Publications by authors named "Robert C Cantu"

132 Publications

Return to Play Guidelines After Cervical Spine Injuries in American Football Athletes: A Literature-Based Review.

Spine (Phila Pa 1976) 2021 Jul;46(13):886-892

Department of Orthopaedic Surgery and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL.

Study Design: Literature-based review.

Objective: We sought to evaluate clinical and case studies related to return to play (RTP) after cervical spine injuries in elite American football athletes and to formulate guidelines to help health care practitioners manage these conditions.

Summary Of Background Data: American football athletes are at unique risk of cervical spine injury and appropriate case-by-case management of cervical spine injuries is necessary for these athletes. Despite this need, no standardized guidelines exist for RTP after cervical spine injury.

Methods: Observational or case-based articles relating to RTP after cervical spine injury in American football athletes were curated from PubMed/EMBASE databases. Primary literature published before December 1, 2019 involving National Football League (NFL) or National Collegiate Athletic Association (NCAA) athletes met inclusion criteria.

Results: The data acquisition process yielded 28 studies addressing cervical spine injuries and RTP in American football athletes. Stingers/burners were the most common injury and placed athletes at higher risk of a more severe re-injury. Transient quadriplegia, cervical stenosis, cervical disc herniation (CDH), and cervical fractures have a more significant impact on the long-term health and career longevity of the American football athlete. As such, the literature offers some guidance for management of these athletes, including average time for RTP in patients treated nonoperatively, thresholds involving cervical stenosis, and postoperative recommendations after spinal decompression and/or fusion surgery.

Conclusion: Elite American football athletes are at high risk for cervical spine injury due to the nature of their sport. The decision to allow these athletes to return to play should involve an understanding of the average RTP time, the potential risks of recurrence or re-injury, and individual characteristics such as position played and pathology on imaging.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003931DOI Listing
July 2021

Athlete Enjoyment of Prior Education Moderates change in Concussion-Reporting Intention after Interactive Education.

Inquiry 2021 Jan-Dec;58:469580211022641

Stanford School of Medicine, Palo Alto, CA, USA.

Undiagnosed concussions increase risk of additional injuries and can prolong recovery. Because of the difficulties recognizing concussive symptoms, concussion education must specifically target improving athlete concussion reporting. Many concussion education programs are designed without significant input from athletes, resulting in a less enjoyable athlete experience, with potential implications on program efficacy. Athlete enjoyment of previous concussion education programs moderates the improvement in concussion-reporting intention after experiencing the research version of CrashCourse (CC) concussion education. Prospective cohort study. Level of evidence: Level IV. Quantitative assessment utilizing ANOVA with moderation analysis of 173 male high school football players, aged 13 to 17, who completed baseline assessments of concussion knowledge, concussion reporting, and attitudes about prior educational interventions. Athletes were subsequently shown CC, before a follow-up assessment was administered assessing the same domains. At baseline, only 58.5% of athletes reported that they enjoyed their previous concussion education. After CC, athletes were significantly more likely to endorse that they would report a suspected concussion (from 69.3% of athletes to 85.6%;  < .01). Enjoyment of previous concussion education moderated concussion-reporting intention after CC ( = .02), with CC having a greater effect on concussion-reporting intention in athletes with low enjoyment of previous concussion education ( = 0.21,  = .02), than on individuals with high enjoyment of previous concussion education ( = .99). Enjoyment of CC did not have a moderating effect on concussion-reporting intention. Athletes who previously did not enjoy concussion education exhibited greater gains in concussion-reporting intention than athletes who enjoyed previous education. Given the potential risks associated with undiagnosed concussions, concussion education has sought to improve concussion reporting. Because most athletes participate in concussion education programs due to league or state mandates, improving concussion-reporting intention in these low-enjoyment athletes is of particular relevance to improving concussion-reporting intention broadly.
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http://dx.doi.org/10.1177/00469580211022641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170270PMC
May 2021

Validity of the 2014 traumatic encephalopathy syndrome criteria for CTE pathology.

Alzheimers Dement 2021 Apr 7. Epub 2021 Apr 7.

Boston University Alzheimer's Disease and CTE Centers, Boston University School of Medicine, Boston, Massachusetts, USA.

Introduction: Validity of the 2014 traumatic encephalopathy syndrome (TES) criteria, proposed to diagnose chronic traumatic encephalopathy (CTE) in life, has not been assessed.

Methods: A total of 336 consecutive brain donors exposed to repetitive head impacts from contact sports, military service, and/or physical violence were included. Blinded to clinical information, neuropathologists applied National Institute on Neurological Disorders and Stroke/National Institute of Biomedical Imaging and Bioengineering CTE criteria. Blinded to neuropathological information, clinicians interviewed informants and reviewed medical records. An expert panel adjudicated TES diagnoses.

Results: A total of 309 donors were diagnosed with TES; 244 donors had CTE pathology. TES criteria demonstrated sensitivity and specificity of 0.97 and 0.21, respectively. Cognitive (odds ratio [OR] = 3.6; 95% confidence interval [CI]: 1.2-5.1), but not mood/behavior or motor symptoms, were significantly associated with CTE pathology. Having Alzheimer's disease (AD) pathology was significantly associated with reduced TES accuracy (OR = 0.27; 95% CI: 0.12-0.59).

Discussion: TES criteria provided good evidence to rule out, but limited evidence to rule in, CTE pathology. Requiring cognitive symptoms in revised criteria and using AD biomarkers may improve CTE pathology prediction.
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http://dx.doi.org/10.1002/alz.12338DOI Listing
April 2021

National Institute of Neurological Disorders and Stroke Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome.

Neurology 2021 05 15;96(18):848-863. Epub 2021 Mar 15.

