Troubling Sleep Disorder in Athletes a
Sign of CTE?

Megan Brooks

September 30, 2020

Rapid eye movement sleep behavior disorder (RBD) is surprisingly common in athletes and may signal chronic traumatic encephalopathy (CTE) caused by brainstem tau and Lewy body pathologies, new research suggests.

CTE is a neurodegenerative disorder linked to years of repetitive head impacts from playing professional football and other contact sports.

"Repetitive head impacts may damage sleep-relevant brainstem nuclei and lead to REM sleep behavior disorder," senior author Thor Stein, MD, PhD, neuropathologist at VA Boston Healthcare in Massachusetts, said in a webinar hosted by the Concussion Legacy Foundation.

"This is something both athletes and their doctors need to be aware of," added Stein, who is an assistant professor of pathology and laboratory medicine at Boston University School of Medicine.

The findings were published online September 17 in Acta Neuropathologica.

Surprising Findings

In RBD, the paralysis that normally occurs during REM sleep is incomplete or absent, causing people to act out their dreams by talking, flailing their arms and legs, punching, kicking and other behaviors while asleep. 

"The disorder often comes to medical attention when there is an injury or potential for injury to the individual or the individual's bed partner," Stein noted.

To investigate ties between CTE and RBD, the researchers analyzed the brains of 247 deceased male athletes who played contact sports; the brains were donated to the Veterans Affairs-Boston University-Concussion Legacy Foundation (VA-BU-CLF) Brain Bank.

The athletes died at a mean age of 63 years. They all had a neuropathological diagnosis of CTE. Their relatives provided information on sleep.

Nearly one third of these athletes (n = 80, 32%) with CTE displayed symptoms characteristic of RBD when they were alive. "That really surprised us," said Stein. "This is about 30 times more than what's reported in the general population, where it has been estimated to be present in about 1% of people," he noted.

In addition, there was a clear dose-response effect. Athletes with CTE and RBD had played contact sports for significantly more years than their peers without RBD (18.3 vs 15.1 years; P = .02). 

"The odds of reporting RBD symptoms increased about 4% per year of play," first author Jason Adams, an MD/PhD student now at the University of California San Diego, said in a statement.

New Insight

The results also point to a potential cause for RBD.

Compared with athletes who had CTE and no RBD, those with CTE and RBD were four times more likely to have tau pathology within brainstem nuclei involved in REM sleep (odds ratio [OR], 3.96; 95% CI, 1.43 - 10.96; P = .008). Athletes with CTE and RBD were also more likely to have Lewy body pathology (OR, 2.36; 95% CI, 1.18 - 4.72; P = .02).

"Contrary to our expectations, tau pathology in the raphe nuclei was more strongly associated with RBD than Lewy body pathology, suggesting that tau pathology is more likely to lead to sleep dysfunction in CTE," Stein said.

Reached for comment on the study, Carmela Tartaglia, MD, chair in brain injury and concussion research, University of Toronto, Canada, said sleep studies are "the most important" factor that needs to be considered when making a diagnosis of probable RBD.

"It is very important to do sleep studies as it is often difficult to rely on informants since nightmares and talking in sleep [are] often misreported as RBD. A polysomnography is the gold standard," Tartaglia told Medscape Medical News.

Another factor is the use of medications. "Although the authors mention [that] antidepressants and benzodiazepines can cause sleep changes, acetylcholinesterase inhibitors (used to treat Alzheimer's disease) are often associated with nightmares and so could be playing an even larger role in misdiagnosis of RBD," Tartaglia said.

In her view, the results of increased brainstem tau pathology associated with RBD should be "pondered in light of recent findings that brainstem tau pathology is an early finding in Alzheimer's disease and that is an illness not associated with RBD."

Summing up, Tartaglia said "changes in sleep are increasingly recognized in concussion and should be [investigated] in prospective studies that include polysomnography so that an accurate diagnosis of RBD can be made. It would be interesting to see the replication of these results in a cohort of such patients."

Christopher John Nowinski, PhD, cofounder and CEO of the Concussion Legacy Foundation, said this study is important because it identifies a potential cause of RBD.

The 42-year-old Nowinski, a former WWE professional wrestler and college football player at Harvard, developed RBD after suffering years of concussions and still suffers from the disorder today.

"Living through this, I can tell you, this is not a benign symptom by any stretch of the imagination," said Nowinski, who moderated the webinar. "You are a danger to yourself; you are a danger to others. Hopefully, this study will help us better understand treatment going forward," he said.

Support for the study was provided by the Department of Veterans Affairs, the Alzheimer's Association, the National Institutes of Health, Concussion Legacy Foundation, Andlinger Foundation, and World Wrestling Entertainment (WWE). Adams and Stein have no relevant disclosures.

Acta Neuropathol. Published September 17, 2020. Abstract

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