BU CTE Center post-mortem presentation on Aaron Hernandez: stage 3 CTE

This past Thursday, Boston University CTE Center director Ann McKee presented the specific findings of the brain examination of New England Patriots’ player Aaron Hernandez. Mr. Hernandez was serving a life sentence for murder when he committed suicide in his Massachusetts prison cell. The family donated his brain after his death. At age 27, his brain was determined to have Stage 3 (of 4) chronic traumatic encephalopathy (CTE), with severe deposition of tau protein in the frontal lobes of the brain.

Dr. McKee noted, “These are very unusual findings for someone so young”, stating that this level of damage usually is found in players at least 20 years older. In a 2016 New York Times interview after the death of Oakland Raiders quarterback Ken Stabler, Dr. McKee correlated long careers plus the increasing age of the player with the severity of CTE.

Dr. McKee confined herself to presenting the pathology, but the CTE Center’s research has associated CTE with aggressiveness, explosiveness, impulsivity, depression, memory loss and other cognitive changes. The CTE Center has pioneered research in the prevalence of CTE in NFL players’ brains [TTA 26 July] and is conducting longitudinal research on the relationship between concussive and sub-concussive head trauma and behavioral change [TTA 21 Sept] in the living. More details and video available here: Boston Herald, CNN. The September BU CTE Center diagnosis of Mr. Hernandez.

The importance to health tech is in the prevention, mitigation, and early diagnosis (not possible yet) of the end result of repeated concussive and sub-concussive damage, sustained in contact sports, military service (usually combat), and in civilian trauma from, for instance, car and industrial accidents. TTA’s long-standing coverage of CTE and brain trauma can be gleaned from searches on these terms.

Youth football playing may contribute to long-term cognitive, behavioral issues: BU study

An extension of Boston University’s pioneering CTE brain research [TTA 26 July] is this newly published study in Translational Psychiatry on cognitive and behavioral changes in former football players. This sampled 214 living former American football players who played high school, college or professional football and did not participate in any other organized contact sports. These players were recruited through BU’s LEGEND longitudinal research registry of living active and former contact and non-contact sports athletes to examine the short/long-term outcomes of repetitive head impacts (RHI). Participants in the program performed over time a battery of cognitive and functional tests. It also screened out those who self-reported concussion within one year of the study inception.

The findings point a very long finger at early tackle football playing in youth football programs, typically from age 5 to 14 when the brain is undergoing massive development. Below quotes are direct from the study:

  • Those who began playing football before age 12 had >2 × increased odds for clinically meaningful impairments in reported behavioral regulation, apathy and executive function, and >3 × increased odds for clinically elevated depression scores, compared with those who began playing at 12 or older.
  • Effects were independent of age, education and duration of football play.
  • Younger AFE (age of first exposure-Ed.) to football, in general, corresponded with worse behavioral regulation, depression, apathy and executive function, as well as increased odds for clinical depression and apathy.

To our knowledge, this study is the first to show a relationship between younger AFE to football and reported clinical dysfunction in a cohort that included both former amateur and professional football players. There was no difference in the effect of AFE by highest level of play. These findings validate and expand upon our previous work in a small, entirely distinct sample of former NFL players, and extend the influence of AFE to football on clinical function to former football players who only played through high school or college. Overall, this study provides further evidence that playing youth American football may have long-term clinical implications, including behavioral and mood impairments.

The study has an extensive discussion of brain development in the young and how ages 9-12 are critical. Two studies using helmet accelerometry on current youth American football players estimate 240 to 252 median head impacts per season.

There are a considerable number of caveats throughout the study, including the kind of protection available in past youth football for the average age respondent (51) and the self-reporting methodology. It is not a risk study for CTE, nor is it intended to advocate the reduction or elimination of youth football. It does advocate for more longitudinal studies. This Editor has attended at least two talks by the CTE Center’s Robert Stern, MD, and he has been never been content with limiting his study to either football or to purely concussive damage. 

