Qmetis Blog by A. Maerlender: https://www.qmetis.com/the-challenge-of-concussion-care/

11 Jan The Challenge of Concussion Care

Media attention on concussions has raised the profile of this frequent injury. But because the underlying biological pathophysiology is not clearly defined, progress has been slow in defining the critical features, course, and prognostic signs. Variability in diagnosis and treatment becomes a rate-limiting step as research studies include cases of unknown diagnostic validity. The relatively mild nature of the injury means that: 1. There is no visible mark to denote injury, and 2. most cases do not become incapacitated. Thus, the relatively mild nature belies the all-too-frequent lengthy consequences of sub-optimal performance in academic, social, vocational, and athletic arenas that result in many cases.

Obtaining a clear understanding of concussions’ etiology and nature has been bedeviled by the lack of a biologic gold standard that defines the injury. Clinical signs and symptoms are the standard and are less than reliable. Further, clinical diagnoses are often made out of caution and not certainty. While this may protect the individual, having less than certain diagnoses can influence research findings by injecting measurement error. It is therefore not too surprising that there is so little consensus in concussion research. Almost every issue has support on both sides. There is also a socio-economic consequence of over-diagnosis, particularly for athletes. Individuals with “too many” concussions have been denied college scholarships and potential draft positions. Yet, there is no consensus on what “too many” means. Characterizing diagnoses such as definite, likely, possible, no-diagnosis is one approach; however, some criteria need to be created for such a scheme to have validity and usefulness.

Until such work is undertaken, it remains important to provide the best possible care in spite of diagnostic accuracy. There are several key pieces to concussion management that are important for a swift and positive recovery

1. Appropriate removal from play if a concussion is suspected
2. Timely and accurate diagnosis based on signs and/or symptoms and mental status.
3. Communicating with appropriate parties (parent, PCP, school)
4. Standardized assessment protocol
5. An initial rest period followed by supervised and structured increases inactivity
6. Regular monitoring and adjustments based on response to “treatment” including a step-wise physical exertion challenge
7. Assessing recovery; includes a return to full academic functioning before returning to sport. 

Besides the difficulty in diagnostic accuracy, documentation of these stages of the course and management of concussion has proven to be difficult due to the decentralized nature of care. Athletes are hurt at one venue and may or may not be seen by medical staff at the venue or even the next day. They may return to school where athletic training (physiotherapy) services may or may not be provided. A primary care physician may be the first trained medical personnel to see them 5 or 6 days from injury. While self-management is not recommended, even when all of the steps are properly taken by professionals, communication is difficult amongst them. However, closing the communication loop is critical to ensure that steps are not missed and not duplicated.

One useful strategy with clinically defined disorders is to standardize protocols for assessment and treatment as much as possible. In this way, comparisons between centers and labs become more feasible, and clinical questions can become more focused. However, situations requiring urgent care and subsequent follow-up can be chaotic and pressured. Using technology to create decision support tools would be important for achieving these goals.

Prior to appropriate clinical considerations below, consider the following minimum criteria:

• 20 days after last positive test
• No current symptoms such as runny nose, sneezing, coughing, etc. (other than associated with longstanding allergies)
• 72 hours fever free without help from fever-reducing medications (actual guideline is 24-hours but err on the safe side)

Beyond the point of verifying that the person is no longer infectious, consider the following. 

• For example, is the person still subjectively improving (in which case a shorter screen now followed by more detailed assessment later may be appropriate) or have they hit a plateau? 
• Do they have residual conditions that are disruptive to the point it would interfere with reliable assessment? 
• Are there practical considerations that need to be addressed currently, such as return to work or decisional capacity? 
• In return to play situations, how important is RTP for this person?
• Are there significant behavioral health factors that need to be disentangled in order to determine the most appropriate course of treatment? 

Recommendations for Sports Concussion Baseline and Post-injury Testing

posted Summer 2020

During COVID-19 Pandemic*

*assuming resumption of contact sports

1. As close in time as possible to the assessment, all athletes should be tested for the presence of COVID-19 (not the antibody test).  While this does not prevent someone from getting the virus, it will help to assure that there is no active virus at the start.

a) screening of viral symptoms should also take place prior to testing.

