Repetitive head trauma resulting from collision sports such as football and boxing may be associated with a motor neuron disease that is similar to, yet distinct from, amyotrophic lateral sclerosis (ALS), researchers reported in the September issue of the Journal of Neuropathology and Experimental Neurology. The findings may represent the first pathologic evidence of a connection between motor neuron disease and head trauma, but they may also call into question past diagnoses of ALS, particularly in the case of athletes who play contact sports and military veterans, who are diagnosed with ALS at a higher rate than the general population.
Ann C. McKee, MD, and colleagues observed the brains and spinal cords of 12 deceased athletes who had chronic traumatic encephalopathy (CTE), 10 of whom had widespread TDP-43 proteinopathy affecting multiple areas of the brain. Three of the former athletes with CTE also had TDP-43 and abnormal tau protein in their spinal cords and had developed a progressive motor neuron disease several years before death.
Two of the athletes were former football players and had been clinically diagnosed with ALS, and the third, an ex-boxer and military veteran, had been diagnosed with atypical ALS with dementia. The three athletes with motor neuron disease had a distinctive pattern of TDP-43 pathology in the brain and spinal cord that has not been described in sporadic ALS. In addition, tau pathology was found in their brain and spinal cord tissue, whereas tau pathology is not a feature of sporadic ALS, noted Dr. McKee.
“We found a unique pathologic disease in three professional athletes who suffered long-standing repetitive brain trauma,” Dr. McKee, Associate Professor of Neurology and Pathology and Codirector of the Center for the Study of Traumatic Encephalopathy, Boston University School of Medicine, toldNeurology Reviews. “The disease—chronic traumatic encephalomyelopathy (CTEM)—is characterized by the build-up of two abnormal proteins—tau and TDP-43—in the brain and spinal cord and is associated with symptoms that mimic ALS.”
Motor neuron disease is similar to dementia, in that its etiology is heterogeneous, according to Dr. McKee, who is also Director of Neuropathology for the New England Veterans Health Care System. “Although the most common cause of motor neuron disease is sporadic ALS, our findings indicate that other disorders may have a similar clinical presentation and should be considered in the differential diagnosis,” she commented. “Understanding how traumatic injury may trigger a motor neuron disease offers the hope of better insight into pathogenetic mechanisms underlying this neurodegenerative process. Analyzing the nervous system response to repetitive mild trauma may provide critical discoveries in understanding motor neuron disease in general.”
Concussions in Sports
The 12 former athletes in the study ranged in age from 42 to 85 and included seven former football players, four retired professional boxers, and one hockey player. Prior research by Dr. McKee and colleagues found that repetitive head injury may be associated with CTE in a dozen former National Football League (NFL) players. The findings helped push the NFL to adopt new rules regarding when players could return to the game after being diagnosed with a concussion. When asked if the NFL and other sports organizations should take stronger precautions in light of the new findings, Dr. McKee replied, “Absolutely and immediately.”
Diagnosing Lou Gehrig
The findings have also led some to reconsider whether Lou Gehrig was accurately diagnosed with ALS—subsequently referred to as Lou Gehrig’s disease—in 1939. Gehrig reportedly had multiple concussions, including one in 1934 in which he was knocked unconscious after being hit on the head by a pitched baseball while not wearing a helmet. Gehrig died in 1941 and was cremated.
“We will never know whether Lou Gehrig had sporadic ALS or CTEM,” Dr. McKee commented. “It may be interesting for some to speculate about, as he certainly suffered considerable repetitive head injury while playing baseball and perhaps, football, but we will never know. However, the speculation that he might have had CTEM may be useful as it highlights how long-held assumptions can be wrong.”
Dr. McKee also pointed out that her findings are preliminary. “We have studied only three cases, and certainly, we need to study many more individuals with repetitive head injury and motor neuron disease to fully understand the relationship,” she said.
McKee AC, Gavett BE, Stern RA, et al. TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. J Neuropathol Exp Neurol. 2010;69(9):918-929.
The Mayo Clinic Got It Right—Lou Gehrig Had ALS
Stephen Scelsa, MD, Director of the Neuromuscular Division and ALS Center, Beth Israel Medical Center Associate Professor of Clinical Neurology, Albert Einstein College of Medicine New York City.