Modern Medicine Across a broad array of disease states, biological markers (“biomarkers”) are now central to achieving a precision medicine approach to diagnosis and individualized treatment. While the narrow view of biomarkers is often focused on discovery of “a blood test to diagnose” the presence of a specific condition, their utility extends more broadly into essentially all aspects of modern medicine (see Figure. 1). Biomarkers can include imaging markers, genetic markers, and proteomic markers. Fundamentally, biomarkers help inform the underlying pathophysiological mechanisms of disease. In the setting of clinical care and research, objective markers enable deeper characterization and enrichment of patients for stratification into specific treatment trials suited to provide the individual patient the greatest therapeutic benefit, as well as affording an objective measure of response to treatment and disease modification.1 Prognostically, biomarkers can provide value in predicting an individual patient’s projected course of recovery and outcome.

Figures and Tables.

A powerful demonstration of the role biomarkers play in contemporary medicine is the case of troponin, or the troponin complex in the evaluation and management of myocardial infarction (MI) and acute coronary syndrome (ACS).2 Troponin’s pathway from bench to bedside took several decades, from the discovery of the actomyosin system back in the 1940s to eventual endorsement of troponin by the American College of Cardiology as the preferred biomarker of ACS for clinical use in 2000 and continued refinement of ultra-sensitive assays for enhanced clinical accuracy over the past 20 years. At the same time, biomarkers have become central to precision medicine in cancer, cardiovascular disease, and neurologic disorders.

Biomarker Movement in Traumatic Brain Injury Over the past decade, we have seen the advent of several candidate biomarkers for traumatic brain injury (TBI).3 Biomarkers have proven valuable to informing the complex and heterogenous pathophysiology of TBI4, particularly the mechanisms, character, and dynamic time course of neuronal, axonal, and astroglial damage resulting from TBI.5

Figure 1. Role of biomarkers in modern medicine.

Figure 1. Role of biomarkers in modern medicine.

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BRAIN INJURY professional 27

Several blood biomarkers have been consistently found to be elevated after moderate and severe TBI, including glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neuron-specific enolase (NSE), S100b, tau, neurofilament heavy (NFH) chain protein, neurofilament light (NF-L) and others.6 In severe TBI, biomarker levels correlate with extent of structural injury on neuroimaging and postinjury prognosis.7,8 An estimated 90 percent of TBIs are classified as mild (mTBI) based on traditional criteria, including Glasgow Coma Scale (GCS score 13-15) and observed clinical signs. The overwhelming majority of mTBI patients have no evidence of structural injury on conventional head computed tomography [CT]), but a sizeable percentage of mTBI patients with normal CT have evidence of microstructural injury on advanced brain magnetic resonance imaging (MRI).9 Both CT and MRI findings are predictive of long-range recovery and outcome after mTBI.10 Due to availability and cost, MRI is not routinely deployed in the evaluation of mTBI patients. Further, the clinical diagnosis of mTBI is often challenging because of the subjective and non-specific nature of self-reported symptoms and limited diagnostic utility of the standard clinical testing protocol. In sum, there is a pressing need for easy-to-use, valid, and cost-effective biomarkers for assessment of mTBI, while also advancing our understanding of the underlying pathophysiology of injury.11 Through highly effective public-private partnerships, two large national research initiatives funded by the DoD, NIH, and industry partners are studying the utility of established and emerging blood-based proteomic biomarkers in the setting of mTBI and concussion. The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study is the most comprehensive investigation of civilian TBI conducted in the U.S. to date.12,13 TRACKTBI has collected detailed clinical data on >3,000 participants across the age range (0-100 years), including individuals with brain injury across the TBI spectrum (mild, moderate, severe) and controls, at 18 US Level 1 trauma centers.

In parallel, the Concussion Assessment, Research and Education (CARE) Consortium, is a large-scale investigation of mTBI, sportrelated concussion (SRC) and recovery in US Military Service Academy (MSA) cadets and collegiate student-athletes.14

CARE was commissioned and funded by the DoD and NCAA, who share similar challenges related to evaluation and treatment of mTBI. CARE has enrolled >55,000 cadets and student athletes, collecting detailed post-injury data on >5,500 participants with SRC and military mTBI. Both TRACK-TBI and CARE protocols include detailed clinical outcome assessment, advanced multimodal MRI, and collection of blood biospecimens on injured and control participants.

The infrastructure for TRACK-TBI and CARE includes a robust biorepository for the study of blood-based biomarkers. Recent publications from the studies have indicated favorable performance of select biomarkers in the setting of mTBI and concussion.

Following is a high level summary of the work from TRACK-TBI and CARE studies focused on blood-based proteomic biomarkers.

