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

Posted: Fri Sep 28, 2018 6:29 am
by ViewsAskew
Rustsmith wrote:Here is a new publication that discusses co-morbidities of RLS and appears to present a new idea about how primary and secondary RLS are really the same thing. It will appear in Lancet, but so far only the abstract is available.

https://www.sciencedirect.com/science/article/pii/S1474442218303119



Huh!

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

Posted: Thu Oct 04, 2018 2:13 am
by badnights
Why not. That's what I always thought. There has to be something similar going on to generate similar symptoms. Not everyone who has anemia gets WED/RLS.

Re: Published Research - Suicide and RLS (WED)

Posted: Tue Oct 16, 2018 11:29 pm
by Rustsmith
Here is another publication that is pending, this time a study of the relationship between suicide and RLS. The results summary so far says

192 RLS and 158 control participants were comparable for age, sex, race, and other potential demographic confounders. In general, RLS was moderate-to-severe (mean IRLSS 26.4±7.5). Significantly more RLS than control participants had lifetime suicidal ideation or behavior (27.1% vs. 7.0%; p<0.00001) or lifetime depression history (65.6%% vs. 22.8%; p<0.00001). The odds of having a lifetime suicidal ideation or behavior was higher in those with RLS (2.80 [1.29,6.11]), even after accounting for depression and other confounders. In RLS, the odds of lifetime suicidal ideation or behavior was increased if there was lifetime depression (7.37 [2.65,20.47]) or if RLS in the past was severe or very severe (2.36 [1.03,5.40]).


https://www.sleep-journal.com/article/S1389-9457(18)30489-1/abstract

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

Posted: Fri Oct 26, 2018 5:08 am
by badnights
Iron deficiency in the mitochondria of white blood cells (and other body cells???) in RLS/WED!

Association of mitochondrial iron deficiency and dysfunction with idiopathic restless legs syndrome Movement Disorders, 11 October 2018 https://doi.org/10.1002/mds.27482

ABSTRACT
Background: Restless legs syndrome is a sensorimotor neurological disorder of the limbs that impairs quality of life and disturbs sleep. However, there has been progress in understanding the disease involving the dopaminergic system as well as iron metabolism. The exact pathophysiological mechanisms of restless legs syndrome remain elusive. We tried to elucidate the underlying mechanisms in iron metabolism in restless legs syndrome subjects on a systemic, cellular, and mitochondrial level.

Methods: We conducted a study prospectively recruiting 168 restless legs syndrome patients and 119 age‐matched healthy controls focusing on iron metabolism using human monocytes as surrogates.

Results: Evaluation of systemic iron metabolism parameters in the circulation showed no significant difference between patients and controls. We observed a significant reduction in mRNA levels of heme oxygenase 1 and mitochondrial iron genes like mitoferrin 1 and 2 in monocytes isolated from restless legs syndrome patients, indicating mitochondrial iron deficiency. Interestingly, we also observed reduced expression of iron regulatory protein 2 along with impaired activity of mitochondrial aconitase and reduced mitochondrial superoxide formation in restless legs syndrome subjects. Along this line, patients had reduced mitochondrial respiratory capacity that improved in restless legs syndrome subjects under treatment with dopaminergic drugs compared with untreated patients.

Conclusions: Our data suggest that restless legs syndrome is linked to mitochondrial iron deficiency and associated impairment of mitochondrial function. This is partly corrected by treatment with dopaminergic drugs compared with untreated patients, which may be linked to an effect of dopamine on cellular iron homeostasis.

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

Posted: Sat Oct 27, 2018 12:16 am
by ViewsAskew
Huh! I found it interesting, also, that the doctors were from Austria and I wasn't familiar with most of them. Happy to see more people researching it as well as these very interesting findings!

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

Posted: Tue Oct 30, 2018 2:51 am
by Rustsmith
I was able to take a look at the recent paper on RLS and suicide (link to abstract is near the top of this page). I wish I could post it here, but copyright prohibits it. The relationship isn't surprising to us, but there were a couple of things that stood out. Thoughts of suicide correlate with RLS having a 2.5 times higher correlation than controls. However, actual plans or attempts only correlate with severe to very severe RLS and not the milder forms (IRLSSG <20). Other statistics were not very surprising. The majority of RLS subjects had been through augmentation, most were female, the mean age was 50 and the mean IRLSSG score was 26. Also, the majority of the RLS subjects were Foundation members, which is an indication of the Foundation's recruiting efforts for Clinical Trials. There was a correlation between suicide plans and lifelong struggles with depression, but much less for those who only occasionally struggle with depression. Finally, there was no correlation between RLS suicide plans and sleep deprivation or un-refreshing sleep, which was rather surprising considering how much of a problem that sleep is and how it usually correlates with depression.

