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.

DOD and DVA to Intensively Study PTSD and mTBI

In recent years there has been a lack of clear criteria within the military for diagnosis and treatment of PTSD and this resulted in the reversal of close to 40 percent of PTSD diagnoses.  There is some evidence that 15-20% of all returning combatants from OEF/OIF and Afghanistan have PTSD, and this has led to a concerted effort by the Department of Defense (DOD) and the Department of Veterans Affairs (DVA) to improve the situation.

It was recently announced that traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) will begin using new criteria for diagnosis and treatment in the military, DOD, and by DVA at VA hospitals. Both the DOD and DVA announced last month an investment of more than $100 million for research into improving diagnosis and treatment of mild TBI (mTBI) and PTSD. Two groups, the Consortium to Alleviate PTSD (CAP) and the Chronic Effects of Neurotrauma Consortium (CENC) will be jointly managed by VA, and by the Congressionally Directed Medical Research Programs (CDMRP), on behalf of the DOD. According to Assistant Secretary of Defense for Health Affairs Jonathan Woodson, “these consortia will bring together leading scientists and researchers devoted to the health and welfare of our nation’s service members and veterans.” He added, “a primary goal of CENC is to

As reported in Time online:
– For PTSD, CAP “will study potential indicators of the trauma, as well as prevention strategies, possible interventions, and improved treatments. Biomarker-based research will be a key factor in CAP’s studies,” the CDMRP says. PTSD afflicts some troops after combat tours, and causes anxiety, depression and other mental ills.

– For mTBI, CENC will try “to establish an understanding of the after-effects of a mTBI. Potential comorbidities also will be studied; that is, conditions associated with and worsen because of a neurotrauma,” the CDMRP says. TBI is a physical wound – a concussion – usually suffered by troops near the shock waves of an improvised explosive device. It can bruise the brain and cause mood changes, fatigue and sleeping more – or less – than usual.

Players Accuse NFL in Mega-Suit

With growing concern over the long-term effects of concussions and mTBI sustained by NFL players, as of May 25, 2012, eighty-one lawsuits had been filed with 2,138 former NFL players as plaintiffs, and 3,356 plaintiffs that included players, their spouses and other relatives. On June 7, 2012 a mega-suit, bringing these and others together, was filed in US District Court. The mega-suit stated that “after voluntarily assuming a duty to investigate, study, and truthfully report to the public and NFL players, including the Plaintiffs, the medical risks associated with MTBI in football, the NFL instead produced industry-funded, biased, and falsified research that falsely claimed that concussive and sub-concussive head impacts in football do not present serious, life-altering risks.” 

In response, the NFL released statements about many health programs run by the NFL for current and former players, along with medical benefits available to former players, including joint and traumatic arthritic-related programs such as joint replacement, and neurological evaluations and spine treatment programs. In addition, the NFL provides assisted-living partnerships, long-term care insurance, prescription benefits, life insurance programs, and a Medicare supplement program. The Mild Traumatic Brain Injury Committee, created by the NFL in 1994, recently published a general neurologic medicine article on Medscape entitled Repetitive Head Injury Syndrome.

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.