Early work from the TRACK-TBI pilot study focused on measurement of GFAP, UCH-L1, NF-L, and total tau in plasma samples of participants with TBI using the Quanterix Simoa 4-Plex assay.15 This study found strong correlations between markers of axonal (NFL) and neuronal (UCH-L1) injury. Further, the multiplex of GFAP, UCH-L1, NF-L and total tau performed favorably in differentiating TBI patients with/without abnormal head CT, with area under the curve (AUC) >0.80. These findings and others from TRACK-TBI16-18 showed early promise for the potential clinical utility of these candidate biomarkers in the diagnosis of TBI and identifying specific underlying TBI pathologies. Additional studies outside of TRACK-TBI have also reported high sensitivity and negative predictive value (NPV) of UCH-L1 and GFAP to predict presence of intracranial injury on acute head CT.19 A critical step in the pathway toward eventual clinical utilization of TBI biomarkers involves development, validation, and optimization of point-of-care (POC) testing, which essentially brings the technology from the bench (core lab platform) to the bedside (rapid – within minutes) with POC analysis. TRACK-TBI investigators have deployed prototype assays on a POC platform to study the association between blood-based biomarkers and conventional head CT, to assessing the ability of biomarkers to identify specific TBI pathologies on brain MRI. Okonkwo et al compared the diagnostic performance of POC GFAP test versus S100B for prediction of brain injuries.20 S100B is used as a TBI biomarker in Europe and is part of the

Figure 2. Performance of GFAP, S100, and UCHL1 biomarkers for predicticting Figure 2. Performance of GFAP, and CT UCHL1 biomarkers predicting intracranial injury on head CR and MRI after TBI. intracranial injury onS100, head and MRIfor after TBI.

FIGURE 2A. Reciever operating-characteristic curve comparing performance of plasma GFAP and serum S100 for predicting intracranial injury on head CT. The area under the curve (AUC) demonstrates that GFAP significantly outperforms S100b.

FIGURE 2B. Performace of GFAP and UCH-L1 for prediciting intracranial injury on MRI. The AUC demonstrates that GFAP outperforms UCH-L1. FIGURE 2C. GFAP concentration by MRI pathology. GFAP concentrations are significantly higher in patients with diffuse axonal injury (DAI) versus traumatic axonal ijury (TAI).

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4.2 Figure 3. GFAP, UCH-L1 and NF-L levels in athletes with acute sport-related concussion

2.0

4.0 compared to contact control and non-contact control athletes without concussion.

1.8

Figure 3. Baseline and Postinjury Biomarker Levels in Athletes With Concussion With Either Loss of Consciousness (LOC) or Posttraumatic Amnesia (PTA) (LOC-PTA), Baseline Acute control 24 h Asymptomatic 7 d After Figure 3. BaselineFigure and Postinjury Biomarker Levels in Athletes With Concussion Either Loss ofwith Consciousness or Posttraumatic Amnesia (PTA) (LOC-PTA), 3. GFAP, UCH-L1 and NF-L levelsWith in athletes acute(LOC) sport-related concussion compared to contact and non-contact RTP Athletes Concussion No LOC or (No PTALOC-PTA), (No LOC-PTA), Contact Controls, and Non–Contact Sport Controls Athletes WithWith Concussion WithWith No LOC or PTA Contact SportSport Controls, and Non–Contact Sport Controls

Baseline

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Baseline

Acute

control athletes without concussion.

B B UCH-L1UCH-L1 3.4

A

5.0 5.0

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FIGURE 3A and 3B. GFAP and UCH-L1 levels show significant increase after acute SRC in athletes relative to baseline and D Tau Biomarker levels represent natural log (ln) transformed scale. Error bars indicate SEs. GFAP indicates glial fibrillary acidic protein D Tau non-concussed controls, with highest elevations in those with LOC/PTA. BL=Baseline, PI=<6 hrhydrolase-L1.

Post-injury, 24H=24 hr PI, and UCH-L1, ubiquitin C-terminal 0.4 2.4 0.4 2.4 Asymp=Asymptomatic, Post-RTP=7 days after return to play. 3C. Concussed athletes show increasing levels of NF-L over the first 2 weeks after SRC compared to baseline and controls.

JAMA Network Open. 2020;3(1):e1919771. doi:10.1001/jamanetworkopen.2019.19771 (Reprinted)

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Scandinavian management guidelines for mTBI, to reduce0 the number2.0of CT scans used for TBI evaluation in the emergency 2.0 –0.2 department.21 GFAP (AUC 0.853) was found to substantially –0.2 outperform S100B (AUC 0.665) to predict abnormalities on CT scan (Figure 2A). Importantly, the GFAP test performed through 24 hours –0.4 1.8 in patients across the spectrum of injury from concussion postinjury –0.4 1.8 to coma.

–0.6

Downloaded From: https://jamanetwork.com/ by a Medical College oftraining Wisconsin User on 01/24/2020 cadets who participated in the same combative exercises but did not incur concussions.24 Compared with non-concussed cadets, those in the concussion group had significant increases in GFAP and UCH-L1 levels within 6 hours of injury. GFAP level remained high in the concussion group for several days after injury.

This study's findings indicate the potential for blood biomarkers to help inform our understanding the pathobiological changes and course of physiological recovery associated with mTBI among military service members.