• General guidelines should follow the State recommendations.  Inter-Organizational Practice Committee for testing suggests the following for face to face ( one-to-one) testing:

• Update policies and procedures for COVID era (e.g., hand-washing etc)
• Make arrangements for appropriate level of PPE/ensure clean rooms and equipment
• Create appropriate signage for hallways and treatment rooms
• Pre-appointment screening for COVID-19, and repeat on day of contact

Activities Prior to Student Arrival

• Stagger check-in times, not re-using rooms until the next day, separate waiting rooms for parents or ask to wait in car.
• Have clear space markers in any waiting area

Initial Entry and Forms

• Consider shortened forms to be sent electronically to minimize exposure time

• The priority for baseline testing should be for the most sensitive tool: the SCAT3/5. Computerized neuropsychological testing is not sensitive to injury, so its relative value is lessened. However, SCAT requires individual administration. To lower the burden, we recommend only testing those without a previous baseline.  Individual testing should be done with a plexiglass screen between test administrator and student, and masks should be worn. Waiting areas should be outside or in a well-ventilated area with appropriate physical distancing.

• Group testing: For those schools that have the space and resources to maintain normal computerized neuropsychological test (CNT) baseline procedures while still following restrictions and infection control guidelines, the only changes are related to infection control guidelines.

• For those schools where #4 is not feasible, complete computerized baselines on those who have not had a valid baseline in the past, either in a small group (10 or less) with infection control guidelines, or with individual administration as in #2.  In effect, suspend the two-year repeat testing.  If a student had a CNT in the 8^th grade, they do not need to take it as a freshman if we can have access to the 8^th grade test (will need their passport ID # if using ImPACT).

• For CNT baseline testing in schools where neither of options 4 or 5 is feasible, we recommend no CNT baselines in 2020 and continued post-injury testing.  If staff are not comfortable with individualized administration, it should be discontinued for this year.

• Any post injury testing should follow the guideline above for individual testing (#2), except for extremity testing.  Gloves should be worn in addition to masks to check strength, motor nerves and neck.

Note: baseline testing at home is not appropriate and will not be accepted. Allowing baseline testing at home is a violation of testing ethics and clinical best practice.

Study Abstract and Opinion

ABSTRACT

Associations of Apolipoprotein E ε4 Genotype and Ball Heading With Verbal Memory in Amateur Soccer Players

JAMA Neurol. 2020;77(4):419-426. doi:10.1001/jamaneurol.2019.4828 Published online January 27, 2020.

Liane E. Hunter, PhD; Yun Freudenberg-Hua, MD; Peter Davies, PhD; Mimi Kim, PhD; Richard B. Lipton, MD; Walter F. Stewart, PhD, MPH; Priyanka Srinivasan, BS; ShanShan Hu, MS; Michael L. Lipton, MD, PhD  

IMPORTANCE Emerging evidence suggests that long-term exposure to ball heading in soccer, the most popular sport in the world, confers risk for adverse cognitive outcomes. However, the extent to which the apolipoprotein E ε4 (APOE ε4) allele, a common risk factor for neurodegeneration, and ball heading are associated with cognition in soccer players remains unknown.

OBJECTIVE To determine whether the APOE ε4 allele and 12-month ball heading exposure are associated with verbal memory in a cohort of adult amateur soccer players.

DESIGN, SETTINGS, AND PARTICIPANTS A total of 379 amateur soccer players were enrolled in the longitudinal Einstein Soccer Study from November 11, 2013, through January 23, 2018. Selection criteria included participation in soccer for more than 5 years and for more than 6 months per year. Of the 379 individuals enrolled in the study, 355 were genotyped. Three players were excluded for reporting extreme levels of heading. Generalized estimating equation linear regression models were employed to combine data across visits for a cross-sectional analysis of the data.

EXPOSURES At each study visit every 3 to 6 months, players completed the HeadCount 12-Month Questionnaire, a validated, computer-based questionnaire to estimate 12-month heading exposure that was categorized as low (quartiles 1 and 2), moderate (quartile 3), and high (quartile 4).

MAIN OUTCOME AND MEASURES Verbal memory was assessed at each study visit using the International Shopping List Delayed Recall task from CogState.

RESULTS A total of 352 soccer players (256 men and 96 women; median age, 23 years [interquartile range, 21-28 years]) across a total of 1204 visits were analyzed. High levels of heading were associated with worse verbal memory performance (β = −0.59; 95%CI, −0.93 to −0.25; P = .001). There was no main association of APOE ε4 with verbal memory (β = 0.09; 95%CI, −0.24 to 0.42; P = .58). However, there was a significant association of APOE ε4 and heading with performance on the ISRL task (χ2 = 7.22; P = .03 for overall interaction). In APOE ε4–positive players, poorer verbal memory associated with high vs low heading exposure was 4.1-fold greater (APOE ε4 negative, β = −0.36; 95%CI, −0.75 to 0.03; APOE ε4 positive, β = −1.49; 95%CI, −2.05 to −0.93), and poorer verbal memory associated with high vs moderate heading exposure was 8.5-fold greater (APOE ε4 negative, β = −0.13; 95%CI, −0.54 to 0.29; APOE ε4 positive, β = −1.11, 95%CI, −1.70 to −0.53) compared with that in APOE ε4–negative players.