From the Boston University CTE Center (D.I.K.), Department of Neurology, Boston University School of Medicine, Boston; Brain Injury Program (D.I.K.), Encompass Health Braintree Rehabilitation Hospital, Braintree, MA; University of Washington Memory & Brain Wellness Clinic (C.B.), Department of Neurology, University of Washington School of Medicine, Seattle; Department of Neurology (D.W.D., C.H.A.), Mayo Clinic, Scottsdale, AZ; Boston University CTE Center (J.M., M.L.A.), Boston University Alzheimer's Disease Center, Department of Neurology, Boston University School of Medicine; Boston University CTE Center (M.L.M.), Boston University School of Medicine, MA; Departments of Neurology (L.J.B.), Ophthalmology, and Population Health, New York University Grossman School of Medicine; Departments of Neurosciences and Psychiatry University of California San Diego (S.J.B.), La Jolla; Departments of Neurology and Psychiatry (W.B.B.), New York University Grossman School of Medicine; Center for Neuroscience and Regenerative Medicine (D.L.B.), Uniformed Services University of the Health Sciences, Department of Neurology, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Boston University CTE Center (R.C.C.), Boston University Alzheimer's Disease Center, Departments of Neurology and Neurosurgery, Boston University School of Medicine, MA; Departments of Rehabilitation Medicine and Neurology (K.D.-O.C.), Icahn School of Medicine, Mount Sinai, New York; Department of Neurology (Y.E.G.), Barrow Neurological Institute, Phoenix, AZ; Rancho Los Amigos National Rehabilitation Center (B.D.J.), Downey, CA; Department of Neurology (B.D.J.), Keck School of Medicine of USC. Los Angeles, CA; Departments of Psychiatry and Neurology (T.W.M.), Indiana University School of Medicine, Indianapolis; Veterans Affairs Northwest Mental Illness (E.R.P.), Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA; Department of Psychiatry and Behavioral Sciences (E.R.P.), University of Washington School of Medicine, Seattle; Mayo Clinic Alzheimer's Disease Research Center (R.C.P.), Mayo Clinic, Rochester, MN; Department of Psychiatry and Psychology (J.V.W.), Mayo Clinic, Scottsdale, AZ; Department of Physical Medicine and Rehabilitation (R.D.Z.), Spaulding Rehabilitation Hospital, Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston; Faculty of Psychology and Neuroscience (É.M.F.), Maastricht University, the Netherlands, Department of Psychiatry, University of Cambridge, United Kingdom; National Institute of Neurological Disorders and Stroke (D.J.B.), National Institutes of Health; National Institute of Neurological Disorders and Stroke (W.J.K.), Bethesda, MD; Boston University CTE Center (Y.T.), Boston University Alzheimer's Disease Center, Boston University School of Medicine, Department of Biostatistics, Boston University School of Public Health; Boston University CTE Center (A.C.M.), Boston University Alzheimer's Disease Center, Departments of Neurology and Pathology & Laboratory Medicine, Boston University School of Medicine; VA Boston Healthcare System (A.C.M.), US Department of Veteran Affairs, MA; Psychiatry Neuroimaging Laboratory (M.E.S.), Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, University of Nevada School of Integrated Health Sciences; Cleveland Clinic Lou Ruvo Center for Brain Health (J.L.C.), Las Vegas, NV; Banner Alzheimer's Institute (E.M.R.), Arizona State University; Department of Psychiatry (E.M.R.), University of Arizona, Phoenix, AZ; and Boston University CTE Center (R.A.S.), Boston University Alzheimer's Disease Center, Departments of Neurology, Neurosurgery, and Anatomy & Neurobiology, Boston University School of Medicine, MA.

Objective: To develop evidence-informed, expert consensus research diagnostic criteria for traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE).

Methods: A panel of 20 expert clinician-scientists in neurology, neuropsychology, psychiatry, neurosurgery, and physical medicine and rehabilitation, from 11 academic institutions, participated in a modified Delphi procedure to achieve consensus, initiated at the First National Institute of Neurological Disorders and Stroke Consensus Workshop to Define the Diagnostic Criteria for TES April, 2019. Before consensus, panelists reviewed evidence from all published cases of CTE with neuropathologic confirmation, and they examined the predictive validity data on clinical features in relation to CTE pathology from a large clinicopathologic study (n = 298).

Results: Consensus was achieved in 4 rounds of the Delphi procedure. Diagnosis of TES requires (1) substantial exposure to repetitive head impacts (RHIs) from contact sports, military service, or other causes; (2) core clinical features of cognitive impairment (in episodic memory and/or executive functioning) and/or neurobehavioral dysregulation; (3) a progressive course; and (4) that the clinical features are not fully accounted for by any other neurologic, psychiatric, or medical conditions. For those meeting criteria for TES, functional dependence is graded on 5 levels, ranging from independent to severe dementia. A provisional level of certainty for CTE pathology is determined based on specific RHI exposure thresholds, core clinical features, functional status, and additional supportive features, including delayed onset, motor signs, and psychiatric features.

Conclusions: New consensus diagnostic criteria for TES were developed with a primary goal of facilitating future CTE research. These criteria will be revised as updated clinical and pathologic information and in vivo biomarkers become available.
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http://dx.doi.org/10.1212/WNL.0000000000011850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166432PMC
May 2021

Sport-Related Structural Brain Injury and Return to Play: Systematic Review and Expert Insight.

Neurosurgery 2021 May;88(6):E495-E504

Department of Neurosurgery, Johns Hopkins University Medical Center, Baltimore, Maryland, USA.

Background: Sport-related structural brain injury (SRSBI) is intracranial pathology incurred during sport. Management mirrors that of non-sport-related brain injury. An empirical vacuum exists regarding return to play (RTP) following SRSBI.

Objective: To provide key insight for operative management and RTP following SRSBI using a (1) focused systematic review and (2) survey of expert opinions.

Methods: A systematic literature review of SRSBI from 2012 to present in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a cross-sectional survey of RTP in SRSBI by 31 international neurosurgeons was conducted.

Results: Of 27 included articles out of 241 systematically reviewed, 9 (33.0%) case reports provided RTP information for 12 athletes. To assess expert opinion, 31 of 32 neurosurgeons (96.9%) provided survey responses. For acute, asymptomatic SRSBI, 12 (38.7%) would not operate. Of the 19 (61.3%) who would operate, midline shift (63.2%) and hemorrhage size > 10 mm (52.6%) were the most common indications. Following SRSBI with resolved hemorrhage, with or without burr holes, the majority of experts (>75%) allowed RTP to high-contact/collision sports at 6 to 12 mo. Approximately 80% of experts did not endorse RTP to high-contact/collision sports for athletes with persistent hemorrhage. Following craniotomy for SRSBI, 40% to 50% of experts considered RTP at 6 to 12 mo. Linear regression revealed that experts allowed earlier RTP at higher levels of play (β = -0.58, 95% CI -0.111, -0.005, P = .033).

Conclusion: RTP decisions following structural brain injury in athletes are markedly heterogeneous. While individualized RTP decisions are critical, aggregated expert opinions from 31 international sports neurosurgeons provide key insight. Level of play was found to be an important consideration in RTP determinations.
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http://dx.doi.org/10.1093/neuros/nyab041DOI Listing
May 2021

Who Will Protect the Brains of College Football Players?

JAMA Neurol 2021 Mar;78(3):273-274

Concussion Legacy Foundation, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamaneurol.2020.4740DOI Listing
March 2021

Effects of Interval-Training Exercise on People Who Have Had Persistent Post-Concussive Symptoms for Less Than One Year: A Pilot Study.

J Neurotrauma 2021 Mar 18;38(5):573-581. Epub 2020 Nov 18.

Dr. Robert C. Cantu Concussion Center, Emerson Hospital, Concord, Massachusetts, USA.

This study is to examine the effects of a 12-session moderate intensity-interval-training program with blood flow restriction (BFR) and body cooling (BC) on people who have had persistent post-concussive symptoms (PPCS) for <1 year. A single-blind randomized controlled trial of interval-training exercise with BFR and BC was conducted. Twenty-five adults with PPCS were assigned to the experimental group ( = 14) or the control group ( = 11). Both groups rode a recumbent elliptical machine for 21 min at moderate intensity (65% predicted maximum heart rate) twice a week for 6 weeks, but only the experimental group received BFR and BC while riding. The variances of overall PPCS scale scores and their sub-domain scores for individuals during the 6-week intervention and 6-week follow-up period were calculated. During the intervention, the fluctuation of overall symptom severity, severity in the cognitive domain and severity in the mood domain were significantly less in the experimental group ( = 0.03;  = 0.02;  = 0.02). During the follow-up period, the number of symptoms remained more stable in the experimental group ( = 0.02), and a trend toward less fluctuation of symptom severity ( = 0.05) was also observed. The reduced number of symptoms in the cognitive and sleep domains remained more stable in the experimental group following the intervention ( = 0.007;  = 0.02). The severity of mood and sleep symptoms also remained more stable during the follow-up period in the experimental group ( = 0.04). More stable recovery was found in individuals who exercised using BFR and BC than in those who underwent exercise without BFR and BC. Moderate intensity-interval-training exercise with BFR and BC alleviated post-concussive symptoms in people who have had PPCS <1 year.
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http://dx.doi.org/10.1089/neu.2019.6915DOI Listing
March 2021

Memory in repeat sports-related concussive injury and single-impact traumatic brain injury.