–0.6 head CT Yue et al compared mTBI patients (GCS 13-15) with normal 1.6 who consented to blood draw within 24 hours of injury and who had 1.6 Acute 24 h 22 Asymptomatic 7 d After Baseline Acute 24 h Asymptomatic 7 d After The study sample included 450 mTBI Biomarkers have also shown promise in the setting of SRC. A recent brain MRI 2 Baseline weeks postinjury.

RTP 7 d After Baseline Acute 24 h AsymptomaticRTP 7 d After Baseline Acute 24 h Asymptomatic RTP RTP patients with normal head CT (330 with negative brain MRI; 120 CARE Consortium study investigated the utility of GFAP, UCH-L1, NF-L 25 with positive brain 122 orthopedic trauma controls, and 209 andlighttau acute Biomarker levels represent natural MRI), log (ln) transformed scale. Error bars indicate SEs. GFAP indicates glial fibrillary acidic protein; NF-L, neurofilament chain;after RTP, return to play; SRC in college athletes. In the largest study of levels represent log (ln) transformed scale. Error bars indicate SEs.well GFAP indicates glial fibrillary acidic protein; NF-L, neurofilament RTP, return to play; with concussion had significant elevation andBiomarker UCH-L1, ubiquitin C-terminalnatural hydrolase-L1. its kindlight tochain; date, athletes healthy controls.

In this study, GFAP performed in distinguishing and UCH-L1, ubiquitinwho C-terminal hydrolase-L1. in GFAP, UCH-L1, and tau levels within 6 hours postinjury compared mTBI patients were CT-/MRI+ from those who were CT-/MRJAMA Network Open.=2020;3(1):e1919771. doi:10.1001/jamanetworkopen.2019.19771 (Reprinted) the degree 2020 10/16 baseline levels and non-concussed control with January both24,preseason (Fig. 2B, AUC 0.777). GFAP was also able to distinguish JAMA Network Open.on 2020;3(1):e1919771. doi:10.1001/jamanetworkopen.2019.19771 (Reprinted) different January (Figure 24, 2020 10/16 athlete levels 3A-C). Beyond the assessment of subjective of injuries seen MRI (Figure 2C.) Comparisons amongst symptoms, GFAP at the acute postinjury time point was associated lesion types showed that patients with diffuse axonal injury (DAI, with the accurate classification of athletes with concussion from >3 foci of axonal shear injury) had higher GFAP than patients with Downloaded From: https://jamanetwork.com/ a Medical of Wisconsin on 01/24/2020 contact controls and non–contact sport controls. CARE study results traumatic axonal injury by(TAI, 1-3College foci of axonalUser shear).

Both mTBI Downloaded From: https://jamanetwork.com/ by a Medical College of Wisconsin User on 01/24/2020 also indicate that acute biomarker levels predict time for recovery groups showed significantly higher median GFAP levels than both and return to play after SRC.26 orthopedic trauma controls and healthy controls within 24 hours of injury, even those TBI patients with no CT or MRI abnormalities.

In summary, blood-based biomarkers show promise in detecting In addition, mTBI groups showed significantly higher median GFAP underlying pathologies of TBI, including sensitivity in the setting of levels than both orthopedic trauma controls and healthy controls mTBI and SRC that goes well beyond our conventional methods (e.g., within 24 hours of injury, even in those TBI patients with no CT or clinical evaluation, symptom reporting, GCS, head CT and MRI).

MRI abnormalities. These findings and others from TRACK-TBI23 add further support to the potential for GFAP and POC testing to There is also the potential for blood biomarkers to serve as aid clinicians in diagnosing mTBI, determing need for head CT, and secondary endpoints in TBI clinical trials, thereby providing more identifying patients who might need follow-up MRI. objective means to assess disease modification and response to treatment at the neurobiological or “mechanistic” level. Many CARE Consortium studies also highlight the sensitivity of bloodother candidate biomarkers are rapidly emerging. Across the mTBI based proteomic biomarkers to acute concussion in athletes and spectrum, diagnostic biomarkers have potential to objectively assess military service members. A recent CARE study led by Giza and injury presence and severity and to monitor recovery while also colleagues compared levels of GFAP, UCH-L1, NF-L and tau in military advancing our understanding of the underlying pathophysiological cadets who incurred concussions during combative training with mechanisms of concussion. The pathway to clinical implementation

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of blood-based biomarkers will require further validation studies to optimize the best performing panels that provide maximal diagnostic and prognostic accuracy at the level of the individual patient. From a pragmatic standpoint, the availability of POC biomarker testing is critical for clinical use in acute trauma and ambulatory care settings. Further, field-deployable POC options may be necessary for widespread use in sports and military medicine.

While not yet part of routine care in brain injury medicine, we have achieved enormous progress along the pathway of translation from discovery to eventual clinical utility of TBI biomarkers over the past 20 years, and future research is sure to fuel the movement forward.

(Figure 4).

