summary: Researchers are looking into RBD sleep behavior disorder, a condition in which people physically act out their dreams. This parasomnia is more than just a nocturnal risk: Research indicates a strong link between RBD and neurodegenerative diseases such as Parkinson’s disease.
A multisite study called the NAPS Consortium aims to collect extensive data on RBD, providing a basis for future clinical trials of neuroprotective therapies. While no intervention can change course yet, the researchers hope to develop bioelectronic devices for early diagnosis and treatment.
- Mayo Clinic researchers found that between 50% and 80% of people with RBD go on to develop neurodegenerative disorders, specifically neuropathies such as Parkinson’s disease.
- A Mayo Clinic team leads the NAPS Consortium, which aims to collect extensive data on RBD from nine different sites across North America.
- Bioelectronic devices and therapies such as transcranial magnetic stimulation are being explored as potential future treatments for neuropathic arthropathies.
source: Mayo Clinic
Early one morning, while examining a sleeping patient at the Sleep Medicine Center, Dr. Eric St. Louis noticed something strange.
The patient, a woman in her early 60s, started running under her bed sheets. As her eyelids fluttered, her legs moved, slowly at first but then rapidly increasing speed, propelling herself along the path that only he could see. After running for about 30 seconds, she suddenly stopped and opened her eyes.
This was not how Dr. St. Louis expected a person with sleep apnea to behave.
Later, when he met her in his office, he asked her what had happened. “Well,” she replied, “I have these crazy dreams sometimes.”
I dreamed that two men were chasing me. I could see the getaway car that was going to help me escape – I could see the taillights and it was slowly pulling away so I ran faster and faster to catch up. Finally, when I was about to jump in the car, I woke up.
Dr. St. Louis, a Mayo Clinic neurologist and sleep medicine physician, has heard different versions of the same story countless times before. Acting out dreams during sleep is a key feature of REM (rapid eye movement) sleep behavior disorder, or RBD, a type of parasomnia that he and his Mayo Clinic colleagues have treated for decades.
They found that, in addition to potentially infecting patients and their bed partners, RBD can be an early sign of neurodegenerative diseases such as Parkinson’s disease.
It’s thought to affect only about 1% of the general population, and it’s prevalent enough that Dr. St. Louis sometimes catches it while evaluating a patient for another, more common sleep condition. “It can be completely unexpected and a revelation for both me and the patient,” he says.
A team of sleep researchers at Mayo Clinic is helping lead an ambitious effort to collect as much data as possible about RBD.
“The ultimate goal is to understand the natural history of the disorder well enough so that we can conduct a neuroprotective treatment trial with a drug or intervention that can prevent Parkinson’s disease or dementia from developing in the future,” says Dr. St. Louis.
In REM sleep behavior disorder, your brain goes through REM sleep several times during the night, each cycle getting longer and longer until in the morning it reaches about a quarter of the night’s sleep. During REM sleep, your eyes move rapidly under your eyelids, your dreams become more vivid and intense, and most of your muscles are paralyzed.
“Evolutionarily, this paralysis is a good thing. Otherwise, every time we dreamed of a tiger chasing us, we’d jump out of bed and run down the hall, which definitely wouldn’t be healthy,” says Mayo neurologist and sleep medicine doctor Michael Silber , holder of a Bachelor of Medicine and Medicine.
However, patients with REM sleep behavior disorder lose this paralysis and thus appear to achieve their dreams.
As a result, they can spend the night singing, screaming, screaming, hitting, jumping, kicking and banging their arms, injuring themselves and others, sometimes seriously. One patient jumped across the room to catch an imaginary football and hit his head on the dresser.
He pulled out his last revolver and fired it in the hall at attackers who were not there. One of them mistook his wife for a bear and began to strangle her. Another got up on his bunk and skated, jumped on a stage pole and hurt his ankle when he hit the ground.
