Blood-based biomarkers

Over the last 12 months significant interest and research in mild TBI and concussion, including expanding the horizon for blood-based biomarkers, has increased. Because TBI, especially mTBI and concussion, present significant challenges to accurately, reproducibly and rapidly establish diagnosis and provide serial monitoring the need for objective, non-invasive biomarkers exposing underlying fundamentals of host defense responses to the trauma has mushroomed. Researchers from Baylor College of Medicine, Houston, TX and the University of Pennsylvania, Philadelphia reported that plasma levels of calpain-cleaved aII-spectrin N-terminal fragment (SNTF) was elevated in 7 of 17 mTBI cases but in no uninjured controls (Front. Neurol., 18 November 2013 | doi: 10.3389/fneur.2013.00190). However, specificity for mTBI was questioned because SNTF levels were increased in some individuals with orthopedic injuries.


Swedish and UK scientists, using techniques developed at Quanterix Corp, Lexington, Massachusetts, reported in a paper published in JAMA Neurology (JAMA Neurol. doi:10.1001/jamaneurol.2014.367) that total tau (T-tau) correlated well with concussion in plasma of professional hockey players in Sweden, and influenced decision of players for return to play. In addition to T-tau they evaluated several other protein-based biomarkers, which did not correlate well. This paper is important since techniques developed at Quanterix used SIMOA (Single Molecule Array) technology an ultrasensitive, multiplexed technique for detection of proteins and nucleic acids. They concluded that since sports-related concussion in professional ice hockey players is associated with acute axonal and astroglial injury, T-tau may prove useful in larger studies.

A Long Way from Being Over

Furthermore, the concussions problems for football are a long way from being over.  It may just be the beginning with a sustained wave of future lawsuits, additional stories, and demands for fundamental changes in how football is played, at the earliest times and levels: Pop Warner leagues, middle and high school, college all the way to the NFL.  Although the three-quarters of a billion dollar settlement suppresses discovery into the aspects of the suit, other pressures will clearly pave the way for further research into the long-term effects of brain damage from repeated blows to the head.


NFL Players File Separate Lawsuit

Although the NFL would prefer it, the matter is not settled since several days later,  four other former NFL players filed a separate lawsuit against the NFL.

Subsequent information indicated that older players might not actually participate in the settlement, especially older players and those who died before 2006, even if their brains demonstrated changes of either Alzheimer’s disease (AD) or Chronic Traumatic Encephalopathy (CTE). Furthermore, newer information was that possibly legal fees WOULD come out of the settlement.

NFL Concussion Settlement

On August 29, 2013, Federal District Judge Anita Brody approved a settlement between the NFL and more than 2000 former NFL payers amounting to $765 million:

According to the agreement, the NFL will pay $675 million to players and their families according to an agreed-upon schedule. Forbes Magazine broke the remainder down as follows:

In addition to the monetary relief provided to the players and their families, the NFL and NFL Properties will make the following payments:

  • No more than $75 million for baseline medical exams;
  • $10 million for a research and education fund;
  • No more than $4 million to pay for the costs of notice to the members of the class of plaintiffs;
  • $2 million representing one-half of the compensation of the Settlement Administrator; and
  • Legal fees and litigation expenses to the plaintiffs’ counsel (to be determined by the court).


Concussions in the NFL

Below are links to some recent articles addressing the ongoing issue of concussions among NFL players.

NFL Reports Remain Inconsistent

NFL’s Progress on Concussions Blurred by Inconsistencies

NFL Concussions: The 2012-2013 Season in Review

NFL Looks to Helmet Technology to Combat Concussions

The NFL Teams Up With GE on Concussion Technology

Why Philadelphia Court Should Toss NFL Concussion Lawsuit

The NFL’s CTE Clock is Beginning to Click in Real Time

Bad Brains: The NFL and its Concussion Crisis

Game Change: Brain Scans Offer New View of NFL Concussions




NFL Responds to Player Lawsuits

In response to the NFL Players Association (NFLPA) supported mega-suit discussed in a previous blog post, the NFL released a statement: “Our legal team will review today’s filing that is intended to consolidate plaintiffs’ existing claims into one ‘master’ complaint,” The statement went on to read, “the NFL has long made player safety a priority and continues to do so. Any allegation that the NFL sought to mislead players has no merit. It stands in contrast to the league’s many actions to better protect players and advance the science and medical understanding of the management and treatment of concussions.”  The NFL then filed a motion to dismiss the lawsuits, including the mega-suit, and the players countered, in a brief filed in US District Court, by disputing efforts by the NFL to frame the cases as a labor issue. Their argument was that the legal system, rather than the sport’s collective bargaining agreements, should govern this exceptional case.

Football’s Link to Mild Traumatic Brain Injury

Is football too dangerous? This was the title of an article in Junior Scholastic, a publication aimed at high schoolers and their parents. The article went on to discuss the sequelae (conditions the consequence of a previous disease or injury) and quoted Robert Cantu, MD, a Clinical Professor of Neurosurgery at Boston University School of Medicine (BUSM), who said that he’s seen far too many players, even young ones, “who’ve had their lives altered” by concussions. Cantu is also Co-Director of the Center for the Study of Traumatic Encephalopathy (CSTE) at BUSM.

It is important to realize that football players might suffer thousands of small blows to the head over a lifetime of playing, especially if they go on to play at the professional level. Such repetitive blows can lead to repeated bouts of mild TBI (mTBI) or concussions that eventually can lead to a brain disorder known as chronic traumatic encephalopathy (CTE). CTE, known previously as punch-drunk syndrome, was first observed in boxers (dementia pugilistica) and in clinical terms can cause memory loss, depression, and even dementia. As recently as the 1990s repetitive blows to the head were not considered a cause of later problems for either American or Australian football players but, beginning in late 2010, CTE has received greater attention with publications from BUSM and others.

CTE differs from Alzheimer’s disease (AD) neuropathologically in that it consists primarily of neuroinflammation and abnormal deposits within and outside nerve cells (neurons) called neurofibrillary tangles (NFTS). AD also has NFTs but is also primarily characterized by amyloid plaques outside of neurons. The NFTs are composed chiefly of abnormal amounts and types of a microtubule-associated protein called tau, and CTE and other conditions, including AD, are referred to as tauopathies.