Figure 4.4.Translational Pathway for TBI for Biomarkers Figure Translational Pathway TBI Biomarkers

References 1. FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource. 2016; Silver Spring, MD.

in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study.

Lancet Neurol. 2019;18(10):953-961.

2. Connelly A, Findlay IN, Coats CJ. Measurement of troponin in cardiomyopathies. Cardiogenetics. 2016;6(1).

23. Xu LB, Yue JK, Korley F, et al. High-Sensitivity C-Reactive Protein is a Prognostic Biomarker of Six-Month Disability after Traumatic Brain Injury: Results from the TRACK-TBI Study. J Neurotrauma. 2021;38(7):918927.

3. Dadas A, Washington J, Diaz-Arrastia R, Janigro D. Biomarkers in traumatic brain injury (TBI): a review.

Neuropsychiatr Dis Treat. 2018;14:2989-3000.

4. Martinez BI, Stabenfeldt SE. Current trends in biomarker discovery and analysis tools for traumatic brain injury. J Biol Eng. 2019;13:16.

5. Zetterberg H, Smith DH, Blennow K. Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood. Nat Rev Neurol. 2013;9(4):201-210.

6. Agoston DV, Shutes-David A, Peskind ER. Biofluid biomarkers of traumatic brain injury. Brain Inj. 2017;31(9):1195-1203.

7. Strathmann FG, Schulte S, Goerl K, Petron DJ. Blood-based biomarkers for traumatic brain injury: evaluation of research approaches, available methods and potential utility from the clinician and clinical laboratory perspectives. Clin Biochem. 2014;47(10-11):876-888.

24. Giza CC, McCrea M, Huber D, et al. Assessment of Blood Biomarker Profile After Acute Concussion During Combative Training Among US Military Cadets: A Prospective Study From the NCAA and US Department of Defense CARE Consortium. JAMA Netw Open. 2021;4(2):e2037731.

25. McCrea M, Broglio SP, McAllister TW, et al. Association of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortium.

JAMA Netw Open. 2020;3(1):e1919771.

26. Pattinson CL, Meier TB, Guedes VA, et al. Plasma Biomarker Concentrations Associated With Return to Sport Following Sport-Related Concussion in Collegiate Athletes-A Concussion Assessment, Research, and Education (CARE) Consortium Study. JAMA Netw Open. 2020;3(8):e2013191.

8. Yokobori S, Hosein K, Burks S, Sharma I, Gajavelli S, Bullock R. Biomarkers for the clinical differential diagnosis in traumatic brain injury--a systematic review. CNS Neurosci Ther. 2013;19(8):556-565.

9. Yuh EL, Mukherjee P, Lingsma HF, et al. Magnetic resonance imaging improves 3-month outcome prediction in mild traumatic brain injury. Ann Neurol. 2013;73(2):224-235.

10. Nelson LD, Temkin NR, Dikmen S, et al. Recovery After Mild Traumatic Brain Injury in Patients Presenting to US Level I Trauma Centers: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study. JAMA Neurol. 2019;76(9):1049-1059.

11. McCrea M, Meier T, Huber D, et al. Role of advanced neuroimaging, fluid biomarkers and genetic testing in the assessment of sport-related concussion: a systematic review. Br J Sports Med. 2017;51(12):919-929.

12. Yue JK, Vassar MJ, Lingsma HF, et al. Transforming research and clinical knowledge in traumatic brain injury pilot: multicenter implementation of the common data elements for traumatic brain injury. J Neurotrauma. 2013;30(22):1831-1844.

13. Manley GT, Maas AI. Traumatic brain injury: an international knowledge-based approach. JAMA. 2013;310(5):473-474.

14. Broglio SP, McCrea M, McAllister T, et al. A National Study on the Effects of Concussion in Collegiate Athletes and US Military Service Academy Members: The NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium Structure and Methods. Sports Med. 2017;47(7):1437-1451.

15. Korley FK, Yue JK, Wilson DH, et al. Performance Evaluation of a Multiplex Assay for Simultaneous Detection of Four Clinically Relevant Traumatic Brain Injury Biomarkers. J Neurotrauma. 2018.

16. Okonkwo DO, Yue JK, Puccio AM, et al. GFAP-BDP as an acute diagnostic marker in traumatic brain injury: results from the prospective transforming research and clinical knowledge in traumatic brain injury study. J Neurotrauma. 2013;30(17):1490-1497.

17. Diaz-Arrastia R, Wang KK, Papa L, et al. Acute biomarkers of traumatic brain injury: relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein. J Neurotrauma.

2014;31(1):19-25.

18. Wang KK, Yang Z, Yue JK, et al. Plasma Anti-Glial Fibrillary Acidic Protein Autoantibody Levels during the Acute and Chronic Phases of Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study. J Neurotrauma. 2016;33(13):1270-1277.

19. Bazarian JJ, Biberthaler P, Welch RD, et al. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol.

2018;17(9):782-789.

