Is it possible that sustaining multiple head injuries, such as concussions, could result in the development of motor neuron disease? That's the provocative question posed in a study from the Journal of Neuropathology and Experimental Neurology in August. The study authors suggest that it is possible—and that some people diagnosed with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease after the famous Yankees' baseball player, may not actually have the disease.
“A claim that head injury contributes to ALS cannot be based on findings seen in just three patients.” - —ROBERT G. MILLER, M.D.
The study grabbed national headlines and ignited a firestorm of debate among ALS experts when study author Anne C. McKee, M.D., was quoted in the Aug. 17 New York Times speculating that Lou Gehrig may not have had ALS, which is the most common form of motor neuron disease. Dr. McKee, director of the neuropathology laboratory for the New England Veterans Administration Medical Center, made her remark based on the many concussions Gehrig sustained during his baseball career. However, nowhere in the study did the investigators present evidence to support this claim.
More than 30,000 people in the U.S. have ALS, according to The ALS Association. Many contacted their neurologist to ask if they had been inaccurately diagnosed with the disease. Neurology Now spoke with experts in the field to clear up the misconceptions presented in the media.
On what evidence did the investigators base their findings?
Dr. McKee and colleagues studied the brains and spinal cords of 12 deceased, former athletes who had chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease caused by multiple head injuries. The disorder is characterized by the buildup of a toxic protein called “tau” throughout the brain.
People with the disease typically experience progressive loss of memory and other cognitive abilities. They also may also show personality changes, emotional instability, erratic behavior, inability to concentrate, and progressive loss of consciousness, according to the National Institute of Neurological Disorders and Stroke (NINDS).
Three of the 12 patients with CTE had also been diagnosed with motor neuron disease, which is a group of progressive neurologic disorders, including ALS, that destroy nerve cells called motor neurons. These nerve cells are involved in various muscle functions such as sleeping, walking, breathing, and swallowing, according to NINDS. Lucie Bruijn, Ph.D., chief scientist for The ALS Association, notes that the term “motor neuron disease” can refer to the impairment of the upper motor neurons (located in the brain) or the lower motor neurons (located in the brain stem and spinal cord) or both. For an ALS diagnosis, Dr. Bruijn says, both sets of motor neurons must be affected.
Recent studies have shown that the accumulation of the protein TDP-43 throughout the brain and spinal cord can cause ALS.
Dr. McKee and colleagues looked at the proteins tau and TDP-43 in the 12 athletes and compared their findings to a deceased “control group” comprised of 12 people who did not have neurologic disease and 12 others who had non-genetic (also called “sporadic”) ALS.
What did the investigators observe in the patients?
The researchers found accumulations of tau throughout the brains and spinal cords of all nine athletes who had a diagnosis of CTE prior to death. However, they did not find tau accumulations in any of the 24 controls. Researchers also noticed a buildup of TDP-43 in the brains and spinal cords of these nine athletes, which they also found in the 12 controls with ALS, but not in the 12 normal controls.
Robert G. Miller, M.D., program director of the Forbes Norris MDA/ALS Research Center at the California Pacific Medical Center, says finding TDP-43 accumulation in the CTE patients is an interesting discovery. “It raises the possibility that TDP-43 buildup may be created by head injury,” Dr. Miller says. Although TDP-43 had previously been found in the brains of people with ALS, he adds, “It hadn't been specifically related to brain trauma or injury.”
The three athletes with CTE as well as motor neuron disease had different patterns of TDP-43 accumulation than did the people with sporadic ALS. The three athletes also had tau buildup, which was absent in the sporadic ALS patients and also the controls without neurologic disease.
Since investigators found both proteins in different accumulation patterns than is typically seen in ALS, they concluded that head injury “results in motor-neuron degeneration, and that the resulting disease is not actually ALS. It is a different disorder...that compromises nerve function.”
Is the evidence strong enough to suggest head injury can cause motor neuron disease?
“The study authors are entitled to have any opinion they like regarding the study's findings,” says Carmel Armon, M.D., professor of neurology at Tufts University School of Medicine and chief of the Division of Neurology at Baystate Medical Center. “My critique is that the data do not provide a factual foundation for the opinion.”
“To make a claim that head injury contributes to ALS—and may even cause ALS—cannot be based on findings seen in just three patients,” Dr. Miller says, adding that the majority of people who have been diagnosed with ALS don't have a history of repeated head injuries.
“The number of patients I see who played professional [sports] or had repeated head injuries is infinitesimally small,” Dr. Miller says. “To select three patients who played professional sports and also had repeated head injuries, and to say on the basis of those three patients that this probably is the cause of ALS is ludicrous.”
Where can I go for more information?
The sensationalized Times article outraged many neurologists and caused a significant amount of undue anxiety in people with and without ALS, says Dr. Bruijn. Many people contacted The ALS Association with their concerns, from those who believed they had been misdiagnosed with ALS to those who were worried they might develop ALS due to a head injury.
The ALS Association released a Q&A on the article in an attempt to alleviate patients' confusion and unease. Here are a few other resources to help you read health and science news with a critical eye.
CLICK AND CONNECT! Access the links in this article by reading it on neurologynow.com.
▸ Lies, Damned Lies, and Science: How to Sort through the Noise around Global Warming, the Latest Health Claims, and Other Scientific Controversies, Sherry Seethaler (FT Press, 2009)
▸ Neurology Now, “Miracle Drug! Or Not”: bit.ly/963H0W
▸ Neurology Today, “Does Concussion Cause Motor Neuron Disease?: The Question Stirs Debate”: bit.ly/9TF1dl
▸ News and Numbers: A Guide to Reporting Statistical Claims and Controversies in Health and Other Fields, Victor Cohn and Lewis Cope (Iowa State Press, 2001)
▸ The ALS Association's Q&A on Head Trauma: bit.ly/cZikU7