Brain Inj 2020 10 29;34(12):1666-1673. Epub 2020 Sep 29.

Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine , Los Angeles, California, USA.

Repeat sports-related concussive/subconcussive injury (RC/SCI) is related to memory impairment. : We sought to determine memory differences between persons with RC/SCI, moderate-to-severe single-impact traumatic brain injury (SI-TBI), and healthy controls. MRI scans from a subsample of participants with SI-TBI were used to identify the neuroanatomical correlates of observed memory process differences between the brain injury groups. : Both brain injury groups evidenced worse learning and recall in contrast to controls, although SI-TBI group had poorer memory than the RC/SCI group. Regarding memory process differences, in contrast to controls, the SI-TBI group evidenced difficulties with encoding, consolidation, and retrieval, while the RC/SCI group showed deficits in consolidation and retrieval. Delayed recall was predicted by encoding, with consolidation as a secondary predictor in the SI-TBI group. In the RC/SCI group, delayed recall was only predicted by consolidation. MRI data showed that the consolidation index we used mapped onto hippocampal atrophy. : RC/SCI is primarily associated with consolidation deficits, which differs from SI-TBI. Given the role of the hippocampus in memory consolidation and the fact that hyperphosphorylated tau tends to accumulate in the medial temporal lobe in RC/SCI, consolidation deficits may be a cognitive marker of chronic traumatic encephalopathy in athletes.
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http://dx.doi.org/10.1080/02699052.2020.1825806DOI Listing
October 2020

Association of probable REM sleep behavior disorder with pathology and years of contact sports play in chronic traumatic encephalopathy.

Acta Neuropathol 2020 12 17;140(6):851-862. Epub 2020 Sep 17.

Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA.

Probable rapid eye movement (REM) sleep behavior disorder (pRBD) is a synucleinopathy-associated parasomnia in which loss of REM sleep muscle atonia results in motor behavior during REM sleep, including dream enactment. Traumatic brain injury is independently associated with increased risk of pRBD and Lewy body disease, and both pRBD and Lewy body disease are often observed in chronic traumatic encephalopathy (CTE). However, the frequency and pathological substrate of pRBD in CTE have not been formally studied and remain unknown. Of the total sample of 247 men, age at death of 63.1 ± 18.8 years (mean ± SD), 80 [32%] were determined by informant report to have symptoms of pRBD. These participants had played more years of contact sports (18.3 ± 11.4) than those without pRBD (15.1 ± 6.5; P = 0.02) and had an increased frequency of Lewy body disease (26/80 [33%] vs 28/167 [17%], P = 0.005). Of the 80 participants with pRBD, 54 [68%] did not have Lewy body disease; these participants were more likely to have neurofibrillary tangles and pretangles in the dorsal and median raphe (41 of 49 [84%] non-LBD participants with pRBD symptoms vs 90 of 136 [66%] non-LBD participants without pRBD symptoms, P = 0.02), brainstem nuclei with sleep regulatory function. Binary logistic regression modeling in the total study sample showed that pRBD in CTE was associated with dorsal and median raphe nuclei neurofibrillary tangles (OR = 3.96, 95% CI [1.43, 10.96], P = 0.008), Lewy body pathology (OR = 2.36, 95% CI [1.18, 4.72], P = 0.02), and years of contact sports participation (OR = 1.04, 95% CI [1.00, 1.08], P = 0.04). Overall, pRBD in CTE is associated with increased years of contact sports participation and may be attributable to Lewy body and brainstem tau pathologies.
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http://dx.doi.org/10.1007/s00401-020-02206-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669574PMC
December 2020

United States Under-19 Rugby-7s: Incidence and Nature of Match Injuries During a 5-year Epidemiological Study.

Sports Med Open 2020 Aug 27;6(1):41. Epub 2020 Aug 27.

Sports Medicine Institute, Hospital for Special Surgery, New York, NY, USA.

Background: There is a lack of injury data for the new Olympic sport of Rugby-7s, particularly for involved youth.

Objective: To determine injury rates and characteristics for players participating in U.S. Rugby-7s U19 (under 19 years of age) tournaments.

Methods: Injury data were collected, using the Rugby Injury Survey & Evaluation report methodology, at 24 U.S. Rugby-7 s U19 tournaments over 30 tournament days (2010-2014). Tournament medical-attention injuries and time-loss injuries (days absent before return to training/competition including post tournament) were recorded.

Results: During the 2101 playing hours (3072 males, aged 17.2 ± 1.5 years; 732 females, 16.6 ± 1.3 years of age), there were 173 tournament injuries with an overall injury incidence of 82.4/1000 player-match-hours (ph) (CI 70.5-95.6). Acute injuries (79.5/1000 ph) occurred during tackling (56.2/1000 ph) and involved joints/ligaments (32.8/1000 ph) of lower extremities (31.9/1000 ph). Head and neck injuries, including concussions, were common (males 21.9/1000 ph; females 22.0/1000 ph). Medical-attention injury incidences (49.5/1000 ph; n = 104; 95% CI 40.5-60.0) were higher than time loss (32.8/1000 ph; n = 69; 95% CI 25.5-41.6). Overall, injury incidences found no difference between sex (RR 0.78; p = 0.369). Time-loss injuries resulted in an average of 35.5 d to return to sport.

Discussion: This study is the first to report match injury incidences for U19 participants in Rugby-7s. Overall, match injury incidence among U.S. U19 Rugby-7s tournaments was similar compared to adult U.S. community Rugby-7s. Recurrent injury risk was notable in this population. Community injury surveillance studies are essential to understand risk from participation in amateur sports. Knowledge of these injury patterns in U19 Rugby-7s will help identify areas to direct resources to enable growth of Rugby-7s in youths and emerging countries being exposed to Rugby-7 s. Age-based injury frequency and patterns in rugby and its various formats are needed for the development of evidence-based, sport-specific, and population-specific injury prevention initiatives.

Conclusions: The match injury incidence of U19 participants in U.S. Rugby-7s was similar to the incidence among adult participants. Recurrent match injury risk was high at 23%. There were no significant differences in injury incidences between males and females. The first three matches of a tournament day result in the most injuries.
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http://dx.doi.org/10.1186/s40798-020-00261-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452962PMC
August 2020

Characterizing tau deposition in chronic traumatic encephalopathy (CTE): utility of the McKee CTE staging scheme.

Acta Neuropathol 2020 10 11;140(4):495-512. Epub 2020 Aug 11.

Department of Neurology, Boston University Alzheimer's Disease and CTE Centers, Boston University School of Medicine, Boston, USA.