Why is this research important to healthcare and to technology? (I’ll expand upon a previous closing.)

  • First, because repetitive brain trauma–concussive and sub-concussive–now has an even better-documented relationship to significant medical and behavioral conditions. This study is now another part of fundamental research to deepen our knowledge about the effects and long term brain outcomes of head trauma, whether from football, other contact sports, combat service (e.g. IED explosions), car accidents, and even repetitive actions by a person who is developmentally disabled.
  • Second, avoiding or minimizing head trauma in sports and warfare, plus correctly diagnosing and treating concussion and sub-concussion, are huge areas for technology about which this Editor has advocated for several years.
  • The message here is not that football is bad, but in the present state and starting age is played dangerously for long term brain development and the subsequent mental health of players. This does not exclude other high contact sports such as flag football, hockey and rugby–the orthopedist’s gift–and heading the ball in soccer. We need to know more, minimize it now, and both playing the game, with the aid of health tech, should be part of this.

Translational Psychiatry (Nature.com), STATNews has further analysis

Related reading: Our extensive backfile of CTE research coverage is here, including this Editor’s reports on Dr. Stern’s presentations at NYC MedTech and GCRI. 

CTE found in 99% of former, deceased NFL players’ brains: JAMA study (updated)

click to enlargeUpdated for additional information and analysis at conclusion. In the largest-ever case study published of CTE–chronic traumatic encephalopathyVA Boston Healthcare System (VABHS) and the Boston University School of Medicine’s CTE Center found mild to severe CTE pathology in nearly all of the brains of former football players studied. Jesse Mez, MD, BU Medical assistant professor of neurology and lead author on the JAMA study, said that “The data suggest that there is very likely a relationship between exposure to football and risk of developing [CTE].” The CTE is marked by defective tau (stained red in the brain sample pictures, click to expand), which is also evident in Parkinson’s and Alzheimer’s Disease.

Of the 202 brains donated to the VA-BU-CLF (Concussion Legacy Foundation) Brain Bank:

  • The most dramatic finding is the detection of CTE in 110 of 111 donated former NFL players’ brains (defined as having played one play in a regular NFL season game).
  • In addition, the brains of other football players were studied. CTE was detected in seven of eight Canadian Football League former players (88 percent), nine of 14 semi-professional players (64 percent), 48 of 53 college players (91 percent), and three of 14 high school players (21 percent).
  • The severity increased with length of play, with the majority of former college, semi-professional and professional players having severe pathology. The deceased high school players diagnosed with CTE had mild pathology findings. Age at death ranged from 23 to 89.
  • Player position mattered. Linemen, running backs, defensive backs, and linebackers, who take most of the punishment in football, were the bulk of the donated brains with CTE.

Separately, and with no knowledge of the pathology, backgrounds on each donor were compiled to gather medical history and symptoms. What was striking were the personality changes evident with even mild CTE. Dr. Mez: “We found cognitive, mood and behavioral symptoms were very common, even among players with mild CTE tau pathology. This suggests that tau pathology is only the tip of the iceberg and that other pathologies, such as neuroinflammation and axonal damage, contribute to the clinical symptoms.” 

Preliminary to the current study was UNITE (more…)

Congressional investigation confirms NFL attempted to influence concussion, CTE research

Not shocking to our Readers. In December, sports network ESPN reported that the National Football League (NFL) refused to fund research on detecting in vivo chronic traumatic encephalopathy (CTE) from a long-term $30 million unrestricted grant to the National Institutes of Health (NIH) [TTA 23 Dec 15]. A 91-page report by Democratic members of the House Committee on Energy and Commerce, which started after the December reports, confirmed that the NFL improperly attempted to shape the research after the grant, violating NIH peer-review process policies that stipulated no grantor interference. The NFL specifically objected to the objectivity of Boston University’s Robert Stern, MD heading up the $16 million project before the award in 2015, then tried to redirect the money, so to speak, in-house–to a group including Dr. Richard Ellenbogen, a member of the league’s panel on brain injuries and their bid for the project. Ultimately, the NFL withdrew the funding from the NIH, which went ahead with it. The project was awarded to BU, the Cleveland Clinic, Banner Alzheimer’s Institute (Arizona) and Brigham and Women’s Hospital in Boston.