20. Okonkwo DO, Puffer RC, Puccio AM, et al. Point-of-Care Platform Blood Biomarker Testing of Glial Fibrillary Acidic Protein versus S100 Calcium-Binding Protein B for Prediction of Traumatic Brain Injuries: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study. J Neurotrauma.

2020;37(23):2460-2467.

21. Unden J, Ingebrigtsen T, Romner B, Scandinavian Neurotrauma C. Scandinavian guidelines for initial management of minimal, mild and moderate head injuries in adults: an evidence and consensus-based update. BMC Med. 2013;11:50.

22. Yue JK, Yuh EL, Korley FK, et al. Association between plasma GFAP concentrations and MRI abnormalities

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Author Bios Michael A. McCrea, PhD, is Tenured Professor of Neurosurgery and Co-Director of the Center for Neurotrauma Research at the Medical College of Wisconsin. He has been an active researcher in the neurosciences, with numerous scientific publications, book chapters, and national and international lectures on the acute and chronic effects of traumatic brain injury. Dr. McCrea has led several large, multi-center studies on traumatic brain injury (TBI) and concussion. He is currently co-PI of the NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium and co-I on the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study and TBI Endpoints Development (TED) study. He serves on the National Academies of Sciences, Engineering, and Medicine (NASEM) Committee on Accelerating Progress in TBI Research and Care and has served on several other expert panels related to TBI over the past 25 years.

Geoffrey T. Manley, MD, PhD, is the Chief of Neurosurgery at Zuckerberg San Francisco General Hospital and Professor and Vice Chairman of Neurological Surgery at UCSF. He also serves as a trauma neurosurgeon and Co-Director of the Brain and Spinal Injury Center. His research focuses on traumatic brain injury (TBI) translational research and clinical care of TBI patients. He is the Contact Principal Investigator for the 18-site Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACKTBI) U01 Research Project funded by the National Institute of Neurological Disorders and Stroke and the Department of Defense TBI Endpoints Development (TED) Initiative award.

Technology: Read&Write: Literacy support software with wider application for concussion care Alexandra Cayias, MS, CCC-SLP • Stephen Trapp, PhD, MEd Repurposing off-the-shelf objects is a common practice within neurorehabilitation. Consider the simple reimagining of foam earplugs marketed for loud activities, such as heavy construction, to assist individuals in brain injury recovery by minimizing overstimulation and maximizing cognitive endurance in noisy environments. Further, the repurposing of digital technology offers a new frontier for novel rehabilitation solutions. Finding new uses for already imagined digital technology can be as simple as leveraging common smartphone apps for symptom tracking or be as playful as the use of video game inputs for assessing postural stability post-concussion.1,2 This brief report will describe Read&Write, a software package targeting literacy support, and one that offers a great deal for those rehabilitating from concussion.

Read&Write is promoted as an assistive technology application to enhance educational and workplace activities. This software is developed by Texthelp, an edtech company with a suite of applications for diverse learning and working styles. Read&Write offers visual and auditory enhancements to textual content, such as bidirectional conversion of text and sound, word prediction, verb and spell checking, speech input/output, and optical character recognition from scanned documents. The features of Read&Write operate with conventional Microsoft products to expand activities such as word processing, presentation creation, and internet browsing. This also furthers equity in technology access by means of discrete integration – a potential to reduce one aspect of stigma associated with the use of assistive technology.

Although much of the marketing expresses a value in education and for individuals with learning disabilities, this software has a range of applications for concussion care. For example, the capability to record and then transcribe information in a work meeting assists an individual with a brain injury to recall necessary occupational information when it is difficult to alternate their attention between listening and taking written notes. Additionally, the software allows individuals rehabilitating from a brain injury to highlight and notate on digital texts and pdfs, improving their ability to comprehend information effectively and efficiently. As vocational and educational domains become more and more layered with disparate content and demands, assistive options that enhance efficiency can expand a person’s engagement in these meaningful life activities.

Nikki Goode, an account manager with Texthelp, offered a personal story about using Read&Write. In 2014, Ms. Goode experienced subarachnoid and intracranial hemorrhages, resulting in brain injuries that led her providers to believe she would not return to employment. Determined to reengage with the work she valued, Ms. Goode enrolled in Access to Work – a public health employment support program in the United Kingdom that assists individuals with injuries to return to meaningful vocations. Through this service she began using Read&Write as she transitioned back to employment.

“It pulled me out of the darkness and allowed me to access my knowledge,” described Ms. Goode. After using Read&Write for a number of years, Ms. Goode eventually sought a job with Texthelp and now sees her role as being able to, “carry the torch for people and educate that yes, we have difficulties, but we can do it too.”

Together, Read&Write offers a range of options for neurorehabilitation to support a return to meaningful occupations and celebrated independence. The features highlighted above offer unobtrusive assistance that accommodate different cognitive styles and optimize vocational engagement. Although this software was originally ideated for literacy support, it represents one of the many opportunities rehabilitation clinicians have to creatively repurpose off-the-shelf digital technology to enhance concussion care. Read&Write is available for Windows, Mac, Google Chrome, Microsoft Edge, iPad and Android. To learn more about the software and pricing, see https://www.texthelp.com/products/read-and-writeeducation/.