Chronic traumatic encephalopathy (CTE) is a tauopathy associated with repetitive head impacts (RHI) that has been neuropathologically diagnosed in American football players and other contact sport athletes. In 2013, McKee and colleagues proposed a staging scheme for characterizing the severity of the hyperphosphorylated tau (p-tau) pathology, the McKee CTE staging scheme. The staging scheme defined four pathological stages of CTE, stages I(mild)-IV(severe), based on the density and regional deposition of p-tau. The objective of this study was to test the utility of the McKee CTE staging scheme, and provide a detailed examination of the regional distribution of p-tau in CTE. We examined the relationship between the McKee CTE staging scheme and semi-quantitative and quantitative assessments of regional p-tau pathology, age at death, dementia, and years of American football play among 366 male brain donors neuropathologically diagnosed with CTE (mean age 61.86, SD 18.90). Spearman's rho correlations showed that higher CTE stage was associated with higher scores on all semi-quantitative and quantitative assessments of p-tau severity and density (p's < 0.001). The severity and distribution of CTE p-tau followed an age-dependent progression: older age was associated with increased odds for having a higher CTE stage (p < 0.001). CTE stage was independently associated with increased odds for dementia (p < 0.001). K-medoids cluster analysis of the semi-quantitative scales of p-tau across 14 regions identified 5 clusters of p-tau that conformed to increasing CTE stage (stage IV had 2 slightly different clusters), age at death, dementia, and years of American football play. There was a predilection for p-tau pathology in five regions: dorsolateral frontal cortex (DLF), superior temporal cortex, entorhinal cortex, amygdala, and locus coeruleus (LC), with CTE in the youngest brain donors and lowest CTE stage restricted to DLF and LC. These findings support the usefulness of the McKee CTE staging scheme and demonstrate the regional distribution of p-tau in CTE.
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http://dx.doi.org/10.1007/s00401-020-02197-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914059PMC
October 2020

History of Chronic Traumatic Encephalopathy.

Semin Neurol 2020 Aug 10;40(4):353-358. Epub 2020 Aug 10.

Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nevada.

The long-term effects of repetitive head impacts have been recognized for close to a century. What is now referred to as chronic traumatic encephalopathy (CTE) was first described by Martland in 1928 in a series of boxers. Over the years, several important articles were published, including Critchley's 1957 report where he introduced the term "chronic traumatic encephalopathy," Robert's study in 1969 which provided evidence of the prevalence of neurological impairment in retired fighters, and Corsellis' initial description of the pathology of CTE. However, what brought public attention to the issue of CTE in sports were the postmortem findings of CTE pathology in professional American football players, initially reported by Omalu and subsequently in a large series by McKee. There is now standardization of pathological criteria for CTE and recognition that it can be seen across all activities that involve repetitive head impacts.
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http://dx.doi.org/10.1055/s-0040-1713622DOI Listing
August 2020

Interactive Effects of Racial Identity and Repetitive Head Impacts on Cognitive Function, Structural MRI-Derived Volumetric Measures, and Cerebrospinal Fluid Tau and Aβ.

Front Hum Neurosci 2019 20;13:440. Epub 2019 Dec 20.

Boston University Alzheimer's Disease Center and Boston University CTE Center, Boston University School of Medicine, Boston, MA, United States.

Background: Factors of increased prevalence among individuals with Black racial identity (e.g., cardiovascular disease, CVD) may influence the association between exposure to repetitive head impacts (RHI) from American football and later-life neurological outcomes. Here, we tested the interaction between racial identity and RHI on neurobehavioral outcomes, brain volumetric measures, and cerebrospinal fluid (CSF) total tau (t-tau), phosphorylated tau (p-tau), and Aβ in symptomatic former National Football League (NFL) players.

Methods: 68 symptomatic male former NFL players (ages 40-69; = 27 Black, = 41 White) underwent neuropsychological testing, structural MRI, and lumbar puncture. FreeSurfer derived estimated intracranial volume (eICV), gray matter volume (GMV), white matter volume (WMV), subcortical GMV, hippocampal volume, and white matter (WM) hypointensities. Multivariate generalized linear models examined the main effects of racial identity and its interaction with a cumulative head impact index (CHII) on all outcomes. Age, years of education, Wide Range Achievement Test, Fourth Edition (WRAT-4) scores, CVD risk factors, and ε4 were included as covariates; eICV was included for MRI models. -values were false discovery rate adjusted.

Results: Compared to White former NFL players, Black participants were 4 years younger ( = 0.04), had lower WRAT-4 scores (mean difference = 8.03, = 0.002), and a higher BMI (mean difference = 3.09, = 0.01) and systolic blood pressure (mean difference = 8.15, = 0.03). With regards to group differences on the basis of racial identity, compared to White former NFL players, Black participants had lower GMV (mean adjusted difference = 45649.00, = 0.001), lower right hippocampal volume (mean adjusted difference = 271.96, = 0.02), and higher p-tau/t-tau ratio (mean adjusted difference = -0.25, = 0.01). There was not a statistically significant association between the CHII with GMV, right hippocampal volume, or p-tau/t-tau ratio. However, there was a statistically significant Race x CHII interaction for GMV ( = 2206.29, = 0.001), right hippocampal volume ( = 12.07, = 0.04), and p-tau/t-tau ratio concentrations ( = -0.01, = 0.004).

Conclusion: Continued research on racial neurological disparities could provide insight into risk factors for long-term neurological disorders associated with American football play.
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http://dx.doi.org/10.3389/fnhum.2019.00440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933867PMC
December 2019

Duration of American Football Play and Chronic Traumatic Encephalopathy.

Ann Neurol 2020 01 23;87(1):116-131. Epub 2019 Nov 23.

Boston University Alzheimer's Disease and Chronic Traumatic Encephalopathy Center, Boston University School of Medicine, Boston, MA.

Objective: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to contact and collision sports, including American football. We hypothesized a dose-response relationship between duration of football played and CTE risk and severity.

Methods: In a convenience sample of 266 deceased American football players from the Veterans Affairs-Boston University-Concussion Legacy Foundation and Framingham Heart Study Brain Banks, we estimated the association of years of football played with CTE pathological status and severity. We evaluated the ability of years played to classify CTE status using receiver operating characteristic curve analysis. Simulation analyses quantified conditions that might lead to selection bias.

Results: In total, 223 of 266 participants met neuropathological diagnostic criteria for CTE. More years of football played were associated with having CTE (odds ratio [OR] = 1.30 per year played, 95% confidence interval [CI] = 1.19-1.41; p = 3.8 × 10 ) and with CTE severity (severe vs mild; OR = 1.14 per year played, 95% CI = 1.07-1.22; p = 3.1 × 10 ). Participants with CTE were 1/10th as likely to have played <4.5 years (negative likelihood ratio [LR] = 0.102, 95% CI = 0.100-0.105) and were 10 times as likely to have played >14.5 years (positive LR = 10.2, 95% CI = 9.8-10.7) compared with participants without CTE. Sensitivity and specificity were maximized at 11 years played. Simulation demonstrated that years played remained adversely associated with CTE status when years played and CTE status were both related to brain bank selection across widely ranging scenarios.