CONCLUSIONS AND RELEVANCE This study suggests that the APOE ε4 allele is a risk factor for worse memory performance associated with higher heading exposure in the prior year, which highlights that assessing genetic risks may ultimately play a role in promoting safer soccer play.

Opinion

For 20-years studies have pointed to a relationship between soccer heading in adults and negative neurocognitive effects (Levitch et al., 2018; Lipton et al., 2013; E. J. T. Matser, 1999; J. T. Matser et al., 1998; Stewart et al., 2018; Witol & Webbe, 2003). In a recently published paper, a group from Albert Einstein Medical School point to a risk of gene Apolipoprotein E ε4+ (APOE4+) for negative cognitive effects due to heading in the absence of frank concussion (Hunter et al., 2020). The presence of APOE4+ was shown to predispose adult soccer players to lower memory scores on a neuropsychological (International Grocery List Test) test based on the amount of self-reported heading they engaged in over the year.    

APOE4+ has long been known as a risk for early onset Alzheimer’s disease and so it has been a candidate for neurodegeneration in concussion studies.  Several studies have documented a relationship between APOE4 and experiencing a concussion  (Terrell et al., 2008), various MRI modalities and history of concussion (Tremblay et al., 2014; Tremblay et al., 2017) , and post-concussion symptoms (Merritt et al., 2018; Merritt & Arnett, 2016).

The significance of this study is identifying the relationships between subconcussive impacts, memory performance and APOE4.  It has long been suspected that individual differences determined much of the vulnerability to HIE including sub-concussive exposures.  Identifying this “due-to” is important for understanding why some show effects of HIE and others do not.

The Hunter study has its share of weaknesses as these studies are exceedingly difficult to do; but taken in the broader context, the effects of soccer heading has long been a source of concern in terms of brain health.  The role of APOE in concussion risks is becoming quite clear, both through the accumulation of direct studies and its association with neurodegeneration. Clearly, efforts to limit exposure and improve soccer heading technique in youth seem worthwhile. At the same time, it is becoming important to establish risk functions for levels of exposure in the presence of APOE4+.  Genotyping to inform participant decision-making and population safety is becoming a realistic goal.

References

Hunter, L. E., Freudenberg-Hua, Y., Davies, P., Kim, M., Lipton, R. B., Stewart, W. F., Srinivasan, P., Hu, S., & Lipton, M. L. (2020). Associations of Apolipoprotein E ε4 Genotype and Ball Heading With Verbal Memory in Amateur Soccer Players. JAMA Neurology, 77(4), 419. https://doi.org/10.1001/jamaneurol.2019.4828

Levitch, C. F., Zimmerman, M. E., Lubin, N., Kim, N., Lipton, R. B., Stewart, W. F., Kim, M., & Lipton, M. L. (2018). Recent and Long-Term Soccer Heading Exposure Is Differentially Associated With Neuropsychological Function in Amateur Players. Journal of the International Neuropsychological Society, 24(2), 147–155. https://doi.org/10.1017/S1355617717000790

Lipton, M. L., Kim, N., Zimmerman, M. E., Kim, M., Stewart, W. F., Branch, C. A., & Lipton, R. B. (2013). Soccer Heading Is Associated with White Matter Microstructural and Cognitive Abnormalities. Radiology, 268(3), 850–857. https://doi.org/10.1148/radiol.13130545

Matser, E. J. T. (1999). Neuropsychological Impairment in Amateur Soccer Players. JAMA, 282(10), 971. https://doi.org/10.1001/jama.282.10.971

Matser, J. T., Kessels, A. G. H., Jordan, B. D., Lezak, M. D., & Troost, J. (1998). Chronic traumatic brain injury in professional soccer players. Neurology, 51(3), 791–796. https://doi.org/10.1212/WNL.51.3.791

Merritt, V. C., & Arnett, P. A. (2016). Apolipoprotein E (APOE) ϵ4 Allele Is Associated with Increased Symptom Reporting Following Sports Concussion. Journal of the International Neuropsychological Society, 22(1), 89–94. https://doi.org/10.1017/S1355617715001022