Such bizarre episodes of dream activation were not recognized as a medical disorder until 1986. More than a decade later, Dr. Silber, along with neurologist Bradley Boff, MD, and neuropsychologist Tanis Firman, PhD. And others at the Mayo Clinic have published a series of studies showing that RBD can be more than just a nighttime nuisance.
The team found that approximately 50% to 80% of people with RBD go on to develop a neurodegenerative disorder, specifically a disorder in which abnormal deposits of a protein called alpha-synuclein build up in the brain. Synucleinopathy, as these disorders are known, includes Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy.
The toxic clumps of alpha-synuclein appear to damage parts of the brainstem that are responsible for paralyzing our muscles while we sleep before moving to other regions that control more overt daytime activities.
“Our work has shown that RBD develops years, often decades before Parkinson’s disease or cognitive impairment develops,” says Dr. Ferman. “RBD provides a potential window for early detection of synucleinopathies and for future therapies that specifically target proteins responsible for neurodegeneration.”
Mayo Clinic researchers help lead the NAPS Consortium, a study that lays the groundwork for future clinical trials of preventive therapies.
The study enrolls patients with RBD at nine different sites across North America and subjects them to a battery of tests, including brain imaging, muscle activity, blood tests, genetic screens, a neuropsychological evaluation, and polysomnography or sleep studies. sleep.
“We just need to take a broad view before we can see which tests are better for predicting the future,” says Dr. Boff, an associate principal investigator at NAPS.
The team plans to follow more than 300 patients over time, mapping different aspects of their condition as some go on to develop more pronounced neurodegenerative disease. With this data in hand, they will be better equipped to identify those patients who are at imminent risk and assess the impact of different therapies currently under development at pharmaceutical companies.
Researchers now have a few new biomarkers at their disposal that enable them to track the condition more closely. They can detect and measure alpha-synuclein in the cerebrospinal fluid from the spinal tap, as well as in small nerve fibers from a skin biopsy. They recently received a grant from the American Brain Foundation to develop a blood-based biomarker to do the same.
“I always liken this to high cholesterol,” says Dr. Boff. “We now have all these drugs that lower cholesterol and reduce the risk of heart attack and stroke. So can we reduce the risk in someone with RBD, to delay the onset of the disease or prevent the disease from developing in the future?”
Unfortunately, researchers have not yet discovered an intervention that could completely alter the course of patients who would otherwise develop Parkinson’s disease or a similar neurodegenerative disorder. Dr. Silber explains that this presents an ethical dilemma. “Should we be telling our patients what might happen in the future, when we can do nothing to prevent it?” He says.
Recently, a Mayo Clinic research team surveyed 113 patients with RBD to find out what they thought. More than 90% of the participants said they wanted to know they were at risk.
Patients felt that such prognostic information was important to discuss with their family and friends and could help them plan ahead. But when the researchers asked how this knowledge made them feel, a high percentage of patients said it caused them distress and anxiety.
“We have to deal with that anxiety,” says Dr. Silber.
“I spend a lot of time counseling patients, telling them please don’t let this take over your life.”
It may be many years or even decades before neurodegenerative disease appears, and by no means all patients with RBD will develop this disease in their lifetime. He also notes that if patients know they are at risk, they can participate in clinical research, an option that might not have been available if they had been kept in the dark.
Mayo researchers hope to develop more options to offer to patients in the future to prevent the progression of neurodegeneration.
Among the avenues they are exploring are bioelectronic devices, a type of medical device that uses electronic signals to treat or diagnose disease. For example, transcranial magnetic stimulation (TMS), a non-invasive brain stimulation treatment that uses magnetic pulses to stimulate neurons in the brain, has become a standard treatment for depression.
Maria Lapid, a Mayo Clinic psychiatrist, is testing whether TMS can relieve mild cognitive impairment. Dr. Bove believes a similar approach could be applied to neuropathies.
Similarly, Dr. Boff would like to see bioelectronic devices that can monitor and diagnose RBD while patients pursue their dreams in the comfort of their own homes.
“It’s a difficult disorder to diagnose, because if you don’t know what to look for, you’re going to miss it,” he says.
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