Interpretation: The odds of CTE double every 2.6 years of football played. After accounting for brain bank selection, the magnitude of the relationship between years played and CTE status remained consistent. ANN NEUROL 2020;87:116-131.
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http://dx.doi.org/10.1002/ana.25611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973077PMC
January 2020

Association of White Matter Rarefaction, Arteriolosclerosis, and Tau With Dementia in Chronic Traumatic Encephalopathy.

JAMA Neurol 2019 Nov;76(11):1298-1308

Boston University Alzheimer's Disease Center and CTE Center, Department of Neurology, Boston University School of Medicine, Boston, Massachusetts.

Importance: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head impacts, including those from US football, that presents with cognitive and neuropsychiatric disturbances that can progress to dementia. Pathways to dementia in CTE are unclear and likely involve tau and nontau pathologic conditions.

Objective: To investigate the association of white matter rarefaction and cerebrovascular disease with dementia in deceased men older than 40 years who played football and had CTE.

Design, Setting, And Participants: This cross-sectional study involves analyses of data from the ongoing Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Study, which is conducted via and included brain donors from the Veterans Affairs-Boston University-Concussion Legacy Foundation brain bank between 2008 and 2017. An original sample of 224 men who had played football and were neuropathologically diagnosed with CTE was reduced after exclusion of those younger than 40 years and those missing data.

Exposures: The number of years of football play as a proxy for repetitive head impacts.

Main Outcomes And Measures: Neuropathological assessment of white matter rarefaction and arteriolosclerosis severity (on a scale of 0-3, where 3 is severe); number of infarcts, microinfarcts, and microbleeds; and phosphorylated tau accumulation determined by CTE stage and semiquantitative rating of dorsolateral frontal cortex (DLFC) neurofibrillary tangles (NFTs) (none or mild vs moderate or severe). Informant-based retrospective clinical interviews determined dementia diagnoses via diagnostic consensus conferences.

Results: A total of 180 men were included. The mean (SD) age of the sample at death was 67.9 (12.7) years. Of 180, 120 [66.7%]) were found to have had dementia prior to death. Moderate to severe white matter rarefaction (84 of 180 [46.6%]) and arteriolosclerosis (85 of 180 [47.2%]) were common; infarcts, microinfarcts, and microbleeds were not. A simultaneous equations regression model controlling for age and race showed that more years of play was associated with more severe white matter rarefaction (β, 0.16 [95% CI, 0.02-0.29]; P = .03) and greater phosphorylated tau accumulation (DLFC NFTs: β, 0.15 [95% CI, 0.004-0.30]; P = .04; CTE stage: β, 0.27 [95% CI, 0.14-0.41]; P < .001). White matter rarefaction (β, 0.16 [95% CI, 0.02-0.29]; P = .03) and DLFC NFTs (β, 0.16 [95% CI, 0.03-0.28]; P = .01) were associated with dementia. Arteriolosclerosis and years of play were not associated, but arteriolosclerosis was independently associated with dementia (β, 0.21 [95% CI, 0.07-0.35]; P = .003).

Conclusions And Relevance: Among older men who had played football and had CTE, more years of football play were associated with more severe white matter rarefaction and greater DLFC NFT burden. White matter rarefaction, arteriolosclerosis, and DLFC NFTs were independently associated with dementia. Dementia in CTE is likely a result of neuropathologic changes, including white matter rarefaction and phosphorylated tau, associated with repetitive head impact and pathologic changes not associated with head trauma, such as arteriolosclerosis.
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http://dx.doi.org/10.1001/jamaneurol.2019.2244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686769PMC
November 2019

History of Concussion Including Contributions of 1940s Boston City Hospital Researchers.

Authors:
Robert C Cantu

Semin Pediatr Neurol 2019 07 26;30:2-8. Epub 2019 Mar 26.

Boston University of Medicine, Boston, MA; Robert C. Cantu Concussion Center, Emerson Hospital, MA; Emerson Hospital, MA; Department of Exercise and Sport Science, UNC at Chapel Hill, Chapel Hill, NC. Electronic address:

While even today there is no uniformly agreed upon "gold standard" definition of concussion, concussion research dates back to the late 19th century. Historically, most researchers have believed that it does not matter where, how, or why the brain was injured, the only fact that mattered was that the brain was injured. The dangers of repeated concussions were chronicled as far back as 1870 by James Crighton Brown who warned that anyone suffering such an injury should avoid another forever after. In 1952, Harvard Physician Augustus Thorndike proposed that 3 concussions in a collision sport were sufficient to advise retirement from the sport. And in 1975, Gronwall and Wrightson suggested medical authorities had a duty to convince sporting authorities that the effects of concussions were cumulative. While most definitions of concussion prior to the 1970s involved a loss of consciousness or amnesia, there are numerous examples that physicians and surgeons knew concussions could occur without the loss of consciousness prior to Trotter's 1924 publication. It was the decade of the 1940s that seminal work on concussion and subconcussive brain trauma was carried out at Boston City Hospital, a Boston University Hospital. This chapter will not only focus on the history of concussion dating to the 18th Century, but also the wonderful research carried out at Boston City Hospital by Derek Denny-Brown, Donald Munro, Houston Merritt and others.
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http://dx.doi.org/10.1016/j.spen.2019.03.002DOI Listing
July 2019

A helmetless-tackling intervention in American football for decreasing head impact exposure: A randomized controlled trial.

J Sci Med Sport 2019 Oct 7;22(10):1102-1107. Epub 2019 Jun 7.

University of Michigan, School of Kinesiology, United States.

Objectives: To evaluate a behavioral intervention to reduce head impact exposure in youth playing American football.

Design: Nested randomized controlled trial.

Methods: Participants, ages 14-17 years, wore head impact sensors (SIM-G™) during two seasons of play. Those randomized to the intervention group underwent weekly tackling/blocking drills performed without helmets (WoH) and shoulder pads while the control group trained as normal, matching frequency and duration. Research personnel provided daily oversight to maintain fidelity. Head impact frequency (≥10g) per athlete exposure (ImpAE) was analyzed over time (two 11-week seasons) using mixed effect models or ANCOVA. Secondary outcomes included exposure-type (training, game) and participation level (entry-level versus upper-level secondary education).

Results: One-hundred fifteen participants (59 WoH, 56 control) met compliance criteria, contributing 47,382 head impacts and 10,751 athlete exposures for analysis. WoH had fewer ImpAE during games compared to control participants at weeks 4 (p=0.0001 season 1, p=0.0005 season 2) and 7 (p=0.0001 both seasons). Upper-level WoH participants had less ImpAE during games than their matched controls at weeks 4 (p=0.017 and p=0.026) and 7 (p=0.037 and p=0.014) in both seasons, respectively. Upper-level WoH also had fewer ImpAE during training at week 7 (p=0.015) in season one.

Conclusions: Tackling and blocking drills performed without a helmet during training reduced the frequency of head impacts during play, especially during games. However, these differences disappeared by the end of the season. Future research should explore the frequency of behavioral intervention and a dose-response relationship considering years of player experience.

Trial Registration: ClinicalTrials.gov # NCT02519478.
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http://dx.doi.org/10.1016/j.jsams.2019.05.018DOI Listing
October 2019

Contact sport participation and chronic traumatic encephalopathy are associated with altered severity and distribution of cerebral amyloid angiopathy.