Merritt, V. C., Rabinowitz, A. R., & Arnett, P. A. (2018). The Influence of the Apolipoprotein E (APOE) Gene on Subacute Post-Concussion Neurocognitive Performance in College Athletes. Archives of Clinical Neuropsychology, 33(1), 36–46. https://doi.org/10.1093/arclin/acx051

Stewart, W. F., Kim, N., Ifrah, C., Sliwinski, M., Zimmerman, M. E., Kim, M., Lipton, R. B., & Lipton, M. L. (2018). Heading Frequency Is More Strongly Related to Cognitive Performance Than Unintentional Head Impacts in Amateur Soccer Players. Frontiers in Neurology, 9. https://doi.org/10.3389/fneur.2018.00240

Terrell, T. R., Bostick, R. M., Abramson, R., Xie, D., Barfield, W., Cantu, R., Stanek, M., & Ewing, T. (2008). APOE, APOE Promoter, and Tau Genotypes and Risk for Concussion in College Athletes: Clinical Journal of Sport Medicine, 18(1), 10–17. https://doi.org/10.1097/JSM.0b013e31815c1d4c

Tremblay, S., Henry, L. C., Bedetti, C., Larson-Dupuis, C., Gagnon, J.-F., Evans, A. C., Théoret, H., Lassonde, M., & Beaumont, L. D. (2014). Diffuse white matter tract abnormalities in clinically normal ageing retired athletes with a history of sports-related concussions. Brain, 137(11), 2997–3011. https://doi.org/10.1093/brain/awu236

Tremblay, S., Iturria-Medina, Y., Mateos-Pérez, J. M., Evans, A. C., & De Beaumont, L. (2017). Defining a multimodal signature of remote sports concussions. European Journal of Neuroscience, 46(4), 1956–1967. https://doi.org/10.1111/ejn.13583

Witol, A. D., & Webbe, F. M. (2003). Soccer heading frequency predicts neuropsychological deficitsଝ. Archives of Clinical Neuropsychology, 21.

Finding a Biomarker of Concussion

Finding a biomarker has been the holy grail of concussion research. Without an accurate biomarker we are left with using subjective symptoms and relatively weak objective tests of the functional response to concussion as our means for diagnosing and determining recovery.

Recently McCrea et al found that a combination of biomarkers in acutely concussed college athletes was significantly different from their baseline levels and different from non-concussed controls. When the reductions in GFAP, UCH-L1, and tau were combined in the analysis, they appeared to provide a sensitive indicator of injury. Finding a combination of biomarkers has been long-suspected as the most likely approach to finding a sensitive biological indicator of concussion.

Association of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortium

Abstract

IMPORTANCE There is potential scientific and clinical value in validation of objective biomarkers for sport-related concussion (SRC).

OBJECTIVE To investigate the association of acute-phase blood biomarker levels with SRC in collegiate athletes.  

DESIGN, SETTING, AND PARTICIPANTS This multicenter, prospective, case-control study was conducted by the National Collegiate Athletic Association (NCAA) and the US Department of Defense Concussion Assessment, Research, and Education (CARE) Consortium from February 20, 2015, to May 31, 2018, at 6 CARE Advanced Research Core sites. A total of 504 collegiate athletes with concussion, contact sport control athletes, and non–contact sport control athletes completed clinical testing and blood collection at preseason baseline, the acute postinjury period, 24 to 48 hours after injury, the point of reporting being asymptomatic, and 7 days after return to play. Data analysis was conducted from March 1 to November 30, 2019.  

