Posts tagged sleep disorders
Posts tagged sleep disorders
Researchers at the University of Toronto discover how the body’s muscles accidentally fall asleep while awake
Normally muscles contract in order to support the body, but in a rare condition known as cataplexy the body’s muscles “fall asleep” and become involuntarily paralyzed. Cataplexy is incapacitating because it leaves the affected individual awake, but either fully or partially paralyzed. It is one of the bizarre symptoms of the sleep disorder called narcolepsy.
“Cataplexy is characterized by muscle paralysis during cognitive awareness, but we didn’t understand how this happened until now, said John Peever of the University of Toronto’s Department of Cell & Systems Biology. “We have shown that the neuro-degeneration of the brain cells that synthesize the chemical hypocretin causes the noradrenaline system to malfunction. When the norandrenaline system stops working properly, it fails to keep the motor and cognitive systems coupled. This results in cataplexy – the muscles fall asleep but the brain stays awake.”
Peever and Christian Burgess, also of Cell & Systems Biology used hypocretin-knockout mice (mice that experience cataplexy), to demonstate that a dysfunctional relationship between the noradrenaline system and the hypocretin-producing system is behind cataplexy. The research was recently published in the journal Current Biology.
The scientists first established that mice experienced sudden loss of muscle tone during cataplectic episodes. They then administered drugs to systematically inhibit or activate a particular subset of adrenergic receptors, the targets of noradrenaline. They were able to reduce the incidence of cataplexy by 90 per cent by activating noradrenaline receptors. In contrast, they found that inhibiting the same receptors increased the incidence of cataplexy by 92 per cent. Their next step was to successfully link how these changes affect the brain cells that directly control muscles.
They found that noradrenaline is responsible for keeping the brain cells (motoneurons) and muscles active. But during cataplexy when muscle tone falls, noradrenaline levels disappear. This forces the muscle to relax and causes paralysis during cataplexy. Peever and Burgess found that restoring noradrenaline pre-empted cataplexy, confirming that the noradrenaline system plays a key role.
The strongest predictor of whether a man is developing dementia with Lewy bodies — the second most common form of dementia in the elderly — is whether he acts out his dreams while sleeping, Mayo Clinic researchers have discovered. Patients are five times more likely to have dementia with Lewy bodies if they experience a condition known as rapid eye movement (REM) sleep behavior disorder than if they have one of the risk factors now used to make a diagnosis, such as fluctuating cognition or hallucinations, the study found.
The findings were being presented at the annual meeting of the American Academy of Neurology in San Diego. REM sleep behavior disorder is caused by loss of the normal muscle paralysis that occurs during REM sleep. It can appear three decades or more before a diagnosis of dementia with Lewy bodies is made in males, the researchers say. The link between dementia with Lewy bodies and the sleep disorder is not as strong in women, they add.
"While it is, of course, true that not everyone who has this sleep disorder develops dementia with Lewy bodies, as many as 75 to 80 percent of men with dementia with Lewy bodies in our Mayo database did experience REM sleep behavior disorder. So it is a very powerful marker for the disease," says lead investigator Melissa Murray, Ph.D., a neuroscientist at Mayo Clinic in Florida.
The study’s findings could improve diagnosis of this dementia, which can lead to beneficial treatment, Dr. Murray says.
"Screening for the sleep disorder in a patient with dementia could help clinicians diagnose either dementia with Lewy bodies or Alzheimer’s disease," she says. "It can sometimes be very difficult to tell the difference between these two dementias, especially in the early stages, but we have found that only 2 to 3 percent of patients with Alzheimer’s disease have a history of this sleep disorder."
Once the diagnosis of dementia with Lewy bodies is made, patients can use drugs that can treat cognitive issues, Dr. Murray says. No cure is currently available.
Researchers at Mayo Clinic in Minnesota and Florida, led by Dr. Murray, examined magnetic resonance imaging, or MRI, scans of the brains of 75 patients diagnosed with probable dementia with Lewy bodies. A low-to-high likelihood of dementia was made upon an autopsy examination of the brain.
