Head Trauma Linked to ALS-Like Disease

BU researchers find neurological condition in former athletes

| From BU Today | By Caleb Daniloff. Video edited by Devin Hahn

Listen to CSTE codirectors Robert Stern, Christopher Nowinski, and Ann McKee talk about CTE and the discovery of a disease never before described in the medical literature, CTEM, in the video above.

Over the past two years, BU researchers have linked head injuries in former athletes to depression and dementia, making headlines and leading to rule changes in the National Football League. Turns out that these problems may not be the only ones collision athletes like football players, boxers, and hockey players need to worry about. The researchers have now found a link between repetitive head trauma and a new form of motor neuron disease similar to amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease. Their findings were published in the September 2010 issue of the Journal of Neuropathology and Experimental Neurology.

“The significance of this finding is that not all ALS-like disease attacks out of the blue—sometimes it’s because of our choices in life,” says Ann McKee, a School of Medicine associate professor of neuropathology and neurology and a codirector of BU’s Center for the Study of Traumatic Encephalopathy (CSTE). “The more we know about what behaviors hasten disease, the more we can practice prevention.”

McKee and her colleagues discovered the new disease while examining the brains and spinal cords of 12 deceased athletes stored in the CSTE brain bank. Each showed evidence of the neurodegenerative disease chronic traumatic encephalopathy (CTE), once known as dementia pugilistica, or “punch-drunk syndrome.” But two former NFL players—Wally Hilgenberg of the Minnesota Vikings and Eric Scoggins, who played only three games with the San Francisco 49ers, but spent four seasons in the U.S. Football League—as well as a boxer, developed motor neuron disease late in their lives. Scoggins died in 2009, at age 49, and Hilgenberg in 2008, at 66. All three had been clinically diagnosed with Lou Gehrig’s disease, although they also showed behavioral changes and cognitive decline. ALS attacks motor nerve cells in the brain and spinal cord without warning, leading to muscle weakness, atrophy, and often paralysis. The mind, however, is left intact. Celebrated British physicist and author Stephen Hawking suffers from ALS.

In the three athletes diagnosed with ALS, McKee found the abnormal protein TDP-43 in the brain and spinal cord in a unique pattern and distribution, along with deposits of an abnormal form of tau protein, which can create tangles that strangle and destroy brain cells. Abnormal tau deposits, a marker of CTE, are not found in ALS. The new findings suggest that the motor neuron disease that affected the three athletes, while similar to ALS, represents a distinct disease never before described in the medical literature. McKee and her colleagues have named it chronic traumatic encephalomyelopathy (CTEM), and they believe the cause is repetitive head trauma absorbed in contact sports such as football and boxing.

Lou Gehrig’s disease, the most common form of motor neuron disease, is named after the New York Yankees legend who played in the 1920s and ’30s. Early symptoms include progressive problems with speech, swallowing, and breathing. Some 30,000 Americans, mostly men, live with the disease. The majority of cases are “sporadic,” meaning of unknown cause, although researchers believe the condition involves a complex interaction of genetic and environmental risk factors. ALS is fatal in nearly all cases.

“ALS or CTEM may be the most difficult diseases in existence to watch,” McKee says. “They are slow, agonizing deteriorations that are witnessed helplessly by loved ones.”

The risk of ALS has been reported to be higher among collision athletes and military veterans. A study of professional soccer players in Italy found that the incidence rate of ALS was 6.5 times higher than in the general population. Based on the number of retired NFL players with ALS, it’s estimated that the risk is at least eight times higher than in the adult male population, CSTE researchers say. A 2006 report by the National Academy of Sciences Institute of Medicine found that among military veterans with a history of head injuries, the risk of ALS was 2.3 times higher than normal. Since 2008, the U.S. Department of Veterans Affairs has considered ALS a presumptively compensable illness for all veterans.

“When we read reports about cases of the disease being linked to specific activities or experiences, such as the increased risk associated with military service or this one regarding professional athletes, we are reminded of just how complex of a disorder ALS is,” says Steven Perrin, CEO and chief scientific officer of the ALS Therapy Development Institute in Cambridge, Mass. “We’re hopeful that this new work may shed light on potentially exciting new possibilities for biomarker and therapy development.”

CSTE’s findings raise the question of whether Gehrig suffered from CTEM rather than the disease that bears his name. Nicknamed the “Iron Horse,” Gehrig played football at Columbia University before joining the Yankees and playing in 2,036 consecutive games, a record that stood for more than 60 years. He suffered at least five documented concussions and was reported to have been knocked unconscious for five minutes after taking a pitch to the head while not wearing a helmet. He played the next day. Gehrig died in 1941, two years after being diagnosed.

The center’s research efforts over the past two years have contributed to cultural changes in collision sports, most notably in the NFL. McKee has analyzed the brains of more than 35 athletes and found evidence of CTE in 12 of 13 former NFL players. Under mounting scientific and political pressure, the NFL changed its return-to-play rules and broadcast PSAs warning youth players of the danger of concussions last year and has been lobbying for youth concussion legislation in all 50 states. New posters spelling out the dangers of concussions and head trauma now hang in all NFL team locker rooms. This past April, the league gave CSTE an unrestricted gift of $1 million for further research and has encouraged its players to donate their brains to BU after they die.

CSTE maintains a registry of more than 350 living athletes who have agreed to leave their brains and spinal cords and to participate in telephone-based interviews and assessments during life. Robert Stern, a MED associate professor of neurology and a CSTE codirector, is about to launch a study of retired NFL players; they will undergo extensive neurological, cognitive, psychiatric, cerebrospinal fluid, and neuroimaging tests.

Fellow CSTE codirector Robert Cantu, a MED clinical professor of neurosurgery, was recently appointed senior advisor to the new NFL Head, Neck and Spine Committee. Cantu, McKee, and CSTE codirector Christopher Nowinski, a former professional wrestler and president of the Sports Legacy Institute, now serve on the NFL Players Association Mackey/White Traumatic Brain Injury Committee.

Responding to the latest findings from BU, physicians Hunt Batjer and Richard Ellenbogen, cochairmen of the Head, Neck and Spine Committee, jointly commented: “We are pleased that the NFL has provided the support necessary for this research and look forward to continued discussion of the findings within our medical committee and with other researchers to better understand their clinical implications.”

The CSTE team is also vigorously researching the impacts on the nervous system of subconcussive head blows and milder brain trauma.

“If repetitive head trauma can spark this kind of neurodegeneration,” McKee says, “then by studying the effects of repetitive mild brain trauma, we can learn about the initial, early triggers of neurodegenerative disease and how to slow, reverse, and lessen them.”

Read more on head trauma and athletes.

---

Editor's Picks