MAIN OUTCOMES AND MEASURES Glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light chain, and tau were quantified using the Quanterix Simoa multiplex assay. Clinical outcome measures included the Sport Concussion Assessment Tool–Third Edition (SCAT-3) symptom evaluation, Standardized Assessment of Concussion, Balance Error Scoring System, and Brief Symptom Inventory 18.  RESULTS A total of 264 athletes with concussion (mean [SD] age, 19.08 [1.24] years; 211 [79.9%] male), 138 contact sport controls (mean [SD] age, 19.03 [1.27] years; 107 [77.5%] male), and 102 non–contact sport controls (mean [SD] age, 19.39 [1.25] years; 82 [80.4%] male) were included in the study. Athletes with concussion had significant elevation in GFAP (mean difference, 0.430 pg/mL; 95%CI, 0.339-0.521 pg/mL; P < .001), UCH-L1 (mean difference, 0.449 pg/mL; 95%CI, 0.167-0.732 pg/mL; P < .001), and tau levels (mean difference, 0.221 pg/mL; 95%CI, 0.046-0.396 pg/mL; P = .004) at the acute postinjury time point compared with preseason baseline. Longitudinally, a significant interaction (group Å~ visit) was found for GFAP (F7,1507.36 = 16.18, P < .001), UCH-L1 (F7,1153.09 = 5.71, P < .001), and tau (F7,1480.55 = 6.81, P < .001); the interaction for neurofilament light chain was not significant (F7,1506.90 = 1.33, P = .23). The area under the curve for the combination of GFAP and UCH-L1 in differentiating athletes with concussion from contact sport controls at the acute postinjury period was 0.71 (95%CI, 0.64-0.78; P < .001); the acute postinjury area under the curve for all 4 biomarkers combined was 0.72 (95%CI, 0.65-0.79; P < .001). Beyond SCAT-3 symptom score, GFAP at the acute postinjury time point was associated with the classification of athletes with concussion from contact controls (β = 12.298; 95%CI, 2.776-54.481; P = .001) and non–contact sport controls (β = 5.438; 95%CI, 1.676-17.645; P = .005). Athletes with concussion with loss of consciousness or posttraumatic amnesia had significantly higher levels of GFAP than athletes with concussion with neither loss of consciousness nor posttraumatic amnesia at the acute postinjury time point (mean difference, 0.583 pg/mL; 95%CI, 0.369-0.797 pg/mL; P < .001).

CONCLUSIONS AND RELEVANCE The results suggest that blood biomarkers can be used as research tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in SRC.

Citation: McCrea, M., Broglio, S. P., McAllister, T. W., Gill, J., Giza, C. C., Huber, D. L., Harezlak, J., Cameron, K. L., Houston, M. N., McGinty, G., Jackson, J. C., Guskiewicz, K., Mihalik, J., Brooks, M. A., Duma, S., Rowson, S., Nelson, L. D., Pasquina, P., Meier, T. B., … DiFiori, J. (2020). Association of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortium. JAMA Network Open, 3(1), e1919771. https://doi.org/10.1001/jamanetworkopen.2019.19771

Notes: GFAP: Glial fibrillary acidic protein GFAP is thought to help to maintain astrocyte mechanical strength^[14] as well as the shape of cells. Astrocytes provide physical and metabolic support for neurons, detoxification, guidance during migration, regulation of energy metabolism, electrical insulation (for unmyelinated axons), transport of blood-borne material to the neuron, and reaction to injury.

UCH-L1: Ubiquitin C-terminal hydrolase-L1: UCH-L1 is an enzyme that is abundantly present in all neurons. Reductions have been noted in neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Reductions may signal neuron degeneration.

Tau: Tau is a family of proteins that have roles in maintaining the stability of microtubules in axons and are abundant in the neurons of the central nervous system. Excessive tau has been associated with CTE.

We note a high percentage of athletes who come to a post-injury assessment after 7 or less hours of sleep.  Limited sleep can interfere in assessment results whether injured or not.  Sleep may be one of the most important treatments to aid in recovery of concussion; however, there are several issues to consider.  Sleep in recovery is a big deal, but little is known.

Is poor sleep as cause or effect of response to injury?

There is very little evidence to answer this question; however, sleep is a universal medicine and so the answer may be irrelevant. 

In a small sample of youth (11 concussed, 9 controls, mean age 12, median of 5 days post-injury) matched for age, sex and race, we examined one night of sleep of these recently concussed participants (in their homes) using actigraphy, rating scales and three salivary samples analyzed for melatonin and cortisol via enzyme-linked immunoassays.*

The salivary melatonin and cortisol showed upon waking (marginally significant). Sleep metrics of the injured group indicated poorer sleep quantity and quality, with sleep latency six times longer in the injured group than the controls. Further, the injured youth endorsed high levels of injury-related stress. This perceived stress also significantly correlated with fatigue ratings and length of sleep onset (latency). While the small sample sizes impacted results, partial support for a relationship between perceived stress, fatigue, and both biological and behavioral measures of sleep following concussion was indicated.

This study raises the question of the role of anxiety in sleep and recovery.  It is well known that anxiety interferes in recovery.  It is also known that anxiety affects sleep.  The stress of injury, both physically and psychologically likely impacts sleep onset.  Whether autonomic responses to injury interfere in other aspects of sleep is not yet known, but encouraging sleep seems to be important.

