Published Research - General Sleep and RLS (WED)

For everything and anything else not covered in the other RLS/WED sections.
badnights
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Re: Published Research - General Sleep and RLS (WED)

Postby badnights » Wed Dec 12, 2018 5:18 am

Gupta, R. & Pandi‑Perumal, S.R. Sleep Vigilance (2018). An editorial from https://link.springer.com/article/10.10 ... 018-0052-y

Sleep and Vigilance (journal)
Addictive Substances and Sleep: More Research is Needed (title)
Ravi Gupta & Seithikurippu R. Pandi‑Perumal (authors)

EDITORIAL
First Online: 04 December 2018
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Since a long time, addictive substances have been found to affect sleep quantity, quality, and sleep architecture. In addition, certain substances have been found to induce other physiological processes during sleep, thereby affecting the quality or quantity of sleep. However, we have limited data to suggest that addictive substances may influence sleep quality and quantity either by inducing or relieving other sleep disorders.

Restless legs syndrome (RLS) also known as Willis–Ekbom disease (WED), named after the doctor who first described it in 1945 [1] is a less understood, but a commonly treatable chronic sleep disorder that is characterized by severe sensory-motor dysfunction. The affected individuals often report an urge to move legs, especially at night with worsening of symptoms at rest and an improvement by movement [2]. This disorder has been linked to the dopamine abnormalities in the brain, which in turn has been found to be regulated by opioid receptors [3, 4]. Furthermore, opioid has found a place in the management of RLS in selected cases [5].

Opioid withdrawal presents with muscle aches and pains, often along with the restlessness [6]. These features often overlap with the symptoms of RLS and considering the neurobiological underpinnings, it may be possible that some of the patients develop RLS during opioid withdrawal. Case reports and case series suggested that RLS is seen in the patients during opioid withdrawal, including dextropropoxyphene and tramadol [7, 8]. However, large studies in this area are limited and to the best of our knowledge, only one study is available that suggested the prevalence of RLS as 13% among patients with opiate withdrawal [9]. Recognition of RLS and its distinction from myalgia that occurs during opioid/opiate withdrawal are important for a number of reasons. First, RLS may induce sleep disturbance in these patients, which is completely amenable to treatment [7, 8]. Addressing the RLS may thus facilitate the detoxification process. Second, in contrast to myalgia, which generally lasts for only initial 3–5 days after opiate/opioid withdrawal, symptoms of RLS may persist for a longer duration, thus, requiring treatment to be continued during the post-detoxification process [7, 8].

A recent study suggested that RLS is seen in around 50% subjects during opioid withdrawal [10]. Moreover, there is evidence that concurrent cannabis use or cannabis itself may either prevent or ameliorate symptoms of RLS [10, 11].

Similarly, tobacco, in particular, smoking is considered a risk factor for the development of RLS [12]. However, contradictory data are also available suggesting improvement in RLS following tobacco chewing and the absence of effect of smoking over RLS [13, 14, 15, 16].

The antinociceptive and psychoaffective effects of cannabis are well known. The potential benefits and the efficacy of cannabis use in the treatment of RLS was first reported in a case study [11]. In a subjective evaluation, all six patients reported an improvement in sleep quality and symptomatic relief of RLS with minimal side effects.

The effect of medical cannabis in the sleep field is gaining much attention. Cannabinoids work on the endocannabinoid system (ECS). Among the various cannabinoids, delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) are extensively studied. Cannabinoids that work on the human ECS act through two main receptors, namely the CB1 and CB2 receptors. One such synthetic cannabinoid is dronabinol, which has undergone preclinical and clinical studies [17, 18, 19]. However, with the limited safety profile of medical cannabis in the field of sleep medicine, the American Academy of Sleep Medicine (AASM) has released a position statement, which clearly pointed out the lack of evidence on the use of medical cannabis and further cautioned that “medical cannabis and/or its synthetic extracts should not be used for the treatment of OSA due to unreliable delivery methods and insufficient evidence of effectiveness, tolerability, and safety” [20]. However, it has been argued that further longitudinal and controlled trials are needed to fully explore the potential use of cannabinoids in the sleep field [21].