The researchers checked the patients’ histories to see if the sleep disorder had been diagnosed while under Mayo care. Using this data and the brain scans, they matched a definitive diagnosis of the sleep disorder with a definite diagnosis of dementia with Lewy bodies five times more often than they could match risk factors, such as loss of brain volume, now used to aid in the diagnosis. The researchers also showed that low-probability dementia with Lewy bodies patients who did not have the sleep disorder had findings characteristic of Alzheimer’s disease.
"When there is greater certainty in the diagnosis, we can treat patients accordingly. Dementia with Lewy bodies patients who lack Alzheimer’s-like atrophy on an MRI scan are more likely to respond to therapy — certain classes of drugs — than those who have some Alzheimer’s pathology," Dr. Murray says.
Three myths about sleepwalking – sleepwalkers have no memory of their actions, sleepwalkers’ behaviour is without motivation, and sleepwalking has no daytime impact – are dispelled in a recent study led by Antonio Zadra of the University of Montreal and its affiliated Sacré-Coeur Hospital. Working from numerous studies over the last 15 years at the hospital’s Centre for Advanced Studies in Sleep Medicine at the Hôpital du Sacré-Cœur de Montréal and a thorough analysis of the literature, Zadra and his colleagues have raised the veil on sleepwalking and clarified the diagnostic criteria for researchers and clinicians. Their findings were published in Lancet Neurology.
Question: What are the causes and consequences of sleepwalking?
A.Z.: “Several indicators suggest that a genetic factor is involved. In 80% of sleepwalkers, a family history of sleepwalking exists. The concordance of sleepwalking is five times higher in monozygotic twins compared to non-identical twins. Our studies have also shown that lack of sleep and stress can lead to sleepwalking. Any situation that disrupts sleep can result in sleepwalking episodes in predisposed individuals.”
A.Z.: “Most sleepwalking episodes are harmless. Apart from the fact that the deep slow-wave sleep of sleepwalkers is fragmented, wanderings are usually brief and pose no danger, or when they do, it is minimal. In rare cases, wandering episodes may be longer, and sleepwalkers may injure themselves and put themselves or others in danger: some have even gone as far as driving a car!”
Question: It is said that the sleep disorder mainly affects children. Is this true?
A.Z.: “Many children transitionally sleepwalk between 6 and 12 years of age. It is thought that passing from sleep to wakefulness requires a certain maturation of the brain. In some children, the brain may have difficulty making this transition. Often, the problem disappears after puberty. But sleepwalking may persist into adulthood in almost 25% of cases. It decreases with age, however, because the older you get, the fewer hours of deep slow-wave sleep you enjoy, which is the stage in which sleepwalking episodes occur.”
A.Z.: “Both children and adults are in a state of so-called dissociated arousal during wandering episodes: parts of the brain are asleep while others are awake. There are elements of wakefulness since sleepwalkers can perform actions such as washing, opening and closing doors, or going down stairs. Their eyes are open and they can recognize people. But there are also elements specific to sleep: sleepwalkers’ judgment and their ability for self-thought are altered, and their behavioural reactions are nonsensical.”
Question: According to you, the idea that people are partially awake and partially asleep is something that must be considered in conceptualizing sleepwalking?
A.Z.: “Absolutely. This is one of the points we outline in our article. There are increasing signs that even in normal subjects the brain does not fall asleep in a single block all at once. Sleep may occur in a localized manner. Parts of the brain can fall asleep before others.”
Question: This may explain why the amnesia of sleepwalkers is not always complete. But can sleepwalkers really remember their actions while sleeping vertically?
A.Z.: “Yes. In children and adolescents, amnesia is more frequent, probably due to neurophysiological reasons. In adults, a high proportion of sleepwalkers occasionally remember what they did during their sleepwalking episodes. Some even remember what they were thinking and the emotions they felt.”
Question: Your work has also shown that the behaviour of sleepwalkers is not simply automatic. Can you explain?
