Published Research - General Sleep and RLS (WED)

For everything and anything else not covered in the other RLS/WED sections.
cornelia

Re: Published Research - General Sleep and WED (RLS)

Postby cornelia » Tue Jul 08, 2014 2:38 pm

It is difficult (for me) to understand but it seems to me that this can be good news:

Exp Neurol. 2014 Jul 3. pii: S0014-4886(14)00219-2. doi: 10.1016/j.expneurol.2014.06.023. [Epub ahead of print]
Low Brain Iron Effects and Reversibility on Striatal Dopamine Dynamics.
Unger EL1, Bianco LE1, Jones BC2, Allen RP3, Earley CJ4.
Author information
Abstract
Iron deficiency (ID) in rodents leads to decreased ventral midbrain (VMB) iron concentrations and to changes in the dopamine (DA) system that mimic many of the dopaminergic changes seen in RLS patient where low substantia nigra iron is a known pathology of the disease. The ID-rodent model, therefore, has been used to explore the effects that low VMB iron can have on striatal DA dynamics with the hopes of better understanding the nature of iron-dopamine interaction in Restless Legs Syndrome (RLS). Using a post-weaning, diet-induced, ID condition in rats, the No-Net-Flux microdialysis technique was used to examine the effect of ID on striatal DA dynamics and it reversibility with acute infusion of physiological concentrations of iron into the VMB. This study replicated prior findings by showing that the ID condition is associated with increased extracellular striatal DA, reduced striatal DA uptake, and blunted DA-2-receptor-agonist feedback enhancement of striatal DA uptake. Despite the increase in extracellular striatal DA, intracellular striatal DA, as determined in tissue homogenates, was decrease in the ID rat. The study's key finding was that an infusion of physiological concentrations of iron into the VMB reversed the ID-induced increase in extracellular striatal DA and the ID-induced decrease in intracellular striatal DA but had no effect on the ID-induced changes in DA uptake or on the blunted DA-uptake response to quinpirole. In summary, the ID-rodent model provides highly reproducible changes in striatal DA dynamics that remarkably parallel dopaminergic changes seen in RLS patients. Some but not all of these ID-induced changes in striatal DA dynamics were reversible with physiological increases in VMB iron. The small changes in VMB iron induced by iron infusion likely represent biologically relevant changes in the non-transferrin-bound labile iron pool and may mimic circadian-dependent changes that have been found in VBM extracellular iron.


Corrie

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Re: Published Research - General Sleep and WED (RLS)

Postby ViewsAskew » Wed Jul 09, 2014 7:47 am

That's a tough read. I need to sleep and try again when I wake up.... As you did, Corrie, I am understanding that this is a good thing. It sounded as if the DA uptake was not improved, but that two other DA systems affected were improved with the iron. That alone might help us. I wonder how they were able to put the iron in the midbrain???

Mostly, it sounds as if they can study the rats in a way they can't study humans. They might actually figure something out that would be helpful.
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Re: Published Research - General Sleep and WED (RLS)

Postby Polar Bear » Wed Jul 09, 2014 1:27 pm

Takes some very slow reading.... several times.... :)
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Re: Published Research - General Sleep and WED (RLS)

Postby badnights » Sun Jul 13, 2014 8:38 pm

this seems to imply that some of the 'bad' effects of iron deprivation can be reversed by iron infusion (directly into the rat midbrain!), whereas others of the bad effects are not reversible by this means. 'The bad' effects they measured all had to do with dopamine.

The dopamine-related effects of an iron deficient diet in rats were already known, and resemble the changes in a WED/RLS brain: increased dopamine outside the cells of the striatum (which is a brain structure that sends messages to the basal ganglia, which you may have heard of already since it is involved in RLS/WED), reduced dopamine uptake by cells of the striatum, a reduction in the effect of a drug (quinpirole) that normally enhances dopamine uptake, and decreased dopamine inside the cells of the striatum.