Disclaimer: The authors have nothing to disclose or financial associations with the companies, research, or technology reviewed in this article.

References 1. Merchant-Borna K, Jones CMC, Janigro M, Wasserman EB, Clark RA, Bazarian JJ. Evaluation of Nintendo Wii Balance Board as a tool for measuring postural stability after sport-related concussion.

Journal of athletic training. 2017;52(3):245-255.

2. Rhine TD, Byczkowski TL, Clark RA, Babcock L. Investigating the feasibility and utility of bedside balance technology acutely following pediatric concussion: A pilot study. Clinical journal of sport medicine: official journal of the Canadian Academy of Sport Medicine. 2016;26(3):221.

Author Bios Alexandra Cayias, MS, CCC-SLP, is a speech language pathologist who has worked in the outpatient hospital setting for 11 years providing cognitive rehabilitation to individuals with neurological diagnoses. Collaborating with patients to individualize implementation of digital and non-digital tools in their home, work and school environments for optimal success and independence is one of her favorite aspects of cognitive rehabilitation.

Stephen K. Trapp, PhD, MEd, is a rehabilitation psychologist and Director of the Center of Health Creation at the Metrodora Institute. His clinical and research efforts focus on a range of neurorehabilitative conditions, rehabilitation technology, and cross-cultural topics.

Among other roles, he is the Technology Editor for Brain Injury Professional and affiliated with the Department of Psychiatry at the University of Utah.

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BIP

expert interview

The Long-term Impact of TBI and Rehabilitation Needs: Findings from IMAP An Interview with Risa Nakase-Richardson, PhD, FACRM The interview will highlight recently published findings regarding common comorbidities in chronic stages of TBI, rehabilitation and family needs, and healthcare access issues in Veterans and Service Members enrolled in a large multi-center study (IMAP). Findings are included in a recent report to Congress regarding the long-term impact o[f] TBI on Service Members, Veterans, and their families.

Risa Nakase-Richardson, PhD, FACRM is a Neuropsychologist at the James A. Haley Veterans Hospital and Professor and Research Director in Sleep Medicine at the University of South Florida. She has over 125 peer-reviewed publications and has served as PI or Investigator on 21 grants funded by various federal agencies and private organizations. She has worked at the VA Polytrauma Rehabilitation Center in Tampa Florida since 2008 where she serves as the Project Director for the VA TBI Model Systems and the Overall PI for Improved Understanding of Medical and Psychological Needs (I-MAP) in Veterans and Service Members with Chronic TBI.

As the overall Principal Investigator for the Improved Understanding of Medical and Psychological Needs (I-MAP) study, can you briefly summarize your role and the primary objectives of this congressionally-mandated study?

Following our nation’s longest war, Congress wanted to garner evidence about the long-term effects of TBI. A 15-year study was stood up led by Dr. Lou French within DOD. To represent the full spectrum of military health, the VA-arm of this study is being led by me. As the principal investigator, I work with investigators across the VA TBI rehabilitation centers of excellence to enroll active-duty service members and Veterans who are hospitalized for TBI. The VA and DOD have a longstanding collaborative agreement thus Service Members are treated in VA healthcare systems for specific conditions including TBI. For this study, participants admitted for TBI are enrolled in the VA TBI Model Systems program of research which was enhanced to address the informational needs of congressional policymakers and utilizes a mixed methods approach informed by a wide variety of scientists. Congress has focused on four key informational needs including overall health (psychological, physical), rehabilitation needs, health service needs, and family impact of TBI. We submit reports at regular intervals to DOD and VA policymakers who finalize an official Congressional Report submitted at 3, 7, 11, and 15 years since the mandate inception.

We garner input from a wide variety of scientists and gather stakeholder input to ensure we are considering all perspectives on study findings. Last year the 11-year report was submitted to Congress, and we are busy collecting, analyzing, and disseminating results for the final 15-year report.

What were the most prominent study findings and priorities outlined in your latest report to Congress?

The most prominent finding was that comorbidities (both physical and psychological) are the norm in chronic stages and add to the burden that we normally consider unique to TBI. The report spoke at length about the impact of PTSD on the patients and their families and was notably associated with poor outcomes including negative legal consequences. From a physical health standpoint, chronic pain, sleep disorders, orthopedic injuries, cardiovascular disease, sexual dysfunction, and gastrointestinal disease were among the most common comorbid conditions. One of the challenges in managing comorbidities is misattribution that symptoms are due to TBI rather than other health disorders which can be treated with evidence-based interventions.

Indeed, our work has highlighted that these comorbidities

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are common in chronic stages and are uniquely associated with impaired cognition, poor physical health, lower rates of community re-entry including employment/participation, and poor psychological health after controlling for TBI. Earlier recognition of these comorbidities and access to evidence-based treatments may help improve outcomes even for those in chronic stages.