A.Z.: “This is another popular myth. There is a misconception that sleepwalkers do things without knowing why. However, there is a significant proportion of sleepwalkers who remember what they have done and can explain the reasons for their actions. They are the first to say, once awake, that their explanations are nonsensical. However, during the episode, there is an underlying rationale. For example, a man once took his dog that had been sleeping at the foot of his bed to the bathtub to douse it with water. He thought his dog was on fire! There was neither the logic nor the judgment typical of wakefulness. But the behaviour was not automatic in the sense that a motivation accompanied and explained the action.”
Question: Another myth you are interested in relates to impact on the waking state. According to you, beyond the nocturnal phenomenon, sleepwalking is associated with diurnal disorders characterized by somnolence.
A.Z.: “Around 45% of sleepwalkers are clinically somnolent during the day. Younger sleepwalkers are able to hide it more easily. Compared to control subjects, however, they perform less well in vigilance tests. And if given the opportunity to take a nap, they fall asleep faster than normal subjects do.”
A.Z.: “Over the last few years, we have shown that the deep slow-wave sleep of sleepwalkers is atypical. Fragmented by numerous micro-arousals of 3 to 10 seconds, their sleep is less restorative. Sleepwalking is therefore not only a problem of transitioning between deep sleep and wakefulness. There is something more fundamental in their sleep every night, whether or not they have sleepwalking episodes.”
A new drug may bring help for people with insomnia, according to a study published in the November 28, 2012, online issue of Neurology®, the medical journal of the American Academy of Neurology.
The drug, suvorexant, blocks the chemical messengers in the brain called orexins, which regulate wakefulness. Other drugs for insomnia affect different brain receptors.
Taking the drug suvorexant increased the amount of time people spent asleep during the night, according to the study. The study involved 254 people ages 18 to 64 who were in good physical and mental health but had insomnia that was not due to another medical condition.
The participants took either the drug or a placebo for four weeks, then switched to the other treatment for another four weeks. The participants spent the night in a sleep laboratory with their sleep monitored on the first night with each treatment and then again in the fourth week of each treatment.
While taking the drug, participants’ “sleep efficiency,” which reflects the total amount of time they slept during a fixed, eight hour time in bed, improved by 5 to 13 percent compared to those taking the placebo. They also experienced 21 to 37 fewer minutes awake during the night after they had fallen asleep than those who took the placebo. “This study provides evidence that suvorexant may offer a successful alternative strategy for treating insomnia,” said study author W. Joseph Herring, MD, PhD, of North Wales, Penn., Executive Director of Clinical Research with Merck, the maker of suvorexant, and a member of the American Academy of Neurology. “Suvorexant was generally well-tolerated, and there were no serious side effects.”
Herring said larger, longer studies have recently been conducted on suvorexant, along with studies to determine whether the drug could be safe and effective for elderly people, who make up a large percentage of those suffering from insomnia.
What Drives Your Daily Biological Clock?
Researchers working with fruit flies say they have discovered one way that the body’s biological clock controls brain-cell activity that influences daily rhythms.
They believe their findings might improve understanding about sleep-wake cycles and lead to new treatments for sleep disorders and jet lag.
"The findings answer a significant question: how biological clocks drive the activity of clock neurons, which, in turn, regulate behavioral rhythms," study senior author Justin Blau, associate professor in New York University’s department of biology, said in a university news release.
Previous research with fruit flies’ “clock genes” led to the discovery of similar genes in humans, according to the news release.
It was known that biological clocks control neuronal activity, but it wasn’t known how information from biological clocks drives rhythms in the electrical activity of pacemaker neurons that control daily rhythms.
The NYU team looked at pacemaker neurons in the central brain of fruit flies that set the timing of the daily transitions between sleep and wake. They isolated these neurons and identified sets of genes with different levels of activity at dawn and dusk.
Follow-up experiments found that the activity of a gene called Ir was much higher at dusk than at dawn and that it was more active in the pacemaker neurons than in the rest of the brain. The researchers also found that increasing or decreasing levels of Ir affected behavioral rhythms and changed the timing and strength of variations in the core clock.