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

Posted: Wed Oct 31, 2018 12:48 am
by debbluebird
I'm surprised there was no correlation between sleep deprivation and and RLS suicide plans. The times that I have been at my worst and sleep deprived, I just did not want to live. I don't live alone, but I had been alone I'm not sure what would have happened. On the other side, I have never felt that I would follow through with anything.
I just felt so desperate.

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

Posted: Wed Oct 31, 2018 3:10 am
by Rustsmith
Deb, I think that the authors were also surprised with that result, which is why they specifically pointed out the lack of correlation.

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

Posted: Sun Nov 18, 2018 7:49 pm
by ViewsAskew
The original is in German, I think... No idea if this is a solid study.

A quote from the following article: "For the first time the researchers show that, in fact, it is not only the central nervous system but also the nerve cells targeting the muscles themselves that are responsible."

https://www.sciencedaily.com/releases/2 ... 234848.htm

This is interesting specifically, I think, for those with painful symptoms, if this is a good study and more research bears this out. Wonder if this could pave the way for a differentiation between types?

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

Posted: Sun Nov 25, 2018 3:33 am
by badnights
Trenkwalder is a co-author so it's probably good research. The idea that the peripheral nervous system is involved in WED/RLS has been tossed about for years now, based on various indirect lines of evidence. So it;s good to see that there may be some direct evidence.

The summary is confusing though - first, the title is misleading (there has been no breakthrough in treatment). Also it says that PLMs ("involuntary leg movements") were found to be caused by peripheral NS over-excitability; but later it seems to indicate that what was actually discovered was that neurons supplying leg muscles in people with WED/RLS have greater excitability than those of controls. I imagine that the authors speculated that this caused PLMs (or maybe WED/RLS sensations).

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

Posted: Sun Nov 25, 2018 3:44 am
by Rustsmith
Here is a link to the full paper

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/JP275341

I don't understand most of the testing that was done. But what strikes me is that they seem to have what appears to be a fairly simple, painless test that differentiates RLS from non-RLS test subjects. Something like this combined with the ultrasound technique that Dr Allen mentioned for measuring iron levels in the brain MIGHT lead to a way to actually diagnose RLS using testing rather than the current series of patient answered questions. If so, that would advance our cause tremendously since it would silence the naysayers who claim that this is a made-up disease or that it is all in our heads. If so, this could end up being something like the change that was made when MRI machines were first used to diagnose MS. My wife had to spend a week in the hospital having every neurological test available run (one of which was extremely painful) to rule out everything else. Now they send you for an MRI and can have a diagnosis almost immediately.

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

Posted: Mon Nov 26, 2018 4:50 am
by badnights
Cool! Even though the abstract sounds like they're only talking about PLMs, the discussion suggests that their discovery bears on both the urge to move and PLMs.

It's interesting that they did their tests on the arms of the subjects and not the legs, but still found that difference between WED/RLS patients and controls.

Thanks for posting, Steve. The implications for diagnosis are wonderful. Perhaps even for treatment, eventually!

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

Posted: Thu Nov 29, 2018 12:57 am
by debbluebird
Interesting.

Re: Published Research - Vitamin D no effect

Posted: Wed Dec 05, 2018 6:21 am
by badnights
A recent study of 35 WED/RLSers, 17 assigned to receive vitamin D and 18 a placebo, showed no effect on IRLSSG score after 12 weeks. The vitamin D dose was 50,000 IU. Abstract here: https://link.springer.com/article/10.10 ... 018-1751-2. I didn't access the actual paper, so I don't know what the D levels or IRLSSG scores were before the study started.

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

Posted: Wed Dec 05, 2018 6:57 am
by ViewsAskew
Darn. Glad they studied it, even if it was a small group. They need to study other similar substances - vitamins, minerals, etc.