Acta Neuropathol 2019 09 10;138(3):401-413. Epub 2019 Jun 10.

Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston University, Boston, MA, 02118, USA.

Cerebral amyloid angiopathy (CAA) consists of beta-amyloid deposition in the walls of the cerebrovasculature and is commonly associated with Alzheimer's disease (AD). However, the association of CAA with repetitive head impacts (RHI) and with chronic traumatic encephalopathy (CTE) is unknown. We evaluated the relationship between RHI from contact sport participation, CTE, and CAA within a group of deceased contact sport athletes (n = 357), a community-based cohort (n = 209), and an AD cohort from Boston University AD Center (n = 241). Unsupervised hierarchal cluster analysis demonstrated a unique cluster (n = 11) with increased CAA in the leptomeningeal vessels compared to the intracortical vessels (p < 0.001) comprised of participants with significantly greater frequencies of CTE (7/11) and history of RHI. Overall, participants with CTE (n = 251) had more prevalent (p < 0.001) and severe (p = 0.010) CAA within the frontal leptomeningeal vessels compared to intracortical vessels. Compared to those with AD, participants with CTE had more severe CAA in frontal than parietal lobes (p < 0.001) and more severe CAA in leptomeningeal than intracortical vessels (p = 0.002). The overall frequency of CAA in participants with CTE was low, and there was no significant association between contact sport participation and the presence of CAA. However, in those with CAA, a history of contact sports was associated with increased CAA severity in the frontal leptomeningeal vessels (OR = 4.01, 95% CI 2.52-6.38, p < 0.001) adjusting for AD, APOE ε4 status, and age. Participants with CAA had increased levels of sulcal tau pathology and decreased levels of the synaptic marker PSD-95 (p's < 0.05), and CAA was a predictor of dementia (OR = 1.75, 95% CI 1.02-2.99, p = 0.043) adjusting for age, sex, and comorbid pathology. Overall, contact sport participation and CTE were associated with more severe frontal and leptomeningeal CAA, and CAA was independently associated with worse pathological and clinical outcomes.
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http://dx.doi.org/10.1007/s00401-019-02031-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689453PMC
September 2019

A magnetic resonance spectroscopy investigation in symptomatic former NFL players.

Brain Imaging Behav 2020 Oct;14(5):1419-1429

Center for Clinical Spectroscopy, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 4 Blackfan Street HIM-820, Boston, MA, 02115, USA.

The long-term neurologic consequences of exposure to repetitive head impacts (RHI) are not well understood. This study used magnetic resonance spectroscopy (MRS) to examine later-life neurochemistry and its association with RHI and clinical function in former National Football League (NFL) players. The sample included 77 symptomatic former NFL players and 23 asymptomatic individuals without a head trauma history. Participants completed cognitive, behavior, and mood measures. N-acetyl aspartate, glutamate/glutamine, choline, myo-inositol, creatine, and glutathione were measured in the posterior (PCG) and anterior (ACG) cingulate gyrus, and parietal white matter (PWM). A cumulative head impact index (CHII) estimated RHI. In former NFL players, a higher CHII correlated with lower PWM creatine (r = -0.23, p = 0.02). Multivariate mixed-effect models examined neurochemical differences between the former NFL players and asymptomatic individuals without a history of head trauma. PWM N-acetyl aspartate was lower among the former NFL players (mean diff. = 1.02, p = 0.03). Between-group analyses are preliminary as groups were recruited based on symptomatic status. The ACG was the only region associated with clinical function, including positive correlations between glutamate (r = 0.32, p = 0.004), glutathione (r = 0.29, p = 0.02), and myo-inositol (r = 0.26, p = 0.01) with behavioral/mood symptoms. Other positive correlations between ACG neurochemistry and clinical function emerged (i.e., behavioral/mood symptoms, cognition), but the positive directionality was unexpected. All analyses controlled for age, body mass index, and education (for analyses examining clinical function). In this sample of symptomatic former NFL players, there was a direct effect between RHI and reduced cellular energy metabolism (i.e., lower creatine). MRS neurochemicals associated with neuroinflammation also correlated with behavioral/mood symptoms.
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http://dx.doi.org/10.1007/s11682-019-00060-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994233PMC
October 2020

Catastrophic neurologic injuries in sport.

Handb Clin Neurol 2018 ;158:25-37

Department of Exercise and Sport Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. Electronic address:

Tens of millions of children and adults participate in organized sport in the United States each year. Although uncommon, fatal and severe nonfatal brain and spine injuries can occur during these activities. These "catastrophic" injuries have been noted in contact sports such as football, rugby, and ice hockey, as well as in noncontact sports including baseball, cheerleading, swimming and diving, equestrian, gymnastics, pole vault, rodeo, snow skiing, snowboarding, and wrestling. They happen at all levels of play, from youth to professional. Among all sports, football has the highest number of fatal brain and cervical spine injuries. While these injuries are more frequent in high school football, the rate is higher amongst college football athletes. Patterns exist in the types of brain and spine injuries most often occurring as a result of traumatic impacts in sport, but incidence and mechanisms of injury vary dramatically between sports. Understanding these patterns is essential to informing prevention efforts; football, pole vault, and cheer are all examples of sports benefiting from successful catastrophic injury prevention efforts. Participating in sport provides many benefits to physical and mental health. Despite these benefits, rare devastating injuries can be traumatic for the athletes, their families, and communities and can raise safety concerns that may reduce participation in sport. Understanding and preventing these types of injuries are critical to fostering participation in sport and ensuring both children and adults reap the physical, social, and mental benefits of sport.
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http://dx.doi.org/10.1016/B978-0-444-63954-7.00004-5DOI Listing
March 2019

Variation in TMEM106B in chronic traumatic encephalopathy.

Acta Neuropathol Commun 2018 11 4;6(1):115. Epub 2018 Nov 4.

Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, 72 E Concord Street, B7800, Boston, MA, 02118, USA.

The genetic basis of chronic traumatic encephalopathy (CTE) is poorly understood. Variation in transmembrane protein 106B (TMEM106B) has been associated with enhanced neuroinflammation during aging and with TDP-43-related neurodegenerative disease, and rs3173615, a missense coding SNP in TMEM106B, has been implicated as a functional variant in these processes. Neuroinflammation and TDP-43 pathology are prominent features in CTE. The purpose of this study was to determine whether genetic variation in TMEM106B is associated with CTE risk, pathological features, and ante-mortem dementia. Eighty-six deceased male athletes with a history of participation in American football, informant-reported Caucasian, and a positive postmortem diagnosis of CTE without comorbid neurodegenerative disease were genotyped for rs3173615. The minor allele frequency (MAF = 0.42) in participants with CTE did not differ from previously reported neurologically normal controls (MAF = 0.43). However, in a case-only analysis among CTE cases, the minor allele was associated with reduced phosphorylated tau (ptau) pathology in the dorsolateral frontal cortex (DLFC) (AT8 density, odds ratio [OR] of increasing one quartile = 0.42, 95% confidence interval [CI] 0.22-0.79, p = 0.008), reduced neuroinflammation in the DLFC (CD68 density, OR of increasing one quartile = 0.53, 95% CI 0.29-0.98, p = 0.043), and increased synaptic protein density (β = 0.306, 95% CI 0.065-0.546, p = 0.014). Among CTE cases, TMEM106B minor allele was also associated with reduced ante-mortem dementia (OR = 0.40, 95% CI 0.16-0.99, p = 0.048), but was not associated with TDP-43 pathology. All case-only models were adjusted for age at death and duration of football play. Taken together, variation in TMEM106B may have a protective effect on CTE-related outcomes.
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http://dx.doi.org/10.1186/s40478-018-0619-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215686PMC
November 2018

Catastrophic High School and Collegiate Cheerleading Injuries in the United States: An Examination of the 2006-2007 Basket Toss Rule Change.