In conclusion, this is an important area that requires attention. There is a need to conduct two kinds of studies for a better understanding—experimental as well as epidemiological. Robust data generated from both kinds of trials simultaneously will help us to understand sleep physiology in a better manner.
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See original page for references
Beth - Wishing you a restful sleep tonight
Click for info on WED/RLS AUGMENTATION & IRON
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badnights
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The impact of the use of amalgam in dental treatment on the prevalence of restless legs syndrome in older people

Postby badnights » Sun Dec 30, 2018 6:11 am

Yikes. I have often wondered about this. 104 people were questioned about their dental fillings and RLS/WED symptoms:

http://medpr.imp.lodz.pl/The-impact-of- ... 2,0,2.html

Results: Subjects who answered “yes” (indicating presence of RLS) to the 4 subsequent questions had a significantly higher number of amalgam dental fillings as compared to the subjects without RLS symptoms. Presence of other metal dental restorative materials and the number of amalgam dental fillings reported in the past had no significant influence on RLS symptomatology.
Conclusions: Authors conclude that while examining the correlates of the appearance of restless legs syndrome the use of amalgam in the dentition should be taken into account.

Mine are all gone now.... I think!!! Gee, I'd better check into that - - the big ones for sure have all been replaced.
Beth - Wishing you a restful sleep tonight
Click for info on WED/RLS AUGMENTATION & IRON
I am a volunteer moderator. My posts are not medical advice. My posts do not reflect RLS Foundation opinion.

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

Postby Rustsmith » Sun Dec 30, 2018 5:44 pm

As a metallurgist who started out my career working with alloys that contain mercury, I am always very skeptical of any health claims that attribute some sort of malady to amalgam fillings. Since almost everyone over a certain age had these performed when they were younger, you can use statistics to blame almost anything on them.

From a technical standpoint, the chemical bond between the mercury and the silver in the amalgam is very strong. Silver is recovered from amalgam by heating it to the boiling point of mercury, not something that is going to come close to happening in your mouth. Also, the total amount of mercury in the amalgam is not that great, so even if all of it was extracted from the filling over the years since you had the dental work done, the exposure is much lower than the government limits for workers in facilities handling mercury. You were probably exposed to more mercury by playing with it from broken thermometers or in chemistry class. Now, if they had investigated the correlation between RLS incidence and dentists who installed numerous fillings every day and therefore were exposed to far more mercury vapors and to workers in plants where mercury was handled on a regular basis, then I might pay attention.
Steve

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

Postby Yankiwi » Sun Dec 30, 2018 9:37 pm

Thanks, Steve. I never have believed the hysteria about amalgam fillings but your scientific explanation is valuable.

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

Postby restlessknight » Fri Jan 18, 2019 11:38 am

Absence of evidence is not evidence of absence.

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

Postby ViewsAskew » Mon Mar 04, 2019 2:59 am

Ann - Take what you need, leave the rest

Managing Your RLS

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

Postby Rustsmith » Mon Mar 04, 2019 4:21 pm

Very interesting article, even though it is rather old (2000). So, I wonder what Dr Allen would have to say today about this. Some of the current articles seem to be moving in the direction of a single cause for RLS and PLMD with low brain iron. But this may relate more to the cause of the low iron rather than anything else. This also may relate to why at my first appointment with him, Dr Ondo was very interested in why my first symptoms occurred. He said that because it was before age 40, then it was genetic. This study might be the basis for his interest and comment.
Steve

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

Postby Polar Bear » Mon Mar 04, 2019 4:25 pm

He said that because it was before age 40, then it was genetic.


My rls symptoms started at around age 34 however I'm unaware of anyone within my parents/grandparents, close family who also has this disease.
Betty
http://www.willis-ekbom.org/about-rls-wed/publications
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Re: Published Research - General Sleep and RLS (WED)

Postby stjohnh » Mon Mar 04, 2019 5:45 pm

Rustsmith wrote:... Some of the current articles seem to be moving in the direction of a single cause for RLS and PLMD with low brain iron. ...


I wonder if this would help explain the substantial number of people that do not seem to respond to IV Iron infusions.
Blessings,
Holland

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

Postby Rustsmith » Mon Mar 04, 2019 6:44 pm

My rls symptoms started at around age 34 however I'm unaware of anyone within my parents/grandparents, close family who also has this disease.


Betty, I wouldn't have remembered having RLS prior to age 40 if it hadn't been for many very uncomfortable airplane flights starting in my late 20's. At the time, I thought that everyone had these problems when the fasten seat belt sign was lit or when the food carts blocked the aisle. As for family, I would never have known that my father probably had PLMD if not for a comment that he made to my wife one day while on a family vacation and the two of them were resting on a park bench while everyone else wandered about.

I wonder if this would help explain the substantial number of people that do not seem to respond to IV Iron infusions.


Holland, I have very little to base this on, but I suspect that the reason why my RLS did not respond to iron therapy is due to genetics. One of the presentations given at the Foundation Patient Symposium last fall talked about cutting edge work that is being done to study iron transport across the blood-brain barrier (unfortunately that was the one talk who could not supply his slides because they were still too new). The work so far hinted at at least two issues, one having to do with getting the iron from the blood and through the cell wall of the barrier and the other where the iron gets trapped inside the cells that make up the barrier and not into the brain.
Steve

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

Postby stjohnh » Mon Mar 04, 2019 7:14 pm

Polar Bear wrote:My rls symptoms started at around age 34 however I'm unaware of anyone within my parents/grandparents, close family who also has this disease.