This study showed that infusion of iron into the rats' brains reversed some but not all of those effects: the amounts of dopamine inside and outside the cells became closer to normal, but uptake of dopamine remained reduced, and the effect of the drug that was supposed to enhance uptake remained blunted - those things were not reversed by the type of iron infusions done.

I am dopey and may have missed something important here, but that's what I got out of it.
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Broken sleep is as bad as no sleep

Postby badnights » Sun Jul 13, 2014 8:42 pm

Finally a study corroborating what we all know already (from http://www.sciencedaily.com/releases/20 ... ceDaily%29):

The familiar cry in the night, followed by a blind shuffle to the crib, a feeding, a diaper change, and a final retreat back into oblivion -- every hour on the hour. Such is the sleep pattern of most new parents, who report feeling more exhausted in the morning than when they went to bed the night before.

Now, in the first study of its kind, Prof. Avi Sadeh and a team of researchers from Tel Aviv University's School of Psychological Sciences explain why interrupted sleep can be as physically detrimental as no sleep at all. In the study, published in the journal Sleep Medicine, Prof. Sadeh and his colleagues Michal Kahn, Shimrit Fridenson, Reut Lerer, and Yair Ben-Haim establish a causal link between interrupted sleep patterns and compromised cognitive abilities, shortened attention spans, and negative moods. The researchers discovered that interrupted sleep is equivalent to no more than four consecutive hours of sleep.
"The sleep of many parents is often disrupted by external sources such as a crying baby demanding care during the night. Doctors on call, who may receive several phone calls a night, also experience disruptions," said Prof. Sadeh. "These night wakings could be relatively short -- only five to ten minutes -- but they disrupt the natural sleep rhythm. The impact of such night wakings on an individual's daytime alertness, mood, and cognitive abilities had never been studied. Our study is the first to demonstrate seriously deleterious cognitive and emotional effects."

Putting Mom and Dad in a bad mood

"In the process of advising these parents, it struck me that the role of multiple night wakings had never been systematically assessed," said Prof. Sadeh, who directs a sleep clinic at TAU, where he advises exhausted and desperate parents on how to cope with their children's persistent night wakings. "Many previous studies had shown an association, but none had established a causal link. Our study demonstrates that induced night wakings, in otherwise normal individuals, clearly lead to compromised attention and negative mood."

The study was conducted on student volunteers at TAU's School of Psychological Sciences. Their sleep patterns were monitored at home using wristwatch-like devices that detected when they were asleep and when they were awake. The students slept a normal eight-hour night, then experienced a night in which they were awakened four times by phone calls and told to complete a short computer task before going back to sleep after 10-15 minutes of wakefulness. The students were asked each following morning to complete certain computer tasks to assess alertness and attention, as well as to fill out questionnaires to determine their mood. The experiment showed a direct link between compromised attention, negative mood, and disrupted sleep -- after only one night of frequent interruptions.

Paying a high price

"Our study shows the impact of only one disrupted night," said Prof. Sadeh. "But we know that these effects accumulate and therefore the functional price new parents -- who awaken three to ten times a night for months on end -- pay for common infant sleep disturbance is enormous. Besides the physical effects of interrupted sleep, parents often develop feelings of anger toward their infants and then feel guilty about these negative feelings.

"Sleep research has focused in the last 50 years on sleep deprivation, and practically ignored the impact of night-wakings, which is a pervasive phenomenon for people from many walks of life. I hope that our study will bring this to the attention of scientists and clinicians, who should recognize the price paid by individuals who have to endure frequent night-wakings."
Prof. Sadeh is currently researching interventions for infant sleep disturbances to reduce the detrimental effects of disrupted sleep on parents.

Story Source:
The above story is based on materials provided by American Friends of Tel Aviv University. Note: Materials may be edited for content and length.
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Re: Published Research - General Sleep and WED (RLS)

Postby ViewsAskew » Mon Jul 14, 2014 6:31 am

Excellent information - thanks for finding and posting.

