December 8, 2022
John and Mary Beth Poma had gone to bed early after a relaxing day at their vacation home near the Rappahannock River in Virginia. Shortly before dawn, John was ripped from his slumber by the sound of his wife screaming.
He sat up, bewildered. Mary Beth cowered on the bedroom floor, bruised and frightened. She'd leapt from the bed to escape him.
Mary Beth and John Poma
"He has this gentle spirit. But he was flinging his arms and legs with a force I'd never seen," she says of her husband of 35 years. "When he woke up, he was devastated."
It took more than a year before John, a respected attorney, was diagnosed with a little-known condition called REM Sleep Behavior Disorder (RBD). Discovered in 1982, RBD is a "parasomnia," loosely described as abnormal behavior during sleep, like sleepwalking and sleep terrors.
As Poma would learn, RBD is often a warning sign of other serious brain troubles to come. About half of people diagnosed with RBD will develop Parkinson's disease within a decade. And more than 80% will go on to have one of the "synucleinopathies," a broader family of neurological diseases, which also includes Lewy body dementia and multiple system atrophy (a rare illness that rapidly targets muscle coordination, speech, and vision).
"This is probably the hardest diagnosis for me" to deliver to patients, says Yo-El Ju, MD, a sleep specialist and associate professor of neurology at Washington University in St. Louis, MO. "The worst part is saying, 'Chances are, you are going to get Parkinson's or another dementia and there is nothing I can give you to stop it.' But I believe we can change that."
Brain Glitch During Sleep
Your body might seem idle while you sleep. But your brain is hard at work.
You cycle through non-REM (rapid eye movement) and REM sleep throughout the night. During non-REM sleep, dreams are typically mundane: getting stuck in traffic, a trip to the bagel shop, cleaning the fridge. Many parasomnias, including sleepwalking, tend to occur during non-REM sleep. RBD is an exception; it only happens during REM sleep.
But during REM, the cortex revs up. It reaches a state more like wakefulness. The brain sifts through your emotional moments and thoughts from the day and turns them into technicolor. A parent whose child runs too close to the road has a nightmare that she's hit by a car. A student unprepared for a test dreams of failing. A spouse who feels guilty about something might have an erotic dream that they're being unfaithful.
REM sleep is "critically important" for consolidating emotional memories, says sleep specialist Michael Howell, MD, a neurology professor at the University of Minnesota Medical School in Minneapolis. Such intense dreams, unpleasant as they may be, can foster what he calls "instinctual vigilance" - like watching your child more closely by the roadway - that helps our survival as a species.
And REM sleep is primetime for RBD. Usually, the brain tells our arm and leg muscles to stay still during REM sleep. But not in people with RBD. They can physically act out or respond to their mind's movies. These "enactments" can endanger themselves and others.
"Sleep is supposed to be restful, but every night I went to bed wondering what was going to happen next," Poma says. "It took a huge emotional toll." He feared for his psychological health and worried that he might inadvertently harm his wife again during a dream enactment. Her sleep suffered, too.
"Moving Nightmares"
Carlos Schenck, MD, arrived for his first day of work at the Minnesota Regional Sleep Disorders Center in 1982 to find a man named Donald Dorff in the waiting room. Dorff, then 67, told him of "violent moving nightmares," Schenck recalls. Once, Dorff dreamed he was running, ball in hand, across the football field and leapt to tackle. He woke up in a pile of glass, a deep gash on his forehead, having smashed his dresser and broken the mirror.
Schenck ran an electroencephalogram (EEG) on Dorff during sleep. It showed when he was in REM sleep, though his arms and legs were clearly not at rest.
"In the beginning, we thought it was extremely rare, an interesting curiosity of nature," says Schenck, now a University of Minnesota psychiatry professor. Decades later and thanks to researchers, we know now that as many as 1 in 100 people have RBD. It's more common after age 50 and in men.
RBD is often tied to a brainstem tumor, stroke, or traumatic injury. It can happen in people with narcolepsy. Alcohol withdrawal and antidepressant medications, including selective serotonin reuptake inhibitors (SSRIs), can also trigger symptoms of RBD.
Most of the time, RBD is an early warning sign of a budding neurological disease.
Schenck and Howell have seen hundreds of patients over the years. Many have seriously hurt themselves or their bed partners. There was a 46-year-old man who cannonballed off his bed while dreaming of a pool party; he ended up in the ER. Another man grabbed his wife's neck with both hands. Later, he said he did this while dreaming he was snapping the neck of a deer he'd hunted.
After that, she slept in a different room, and he tied himself to the bed at night.
"The home remedies people come up with to protect themselves are incredible," Schenck says.