Sleep schedules and disrupting natural routines

We recommend napping during early stages of recovery. Admittedly, there is little data on this.  Some say that napping will interfere in normal sleep patterns. That is something to consider, but as with all chronic sleep debt in children, making it up is seen as useful.  Chronic sleep debt is a very large problem in schools where adolescents start the day too early to accommodate normal circadian sleep rhythms.  We recommend later start times when feasible (transportation, work schedules, etc).

Social activities and sleep

One of the unforeseen consequences of concussion and being in a concussion protocol is the effect on social relationships.  Bullying has been identified as a problem for both male and female athletes when concussed, so maintaining relationships is important.  Further, not being able to maintain usual activity levels is a known contributor to depression in youth.  Thus, finding ways to maintain some team activity without interfering in recovery is an important goal.  Sleep is one of those things that should not be disrupted any more than necessary.

Some practice caveats:  Attending practices is risky (and the goal of management is to reduce risk of re-injury).  Attending early morning practices is not helpful from a sleep perspective. Anecdotally, it seems athletes who stand on the sidelines are magnets for balls, pucks, sticks.  Also, the noise and lighting may increase symptoms.  Attendance at practices can be  good thing, but needs to be monitored.

Social media is another sleep-interfering activity.   Again, limiting social contact should be done on the basis of its effects on the student.  Much social activity – even face to face – involves keeping one eye on a phone or screen.  If screen viewing is generally symptom-exacerbating, then this should be limited.  But keeping the phone by the bed and interacting past 10 or 11 PM will interfere in sleep (10-11 is the normal time Circadian rhythms produce melatonin for sleep in adolescents).

Summary

Current knowledge supports the idea that recovering from a concussion is supported by sleep.  If the student feels tired, fatigued, or sleepy, they should sleep.  This is particularly true in the first 1-2 weeks of recovery.  Assessing sleep hygiene should be a part of the concussion assessment protocol. However, if napping begins to make night-time sleep problematic, reducing naps makes sense. While symptomatic, starting school later (rather than skipping school altogether) is a more appropriate procedure as it supports an active rehabilitation approach.  If sleep continues to be problematic, and hygiene appears appropriate, referral to a sleep specialist is recommended.  Facilitating sleep medically may improve the body’s ability to restore equilibrium and recovery.

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* Study funded by Nebraska Research Initiative.

FEBRUARY 10, 2018 

Limiting Head Impacts Among Youth Is Smart, Overstating Scientific Consensus Is Not

Jason Chung (+cosignees)

On January 18, 2018, an article by Dr. Lee Goldstein of Boston University and colleagues in Brain, a leading neurological journal, was released and touted as proving the link between subconcussive hits to the head and chronic traumatic encephalopathy (CTE).  That same day the CTE advocacy group – the Concussion Legacy Foundation – announced a national campaign called F14G Football to convert all under-14 football into flag football, thereby eliminating tackle football.

The message sent to assembled media and onlookers was that eliminating tackle football for youth is the key to securing the brains and futures of America’s youth.

The truth is not so simple.

The scientific evidence linking casual sports play to brain injury, brain injury to CTE, and CTE to dementia is not strong. We believe that further scientific research and data are necessary for accurate risk-benefit analysis among policymakers for two reasons.

First, evidence-based science calls for research to be conducted under generally accepted principles. The case series presented by the Boston University group, primarily due to its ascertainment bias, is weaker than the evidentiary standard sufficient to demonstrate an association or causation and conflicts with pathologic findings in other studies. CTE pathology in the brain has been shown by British pathologists to be present in approximately 12% of normal healthy aged people who died at an average age of 81 years (Ling et al Acta Neuropathologica). The presence of CTE pathology in the brain on autopsy has not been shown to correlate with neurologic symptoms prior to death. To be clear, CTE pathology could be present in a normal person.

Indeed, even Dr. Goldstein’s article was more measured than his press. His article speaks in terms of likelihoods and qualifiers in noting that, “… the causal mechanisms, temporal relationships, and contextual circumstances that link specific brain pathology to a particular antemortem insult are impossible to ascertain with certainty based solely on post-mortem neuropathology.”

There is a disconnect between the categorical rhetoric in media and press releases describing “concussion” research with the muddled and contentious scientific reality. Medical professionals are still debating the long-term effects of head impacts.  As noted by Dr. Goldstein’s own research, the pathology and link between head impacts and long-term neurological conditions such as CTE is still unclear with questions of causation yet to be settled.  This is not to say that head impacts or injuries are desirable – far from it. But there is scientific ambiguity about the prevalence of CTE in the general population in comparison to professional athletes and also about the significance of its presence.  In fact, after reviewing all available evidence, the consensus statement from the International conference on concussion in sports states:

“A cause-and-effect relationship has not yet been demonstrated between (CTE) and sport-related concussions or exposure to contact sports. As such, the notion that repeated concussion or subconcussive impacts cause CTE remains unknown.”