Wow - so interrupted sleep is the equivalent of 4 hours of uninterrupted. I think of all the years I awakened between 10 and 30 times a night with the PLMs. I can't imagine how any of us function in the long term!
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Re: Published Research - General Sleep and WED (RLS)

Postby jul2873 » Mon Jul 14, 2014 10:41 pm

Well yes, but there is also considerable research showing that sleeping for eight hours straight is a fairly new phenomena. Apparently, before the invention of electricity, people had "first sleep" and then "second sleep" with an hour or two in between. http://www.history.vt.edu/Ekirch/sleepcommentary.html

I realize this is very different from being awakened every hour or so by a baby, but it still shows that some interruption in sleep can be okay. I do pretty well with two WED awakenings at night as long as I can get a nap.

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Re: Published Research - General Sleep and WED (RLS)

Postby ViewsAskew » Wed Jul 16, 2014 1:45 am

jul2873 wrote:Well yes, but there is also considerable research showing that sleeping for eight hours straight is a fairly new phenomena. Apparently, before the invention of electricity, people had "first sleep" and then "second sleep" with an hour or two in between. http://www.history.vt.edu/Ekirch/sleepcommentary.html

I realize this is very different from being awakened every hour or so by a baby, but it still shows that some interruption in sleep can be okay. I do pretty well with two WED awakenings at night as long as I can get a nap.


Yes- and I found that fascinating when I read it. But, it was still only one interruption, not many. And it likely wasn't an interruption, but occurred naturally in Stage 1 after Stage 5. These interruptions come in the middle of Stage 2-5 - they prevent you from getting enough of whatever - likely deep sleep or REM.
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Depression and stress may change how people process fat

Postby ViewsAskew » Fri Jul 18, 2014 10:06 am

There is almost always a relationship between WED and obesity. For years, I've said it's not because fat people get WED, but because WED helps create fat people. It clearly doesn't always happen. And, some of it may be random late night eating to take away the anxiety or keep us occupied. But I've always thought something about our condition/disease was helping to create the obesity.

This could indeed be part of it.

http://uk.reuters.com/article/2014/07/1 ... YQ20140716

The source for the article: bit.ly/1r1ji5U Biological Psychology, online July 13, 2014.

[The following is copied here in case the link breaks - not trying to violate copyright.]

Stress and depression have long been linked with a heightened risk of weight gain, but a new study sheds light on how those mental states may alter the way the body processes fatty foods.

Compared to women without stress in the study, stressed-out women burned both calories and fat more slowly for seven hours after eating the equivalent of an average fast-food burger meal.

“Stress can promote weight gain by slowing your metabolism,” Janice Kiecolt-Glaser told Reuters Health.

“The difference with one stressor versus none the day before was 104 calories, which is no big deal on a daily basis, but over the course of the year that would be up to 11 pounds,” said Kiecolt-Glaser, a researcher with The Ohio State University College of Medicine, who led the new study.

For their experiment, published in Biological Psychology, Kiecolt-Glaser and her colleagues enrolled 58 middle-aged women to eat high-fat meals on two separate days while their metabolism was monitored.

To prepare for the study, the women were provided with three standardized meals a day to eat at home on the days leading up to their admission to Ohio State’s Wexner Medical Center.

Then on each day of the study, the participants answered questionnaires designed to assess their depression symptoms and their usual diet and physical activity. They were also asked about any stressful events that occurred on recent days.

Researchers began by measuring how many calories each woman burned while at rest. Next, the women were given a test meal consisting of eggs, turkey sausage, biscuits and gravy.

The meals contained about 930 calories and 60 grams of fat, around the same amounts of fat and calories as a double cheeseburger and fries from the leading fast food restaurant chains, according to the researchers.

On one of the days, the women were given a version of the test meal that was high in saturated fats, and then on the other day they were given a meal high in monounsaturated fats from sunflower oil.