Soon after learning that he had RBD, John Poma crafted a plexiglass barrier to separate him from Mary Beth in bed. At times he also slips inside a sleep sac, like a giant pillowcase. Some people with RBD install an alarm on their bed that senses when their movements become violent and wakes them up.
Doctors advised sleeping in separate beds. Mary Beth refused. She learned to coax John from a dream with her voice.
"This is hard on him," she says. "I want to be there for him."
To help with RBD, clonazepam (a sedative used to treat seizures, panic disorder, and restless legs syndrome) can quiet stirring limbs during REM sleep and also change the nature of the dreams themselves, making them less confrontational. Melatonin has also shown to be effective.
But RBD often goes undiagnosed. A lot of people don't know about it or feel embarrassed to talk about its symptoms.
Ray Merrell found relief in finally getting diagnosed with RBD.
Before his diagnosis at age 54, Ray Merrell, of Allamuchy, NJ, endured more than 4 years of violent dream enactments, often of being chased by animals or zombie-like beasts.
He blamed work stress. Still, he worried until he got diagnosed.
"Just knowing what it was was a great relief," Merrell says.
The "Check Engine" Light Is On
By the time of Poma's pivotal night in July 2018, trouble had likely been brewing in his brain stem for years.
Just as proteins called amyloid plaques are believed to build up in the brain decades before Alzheimer's symptoms show up, a protein called alpha-synuclein is thought to clump in the brain long before symptoms of Parkinson's or other synucleinopathies appear, Ju explains.
"When people have early brain changes but before they have symptoms, that is a golden window of opportunity during which we could potentially intervene," Ju says.
Enter RBD.
Scientists are learning that when RBD strikes, alpha-synuclein - the same protein seen in Parkinson's - has likely begun to clump and damage certain brain cells in two brain areas: the pons and the medulla. This jams the switch that causes sleep paralysis during REM, Ju says.
Research is also finding that those same misfolding proteins tend to attack nerves involved in the sense of smell and parts of the nervous system that aid digestion. Long before showing signs of Parkinson's, many people with RBD also lose their sense of smell and struggle with constipation.
It's just a matter of time before the damage moves upward in the brain.
Having RBD is "a lot like the 'check engine' light on your dashboard," Poma says. "It goes on long before the engine fails and gives you a chance to look under the hood early and figure out what has gone wrong."
"My absolute dream would be that someday … everyone has a sleep study to see who may be at risk for brain diseases." — Yo-El Ju, MD
Scientists from nine research centers have teamed up to form the North American Prodromal Synucleinopathy (NAPS) Consortium for RBD. They're using brain scans, spinal taps, blood and DNA samples, sleep studies, and more to search for biomarkers or other measurable changes that predict brain diseases like Parkinson's and Alzheimer's. They aim to study 430 RBD patients (including Poma and Merrell) over 5 years, funded by a $35.1 million grant from the National Institutes of Health.
"My absolute dream would be that someday, just like everyone gets a colonoscopy in midlife, everyone has a sleep study to see who may be at risk for brain diseases," says Ju, co-principal investigator for the NAPS studies. "We could then follow up to see who has true biomarkers for the disease, and then give them a safe treatment so they never get them."
Several drugs and immunotherapies targeting alpha-synuclein, the protein that clumps in RBD, are also in the works. These could be ready for clinical trials within a few years, Ju says. Some of the ways these medications would work would be to block alpha-synuclein receptors, reduce it, or thwart it from clumping. People with RBD could be the ideal group in which to test them.
Trading Fear for Hope
With friends around, Poma lit the candles on Mary Beth's birthday cake. His right hand began to tremble. Not long after, he stumbled over an ottoman in his living room. By summer 2021, he was growing increasingly concerned about balance problems.
In June 2022, he began taking levodopa to treat Parkinson's disease.
"In the beginning, it was very difficult," Poma says. Taking that first pill forced him to accept a new reality. "There's just this sense of fear and anxiety about what the future might hold."
And yet, he is grateful for RBD.
"Ultimately, I want to be known for what I did to help advance progression toward the cure." — John Poma
It prompted him to get regular exercise to try to slow down his brain disease. To listen when his doctor said to make sure he has good long-term care insurance. And to find and join a clinical trial to treat his early Parkinson's symptoms.
Aside from the occasional dream enactment, often when he is ill or stressed, his sleep has quieted. At last, when they lay down at night, he and Mary Beth feel safe. And he's grateful to remain cognitively as sharp as ever.
He's laser-focused on helping others via NAPS and other RBD studies.
"Ultimately, I want to be known for what I did to help advance progression toward the cure, not for the effects this disease has had on me as a person," he says. "Instead of fear, I'm full of hope now."