The Congressional report’s six major conclusions were highly critical of the NFL in several ways and also scored the Foundation for the NIH for not acting as a ‘buffer’:

  1. The NFL improperly attempted to influence the grant selection process at NIH.
  2. The NFL’s Head, Neck and Spine Committee members played an inappropriate role in attempting to influence the outcome of the grant selection process.
  3. The NFL’s rationalization that the Boston University study did not match their request for a longitudinal study is unfounded.
  4. FNIH (Foundation for the NIH) did not adequately fulfill its role of serving as an intermediary betweenNIH and the NFL.
  5. NIH leadership maintained the integrity of the science and the grant review process.
  6. The NFL did not carry out its commitment to respect the science and prioritize health and safety.

When the grants were announced in September 2012 [TTA 7 Sept 12], there was great cheer that finally the NFL had decided that denial was, to use the old joke, a river in Egypt, and to do something about it. This also followed Army research on TBI being supported by the NFL. The first indicator that the funds were going elsewhere, as we noted a year later, was that a year later the Sports and Health Research Program (SHRP) funds were going to other medical problems like joint diseases and sickle cell anemia. While worthy, it had not been the prime publicized objective of the funds. The Congressional committee report also details how the NFL tried to steer the research away from Dr Stern, one of the leading researchers in the field, citing his support of players who refused to accept the CTE settlement in 2014. Beyond the NFL, research on CTE and concussion will impact any contact sports as well as the military and other head traumas. This Editor has previously reported on Dr Stern’s CTE research presentations in NYC and from other researchers in the field; search on NFL and Dr Stern both in current index and the back file. Congressional report, ESPN.com, New York Times.

NIH funds in vivo CTE research with $16 million–$0 from NFL; “Concussion” released

CTE research funded–and at a US theater near you Christmas Day

In the run-up to the holidays, our Readers may have missed another gift to those concerned with brain health–the National Institutes of Health (NIH) awarding of a major grant to fund research on chronic traumatic encephalopathy (CTE) to diagnose victims in vivo (while still alive). Awarded by NIH in conjunction with the National Institute of Neurological Disease and Stroke, the $16 million will go to researchers from Boston University, the Cleveland Clinic, Banner Alzheimer’s Institute (Arizona) and Brigham and Women’s Hospital in Boston. Leading the team is Robert Stern MD, Boston University professor and director of clinical research for BU’s Alzheimer’s disease and CTE centers, and a researcher we’ve followed since his June 2013 presentation at NYC’s German Center. According to a report in sports network ESPN’s ‘Outside the Lines’, the National Football League (NFL) refused to fund this research from their long term $30 million grant to the NIH due to Dr Stern’s alleged lack of objectivity; according to ESPN, a NIH official told ‘Outside the Lines’ that “the NFL’s $30 million gift was contingent on the league being able to veto decisions on projects that the money was funding.” Seemingly outside this research is another area of interest to Dr Stern–why some athletes have CTE, and others do not, as discussed in the May 2014 NYC MedTech ‘Brain Games’ presentation attended by this Editor.  Medical-Net (BU release), New York Times

Sports CTE and brain injury is back on the front pages with the release of the film ‘Concussion’, starring Will Smith as foundational researcher Bennet Omalu MD, the then-Pittsburgh forensic pathologist who uncovered CTE after performing a detailed brain examination of Pittsburgh Steelers center Mike Webster, who died of a heart attack aged 50 in 2002. His 2005 case report with others from University of Pittsburgh in Neurosurgery was the kick-off (so to speak) and so enraged the NFL that they attempted to have it withdrawn from the journal. In this interview with Medscape EIC Eric Topol MD, Dr Omalu discusses (more…)