Nothing in Dr. Goldstein’s recent study changes this ambiguity, which brings us to our second point. Before enacting sweeping legislation or policy spurred by fears of CTE, policymakers must also conduct a risk-benefit analysis based on a holistic survey of public health concerns.

American youth are currently more sedentary than ever before.  Compelling evidence from multiple sources shows that organized sports offers youth a way off the couch and promotes the adoption of an active lifestyle thereby mitigating the risks of, among other conditions, obesity, high blood pressure, diabetes, depression, osteoporosis, cardiovascular disease, stroke, drug use, teen pregnancy, and, ironically, dementia. The uncomfortable truth is that tackle football is the number one participation sport among high schoolers in America, it is accessible to children with diverse physiology in ways that other sports are not, and greater public consultation should take place to see if participation rates would remain as high for alternatives to tackle football. Three recently published major studies found no increased risk for later-in-life brain diseases in men who played high school football (citation here). One might also speculate that children who engage in football would seek other less organized risk-taking behaviors if football were not an option.

Setting legislation and public policy is already a tricky process and overstating the degree to which scientific consensus exists may lead to pyrrhic victories.  What we seek to establish are meaningful and durable standards based on validated and replicated diagnostic criteria so that the public health response to head impacts and CTE are not emotive or political, but data-driven.  The political winds being as fickle as they are, laws and policies enacted without such scientific support will be vulnerable to backlash from those with deep economic and cultural ties to contact sports such as tackle football, rejection by the scientific community, and general confusion and misunderstanding by the public.

In the drive to protect young brains, there are not just two sides.  Not everyone is a moral crusader or an NFL stooge. No reasonable person, least of all the professionals signing this letter, want to see youth injured. But when arguing for intervention based on public health or scientific principles, the data must inform the recommendation.

Additional data is required to make a truly informed decision regarding banning of sports.  To do so, what is desperately needed is (1) funding from federal and private sources to launch longitudinal, multi-center statistically sound studies, (2) consistent coordinated measures and standards, and (3) facilitation from either government or a consortia of concussion research centers.

Only then will we know whether the perceived neurological risks of tackle football outweigh the benefits. And only then can we more confidently say that we are acting in the public interest.

Jason Chung, Esq. is the senior researcher and attorney at NYU Sports and Society, an interdisciplinary think tank dedicated to the study of social issues through sports.

Peter Cummings, M.Sc., M.D is Forensic Pathologist & Neuropathologist, Assistant Professor Anatomy & Neurobiology, Boston University School of Medicine

Uzma Samadani MD PhD is an Associate Professor in Neurosurgery at the University of Minnesota and Rockswold Kaplan Endowed Chair for Traumatic Brain Injury at Hennepin County Medical Center

Lili-Naz Hazrati, MD, PhD, FRCPC is an Associate professor of Neuropathology, University of Toronto

Clinician-Scientist Hospital for Sick Children- Toronto, Ontario, Canada

John Leddy MD FACSM FACP is a Professor of Clinical Orthopaedics and Rehabilitation Sciences at the SUNY Buffalo Jacobs School of Medicine and Biomedical Sciences

Barry Willer PhD, is a Professor in the Department of Psychiatry at the SUNY Buffalo Jacobs School of Medicine and Biomedical Sciences.

Rocco Armonda, MD is the President of ThinkFirst, a brain injury prevention foundation.  He is Director, Neuroendovascular Surgery & Neurotrauma, Co-Director Neurocritical Care, Professor of Neurosurgery, Georgetown University Hospital & Washington Hospital Center

Jason H. Huang, MD, FACS is Chair of Department of Neurosurgery at Baylor Scott & White Medical Center in Temple, Texas and Professor of Surgery at Texas A&M University College of Medicine.

