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Did concussions play role in Lou Gehrig's disease?

By Stephanie Smith, CNN
Researchers were intrigued by the possibility of a common thread between the athletes they studied and Lou Gehrig.
Researchers were intrigued by the possibility of a common thread between the athletes they studied and Lou Gehrig.
  • Repeated concussions may be risk factor for amyotrophic lateral sclerosis
  • Scientists found abnormal protein in brain, spinal cord of 3 pro athletes who had ALS
  • The athletes had all suffered repeated head trauma
  • Gehrig also had multiple concussions

(CNN) -- With his head bowed and a barely detectable quiver in his voice, the baseball player known as the "Iron Horse" devastated the crowd at Yankee Stadium, not by hitting a home run, but by announcing that he was dying.

It was July 4, 1939, and Lou Gehrig, a first baseman for the New York Yankees, had reached the end of a storied career.

"Fans, for the past two weeks you have been reading about a bad break I got," said Gehrig, who during his career played 2,130 consecutive games and still holds the record for the most grand slams. "Yet today I consider myself the luckiest man on the face of the Earth."

Gehrig's words were chilling considering his diagnosis: amyotrophic lateral sclerosis. ALS is a rare, incurable neurodegenerative disease (eventually named after him) that first manifests as muscle weakness and quickly descends to paralysis, an inability to breathe and death.

More than 70 years after his speech, a new, small study in the Journal of Neuropathology and Experimental Neurology may have unlocked a tantalizing clue about Gehrig's illness -- one that could be connected to his history of concussions.

"He did have three or four major concussions that landed him in the hospital," said Dr. Ann McKee, associate professor of Neurology and Pathology at the Boston University School of Medicine. "It is interesting to speculate that they may have contributed to his ALS."

"I wish we could look at Lou Gehrig's brain and spinal cord. I wish we could look at other athletes who've died and had ALS in the past. There's a lot we need to know."
--Ann McKee, Center for the Study of Traumatic Encephalopathy at the Boston University School of Medicine

McKee, along with colleagues at the Center for the Study of Traumatic Encephalopathy at the Boston University School of Medicine, discovered an abnormal protein in the brain and spinal cord of two former professional football players -- both diagnosed with ALS before they died -- and a former boxer. All of them had a history of repeated head trauma.

"When we looked at these three individuals, they had this hideous abnormal protein called TDP-43," said McKee, director of Neuropathology at the Bedford VA Medical Center. "Large amounts in the spinal cord and brain."

TDP-43 is associated with a handful of motor neuron diseases, including ALS. It is found in the nucleus of cells in the nervous system. McKee said that among the brains she examined, TDP-43 had leaked out of the nucleus, infiltrating the brain and spinal cord.

It is an intriguing possibility and at the same time a huge leap at this early scientific juncture to suggest causality -- that somehow a concussion could cause a degenerative motor neuron disease. Still, study authors were intrigued by the possibility of a common thread between the three athletes' brains, motor neuron disease symptoms they exhibited before dying, and Gehrig's own motor neuron disease.

Dead athletes brains show concussion damage

McKee was careful to add that there are likely distinctions between what she and her fellow researchers in Boston found and the specific array of damage associated with ALS. And yet, they are similar.

"I would refer to it as an ALS-like disease or something that mimics ALS," said McKee. "We may find out in the future that ALS is a heading and there are quite a number of subcategories and maybe this is a subcategory. It doesn't fit into the exact same pathologic pattern that we see in most cases of ALS."

"Is there a possibility that Lou Gehrig did have this new disease instead of sporadic ALS?" said Dr. Robert Stern, co-director of Center for the Study of Traumatic Encephalopathy. "It is possible but we really will never know. What's important to know is that Lou Gehrig, like so many athletes, went back to play over and over again with a repetitive head injury. We know that's not good."

McKee and colleagues took sections of the brain and spinal cord and excised very fine slivers, exposing them to stains that could reveal the presence of specific proteins. In this case, scientists were looking for TDP-43 and tau, a protein associated with head trauma. The three brains had copious amounts of both proteins littered throughout sections of the central nervous system.

Dr. David Hovda, a traumatic brain injury expert and director of the UCLA Brain Injury Research Center, said he is impressed with the study's methodology and findings.

"It is very convincing that these three individuals got this protein and they had the clinical signs and symptoms of a lower motor neuron disease," said Hovda. "I think this particular study doesn't prove that mild traumatic brain injury causes amyotrophic lateral sclerosis, but what it does is strong. It suggests once again that for people whose career is characterized by repeated concussions over a short period of time ... the likelihood of them expressing a disease that looks like ALS is increased."

Could a similar array of abnormal protein explain Lou Gehrig's disease? Perhaps, said McKee.

"I wish we could look at Lou Gehrig's brain and spinal cord," said McKee. "I wish we could look at other athletes who've died and had ALS in the past. There's a lot we need to know."

Lou Gehrig's disease affects about one in 50,000 people, according to the ALS Association. Yet among some groups of athletes participating in contact sports, the rate appears to be higher.

Young NFL player had brain damage usually seen in veterans

A study published in the American Journal of Epidemiology in 2007 revealed an 11-fold increased risk of ALS among Italian soccer players who had suffered multiple head injuries when compared to people who had never had a head injury. According to the study, "One hypothesis proposed to explain these findings is that repeated neurotrauma associated with heading the ball may increase the risk of ALS."

A Harvard University study published in 2005 suggests that serving in the military (where head trauma is common) confers an increased risk of ALS. Similar (but anecdotal) reports of higher-than-normal rates of ALS have also been reported among Canadian and National Football League players.

Still, even the suggestion of a connection between head trauma and ALS is premature, according to some experts.

"Although this is intriguing and there is some interesting data, I would be very careful to make a big broad statement that head trauma is linked to ALS," said Lucie Bruijn, science director of the ALS Association. "Very few people were identified in this study ... it isn't really clear how common this really is and how it is linked to ALS.

For now, the BU study represents a beginning -- a path carved for future investigation. It may also be a cautionary tale about potential long-term consequences of concussion.

"We definitely need to take it much more seriously than we take it," said McKee. "Athletes have gotten to the age where they're starting to develop some consequences and that's making us rethink the play of these games."

Gehrig died two years after delivering his speech. And while the specific underpinnings of his own disease will most likely never be known, it is known that he faced his disease with his familiar quiet dignity.

His final words that day at Yankee stadium: "So I close in saying that I might have had a tough break, but I have an awful lot to live for."