TBI, early brain aging and a seismic analogy

Traumatic brain injury (TBI) has been receiving extra study in the past few years due to battlefield blast/IED injury as well as football and other sports injuries as early as junior high. The insidious nature of TBI is that long-term effects of accelerated brain aging can appear in those who have mild injuries, or who never experienced the usual symptoms indicating TBI such as dizziness, nausea and disorientation. Researchers have struggled for the reasons why “51 percent of sufferers of mild head injuries were reported as still having disability one year later at follow-up” and why a large proportion of military veterans who sustained mild brain injuries experience the heightened and uncontrollable emotionality of pseudobulbar affect (PBA). This article in the Genetic Literacy Project website works with an earthquake analogy: that there are P-waves (blast pressure) that compress tissues and disrupt neuronal communication, and in the long term accelerate brain aging and cognitive decline. Something sports injury, CTE researchers and research organizations within the military such as DARPA and DoD should be investigating. Hat tip to author and reader Dr Ben Locwin via Twitter.

An abundance of related reading in TTA can be found in searches under TBI and chronic traumatic encephalopathy. Also see our 2012 and prior archives for our writing on TBI.

Possible early detection test for chronic traumatic encephalopathy (CTE)

A research study published today in the Proceedings of the National Academy of Sciences (US) presents the results of screening 14 retired professional American football players with suspected CTE. Using a tau-sensitive brain imaging agent, [F-18]FDDNP, the California and Illinois-based researchers were able to detect the abnormal accumulation of tau and other proteins, in the distinct CTE pattern, in the brains of living subjects who had received, during their playing careers, multiple concussions and head trauma. Of the 14, one had been diagnosed with dementia, 12 with mild cognitive impairment and one with no symptoms. Previous studies, such as Robert Stern, MD‘s pathfinding research at Boston University and for the NFL (see below), have been primarily post-mortem on brains donated for research, although Dr Stern’s last presentation at NYC MedTech and Inga Koerte, MD of the Ludwig-Maximilians-Universität München (LMU) have also used brain scan information on live subjects in their studies.

Where this differs is that the imaging agent injected binds to the tau  (more…)

Testing the ‘blast response’ of synthetic bone

While protection against concussive and sub-concussive head blows that lead to brain trauma (TBI) and may lead long-term to chronic traumatic encephalopathy (CTE) is being developed in several areas, by DARPA, US Army research, universities and the NFL‘s helmet providers, the final test has to involve cranial bone similar to those belonging to 20-30 year olds. Testing on humans is out of the question, deceased animal and older human crania are dissimilar and surgical implants do not react like real bone.  The US Army Research Laboratory (ARL) along with university partners are developing synthetic cranial bone that behaves like real 20-30 year old bone when subjected to combat-intensity blasts, for testing devices to mitigate the adverse effects and/or track the effects of those blasts.  Armed With Science

‘Brain Games’ on preventing, diagnosing sub-concussive brain trauma

Tuesday 13 May, presented at NYC MedTech-the NYC Medical Technology Forum, at Troutman Sanders LLP, Chrysler Building, New York City

In a packed (agenda and attendees) two hour evening meeting, three presenters detailed the latest research on the clinical signs of chronic traumatic encephalopathy (CTE), along with new technologies for detecting it as it happens and diagnosing it plus monitoring recovery: Robert Stern, PhD, professor of neurology and neurosurgery at the Boston University School of Medicine and a leading clinical researcher on CTE (as our long-time readers know) ; Isaiah Kacyvenski, head of the sports segment of electronics designer MC10 which developed the Checklight head impact indicator for Reebok; and Uzma Samadani, MD, PhD, co-founder of Oculogica which presented at ELabNYC a few weeks ago.