In response to these findings, the report outlined several priorities, including the incorporation of interdisciplinary treatment planning and dedicated case management to track emerging needs. Speaking as a provider, one of the greatest advantages of providing treatment at a site like a VA polytrauma rehabilitation center is working with an interdisciplinary team that meets regularly and has access to a myriad of specialty providers to help address comorbid conditions.

For example, sleep medicine is co-located at our facility and able to diagnose and implement treatment during hospital stays rather than waiting to have sleep problems identified and treated over a prolonged interval as an outpatient.

With regards to prioritizing case management, our findings indicated that once a person returns to his or her community, access barriers start to emerge. Access barriers differed across injury severity groups and environmental factors are consistently associated with having unmet needs. However, comprehensive and dedicated case management services for TBI patients—like those in place at VA Polytrauma Rehabilitation Centers—have programs and protocols in place to bring patients and families back in later stages to address emerging needs. VA and DOD have committed to case management after TBI in acute and chronic stages (unlike civilian healthcare) to help facilitate those service needs.

One of the cool things to observe in this process is the response from DOD and VA to our study findings. Policymakers from both review study results which can and do result in actionable steps to improve healthcare delivery for our Service Members and Veterans. Indeed, the process of writing the report is a policy intervention which is exciting. The full report can be found at: [https://www.health.mil/Reference-Center/CongressionalTestimonies/2021/05/04/Longitudinal-Study-on-Traumatic-BrainInjury-Incurred-by-Members-of-the-Armed-Forces-in-OIF-OEF] You mention the significance of good case management following a TBI to identify and address emerging needs. Based on your work, can you elaborate a bit on the long-term implications of having unmet rehabilitation needs in chronic TBI?

Our work has highlighted that persons with a history of TBI have unmet rehabilitation needs even at five-years post-TBI and that greater number of unmet needs is associated with lower satisfaction with life. Follow-up work for the next congressional report will look at later years and more impacts. Our use of the term rehabilitation need is not limited to delivery of more PT, OT, SLP, or RT. Rehabilitation as an intervention addresses the whole person thus we asked about needs that encompass many domains often addressed by an multidisciplinary team such as psychological health (emotions, stress, anger), service coordination, physical health, cognitive health, education/employment, independent living, transition to civilian life, maintaining relationships, opportunities for social engagement, addiction, informational needs and more.

Indeed, needs exist in later stages of TBI and a fair number in our study sample are unmet. Most rehabilitation systems are frontloaded in terms of care for TBI thus these findings highlight that our V/SM have needs and many are unmet in later stages. How to best address them is not the focus of our study but it has gotten people talking.

What are the primary concerns amongst patients reporting unmet rehabilitation needs?

Priorities vary across injury severity and racial groups. In terms of prioritization of needs, the data tell us what Active Duty Service Members and Veterans with TBI are most concerned about.

Indeed, the priorities vary by injury severity and by racial groups.

Overall, persons endorsing black racial status reported having a greater number of unmet rehabilitation needs than persons endorsing white racial status. The number one unmet need for black participants was help with managing emotions/psychological health (52% compared to white race, 23%). For white participants, the number one unmet need was in addressing cognition (38% compared to black race, 44%).

Providers should take these racial differences into consideration when developing treatment priorities with patients. Participants endorsing unmet needs consider them important thus should help shape the development of treatment plans. As stated in my response to prior questions, lots of factors contribute to these needs thus practitioners will need to educate their patients and families about other non-TBI contributing factors and make appropriate referrals to address them.

Are there specific rehabilitation treatment models or approaches that you would recommend when addressing these concerns?

Helping patients understand the link between their primary TBI concerns and alternative explanations is really important. Our qualitative data collection with patients highlighted that providers may ignore the primary concern and just refer them to treatments that they didn’t understand were important (for their primary concern). What a patient believes is important (i.e., they identified it as a rehabilitation need) is at the heart of the patient-centered care movement in healthcare delivery. However, the goals of treatment can be aligned in a shared decision-making processes rather than disregarding the opinion of either the patient or the provider. When I have someone concerned about cognition (the number 1 rehab need identified in our study when combining all groups) who believes that their difficulties are due to their history of remote TBI, as a provider I have to provide information about other contributing factors to cognition that may need to be treated.

In that context, I am not ignoring their concerns about cognition but sharing information that they may not know and help them see the connection between other problems (e.g., poor sleep, depression, PTSD) to cognitive dysfunction rather than TBI. In a therapeutic context with good rapport, I try to help patients see that connection to their concerns so that they are willing and motivated to engage in the treatment.

BRAIN INJURY professional 33

Any advice for solo-providers out there?

It is challenging to comprehensively address TBI as a solo provider.

