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New CTE Study Categorizes Stages of Degenerative Brain Disease in Veterans, Athletes

by U.S. Medicine

January 11, 2013

By Brenda L. Mooney

BOSTON – For the first time, researchers have categorized chronic traumatic encephalopathy (CTE), the degenerative brain disease associated with repeated brain trauma in military combat and contact sports, into four stages of severity.

In a recent study from the Veterans Affairs Boston Healthcare System, Boston University Center for the Study of Traumatic Encephalopathy (CSTE) and the Sports Legacy Institute (SLI), 68 cases of CTE were identified among deceased athletes and military veterans whose brain and spinal cords were donated to the VA CSTE Brain Bank. The study, which was published in this month’s issue of the journal Brain, represents the largest case series of CTE published to date.

Co-Directors of the BU CSTE include, in order, former wrestler Chris Nowinski; Robert Stern, PhD, professor of neurology and neurosurgery at BUSM; Ann McKee, MD, professor of neurology and pathology at BUSM and director of VA CSTE Brain Bank at VA; and Robert Cantu, MD, clinical professor of neurosurgery at BUSM.

Of the 68 cases of CTE found in males between 17 and 98 years old, 64 were athletes, and 18 of those were also military veterans. Of the athletes, 34 were professional football players, nine only played college football and six had only played high school football. The group included three additional veterans who did not have a sports background.

Evaluation of one of the study subjects — for whom self-injurious head-banging behavior was the sole environmental exposure — underscored the view that repetitive brain trauma alone is sufficient to trigger CTE in some cases.

“This study extends our knowledge concerning the spectrum of the clinical and pathological abnormalities associated with CTE, although further studies are needed to investigate critical aspects of trauma-induced neurodegeneration, including the incidence and prevalence of CTE; whether the symptoms of CTE are distinctive from other conditions; how genetics influence susceptibility or resistance to CTE; and whether other environmental exposures also play an additive role in the development of CTE,” said lead author Ann McKee, MD, director of the Neuropathology Service for VA New England Healthcare System, professor at Boston University School of Medicine (BUSM) and co-director of the CSTE.

McKee also is director of the CSTE and the Brain Banks for Boston University’s Alzheimer’s Disease Center, which are based at the Bedford, MA, VA Medical Center.

CTE, which appears to be slowly progressive in most individuals, is characterized in early stages by the presence of abnormal deposits of a protein called tau in the form of neurofibrillary tangles, glial tangles and neuropil threads throughout the brain. These tau lesions eventually lead to brain-cell death. Currently, CTE can only be diagnosed postmortem.

Among the veterans found to have CTE were marines, soldiers and sailors from World War II, the Vietnam and Gulf wars, as well as the wars in Iraq and Afghanistan. Researchers also found evidence of the condition in 50 football players, including 33 who played in the National Football League (NFL), one in the Canadian Football League (CFL), one semi-professional player, nine college players and six high school football players. CTE also was identified in four National Hockey League (NHL) players, one amateur hockey player, seven professional boxers, one amateur boxer, and one professional wrestler.

“While it remains unknown what level of exposure to brain trauma is required to trigger CTE, there is no available evidence that occasional, isolated or well-managed concussions give rise to CTE,” explained co-author Robert Cantu, MD, co-director of CSTE and co-founder of SLI.

The new study provides specific pathological criteria for the diagnosis of CTE and divides CTE into four stages of disease (Stages I-IV). Based on interviews with families of the deceased donors, researchers were able to develop a list of symptoms common to stages of the disease:

• In Stage I, headaches and issues related to attention and concentration were common;

• In Stage II, the symptoms expanded to include depression, explosivity and short-term memory impairment;

• In Stage III, reported symptoms included cognitive impairment and problems with executive functions, specifically planning, organization, multitasking and judgment.

• In Stage IV, there was evidence of full-blown dementia (i.e., memory and cognitive impairments severe enough to impact daily living).

While CTE appeared to be slowly progressive in most of the study subjects, it may not progress or progress at the same rate in all patients, study authors noted. Overall, however, 89% of those diagnosed with CTE through pathological studies had demonstrated clinical symptoms involving cognitive, behavioral or mood impairments before death, according to the report.

In addition, one-third of the CTE cases were diagnosed with additional neurodegenerative disease, including:

• Motor neuron disease (12%);

• Lewy body disease (16%;

• Alzheimer’s disease (11%); and

• Frontotemporal lobar degeneration (6%).

Years before the onset of cognitive and behavioral symptoms, most of the individuals with CTE and motor neuron disease (CTE-MND) had suffered symptoms of motor weakness, atrophy and fasciculations, or muscle twitches, the study notes.

The next goal of researchers is developing methods to diagnose CTE during life, according to co-author Robert Stern, PhD, Boston University professor of neurology and neurosurgery.

“The ability to diagnose CTE while someone is alive is an important next step to allow us to address some of these important issues, as well as develop and test treatment and prevention strategies for the disease,” he said.

In addition to raising troubling questions about the safety of contact sports, the research underscores that CTE could have devastating implications for military veterans and the VA’s ability to care for them.

A study released this summer also found CTE indications in brain tissue from blast-exposed military personnel. That study noted that as much as 20% of the 2.3 million troops deployed to Iraq and Afghanistan since 2001 could have suffered a traumatic brain injury (TBI) as a result of exposure to IEDs. In a worst-case scenario, 460,000 veterans could be at risk for CTE.

Honor Roll of Athletes Who Left Brains to Further Neurologic Research

Some notable deceased athletes contributed their brains to further the study of chronic traumatic encephalopathy (CTE).

The Boston University Center for the Study of Traumatic Encephalopathy said it has permission to release the following names of those who were diagnosed with CTE in this study. Those included:

  • NFL Hall of Fame tight end John Mackey, who died in 2011 from complications of dementia and was found to have both CTE and frontotemporal lobar degeneration;
  • NFL Hall of Fame running back Ollie Matson, who died in 2011 from complications of dementia and was diagnosed with Stage IV CTE;
  • Former NFL and CFL running back Cookie Gilchrist, who died in 2011 at age 75 from throat cancer and was diagnosed with Stage IV CTE;
  • Ron Perryman, a former Boston College linebacker who died from respiratory failure associated with Amyotrophic Lateral Sclerosis in 2011 at the age of 42 and was diagnosed with CTE-MND;
  • Eric Pelly, a former high school football and rugby player diagnosed with multiple concussions who died at age 18 from complications resulting from a previous concussion and had Stage I CTE.
Ollie Matson, who played in the National Football League, in 1952 and from 1954 to 1966, was diagnosed posthumously with Stage IV CTE.

In addition, the BU CSTE obtained permission to release the brain images from an anonymous Marine veteran of the wars in Iraq and Afghanistan, who suffered multiple concussions in combat and in sports. He died in his 20s with Stage I CTE.

The VA CSTE Brain Bank, led by the recruiting efforts of former professional wrestler Chris Nowinski, now contains more than 135 brains, of which approximately 80% have shown evidence of CTE.

More than 600 living athletes have committed to donate their brain to the BU CSTE after death and are being followed longitudinally as part of the Longitudinal Examination to Gather Evidence of Neurodegenerative Disease (LEGEND) study. Participants in the LEGEND study take part in yearly telephone interviews as well as yearly online questionnaires. They also have the opportunity to provide a saliva sample for genetic testing. Both those with and without a history of concussions can participate in the LEGEND study.

“We appreciate the generosity and support of the athletes and their families involved in our research. This pathological research is a critical step as we continue to make advances toward our ultimate goal of an effective treatment for CTE,” said Nowinski, a co-author of the report and co-director of the CSTE.


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