Posts tagged sleep disorders
Articles and news from the latest research reports.
‘Exploding head syndrome’ a real, overlooked sleep disorder
It sounds like a phrase from Urban Dictionary or the title of an animated gif, but a Washington State University researcher says “exploding head syndrome” is an authentic and largely overlooked phenomenon that warrants a deeper look.
“It’s a provocative and understudied phenomenon,” said Brian Sharpless, a WSU assistant professor and director of the university psychology clinic who recently reviewed the scientific literature on the disorder for the journal Sleep Medicine Reviews. “I’ve worked with some individuals who have it seven times a night, so it can lead to bad clinical consequences as well.”
People with the syndrome typically perceive abrupt, loud noises—door slams, fireworks, gunshots—as they are going to sleep or waking up. While harmless, the episodes can be frightening.
“Some people start to become anxious when they go into their bedroom or when they try to go to sleep,” said Sharpless. “Daytime sleepiness can be another problem.”
Some patients report mild pain. Some hear an explosion in one ear, others in both ears and yet others within their heads. Some also see what looks like lightning or bright flashes.
Researchers do not know how widespread the problem is, but Sharpless is fielding enough reports of people with the disorder that he thinks it is more widespread than presumed. Just this week, a story on the disorder in Britain’s Daily Mail prompted several people with the syndrome to contact him. (See http://www.dailymail.co.uk/health/article-2620837/Is-exploding-head-syndrome-reason-sleep.html)
The term “exploding head syndrome” dates to a 1988 article in Lancet, but it was described clinically as “snapping of the brain” in 1920. Silas Weir Mitchell, an American physician, wrote in 1876 of two men who experienced explosive-sounding “sensory discharges.”
While the syndrome is recognized in the International Classification of Sleep Disorders, studies using electroencephalogram recordings have only documented the disruptions in periods of relaxed but awake drowsiness.
As with many sleep phenomena, it is largely mysterious.
“In layman’s terms, our best guess is that it occurs when the body doesn’t shut down for sleep in the correct sequence,” said Sharpless. “Instead of shutting down, certain groups of neurons actually get activated and have us perceive the bursts of noise. Behavioral and psychological factors come into play as well, and if you have normally disrupted sleep, the episodes will be more likely to occur.”
Judging from the limited scientific literature and available statistics, Sharpless said the syndrome is more common in women than men. Some medical treatments are available for it, but one possible intervention can be simply reassuring a patient that it is not a dangerous condition.
Sleep disorder linked to brain disease
Researchers at the University of Toronto say a sleep disorder that causes people to act out their dreams is the best current predictor of brain diseases like Parkinson’s and many other forms of dementia.
"Rapid-eye-movement sleep behaviour disorder (RBD) is not just a precursor but also a critical warning sign of neurodegeneration that can lead to brain disease," says associate professor and lead author Dr. John Peever. In fact, as many as 80 to 90 per cent of people with RBD will develop a brain disease."
As the name suggests, the disturbance occurs during the rapid-eye-movement (REM) stage of sleep and causes people to act out their dreams, often resulting in injury to themselves and/or bed partner. In healthy brains, muscles are temporarily paralyzed during sleep to prevent this from happening.
"It’s important for clinicians to recognize RBD as a potential indication of brain disease in order to diagnose patients at an earlier stage," says Peever. "This is important because drugs that reduce neurodegeneration could be used in RBD patients to prevent (or protect) them from developing more severe degenerative disorders."
His research examines the idea that neurodegeneration might first affect areas of the brain that control sleep before attacking brain areas that cause more common brain diseases like Alzheimer’s.
Peever says he hopes the results of his study lead to earlier and more effective treatment of neurodegenerative diseases.
(Source: eurekalert.org)
Narcolepsy confirmed as autoimmune disease
Results also partly explain why the 2009 swine flu virus, and a vaccine against it, led to spikes in the sleep disorder.
As the H1N1 swine flu pandemic swept the world in 2009, China saw a spike in cases of narcolepsy — a mysterious disorder that involves sudden, uncontrollable sleepiness. Meanwhile, in Europe, around 1 in 15,000 children who were given Pandemrix — a now-defunct flu vaccine that contained fragments of the pandemic virus — also developed narcolepsy, a chronic disease.
Immunologist Elizabeth Mellins and narcolepsy researcher Emmanuel Mignot at Stanford University School of Medicine in California and their collaborators have now partly solved the mystery behind these events, while also confirming a longstanding hypothesis that narcolepsy is an autoimmune disease, in which the immune system attacks healthy cells.
Narcolepsy is mostly caused by the gradual loss of neurons that produce hypocretin, a hormone that keeps us awake. Many scientists had suspected that the immune system was responsible, but the Stanford team has found the first direct evidence: a special group of CD4+ T cells (a type of immune cell) that targets hypocretin and is found only in people with narcolepsy.
“Up till now, the idea that narcolepsy was an autoimmune disorder was a very compelling hypothesis, but this is the first direct evidence of autoimmunity,” says Mellins. “I think these cells are a smoking gun.” The study is published today in Science Translational Medicine.
Thomas Scammell, a neurologist at Harvard Medical School in Boston, Massachusetts, says that the results are welcome after “years of modest disappointment”, marked by many failures to find antibodies made by a person’s body against their own hypocretin. “It’s one of the biggest things to happen in the narcolepsy field for some time.”
Loose ends
It is not clear why some people make these T cells and others do not, but genetics may play a part. In earlier work, Mignot showed that 98% of people with narcolepsy have a variant of the gene HLA that is found in only 25% of the general population.
Environmental factors, such as infections, probably matter too. Mellins’ working model is that narcolepsy happens when people with a genetic predisposition, which involves having several narcolepsy-related gene variants, encounter an environmental factor that mimics hypocretin, triggering a response from the immune system. The 2009 H1N1 virus was one such trigger: the team found that these same special CD4+ T cells also recognize a protein from the pandemic H1N1 virus.
Narcolepsy of course was around long before the 2009 pandemic. And since new cases of the disease tend to arise right after winter — following the seasonal peak in flu — it’s possible that other strains or even other viruses are involved, too.
But the results do not fully explain the Pandemrix mystery, because other flu vaccines contained the same proteins but did not lead to a spike in narcolepsy cases. Regardless, Mellins says that it should be possible to avoid repeating the same mistake by ensuring that future flu vaccines do not contain components that resemble hypocretin.
Another loose end is that “they don’t show how these T cells are actually killing the hypocretin neurons”, adds Scammell. “It’s like a murder mystery and we don’t know who the real killer is.” He thinks that it is unlikely that the T cells are the true culprits; instead, they could be acting through an intermediary, or might merely be a symptom of some other destructive event.
“The results are very important, but they need to do a replication study in a large group of patients and controls,” says Gert Lammers, a neurologist at Leiden University Medical Center in the Netherlands and president of the European Narcolepsy Network. “If the findings are confirmed, the first important spin-off might be the development of a new diagnostic test.”
Scientists shed light on the brain mechanisms behind a debilitating sleep disorder
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.
(Source: media.utoronto.ca)
Acting Out Dreams Linked to Development of Dementia
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.
(Source: mayoclinic.org)
Sleepwalkers sometimes remember what they’ve done
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.”
Drug May Offer New Approach to Treating Insomnia
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