Providing education to persons with TBI and caregivers is important so that they will have “buy-in” to pursue other paths for symptom relief. For example, helping them understand the importance of specific follow-up appointments and how that may address their primary concern is so helpful. Engagement with our patient and family stakeholders during the study highlighted that this education from a trusted provider was critical for patient and caregiver buy-in.

The Defense Health Agency TBI Center of Excellence (TBI COE) has excellent educational materials (https://health.mil/TBICOE) as well as the TBI Model Systems Knowledge Translation Center (www. msktc.org) that can be used with persons with TBI and their families to understand TBI and common comorbid conditions.

What are your plans for the final 15-year Report to Congress?

Our big focus quantitatively will be analyzing the VA TBIMS and IMAP data on 10 and 15-year outcomes across each mandated element. Additionally, we have also successfully merged our TBI characterization data with health care administrative data to more comprehensively examine healthcare utilization and VA/ DOD cost across specific time intervals after TBI and for specific injury severity groups using gold-standard metrics of injury. Finally, our qualitative research team will be collecting data across the civilian, VA, and DOD healthcare infrastructure to understand perception of needs and how to best address them in chronic stage of military TBI. We are engaging with several stakeholder groups to ensure all perspectives are considered when writing up our final results for policymakers. Indeed, it has been a privilege to work with Dr. French’s DOD team and the VA IMAP team to frame the

consequences of the signature injury of our nation’s longest war for those in a position (policymakers) to change military healthcare for the better. Our collaborations with the National Institute on Disability, Independent Living, and Rehabilitation Research TBI Model Systems has helped inform how findings have implications for civilian healthcare as well. Indeed, ongoing discussions for adapting our methods and area of focus to gather information for civilians with TBI are in progress. Further, our engagement with nonmilitary TBI advocacy organizations and stakeholder groups will help inform where there are system challenges for Veterans and Service Members who utilize civilian healthcare. Our hope is that findings will have policy implications for the TBI healthcare regardless of where services are received.

About the Interviewer Dr. Theresa Teslovich Woo is a neuroscientist and Coordinator of the Translating Research into Practice (TRIP) Initiative at the National Intrepid Center for Excellence (NICoE), Walter Reed’s premier traumatic brain injury clinic. For almost two decades, Dr. Woo has worked in the fields of cognitive developmental neuroscience, serious mental illness and traumatic brain injury employing both standard clinical and behavioral assessments as well as novel neuroimaging modalities to study the brain. Dr. Woo obtained her doctorate in neuroscience from Weill Cornell Medicine and completed her post-doctoral fellowship at Georgetown University and the Washington DC VAMC prior to joining the NICoE.

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Madison Schwartz, Stanford Law, Randall H. Scarlett, Randall A. Scarlett, Ronnie Pang, Olga Rios, Mary Anne Scarlett, and Brendan D. Nay.

SCARLETT LAW GROUP Scarlett Law Group is a premier California personal injury law firm that in two decades has become one of the state’s go-to practices for large-scale personal injury and wrongful death cases, particularly those involving traumatic brain injuries.

With his experienced team of attorneys and support staff, founder Randall Scarlett has built a highly selective plaintiffs’ firm that is dedicated to improving the quality of life of its injured clients. “I live to assist people who have sustained traumatic brain injury or other catastrophic harms,” Scarlett says. “There is simply no greater calling than being able to work in a field where you can help people obtain the treatment they so desperately need.”

To that end, Scarlett and his firm strive to achieve maximum recovery for their clients, while also providing them with the best medical experts available. “As a firm, we ensure that our clients receive both

the litigation support they need and the cutting-edge medical treatments that can help them regain independence,” Scarlett notes.

Scarlett’s record-setting verdicts for clients with traumatic brain injuries include $10.6 million for a 31-year-old man, $49 million for a 23-year-old man, $26 million for a 7-year-old, and $22.8 million for a 52-year-old woman. In addition, his firm regularly obtains eight-figure verdicts for clients who have endured spinal cord injuries, automobile accidents, big rig trucking accidents, birth injuries, and wrongful death.

Most recently, Scarlett secured an $18.6 million consolidated case jury verdict in February 2014 on behalf of the family of a woman who died as a result of the negligence of a trucking company and the dangerous condition of a roadway in Monterey, Calif. The jury awarded $9.4 million to Scarlett’s clients, which ranks as

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one of the highest wrongful death verdicts rendered in recent years in the Monterey County Superior Court.

“Having successfully tried and resolved cases for decades, we’re prepared and willing to take cases to trial when offers of settlement are inadequate, and I think that’s ultimately what sets us apart from many other personal injury law firms,” observes Scarlett, who is a Diplomate of the American Board of Professional Liability Attorneys.

In 2015, Mr. Scarlett obtained a $13 million jury verdict for the family of a one year old baby who suffered permanent injuries when a North Carolina Hospital failed to diagnose and properly treat bacterial meningitis that left the child with severe neurological damage. Then, just a month later, Scarlett secured an $11 million settlement for a 28-year-old Iraq War veteran who was struck by a vehicle in a crosswalk, rendering her brain damaged.