ALS Experts Urge Caution Regarding Head Injury Findings

A new study has claimed professional athletes who have sustained repeated head injuries and developed what's known as "chronic traumatic encephalopathy" (CTE) may also be at higher-than-average risk for developing a motor neuron disease that resembles amyotrophic lateral sclerosis (ALS) or is a subtype of ALS.

The two diseases may be part of a continuum of nervous-system pathology that can start with repeated head trauma and ultimately involve the brain and spinal cord, resulting in cognitive, behavioral and motor abnormalities, the study's investigators say.

However, says neurologist Stan Appel, who directs the MDA/ALS Center at Methodist Neurological Institute in Houston and chairs MDA's Medical Advisory Committee, the study was very small, and the results should be interpreted with extreme caution.

Background on ALS and CTE

Approximately 5 percent to 10 percent of the time, ALS is a clearly genetic, inheritable condition. The other 90 percent to 95 percent of cases — so-called sporadic ALS — are thought to be due to a variety of genetic and environmental causes, with head injury among the contributing factors that have been proposed.

"It's clear that ALS is not a single disease," Appel said. "It's a syndrome that can result from many causes, can present in many different ways, and can follow many different time courses. Among the factors that have been suspected, although not proven, to influence the development of ALS, is trauma [injury]."

Typically, CTE is characterized by cognitive and behavioral symptoms following head injuries, with most of the observable pathology in the brain (visible on autopsy). In contrast, ALS is characterized mostly by motor symptoms (weakness and paralysis), with a majority of the abnormalities visible on autopsy in the spinal cord.

There may be genetic or nongenetic influences that predispose people to developing either CTE or ALS, or both, in response to repeated head injuries. Abnormal or misplaced molecules of proteins may play a role in the degeneration of the nervous system in these conditions.

About the new findings

Ann McKee at Bedford (Mass.) Veterans Administration Hospital and Boston University School of Medicine, coordinated a research group that included 16 investigators from various U.S. institutions.

The researchers, who published their findings online Aug. 18, 2010, in the Journal of Neuropathology and Experimental Neurology, examined autopsy samples from 12 professional athletes, nine of whom carried a clinical diagnosis of CTE alone and three of whom carried a diagnosis of CTE with a motor neuron disease (CTE + MND). The professional athletes played football or hockey or were boxers.

The three with a "CTE + MND" diagnosis showed high levels of abnormally located TDP43 protein molecules in the cells of their spinal cords and brain.

Several of the "CTE alone" patients had significantly elevated levels of  TDP43 in various parts of the brain,  but only one showed it in the spinal cord, and it was only  mildly elevated.

The results confirm the well-accepted finding that TDP43 abnormalities are a pathological hallmark of sporadic and some forms of familial ALS, Appel said. "Since all three patients had received clinical diagnoses of ALS, it is not surprising that they also bore the TDP43 hallmark of ALS pathology," he added. "It is likely that all three had two different disorders, namely CTE and ALS, both of which have been associated with traumatic injury."

The researchers also analyzed the athletes' autopsy samples for the presence of abnormal tau, a protein that appears in Alzheimer's disease and other neurodegenerative conditions.

All 12 patients, including the nine with CTE alone and the three with CTE + MND, had some degree of abnormal tau in various parts of their brains.

The three with CTE + MND had abnormal tau protein in their spinal cords as well as their brains, but so did some of the patients with CTE alone. Therefore, the correlation between the presence of ALS-like symptoms and the presence of abnormal tau in the spinal cord wasn't strong.

The researchers say their study suggests that repeated head trauma may be the origin for both CTE and perhaps can also cause ALS or an ALS-like syndrome as well. They say genetic factors may also be involved.

Appel commented that the study was so small, including only three people who had both CTE and motor symptoms, that it's impossible to draw conclusions about cause and effect. He suggested that "it is more likely that CTE does not cause ALS, but that both are independent consequences of multiple factors, one of which is trauma."

Meaning for people with ALS

The significance of the new findings and the proposed link between head trauma and the development of ALS remain unclear.

An Aug. 17, 2010, article in the New York Times, based on the new study, suggested that a new disease entity — a disorder that looks like ALS but actually isn't ALS — may have been identified, and that therefore famed Yankees baseball player Lou Gehrig may not have had ALS (Lou Gehrig's disease) after all. (See Study Says Brain Trauma Can Mimic ALS.)

Those statements are very misleading, Appel said. ALS has a broad definition to begin with, he noted, and there is no reason to think that Gehrig did not have ALS, whether or not he sustained head injuries during his athletic career. After all, Appel added, there never was any indication in Lou Gehrig of the cognitive dysfunction that is characteristic of CTE.

"There are many causes of ALS that we already have identified, and trauma may be a trigger in some," said neurologist John Day, who directs the MDA neuromuscular disease clinic at Fairview-University Medical Center in Minneapolis. "We need to provide the best possible care and support for all these individuals, no matter what initially started their particular loss of strength. For instance, I don't want current patients or families to think that they don't deserve treatment in an MDA ALS Center or MDA clinic simply because they might have had a previous head injury. I'm afraid many people might be led to that conclusion by reading the New York Times story."

For more about causes of ALS, see

Mutations in FUS Gene Are a Cause of Familial ALS

SOD1 Versus Other ALS: Apples and Oranges?

ALS-Causing TDP43 Overstays Its Welcome

ALS DNA Tests Available

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