Restless Legs Syndrome (RLS) Discussion Board

More about adenosine. It is not a study, but an editorial and it doesn't come out until May.

https://www.eurekalert.org/pub_releases ... 040319.php

As we all knew .... https://academic.oup.com/sleep/article/ ... 18/5306230. The paper is free.

Statement of Significance
"While many studies indicate that napping is beneficial to cognition, it remains unclear whether the nap itself leads to cognitive improvement, or if the same benefits are achievable by simply getting more nocturnal sleep instead. Here we show that splitting sleep between a nocturnal period and a daytime nap improves hippocampal-dependent cognitive function under conditions of chronic sleep restriction, even when total time available for sleep is controlled. In the absence of adequate nocturnal sleep, a split sleep schedule may optimize cognition"

Abstract
Study Objectives
Chronic sleep restriction in adolescents is widespread, yet we know little about how to apportion the limited amount of sleep obtained to minimize cognitive impairment: should sleep occur only nocturnally, or be split across separate nocturnal and daytime nap periods? This is particularly relevant to hippocampal-dependent cognitive functions that underpin several aspects of learning.

Results
Performance of the 5.0h and 6.5h nocturnal TIB groups was significantly impaired relative to the 9.0h control group. Performance of participants on the split- sleep schedule (5.0 + 1.5h) did not significantly differ from controls.

Conclusions
These findings suggest that hippocampal function is sensitive to moderate multi-night sleep restriction, but deficits can be ameliorated by splitting sleep, at least for a period after waking from a daytime nap. While this split sleep schedule should not be considered a replacement for adequate nocturnal sleep, it appears to benefit the cognitive and neurophysiological functions that underpin learning in those who are chronically sleep deprived.

More about adenosine. It is not a study, but an editorial and it doesn't come out until May.

The editorial (available via a link on the linked page) is written by Ferre and seems to concern the research that was reported in his 2017 paper. But I'm actually too tired to read the editorial. Anyone want to confirm that? I still want to read it, cuz I expect it to be a good summary of the paper.

The editorial (available via a link on the linked page) is written by Ferre and seems to concern the research that was reported in his 2017 paper.

badnights, your assumption is correct. The editorial is more understandable than Ferre's original paper, probably because it was written by the journal editor and not Ferre himself.

Rustsmith wrote:

The editorial (available via a link on the linked page) is written by Ferre and seems to concern the research that was reported in his 2017 paper.

badnights, your assumption is correct. The editorial is more understandable than Ferre's original paper, probably because it was written by the journal editor and not Ferre himself.

I think someone is confused, possibly me LOL... The original link https://www.eurekalert.org/pub_releases ... 040319.php several posts above is to an editorial (by the editors) published in Eureka Alerts regarding another editorial by Ferre (in the Journal of Caffeine and Adenosine Research, not the original paper). Ferre's editorial is at https://www.liebertpub.com/doi/pdf/10.1 ... .2019.0001. Note that this link is free until May 3, 2019. Presumably the link won't work after that, so if you are interested, better do it before May 3.

The editor's editorial is indeed very understandable. Ferre's editorial is still pretty dense, but is indeed more understandable than the original paper. It is shorter and Ferre hypothesizes more in it than in the original paper.

Interesting:

https://www.psychcongress.com/article/m ... p-behavior
A few paragraphs from the article:
By Will Boggs MD

NEW YORK—Nearly four dozen genetic variants appear to be related to sleep quality, quantity, and timing, according to a new genetic study of accelerometer-based sleep measures.

They identified 47 genetic variants associated with seven sleep traits: sleep duration, sleep efficiency, the number of sleep episodes, diurnal inactivity, sleep midpoint, timing of the least-active five hours and timing of the most-active 10 hours.

Most variants were associated with either sleep quality, duration, or timing, but not combinations of these sleep characteristics. Twenty variants were associated with restless legs syndrome, and these variants showed a clear positive association of restless legs syndrome with all sleep traits.

Is this really the first clear indication of the physiological function of sleep? It's the first I've seen but that doesn't mean a lot. They propose - based on what they observed in transparent zebrafish - that sleep is when our cells clean up the damage to DNA that accumulates during wakefulness. It doesn't seem at all surprising.

Sleep increases chromosome dynamics that clear out DNA damage accumulated during waking hours

Date: March 5, 2019 Source: Bar-Ilan University

… The reason why animals sleep -- despite the continuous threat of predators -- still remains a mystery, and is considered among the biggest unanswered questions in life sciences.

Using 3D time-lapse imaging techniques in live zebrafish, the researchers were able to … show, for the first time, that single neurons require sleep in order to perform nuclear maintenance.

DNA damage can be caused by many processes including radiation, oxidative stress, and even neuronal activity. DNA repair systems within each cell correct this damage. The current work shows that during wakefulness, when chromosome dynamics are low, DNA damage consistently accumulates and can reach unsafe levels.

[They] propose that the restorative function of sleep is nuclear maintenance. "We've found a causal link between sleep, chromosome dynamics, neuronal activity, and DNA damage and repair with direct physiological relevance to the entire organism," says Prof. Appelbaum. "Sleep gives an opportunity to reduce DNA damage accumulated in the brain during wakefulness."

"Despite the risk of reduced awareness to the environment, animals -- ranging from jellyfish to zebrafish to humans -- have to sleep to allow their neurons to perform efficient DNA maintenance, and this is possibly the reason why sleep has evolved and is so conserved in the animal kingdom," concludes Prof. Appelbaum.

https://www.sciencedaily.com/releases/2 ... ceDaily%29

This link goes to a preliminary research finding at Stanford Sleep Center that is starting to look at the relationship between SIBO (gut bacteria overgrowth) and RLS. So far, they only are reporting on seven individuals, but it indicates that recruiting of more test subjects is continuing.

https://medicalxpress.com/news/2019-06- ... inked.html

Rustsmith wrote:This link goes to a preliminary research finding at Stanford Sleep Center that is starting to look at the relationship between SIBO (gut bacteria overgrowth) and RLS. So far, they only are reporting on seven individuals, but it indicates that recruiting of more test subjects is continuing.

https://medicalxpress.com/news/2019-06- ... inked.html

This is very interesting particularly given Beth's experiences.