Metabolic tests to see how fast fat and calories were being burned were repeated every hour for seven hours after the meal. In addition, the researchers tracked levels of the stress hormone cortisol, insulin, glucose and blood fats.

A total of 31 women reported at least one stressful event from the day before and 21 reported stressful events on both visits. Six of the women had no stressful events.

On average, the women in the study who had experienced stressful events burned 104 fewer calories than the women with no stress during the seven hours after eating either of the high-fat meals.

The researchers also found that women who had been stressed the day before had higher insulin levels and burned fat at slower rates – both conditions that promote fat storage and are associated with weight gain.

A history of depression did not affect the women’s metabolic rate, although women with depression tended to have high levels of cortisol, which is thought to promote storage of particularly unhealthy fat in the upper abdomen.

Women who had depression combined with any stressors also tended to have a steeper rise in blood fats immediately after the meals.

The only difference between results following the meal high in saturated fat versus monounsaturated fat was a steeper rise in blood sugar after the latter, which the researchers found surprising and said requires further study.

The authors acknowledge some limitations to the study – 38 of the participants were breast cancer survivors, which could have affected the results, although they note that the responses did not differ between those women and the ones who had not had cancer.

The results don’t reveal how the body might respond to low-fat or balanced meals, they add. And it’s also not clear if the findings would apply to men, although Kiecolt-Glaser thinks the effect would be similar.

“It’s hard to tell for sure because they have higher lean body mass, which is one of the factors that goes into resting energy expenditure, but otherwise I don't see a reason why it wouldn’t,” Kiecolt-Glaser said.

Brian Baldo, a researcher in the department of psychiatry at the University of Wisconsin who was not involved in the study, said one theory about stress and obesity is that eating comfort foods high in fat and calories is a way of self-medicating to calm an overactive stress response.

“This study shows another mechanism toward obesity,” he told Reuters Health, adding that the new findings show recent stressors could affect the physical processes that lead to obesity, including lower resting energy expenditure and less burning of fat.

In effect, Baldo said, “The stress directs you to eat higher fat food, and it also prevents your body from trying to effectively burn that fat off and instead you end up storing it,” he said. “So it’s a double whammy.”
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Chronic sleep loss in mice leads to neuron death

Postby badnights » Thu Feb 12, 2015 6:22 am

This is almost a year old but interesting
How lost sleep leads to lost neurons
Date:
March 18, 2014
Source:
University of Pennsylvania School of Medicine
Summary:
Extended wakefulness is linked to injury to, and loss of, neurons that are essential for alertness and optimal cognition, the locus coeruleus neurons, a mouse model of chronic sleep loss has revealed. According to common wisdom, catch up sleep repays one's "sleep debt," with no lasting effects. But the new study shows disturbing evidence that chronic sleep loss may be more serious than previously thought and may even lead to irreversible physical damage to and loss of brain cells

More at: http://www.sciencedaily.com/releases/20 ... ceDaily%29
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Re: Published Research - General Sleep and WED (RLS)

Postby ViewsAskew » Wed Mar 18, 2015 4:57 pm

Sleep and Blood Pressure

http://www.eurekalert.org/pub_releases/ ... 031315.php

Quote: "People exposed to prolonged periods of shortened sleep have significant increases in blood pressure during nighttime hours, Mayo Clinic researchers report in a small study of eight participants."

It's a small study, but it is consistent with the WED findings - we seem to have higher blood pressure at night.
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Re: Published Research - General Sleep and RLS (WED)

Postby Rustsmith » Tue May 05, 2015 8:58 am

The Pain Component of RLS

Sleep Medicine. 03/2015

Prevalence and clinical characteristics of patients with restless legs syndrome with painful symptoms.
Yong Won Cho, Mei Ling Song, Christopher J Earley, Richard P Allen