"We were looking for an output of the biological clock that would link the core clock to neuronal activity," Blau said. "Ir seems to do this, but it also, remarkably, feeds back to regulate the core clock itself. Feedback loops seem to be deeply engrained into the biological clock and presumably help these clocks work so well."
The study was published in the October issue of the Journal of Biological Rhythms. Researchers have noted that results from animal studies do not necessarily translate to humans.
NYU researchers find electricity in biological clock
Biologists from New York University have uncovered new ways our biological clock’s neurons use electrical activity to help keep behavioral rhythms in order. The findings, which appear in the journal Current Biology, also point to fresh directions for exploring sleep disorders and related afflictions.
“This process helps explain how our biological clocks keep such amazingly good time,” said Justin Blau, an associate professor of biology at NYU and one of the study’s authors.
Blau added that the findings may offer new pathways for exploring treatments to sleep disorders because the research highlights the parts of our biological clock that “may be particularly responsive to treatment or changes at different times of the day.”
NYU Biologists Uncover Dynamic Between Biological Clock and Neuronal Activity
Biologists at New York University have uncovered one way that biological clocks control neuronal activity—a discovery that sheds new light on sleep-wake cycles and offers potential new directions for research into therapies to address sleep disorders and jetlag.
“The findings answer a significant question—how biological clocks drive the activity of clock neurons, which, in turn, regulate behavioral rhythms,” explained Justin Blau, an associate professor in NYU’s Department of Biology and the study’s senior author.
Their findings appear in the Journal of Biological Rhythms
June 27, 2012
Smoking, head injury, pesticide exposure, farming and less education may be risk factors for a rare sleep disorder that causes people to kick or punch during sleep, according to a study published in the June 27, 2012, online issue of Neurology, the medical journal of the American Academy of Neurology.
People with the disorder, called REM sleep behavior disorder, do not have the normal lack of muscle tone that occurs during rapid eye movement (REM) sleep, causing them to act out their dreams. The movements can sometimes be violent, causing injury to the person or their bed partner. The disorder is estimated to occur in 0.5 percent of adults.
"Until now, we didn’t know much about the risk factors for this disorder, except that it was more common in men and in older people," said study author Ronald B. Postuma, MD, MSc, with the Research Institute of the McGill University Health Centre (MUHC) in Montreal and a member of the American Academy of Neurology. "Because it is a rare disorder, it was difficult to gather information about enough patients for a full study. For this study, we worked with 13 institutions in 10 countries to get a full picture of the disorder."
The disorder can also be a precursor to neurodegenerative diseases such as Parkinson’s disease and a type of dementia. Studies have shown that more than 50 percent of people with REM sleep behavior disorder go on to develop a neurodegenerative disorder years or even decades later.
"Due to this connection, we wanted to investigate whether the risk factors for REM sleep behavior disorder were similar to those for Parkinson’s disease or dementia," Postuma said.
The results were mixed. While smoking has found to be a protective factor for Parkinson’s disease, people who smoked were found to be more likely to develop REM sleep behavior disorder. Pesticide use, on the other hand, is a risk factor for both disorders. Studies have shown that people who drink coffee are less likely to develop Parkinson’s, but this study found no relationship between coffee drinking and REM sleep behavior disorder.
For the study, 347 people with REM sleep behavior disorder were compared to 347 people who did not have the disorder. Of those, 218 had other sleep disorders and 129 had no sleep disorders.
Those with REM sleep behavior disorder were 43 percent more likely to be smokers, with 64 percent of those with the disorder having ever smoked, compared to 56 percent of those without the disorder. They were 59 percent more likely to have had a previous head injury with loss of consciousness, 67 percent more likely to have worked as farmers, and more than twice as likely to have been exposed to pesticides through work. Those with the disorder also had fewer years of education, with an average of 11.1 years, compared to 12.7 years for those without the disorder.
More information: To learn more about sleep disorders, visit http://www.aan.com/patients
Provided by American Academy of Neurology