Kenneth Blumenfeld, MD is Adjunct Clinical Faculty Department of Neurosurgery, UCSF, Immediate Past President California Association of Neurologic Surgeons, AANS Delegate to the AMA

Richard B. Rodgers, MD, FAANS, FACS is Assistant Professor of Clinical Neurosurgery and Director of Neurotrauma at Indiana University School of Medicine

James MacDonald, M.D., M.P.H., is Clinical Associate Professor of Pediatrics and Family Medicine, Ohio State University College of Medicine, Division of Sports Medicine, Nationwide Children’s Hospital

Michael W. Kirkwood, PhD, ABPP/CN, is the Founder and Co-Director of the Children’s Hospital Colorado Concussion Program and Associate Clinical Professor of Physical Medicine & Rehabilitation, University of Colorado School of Medicine

David R. Howell, PhD, ATC, is the Lead Researcher for the Sports Medicine Center at Children’s Hospital Colorado and Assistant Professor of Orthopedics, University of Colorado School of Medicine

Gary S. Solomon, Ph.D., is Professor of Neurological Surgery, Associate Professor of Orthopedic Surgery & Rehabilitation and Psychiatry & Behavioral Sciences, Co-Director, Vanderbilt Sports Concussion Center, Vanderbilt University School of Medicine

Mark E. Halstead, MD is Associate Professor of Pediatrics and Orthopedics at Washington University in St Louis and Director of the Sports Concussion Clinic at St Louis Children’s Hospital

Francis X. Shen, JD, PhD is Associate Professor of Law, University of Minnesota, and Senior Fellow in Law and Neuroscience, Harvard MGH Center for Law Brain & Behavior and Harvard Law School Petrie-Flom Center

Mark Herceg, Ph.D.  Director, Center for Brain Health, Center for Concussion, Gaylord Specialty Health Care, Wallingford, CT

William B. Barr, Ph.D., ABPP, is the Director of the Neuropsychology Division, Department of Neurology, NYU-Langone Health, New York, NY.

Arthur Maerlender, PhD, ABPP-CN, is Associate Research Professor and Director of Clinical Research, Center for Brain, Biology and Behavior, University of Nebraska –  Lincoln, and Research Director for The B1G10-Ivy League TBI Research Collaboration.

Mapping brain recovery after concussion: From acute injury to 1 year after medical clearance

Nathan W. Churchill, PhD, Michael G. Hutchison, PhD, Simon J. Graham, PhD, and Tom A. Schweizer, PhD

Neurology® 2019;93:e1980-e1992. doi:10.1212/WNL.0000000000008523

This study confirms long-term changes in brain function 1-year post “clearance” from concussion.  Using multi-method imaging, and comparing to a control group, changes in some brain connectivity were found in the concussed sample.  Changes were noted in global connectivity and cerebral blood flow.

The principal finding of this study was that different aspects of brain physiology have different patterns of long-term recovery, with only a subset of MRI parameters showing non-significant concussion effects at 1 year after RTP. For brain function and white matter diffusion anisotropy (a measure of axonal integrity), no significant concussion effects were seen at 1 year after RTP, whereas for CBF and white matter diffusivity (a different measure of axonal integrity), persistent effects were seen at this time. Secondary analyses showed that the effects of concussion on the brain also vary as a function of clinical measures, including acute symptom severity and time to RTP, for all examined MRI parameters.

It is important to note that no subjects were complaining of any problems and had returned to full sports participation.  This highlights one of the ongoing questions: what does this mean?  Also note that the concussed findings are averaged across all 24 participants. About half had 2 previous concussions and half had only 1concussion. The findings are more specific than previous studies and add important information.

Abstract from Article

Objective. To test the hypothesis that concussion-related brain alterations seen at symptomatic injury and medical clearance to return to play (RTP) will have dissipated by 1 year after RTP.

Methods. For this observational study, 24 athletes with concussion were scanned longitudinally within 1 week after injury, at RTP, and 1 year after RTP. A large control cohort of 122 athletes were also scanned before the season. Each imaging session assessed global functional connectivity (Gconn) and cerebral blood flow (CBF), along with white matter fractional anisotropy (FA) and mean diffusivity (MD). The main effects of concussion on MRI parameters were evaluated at each postinjury time point. In addition, covariation was assessed between MRI parameters and clinical measures of acute symptom severity and time to RTP.

Results. Different aspects of brain physiology showed different patterns of recovery over time. Both Gconn and FA displayed no significant effects at 1 year after RTP, whereas CBF and MD exhibited persistent long-term effects. The effects of concussion on MRI parameters were also dependent on acute symptom severity and time to RTP for all postinjury time points.

Conclusion. This study provides the first longitudinal evaluation of concussion focused on time of RTP and 1 year after medical clearance, using multiple different MRI measures to assess brain structure and function. These findings significantly enhance our understanding of the natural course of brain recovery after a concussion.

Correspondence: Dr. Schweizer at SchweizerT@smh.ca