Dr. Stern’s presentation reviewed his clinical work with primarily NFL players in how CTE manifests in both behavior patterns and the brain. His focus remains on sub-concussive trauma, the ‘bottom of the iceberg’ in his analogy, and its cumulative, long-term effects.  Repetitive brain trauma–neuronal shearing which is produced by linear, lateral and rotational forces to the head–produce a cascade of brain changes leading to destruction of brain tissues that show as dark patches on post-mortem samples and scans. These differ from Alzheimer’s disease in the abundance of tau protein distributed fairly early in life around the brain’s blood vessels and in the depths of the cortical sulci, where Alzheimer’s signature beta amyloid does not locate. Dr. Stern’s research also incorporates the behavioral changes that precede diagnosis: the emotional ‘short fuse’, the difficulty in memory, accidents, suicide, drastic changes in behavior and impulse control. There are many examples of degeneration and early death among players [TTA 6 Dec 12 which also refers to Dr. Stern’s research published in Brain; also see TTA 5 June 2013 on his German Center presentation which has additional background on his and his team’s research.]

In addition to the work he has done relating to (American) football (he is on the NFL Players Association brain injury committee and his research was instrumental in the PA’s lawsuit against the NFL), he studies other contact sports such as hockey (brain injury clusters (more…)

Concussion diagnostics a hot area

click to enlargeDiagnosing concussive and sub-concussive head blows both in sports and on the battlefield have been challenging, and your Editors have chronicled several approaches. One of the 2014 graduates of NYCEDC’s ELabNYC was Oculogica; their EyeBox CNS records three key eye movements in a 4 1/2 minute test to determine whether they fit a normal box pattern, with subsequent exams determining rate of brain recovery [TTA 17 Apr]. (We’ll be seeing more of Oculogica at NYC MedTech 13 May, along with MC10 which helped to develop the Checklight impact indicating skullcap with Reebok, seen at last November’s CES preview [TTA 15 Nov 13] and winning CES’ 2014 Design & Engineering award.) Now out of Bethlehem, Pennsylvania is Cerora’s MindReader, developed out of Lehigh University, Ben Franklin Technology Partners of NE Pennsylvania and in the first StartUp Health Academy/GE Entrepreneurship class. It is a wireless dry contact EEG reader which combined with other biosensor data and clinical observation aids speedy diagnosis. The reader is worn either on Google Glass or a headset (pictured above left on CEO Adam J. Simon, PhD). It’s in early days and still in testing; the baselines alone will need data from at minimum tens of thousands of subjects beyond the current testing on Lehigh U. athletes. Dr. Simon is also projecting use for sub-concussion injury, Alzheimer’s, PTSD and other neuropsychiatric disorders. Lehigh Valley Live, release on presentation at the American Academy of Neurology Annual meeting 30 April, WFMZ Ch. 69 News (video)

NIH-NFL research grants on brain injury awarded (US)

In September 2012, the National Football League (NFL) donated $30 million to the Foundation for the National Institutes of Health (FNIH) to focus on brain injury. The Sports and Health Research Program (SHRP) now has a somewhat wider scope inclusive of joint diseases, sudden cardiac arrest, sickle cell anemia and hydration/heat injury. Last week they announced eight projects to be supported. Two ($6 million each) are cooperative agreements focusing on brain injury and after multiple concussions. These research projects are:  Boston University, which has pioneered major CTE research [TTA 5 June], and the VA on CTE; the pathology of CTE and delayed TBI from Mount Sinai Hospital in New York City. The six other studies are ‘pilots’ totalling about $2 million over two years and range from cortical GABA in pediatric sports concussion, the Spot Light concussion management app developed by Inlightened, LLC, and eye movement tracking for concussion detection. FNIH release

