I got my paper and I found at least o... - Restless Legs Syn...

Restless Legs Syndrome

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I got my paper and I found at least one answer

WideBody profile image
5 Replies

Well I found my paper and I found out why I augmented so quickly.

"Lastly, low ferritin serum concentration is a risk factor for the so-called augmentation, defined as a worsening of symptoms under DAergic therapy (Hyacinthe et al., 2015; Unger, Bianco, Jones, Allen, & Earley, 2014).

Overall, these abnormalities may lead to a dysfunctional cortico-striatal-thalamic-cortical circuit and to a defective brain iron homeostasis. However, although the genetic contribution seems to be relevant, at least in some RLS patients, simply an

involvement of the above mentioned network only fails to explain the

hyperarousal state."

So if you ARE taking a DA drug, it's probably best you keep an eye on your Ferritin level. You should anyways, because you have RLS.

SCIENCE!

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WideBody
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5 Replies

Thanks for sharing this.

Just to corroborate wnat you write -

It's well known that low ferritin can be an indicator of brain iron deficiency in people with RLS. UK national guidelines for the management of RLS recommend a ferritin test for ALL people with RLS.

Iron deficiency is a major causative factor in RLS irrrespective of augmentation or not.

There are international guidelines on iron therapy for RLS : See this link

sciencedirect.com/science/a...

Iron therapy, in some cases, can eliminate the need for medication entirely.

I believe the accepted explanation for the hyperarousal in RLS is an imbalance between the two neurotransmitters GABA and Glutamate. i.e. an excess of glutamate.

The gabapentinoids can be effective in treating this, boosting GABA and inhibiting glutamate.

There has been some recent research into a possible underlying dysfunction common to both the dopamine and glutamate issue which is a neurotrsnmitter called adenosine.

You may find this link interesting

gmjournal.co.uk/is-adenosin...

and this

liebertpub.com/doi/10.1089/...

This has promoted some researchers to look at the use of dipyridamole, currently used as an anticoagulant. as a treatment for RLS, because of its effect on adenosine.

This could potentially treat BOTH the hyperdopaminergic and hyperarousal aspects of RLS with one stone!

-

WideBody profile image
WideBody in reply to

I think you will like this.

12. Recent developments

Based on recent finding about the role of glutamate in RLS/WED, two substances have shown promising results in open studies: First, the selective AMPA-glutamate receptor antagonist perampanel was evaluated in 22 RLS patients over a treatment of 8 weeks (Garcia-Borreguero, Cano, & Granizo, 2017). During the eight-week treatment period the200

Vivian Wanner et al.

IRLS score improved from a mean (S.D.) 23.7 4.2–11.5 5.3. Twelve of 20 patients were full responders (improvement 50% in IRLS total score), and four responded partially. The mean effective dose of perampanel at the end of treatment was 3.8 mg/day. Treatment with perampanel also resulted in an improvement in the mean (S.D.) PLMI from 27.8 6.9–4.36 2.0.

The use of dipyridamole (Garcia-Borreguero, Guitart, et al., 2018) was based on recent studies showing that brain iron deficiency in an animal model is associated with a hypoadenosinergic state, with striatal down- regulation of adenosine A1 receptors (A1R) (Quiroz et al., 2016), leading to hypersensitive corticostriatal terminals (Yepes et al., 2017). It was there- fore hypothesized that an increase in the tonic A1R activation mediated by endogenous adenosine could represent a new alternative therapeutic strategy for RLS/WED. Since dipyridamole is an inhibitor of adenosine transport, it was thought that it could cause such an increase in extracellular adenosine and thereby exert a therapeutic effect on RLS/WED symptoms. Out of 13 patients who completed the study, IRLS score improved from a mean (S.D.) of 23.4 4.6 at baseline to 10.7 4.5 at 8 weeks. Six of 13 patients were full responders and four were partial responders. The mean (S.D.) effective dose of dipyridamole at 8 weeks was 281.8 (57.5) mg/day. Sleep variables also improved, and the mean (S.D.)PLMIdecreasedfrom 26.7 7.2–4.3 1.9. These results support the hypothesis of adenosine playing a central role in the pathophysiology of RLS/WED, thus mediat- ing the increase in function of dopamine and glutamate in corticostriatal pathways.

in reply toWideBody

Exactly!!

Munroist profile image
Munroist in reply to

Does this relate to the fact that many people find caffeine helps with RLS, given that caffeine blocks adenosine receptors? The thrust of the article seems to be that too much adenosine is related to worse RLS. From my reading of Michael Walker’s excellent book on sleep, adenosine increases through the day peaking at bedtime when it’s part of the mechanism which brings on sleep. As you sleep the body removes adenosine until it’s at very low levels in the morning from when it builds again through the day. The thing with coffee though is that it only blocks the adenosine receptors which means the adenosine continues to increase and along with it the sleep pressure. I’m sure there are many things working in parallel here e.g. dopamine cycles as well and the fact that not all patients respond to treatment suggests to me that RLS is more complex and this isn’t the whole picture, which is also borne out by the fact that different therapies such as dopamine, opioids and alpha2delta ligands can all have a beneficial effect.

in reply toMunroist

Complex is the word!

👍

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