Other possibilities are:
1. Relatives had RLS that was either never diagnosed or misdiagnosed.

2. RLS is a polygenic abnormality; You could have inherited a few RLS genes from your mom (who did not have clinical RLS) and other RLS genes from your dad (also without clinical RLS), but the combination you inherited DID give you RLS. Also there are likely epigenetic factors influencing the expression of the RLS genes. The most obvious one being the blood iron level.
Blessings,
Holland

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

Postby Rustsmith » Sat Mar 09, 2019 5:17 pm

https://www.sciencedirect.com/science/article/pii/S1389945718305094

This paper reports on work done in Europe looking that the effectiveness of Horizant as a treatment for individuals who have previously received a dopamine agonist. Their work found that prior treatment with a dopamine agonist reduced the effectiveness of Horizant.

Therefore, their conclusion was that alpha-2-deltas should be used prior to trying a dopamine agonist.

This also opens the question about how DA treatment changes us and the role of augmentation.
Steve

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

Postby ViewsAskew » Sun Mar 10, 2019 12:11 am

That definitely fits with the experience of many here. I wonder if, after X time off of the DA, it can work again, or if it never does?
Ann - Take what you need, leave the rest



Managing Your RLS



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

Postby Rustsmith » Mon Mar 25, 2019 9:25 pm

https://academic.oup.com/sleep/advance-article/doi/10.1093/sleep/zsz079/5415757

Title : Extracellular Vesicles Reveal Abnormalities In Neuronal Iron Metabolism In Restless Legs Syndrome

Journal : Sleep, March 2019 issue

Authors : Sahil Chawla, Seema Gulyan, Seema Gulyan, Richard P Allen, Dimitrios Kapogiannis, et al.

Abstract : Study Objectives Determine abnormalities in levels of iron-management proteins in neuronal origin-enriched extracellular vesicles (nEVs) in Restless Legs Syndrome (RLS). Methods: We used immunoprecipitation for neuronal marker L1CAM to isolate nEVs from the serum of 20 RLS subjects from a study including MRI determinations of iron deposition in the substantia nigra and hematologic parameters and 28 age- and sex-matched Controls. Results: RLS compared to Control subjects showed higher levels of nEV total ferritin but similar levels of transferrin receptor and ferroportin. Western blot analysis showed that heavy- but not light-chain ferritin was increased in nEVs of RLS compared to Control subjects. In RLS but not Control subjects, nEV total ferritin was positively correlated with systemic iron parameters; the two groups also differed in the relation of nEV total ferritin to MRI-measures of iron deposition in substantia nigra. Conclusions: Given the neuronal origin and diversity of EV cargo, nEVs provide an important platform for exploring the underlying pathophysiology and possible biomarkers of RLS.

My comment: This work appears to be part of an effort to develop a true diagnostic tool for RLS and to also determine the actual processing of iron in our brains. If I understand the parts of the paper that I have read, they are hypothesizing that the issue in RLS is that we excrete more iron from our brain cells than normal and that this is why we are iron deficient. Interesting idea that could explain things for a lot of us.
Steve

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

Postby stjohnh » Tue Mar 26, 2019 1:06 am

Rustsmith wrote:https://academic.oup.com/sleep/advance-article/doi/10.1093/sleep/zsz079/5415757

Title : Extracellular Vesicles Reveal Abnormalities In Neuronal Iron Metabolism In Restless Legs Syndrome

My comment: This work appears to be part of an effort to develop a true diagnostic tool for RLS and to also determine the actual processing of iron in our brains. If I understand the parts of the paper that I have read, they are hypothesizing that the issue in RLS is that we excrete more iron from our brain cells than normal and that this is why we are iron deficient. Interesting idea that could explain things for a lot of us.


The authors specifically mention the possibility of developing a blood test for RLS. This may be of help in questionable cases or for primary doctors with little experience in RLS. However, the clinical presentation of most people with jumpy legs complaints is clear just by history for most patients. This is just a preliminary investigation. I noted that there was considerable overlap between RLS patients and the controls for several differences, making a test based on their results not too helpful. My personal experience with IV Iron infusions is that a number of unexpected neurologic symptoms, not usually thought to be associated with RLS, have improved along with the near complete resolution of classic RLS symptoms. I fully expect future research to show iron deficiency to be a major factor in several neurologic syndromes of currently unknown etiology.
Blessings,
Holland


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