Sports Health 2019 Jan/Feb;11(1):32-39. Epub 2018 Oct 24.

UNC Chapel Hill, National Center for Catastrophic Sport Injury Research, Chapel Hill, North Carolina.

Background:: Cheerleading is a specialized athletic activity that can lead to catastrophic injuries. Cheerleading rules are in place to maximize safety of participants. The purpose of this study was to describe catastrophic cheerleading injuries among high school and collegiate-level participants in the United States and to explore whether the 2006-2007 basket toss rule change was effective at reducing the number of catastrophic injuries.

Hypothesis:: The 2006-2007 basket toss rule change contributed to a reduction in the number of catastrophic injuries among high school and collegiate cheerleaders.

Study Design:: Case series.

Level Of Evidence:: Level 4.

Methods:: Data on catastrophic cheerleading injuries were collected by the National Center for Catastrophic Sport Injury Research from July 2002 to June 2017. Information collected included cheerleader, event, and injury characteristics. The impact of the 2006-2007 rule change banning the basket toss on any hard surfaces was assessed by comparing injury rates and 95% CIs before and after the rule change.

Results:: There were 54 catastrophic cheerleading injuries, or 3.6 injuries per year. From July 2002 through June 2017, the injury rate was 2.12 per 1,000,000 cheerleaders (95% CI, 1.56-2.69). Most cheerleaders sustained serious injuries (n = 27; 50%) during practice (n = 37; 69%) to the head (n = 28; 52%) and cervical spine (n = 17; 32%). From July 2002 through June 2017, basket tosses were the stunt that accounted for the highest proportion of injuries (n = 19; 35%). The basket toss injury rate decreased from 1.55 to 0.40 per 1,000,000 cheerleaders among both high school and collegiate cheerleaders after the rule change.

Conclusion:: Catastrophic injury rates in cheerleading decreased dramatically after the 2006-2007 rule change banning basket tosses from being performed on any hard surfaces. In particular, there was a nearly 4-fold reduction in the rate of catastrophic basket toss injuries.
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http://dx.doi.org/10.1177/1941738118807122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299346PMC
February 2019

Lewy Body Pathology and Chronic Traumatic Encephalopathy Associated With Contact Sports.

J Neuropathol Exp Neurol 2018 09;77(9):757-768

Department of Neurology.

Traumatic brain injury has been associated with increased risk of Parkinson disease and parkinsonism, and parkinsonism and Lewy body disease (LBD) can occur with chronic traumatic encephalopathy (CTE). To test whether contact sports and CTE are associated with LBD, we compared deceased contact sports athletes (n = 269) to cohorts from the community (n = 164) and the Boston University Alzheimer disease (AD) Center (n = 261). Participants with CTE and LBD were more likely to have β-amyloid deposition, dementia, and parkinsonism than CTE alone (p < 0.05). Traditional and hierarchical clustering showed a similar pattern of LBD distribution in CTE compared to LBD alone that was most frequently neocortical, limbic, or brainstem. In the community-based cohort, years of contact sports play were associated with neocortical LBD (OR = 1.30 per year, p = 0.012), and in a pooled analysis a threshold of >8 years of play best predicted neocortical LBD (ROC analysis, OR = 6.24, 95% CI = 1.5-25, p = 0.011), adjusting for age, sex, and APOE ɛ4 allele status. Clinically, dementia was significantly associated with neocortical LBD, CTE stage, and AD; parkinsonism was associated with LBD pathology but not CTE stage. Contact sports participation may increase risk of developing neocortical LBD, and increased LBD frequency may partially explain extrapyramidal motor symptoms sometimes observed in CTE.
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http://dx.doi.org/10.1093/jnen/nly065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097837PMC
September 2018

Concussion management in combat sports: consensus statement from the Association of Ringside Physicians.

Br J Sports Med 2019 Mar 26;53(6):328-333. Epub 2018 Jul 26.

St. Augustine, Trinidad and Tobago.

Various organisations and experts have published numerous statements and recommendations regarding different aspects of sports-related concussion including definition, presentation, treatment, management and return to play guidelines. To date, there have been no written consensus statements specific for combat sports regarding management of combatants who have suffered a concussion or for return to competition after a concussion. In combat sports, head contact is an objective of the sport itself. Accordingly, management and treatment of concussion in combat sports should, and must, be more stringent than for non-combat sports counterparts.The Association of Ringside Physicians (an international, non-profit organisation dedicated to the health and safety of the combat sports athlete) sets forth this consensus statement to establish management guidelines that ringside physicians, fighters, referees, trainers, promoters, sanctioning bodies and other healthcare professionals can use in the ringside setting. We also provide guidelines for the return of a combat sports athlete to competition after sustaining a concussion. This consensus statement does not address the management of moderate to severe forms of traumatic brain injury, such as intracranial bleeds, nor does it address the return to competition for combat sports athletes who have suffered such an injury. These more severe forms of brain injuries are beyond the scope of this statement. This consensus statement does not address neuroimaging guidelines in combat sports.
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http://dx.doi.org/10.1136/bjsports-2017-098799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579496PMC
March 2019

Cerebrospinal fluid tau, Aβ, and sTREM2 in Former National Football League Players: Modeling the relationship between repetitive head impacts, microglial activation, and neurodegeneration.

Alzheimers Dement 2018 09 23;14(9):1159-1170. Epub 2018 Jul 23.

Boston University Alzheimer's Disease Center and Boston University CTE Center, Boston University School of Medicine, Boston, MA, USA; Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Department of Neurosurgery, Boston University School of Medicine, Boston, MA, USA; Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA. Electronic address:

Introduction: Cerebrospinal fluid (CSF) protein analysis may facilitate detection and elucidate mechanisms of neurological consequences from repetitive head impacts (RHI), such as chronic traumatic encephalopathy. We examined CSF concentrations of total tau (t-tau), phosphorylated tau, and amyloid β and their association with RHI in former National Football League (NFL) players. The role of microglial activation (using sTREM2) was examined as a pathogenic mechanism of chronic traumatic encephalopathy.

Methods: Sixty-eight former NFL players and 21 controls underwent lumbar puncture to quantify t-tau, p-tau, amyloid β, and sTREM2 in the CSF using immunoassays. The cumulative head impact index estimated RHI.

Results: No between-group differences for CSF analytes emerged. In the former NFL players, the cumulative head impact index predicted higher t-tau concentrations (P = .041), and higher sTREM2 levels were associated with higher t-tau concentrations (P = .009).

Discussion: In this sample of former NFL players, greater RHI and increased microglial activation were associated with higher CSF t-tau concentrations.
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http://dx.doi.org/10.1016/j.jalz.2018.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131058PMC
September 2018

National Institute of Neurological Disorders and Stroke and Department of Defense Sport-Related Concussion Common Data Elements Version 1.0 Recommendations.