Here is another publication by Dr Ferre on Adeonsine. The full article is not available, but the free first page is half of what was written. He also adds to the sequence in which the various transmitter/receptors work. The importance is that he postulates that DAs and gabapentin both work through the glutamate receptors and that this is how these meds help treat RLS.

The primary thing not shown on the first page is the summary of current and proposed research. He states that a clinical trial of adenosine action should be "easy" since A1R ligands can be seen using a PET scan. He also states that a large scale, double blind dipyridamole study is already underway. The study must be in Europe since I have been looking for one in the US without finding any.

https://www.liebertpub.com/doi/full/10. ... .2019.0001

"Rustsmith".. He also states that a large scale, double blind dipyridamole study is already underway. The study must be in Europe since I have been looking for one in the US without finding any.

Interesting about dipyridamole. Dipyridamole boosts extracellular adenosine. I re-started dipyridamole at low dose (37.5mg at 8pm and repeat at about 1am) 2 days ago as I am starting to have recurrent RLS symptoms 6 months after my first IV Iron infusion in December. Interestingly, I noticed sleep disruption starting 3-4 weeks ago, then mild urge to move symptoms starting about 10 days ago. The insomnia (hyperalertness?) is more annoying than the urge to move at this point. I should get my repeat IV Iron infusion in a week or two.

I recently, last few years, read in New Scientist magazine that one of the main functions of non REM sleep is clearing the metabolites of brain function from the brain fluid. This was related to dementia, but applies to all sleeping disorders.

Failure to clear the metabolites impacts brain function. A paper I read on dopamine agonists, rls and sleep studies demonstrated that sleep quality wasn't improved, but disrupted symptoms. This supports the failure of advances in rls understanding as there are zealots over neurology, iron, dopamine and circulation that ignore the physical and microbiome aspects, and ultimately more practical solutions.

This supports the failure of advances in rls understanding as there are zealots over neurology, iron, dopamine and circulation that ignore the physical and microbiome aspects, and ultimately more practical solutions.
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I very much disagree with this statement. First, RLS research has been going of for less than 20 yrs, MS research is far better funded and has been going on for many years and yet still there is only a little bit known about that condition.

There are also a number of studies that are being conducted by major research hospitals and universities that address issues such as circulation in the legs (Penn State), microbiome (Stanford and Mayo), the impact of RLS on heart condition, the applicability of yoga (Univ of West Virginia), etc.

The human body is an incredibly complex organism with multiple feedback loops. Each study, be it neurology, genetics, gastroenterology, cardiovascular, behavioral health, gerontology, nutrition or whatever, each contributes a piece of the puzzle. A great deal of study is currently centered on neurology and genetics because powerful new tools have recently opened up avenues of study that have not been available until the last few years. That does not mean that more cannot be done. For example, if government regulators will get out of the way, anecdotal evidence says that there are benefits to the compounds in marijuana. But nothing can be done by scientists now because of legal restrictions. There is so much that remains to be done. But the important thing is that research is making major strides.

Rustsmith wrote:But the important thing is that research is making major strides.

My point is that the research is in the wrong direction. I make these statements presented as a solo and apparent madman, which I’m prepared to accept, based on my own experiences, what I have read on numerous forums, and talking to doctors.

I don’t have a sleeping issue with RLS anymore. My only inconvenience is 5 minutes preparation before bed and some easily resolved mild issues occasionally at night. The problem was, to get to that point required me to ignore all the speculation and indeed dogma on RLS from publications, specialists in the area and the views of most sufferers. Most of the areas that are being researched I can see as dead ends, but I would love to be proved wrong.

There are no neurological conditions that don’t have measurable physiological or cognitive deterioration, and can’t be easily measured. I had RLS that allowed me 2 hours of broken sleep a night, now I’m sleeping and 100% functional again. If it is neurological, how could I return to normal sleep and functioning?

Dopamine is the same, as having been on SSRIs I know what it feels like to be low on dopamine. Why doesn’t everyone on SSRIs get RLS, which didn’t make my RLS worse but does seem to impact others.

Iron doesn’t work for everyone, and some people with haemochromatosis still have RLS symptoms.

Almost all of this isolated focusing is missing what is obvious through experimentation. This is a condition that creates a unique tension in muscles, with susceptibility to those muscles that can’t be stretched due to biomechanics; such as the calf and forearm. During sleep the tension creates the signal for the brain to produce tacit hallucinations, which makes this a psychiatric condition.

The range of successful strategies employed by numerous individuals support this model. Dopamine agonists, benzo’s and opioids basically stop the brain from functioning normally in sleep mode; as a disruptor. Iron is very interesting, but as with many supplements and diet changes its action relates to changing normality through higher than normal levels that impact muscles or through temporary microbiome changes. Once again a disrupter of the condition.

The rapid and often frequent changes in RLS symptoms eliminate a systemic condition, and give a clue to the physical element.

I know I’m on my own with this, but before I lose interest in this condition and disappear from all online discussions due to it no longer being an issue, I would like to promote some more holistic views.

Previous studies found a correlation between cardiovascular disease (CVD) and RLS, particularly in women. This extension to that previous study found that the risk of CVD was almost eliminated by effective treatment of the RLS.

https://academic.oup.com/sleep/article- ... m=fulltext