ABSTRACT The complaint of pain has largely been ignored in the diagnostic criteria for restless legs syndrome (RLS). The purpose of this study was to investigate the prevalence of painful symptoms in RLS, and to compare sleep-related characteristics between the patients who experienced the painful symptoms and those who did not. The patients with RLS were retrospectively screened from July 2011 to December 2013 at a tertiary-care sleep center. For classifying those with pain and those without pain, more than three specialists separately observed the patients' reports and complaints of symptoms, and the final decision was made through consensus. The demographics and clinical characteristics, including sleep, psychiatric-related scales, and polysomnographic data were reviewed for the study. One hundred and sixty patients with RLS were selected, and 23.8% of them reported painful symptoms of RLS. Patients with RLS who experienced painful sensations were found to have lower ferritin levels, more severe RLS symptoms, anxiety and depressive symptoms, and a lower quality of life. The polysomnography data found that patients with RLS who experienced painful sensations had a longer latency to sleep onset and a lower periodic limb movement index (PLMI) (p <0.05). Patients who experienced painful sensations had more severe RLS symptoms and a trend toward lower PLMI during sleep. According to these results, an inference can be made that painful sensations may be one important point in determining the severity of RLS.
Steve

Augmentation Evaluation http://bb.rls.org/viewtopic.php?f=4&t=9005

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Re: Published Research - General Sleep and RLS (WED)

Postby ViewsAskew » Wed May 06, 2015 4:05 am

Well, as someone with severe WED/RLS, I'd be annoyed if they said that I couldn't have a severe case because I had no pain and high PLMI!

That said, I had very mild WED/RLS initially. It was only through DA use and augmentation that my WED became severe. So, in some ways, this would have mostly have applied to me initially (I had a very long sleep latency and my ferritin was at 8 at once point).

I wish they would have done other studies, though. I want to know if people with pain are more likely to have neuropathy, too. And, if they reviewed the medications to see if there were trends. I hope they continue to review this and find other correlations or associations.
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Re: Published Research - General Sleep and RLS (WED)

Postby ViewsAskew » Sun May 17, 2015 6:28 am

Interesting - more about oxygen in the blood (or lack of). This is from May, 2014 - I didn't see that we had it already; we do have one about hypoxia - it's a different article from late 2013.

http://www.neurology.org/content/82/21/ ... bef3cdb74c
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Re: Published Research - General Sleep and RLS (WED)

Postby ViewsAskew » Wed May 27, 2015 8:37 am

Small study - text copied from here: http://www.iol.co.za/lifestyle/health-n ... WWAy0a0tE0

*Applying continuous pressure to the foot offers a way to tackle restless legs, according to US research.

Restless leg syndrome is characterised by unpleasant sensations and an urge to move the legs when at rest, most commonly at night.

In the new study, 30 patients with the condition had a device - known as Restiffic - wrapped around their feet as they slept. It works by applying a squeezing pressure on specific foot muscles.

After eight weeks, 90 percent of the patients felt their symptoms were “much improved” or “very much improved”. When the results were compared with previous research, Restiffic was as effective or better than drugs used for the condition, according to the Journal of Neurology.

The following was added by Beth on July 6, 2015:
The RESTIFFIC™ Foot Wrap is a foot wrap that is designed to help the symptoms of restless legs syndrome that places targeted, adjustable squeeze pressure on the abductor hallucis and flexor hallucis brevis muscles in the foot during periods of rest. An outer cloth wrap holds "T" shaped pads in place over the muscles on the bottom of the foot.

Very little is known about the device and it is not yet commercially available. It has been cleared by the FDA as a safe device for restless leg syndrome. The FDA application indicated that the device will be prescription only. The domain name restiffic.com was registered in Feb 2015, but as at June 2015, there was no website there and just a placeholder.

One preliminary study has been done with the Restiffic wrap. It did not have a proper control group. There was an improvement in symptoms in the group in the study with the wrap, but uncontrolled studies (or studies with historical reference or control groups) tend to overestimate the treatment effects. The trial was registered but has only been presented as a conference abstract and not published in full. (From http://podiapaedia.org/wiki/neurology/h ... foot-wrap/)
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