J Neurotrauma 2018 12 23;35(23):2776-2783. Epub 2018 Jul 23.

25 The Emmes Corporation, Rockville, Maryland.

Through a partnership with the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, and Department of Defense, the development of Sport-Related Concussion (SRC) Common Data Elements (CDEs) was initiated. The aim of this collaboration was to increase the efficiency and effectiveness of clinical research studies and clinical treatment outcomes, increase data quality, facilitate data sharing across studies, reduce study start-up time, more effectively aggregate information into metadata results, and educate new clinical investigators. The SRC CDE Working Group consisted of 32 worldwide experts in concussion from varied fields of related expertise divided into three Subgroups: Acute (<72 h post-concussion), Subacute (3 days-3 months post-concussion) and Persistent/Chronic (>3 months post-concussion). To develop CDEs, the Subgroups reviewed various domains, then selected from, refined, and added to existing CDEs, case report forms and field-tested data elements from national registries and funded research studies. Recommendations were posted to the NINDS CDE Website for Public Review from February 2017 to April 2017. Following an internal Working Group review of recommendations, along with consideration of comments received from the Public Review period, the first iteration (Version 1.0) of the NINDS SRC CDEs was completed in June 2017. The recommendations include Core and Supplemental-Highly Recommended CDEs for cognitive data elements and symptom checklists, as well as other outcomes and end-points (e.g., vestibular, oculomotor, balance, anxiety, depression), and sample case report forms (e.g., injury reporting, demographics, concussion history) for domains typically included in clinical research studies. The NINDS SRC CDEs and supporting documents are publicly available on the NINDS CDE website www.commondataelements.ninds.nih.gov . Widespread use of CDEs by researchers and clinicians will facilitate consistent SRC clinical research and trial design, data sharing, and metadata retrospective analysis.
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http://dx.doi.org/10.1089/neu.2018.5643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247979PMC
December 2018

Age of first exposure to tackle football and chronic traumatic encephalopathy.

Ann Neurol 2018 05;83(5):886-901

Boston University Alzheimer's Disease and CTE Center, Department of Neurology, Boston University School of Medicine, Boston, MA.

Objective: To examine the effect of age of first exposure to tackle football on chronic traumatic encephalopathy (CTE) pathological severity and age of neurobehavioral symptom onset in tackle football players with neuropathologically confirmed CTE.

Methods: The sample included 246 tackle football players who donated their brains for neuropathological examination. Two hundred eleven were diagnosed with CTE (126 of 211 were without comorbid neurodegenerative diseases), and 35 were without CTE. Informant interviews ascertained age of first exposure and age of cognitive and behavioral/mood symptom onset.

Results: Analyses accounted for decade and duration of play. Age of exposure was not associated with CTE pathological severity, or Alzheimer's disease or Lewy body pathology. In the 211 participants with CTE, every 1 year younger participants began to play tackle football predicted earlier reported cognitive symptom onset by 2.44 years (p < 0.0001) and behavioral/mood symptoms by 2.50 years (p < 0.0001). Age of exposure before 12 predicted earlier cognitive (p < 0.0001) and behavioral/mood (p < 0.0001) symptom onset by 13.39 and 13.28 years, respectively. In participants with dementia, younger age of exposure corresponded to earlier functional impairment onset. Similar effects were observed in the 126 CTE-only participants. Effect sizes were comparable in participants without CTE.

Interpretation: In this sample of deceased tackle football players, younger age of exposure to tackle football was not associated with CTE pathological severity, but predicted earlier neurobehavioral symptom onset. Youth exposure to tackle football may reduce resiliency to late-life neuropathology. These findings may not generalize to the broader tackle football population, and informant-report may have affected the accuracy of the estimated effects. Ann Neurol 2018;83:886-901.
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http://dx.doi.org/10.1002/ana.25245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367933PMC
May 2018

Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model.

Brain 2018 02;141(2):422-458

Alzheimer's Disease Center, CTE Program, Boston University School of Medicine, Boston, MA 02118, USA.

The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration. Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset, transient course, and rapid resolution of a concussion-like syndrome characterized by altered arousal, contralateral hemiparesis, truncal ataxia, locomotor and balance impairments, and neurobehavioural deficits. Experimental impact injury was associated with axonopathy, blood-brain barrier disruption, astrocytosis, microgliosis (with activation of triggering receptor expressed on myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co-localized with serum albumin extravasation in the brain that was diagnostically detectable in living mice by dynamic contrast-enhanced MRI. These pathologies were also accompanied by early, persistent, and bilateral impairment in axonal conduction velocity in the hippocampus and defective long-term potentiation of synaptic neurotransmission in the medial prefrontal cortex, brain regions distant from acute brain injury. Surprisingly, acute neurobehavioural deficits at the time of injury did not correlate with blood-brain barrier disruption, microgliosis, neuroinflammation, phosphorylated tauopathy, or electrophysiological dysfunction. Furthermore, concussion-like deficits were observed after impact injury, but not after blast exposure under experimental conditions matched for head kinematics. Computational modelling showed that impact injury generated focal point loading on the head and seven-fold greater peak shear stress in the brain compared to blast exposure. Moreover, intracerebral shear stress peaked before onset of gross head motion. By comparison, blast induced distributed force loading on the head and diffuse, lower magnitude shear stress in the brain. We conclude that force loading mechanics at the time of injury shape acute neurobehavioural responses, structural brain damage, and neuropathological sequelae triggered by neurotrauma. These results indicate that closed-head impact injuries, independent of concussive signs, can induce traumatic brain injury as well as early pathologies and functional sequelae associated with chronic traumatic encephalopathy. These results also shed light on the origins of concussion and relationship to traumatic brain injury and its aftermath.awx350media15713427811001.
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http://dx.doi.org/10.1093/brain/awx350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837414PMC
February 2018

White matter signal abnormalities in former National Football League players.

Alzheimers Dement (Amst) 2018 6;10:56-65. Epub 2017 Nov 6.

Boston University Alzheimer's Disease and CTE Center, Department of Neurology, Boston University School of Medicine, Boston, MA, USA.

Introduction: Later-life brain alterations in former tackle football players are poorly understood, particularly regarding their relationship with repetitive head impacts (RHIs) and clinical function. We examined white matter signal abnormalities (WMSAs) and their association with RHIs and clinical function in former National Football League (NFL) players.

Methods: Eighty-six clinically symptomatic former NFL players and 23 same-age reportedly asymptomatic controls without head trauma exposure underwent magnetic resonance imaging and neuropsychological testing. FreeSurfer calculated WMSAs. A cumulative head impact index quantified RHIs.

Results: In former NFL players, increased volume of WMSAs was associated with higher cumulative head impact index scores ( = .043) and worse psychomotor speed and executive function ( = .015). Although former NFL players had greater WMSA volume than controls ( = .046), these findings are inconclusive due to recruitment of controls based on lack of clinical symptoms and head trauma exposure.

Discussion: In former NFL players, WMSAs may reflect long-term microvascular and nonmicrovascular pathologies from RHIs that negatively impact cognition.
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http://dx.doi.org/10.1016/j.dadm.2017.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699890PMC
November 2017