Further evidence of brain affect of sub-concussive blows

The body of research on the effect of sub-concussive blows to the brain is still developing. This recent study published this month in Neurology (abstract only) of  80 nonconcussed varsity football and ice hockey players and 79 non–contact sport athletes in a Division I NCAA athletic program concluded that head impact exposure negatively affected verbal learning and memory plus changed white matter by the end of the season. The subjects were evaluated before and after the season with brain scans plus learning and memory tests. All wore instrumented helmets that recorded the acceleration-time history of the head following impact. “A total of 20 percent (more…)

International CES unveils in NYC

The trends and items of note for next January’s show in Las Vegas

  • The ‘Internet of Things’ is the phrase-du-jour–embedding anything and everything with sensors (digital elements) and blending the physical and digital worlds
  • Consumer Digital Health Care was listed as #3 of CEA’s 2014 Technology Trends to Watch (PDF link). What is hot is self-tracking (1/3 of mobile users have tracked using a smartphone and tablet, and over half are now concerned about data security), integrating tech for seniors (touching on Selfhelp’s Virtual Senior Center [TTA 17 Mar 2010], remote monitoring (telehealth and telecare) including GrandCare Systems and kiosk HealthSpot Station, patient adherence, FDA approval of apps and the home as a healthcare hub.
  • Robots were the #4 trend: consumer robots such as home cleaners Roomba, Ecovacs; robots in eldercare; humanoid robots like NAO; robotic prosthetics and exoskeletons.

Digital health will again be showcased as a TechZone  (more…)

Counting the hits in a helmet with nano-enabled foam

Cushioning blows to the head, whether in football, soccer (football ex USA), hockey, cycling and in combat, is something that present helmets don’t do terribly well, if worn at all–thus the prevalence of concussions not being diagnosed properly, or the cumulative sub-concussive blows that may result in CTE. A Brigham Young University (Utah) team has developed a helmet with what they dub ‘ExoNanoFoam’ in contact with the player’s head. The foam is piezoelectric–when there is pressure on the foam, it produces an electrical voltage. (more…)

Acknowledging the reality of TBI in sports

Last week’s $765 million settlement by the National Football League (NFL) concluded a lawsuit in the works for over a year [TTA 7 Sept 12] that was brought by more than 4,500 players and their families. The more legally minded will argue that the NFL ‘got away with it’ before the season started; they admitted to no causal role between the game and traumatic brain injury (TBI) or chronic traumatic encephalopathy (CTE), which can only be confirmed post-mortem. The financial settlement sets small caps relative to the nature of the illness and the cost of care. What’s Unsettled About The NFL Concussions Settlement (Forbes) Also N.F.L. Agrees to Settle Concussion Suit for $765 Million (New York Times)

click to enlargeIf not an admission, player injury response may have been a factor in pushing the NFL into the 21st century. Concussion and injury assessment is a component of ‘Surface on the Sidelines’, part of a $400 million deal announced in May for official NFL adoption of the Microsoft Surface Pro (BusinessWeek). Teams have used iPads in many areas away from the sidelines due to outmoded league regulations, but the New York Giants’ medical/trainer staff used iPads last season to assess player injuries and concussions [TTA 23 Oct 2012]. Surface Pros are now loaded with the X2 app and database which stores player testing and medical history. Team doctors and trainers can now take down information on the field, make assessments and also to administer player self-testing. This allows faster determination of  injury and if needed, to pull the player, although it cannot do what Gizmag‘s headline claims it will: Could Microsoft Surface help the NFL to prevent brain injuries? (photo, SurfaceForums.net) (more…)

Cleveland Clinic concussion diagnostic app repurposed

Perhaps seeing a ‘job to be done’  in diagnosing sports concussions in rural areas where direct medical help can be distant, the Cleveland Clinic is now extending the usage of its Concussion Assessment System (C3) to assessing student athletes after suspect head blows. The two-year-old iPad app can be strapped on to the back of the athlete to measure movements that indicate balance problems, and assesses cognitive and motor impairment; information processing ability; attention/memory; balance and visual acuity. (more…)