Doctors have known for years that repeated blows to the head can cause progressive deterioration of the brain. Harrison Stanford Martland, a pathologist who observed this in boxers, called it the "punch drunk syndrome" in a paper he wrote in 1928.
Athletes who suffered from the syndrome, now known as chronic traumatic encephalopathy, have difficulty concentrating, suffer short-term memory loss, bouts of disorientation and confusion, and frequent headaches. CTE sufferers tend to be depressed and paranoid, and they show anti-social behaviors such as anger, aggression and irritability.
In severe cases, the motor movements of a CTE sufferer will slow down; his speech will be impaired, and he could suffer tremors, vertigo and deafness.
Autopsies have found CTE in the brains of more than 50 athletes, including former Cincinnati Bengal wide receiver Chris Henry, who died in 2009 after a fall from a moving pickup truck during a domestic dispute; pro wrestler Chris Benoit, who in 2007 strangled his wife and 7-year-old son and then hanged himself; and former Steeler Justin Strzelczyk, who died in 2004 when he drove his car into a tanker truck after leading police on a 40-mile high-speed chase.
Most of these athletes suffered concussions multiple times. But 21-year-old University of Pennsylvania football player Owen Thomas, who hanged himself last year, never missed playing time because of a concussion. Still, an autopsy showed his brain was in the early stages of CTE.
"This is a person getting many little hits, starting at a young age," Mr. Thomas' mother told the Philadelphia Inquirer. "Football linebackers might get 1,000 little hits. A thousand teaspoons of water could be the same as a big jug."
Although much has been learned about CTE in recent years, exactly what causes it has been something of a mystery. Joseph Maroon and Russell Blaylock think they've figured it out.
Dr. Maroon is vice chair of the department of neurosurgery at UPMC and the team neurosurgeon for the Steelers. Dr. Blaylock is a biology professor at Belhaven University in Jackson, Miss. They published their theory in the August issue of the journal Surgical Neurology International.
Each year between 100,000 and 300,000 high school, college and professional football players suffer concussions, according to their article. One-third of all retired NFL players have some form of mild cognitive impairment. Their paper "will change the course of neurology and neurosurgery," the journal's editor, James Ausman, wrote in an email to 11,000 neurologists. Their discovery "can explain not only the [CTE] of fighters and football players but can be extended to the development of Parkinson's syndrome, Alzheimer's disease and even depression."
When the brain is exposed to hard impact, the trauma stimulates protective cells in the brain to release chemicals called cytokines and excitotoxic amino acids. These interact with receptors on the brain's neurons to contain the area of inflammation or injury.
Under normal circumstances, the inflammatory process gradually dissipates. Then these same cells release chemicals that produce neuro healing, Dr. Maroon said.
But sometimes -- especially if the brain is subjected to even mild additional trauma before the natural healing process has begun -- the inflammatory process never shuts off, triggering a response called "excitotoxicity."
"If you get hit again, you have another outpouring of these cytokines," Dr. Maroon said. "It is akin to a smoldering brush fire in the brain that with repeated trauma burns out of control." Brain cells are destroyed rapidly and neurological problems develop.
Dr. Blaylock coined the term "immunoexcitotoxicity" to describe this reaction.
Their theory isn't that big a deal, said Edward Benzel, chairman of the department of neurosurgery at the Cleveland Clinic.
"This paper is basically an elaborate portrayal of a hypothesis that is yet to be validated or proven," he said. "It makes sense, but there are potentially a lot of gaps in this theory."
But Jack Wilberger, chairman of the department of neurosurgery at Allegheny General Hospital, said, "The biochemistry they describe absolutely is occurring."
He does have a concern. "The problem I have with it is they only quote one clinical study, and it involves only 27 people," Dr. Wilberger said. "The largest study of football players [involving 2,200 subjects] found no increase in Alzheimer's. If this is the driving force [behind CTE], then why aren't we seeing more of it?"
Although their journal article is a review of the literature rather than independent research, Dr. Blaylock and Dr. Maroon have presented a "very intriguing and interesting hypothesis," said Julian Bailes, director of the Brain Injury Research Institute at West Virginia University and a former team physician for the Steelers.
"It could go a long way to helping us to understand if and how there is a common mechanism on a biochemical or cellular basis to explain why certain individuals get chronic effects of multiple concussions," said Dr. Bailes, who this fall will leave WVU, where he was chairman of the neurosurgery department, to take charge of neurosurgery in the four hospitals of the Northshore University Health System in suburban Chicago.
Jack Jallo of Thomas Jefferson University hospital in Philadelphia said the article is "a good synthesis and a good hypothesis." "We all know the immune system is involved in everything. What's interesting in this paper is the idea of priming. That's the real contribution."
The case of former Steeler great "Iron Mike" Webster illustrates why more research is important, Dr. Benzel said. The All-Pro center died in 2002 at the age of 50. After retirement in 1990, Mr. Webster suffered from amnesia, dementia and depression, living frequently out of his pickup truck.
"Mike Webster had an estimated 25,000 hits but never reported a concussion," Dr. Benzel said. "[He] evidently died of CTE."
Indeed some athletes who've suffered only mild concussions develop CTE, but others who've suffered more serious concussions do not. What determines whether an athlete will have an immunoexcitotoxic reaction?
"Generally, we don't know," Dr. Maroon said. "There are several possibilities. The microglia [cells in the brain and spinal cord that provide active immune defense] can be primed by other agents, such as infections, pesticides, prior injuries and genetics."
Research into the role genetics may play in CTE could be the key, Dr. Benzel said. "It may be that years from now we'll be able to identify youth at risk for CTE with a blood test," he said.
If indeed what they've identified is the mechanism that causes CTE, "there are a number of things we can do to keep the fire from being lit," Dr. Maroon said.
Football teams should cut back on the number of practices that involve contact to reduce the likelihood of head injury.
Baseline studies such as ImPACT -- which Dr. Maroon helped develop -- can measure the degree of impairment an athlete has suffered from a concussion, and how rapidly or slowly he or she is healing. This can reduce the likelihood an athlete will resume playing before he or she is fully healed.
Anti-inflammatory drugs and natural anti-inflammatories such as fish oil, vitamin D3, resveratrol and magnesium can diminish the likelihood an immunoexcitotoxic reaction will start, Dr. Maroon said.
Alzheimer's disease proceeds in much the same way as an immunoexcitotoxic reaction in an athlete with a concussion, he said. Studies have indicated sustained treatment with aspirin and other non-steriodal anti-inflammatory drugs can lower the risk of Alzheimer's by 55 percent.
Low magnesium levels are linked to excitotoxicity, so athletes at risk for concussions should take supplements, Dr. Blaylock said.
The omega-3 fatty acids in fish oil have been shown in animal studies to reduce the seriousness of concussions and to help the brain heal, Dr. Maroon said. Vitamin D3 has neuroprotective effects, he said. Dark-skinned athletes in particular should consider taking it because studies indicate 50 to 60 percent of them have low levels of vitamin D3 in their bodies.
Drs. Maroon and Blaylock have long been advocates of natural supplements to promote health and have a financial interest in some of them. They disclosed these interests in their paper.
Jack Kelly: email@example.com or 412-263-1476. First Published September 19, 2011 4:00 AM