Published Research - General Sleep and RLS (WED)

[Lissa496]

Has anyone reviewed the published research on Stellate ganglion block (SGB)? From the description, the patients have more periodic limb sleep movements (PLMS) than RLS. Wondering if this would work for RLS>
Here is a link: https://www.frontiersin.org/journals/ne ... 33188/full

If anyone knows more about this it would be great to hear! ~Lissa

[Rustsmith]

I paper was recently written by many of the IRLSSG RLS experts (Garcia-Borreguero, Earley, Ondo, Winkelman, Trinkwalder, etc) that reviewed problems with RLS clinical trials. They specifically cited the fact that the number of trials has dropped by 50% over the past decade. I would provide a link, but the abstract is almost useless and the paper isn't available to the public.

They covered issues such as difficulties with the severity ranking criteria that fails to capture when a person does well in one area but not in another, such as mood problems vs. sleep. They also discussed things near and dear to many of us, such as the failure of physician education (both schooling and continuing).

But one section really caught my eye and I felt was worth repeating here. It said,

The concepts of primary (formerly “idiopathic”) and secondary (formerly “symptomatic”) RLS are outdated. The different RLS pheno-
types should be taken into consideration by the diagnostic criteria. For example, many RLS patients suffer from periodic limb movements dur-
ing sleep (PLMS), and their frequency is strongly associated with alleles identified in genome-wide association studies [13]. While the influence
of a specific improvement in PLMS on the overall response of RLS to different drugs is unknown, PLMs respond better to dopamine agonists
such as pramipexole than to alpha-2 delta ligands such as pregabalin [14]. Similarly, patients with lower levels of serum iron are more likely
to develop augmentation [15], and previous exposure to dopaminergic agents reduces the response to non-dopaminergic agents such as alpha-2
delta ligands [16]. Other possible phenotypes include decreased brain iron, increased striatal dopamine, response to dopaminergic agents,
propensity to develop augmentation, sleep complaints, circadian trend, and age of onset of symptoms

Much of this may be old news for the experts and makes sense to many of us, but it says things that I have never seen published elsewhere.

[ViewsAskew]

I paper was recently written by many of the IRLSSG RLS experts (Garcia-Borreguero, Earley, Ondo, Winkelman, Trinkwalder, etc) that reviewed problems with RLS clinical trials. They specifically cited the fact that the number of trials has dropped by 50% over the past decade. I would provide a link, but the abstract is almost useless and the paper isn't available to the public.

They covered issues such as difficulties with the severity ranking criteria that fails to capture when a person does well in one area but not in another, such as mood problems vs. sleep. They also discussed things near and dear to many of us, such as the failure of physician education (both schooling and continuing).

But one section really caught my eye and I felt was worth repeating here. It said,

The concepts of primary (formerly “idiopathic”) and secondary (formerly “symptomatic”) RLS are outdated. The different RLS pheno-
types should be taken into consideration by the diagnostic criteria. For example, many RLS patients suffer from periodic limb movements dur-
ing sleep (PLMS), and their frequency is strongly associated with alleles identified in genome-wide association studies [13]. While the influence
of a specific improvement in PLMS on the overall response of RLS to different drugs is unknown, PLMs respond better to dopamine agonists
such as pramipexole than to alpha-2 delta ligands such as pregabalin [14]. Similarly, patients with lower levels of serum iron are more likely
to develop augmentation [15], and previous exposure to dopaminergic agents reduces the response to non-dopaminergic agents such as alpha-2
delta ligands [16]. Other possible phenotypes include decreased brain iron, increased striatal dopamine, response to dopaminergic agents,
propensity to develop augmentation, sleep complaints, circadian trend, and age of onset of symptoms

Much of this may be old news for the experts and makes sense to many of us, but it says things that I have never seen published elsewhere.

Nice to hear them acknowledge what we already know.

[Rustsmith]

The American Academy of Sleep Medicine just published this new set of guidelines for treatment of RLS.

The guidelines recommend against the use of any dopamine agonist and recommend for several IV iron formulations. Dipyridamole is also mentioned.

https://jcsm.aasm.org/doi/10.5664/jcsm.11390

[Polar Bear]

That's good about the 'recommendations. Glad to see it

[badnights]

A recent paper discovered a link between small-vessel disease and WED/RLS. From the abstract:

Peak width of skeletonized mean diffusivity (PSMD) is a novel marker of small vessel disease. This study aimed to investigate small vessel disease in patients with restless legs syndrome (RLS) using PSMD. We ... enrolled 65 patients.. and 59 controls....
Patients with RLS exhibited a higher PSMD than that in healthy controls, indicating the evidence of small-vessel disease in RLS and that the severity increased as RLS severity increased. These findings provide crucial information for clinical management and treatment strategies, highlighting the importance of addressing small vessel disease in patients with RLS.

Small vessel disease, from what I can find out, affects the small arterioles in the heart or the brain and makes those vessels stiff, unable to relax and provide passage for a sufficient volume of blood. I was unable to discover if it could affect blood vessels in other areas of the body.

Link: https://www.jns-journal.com/article/S0022-510X(24)00446-5/abstract

[badnights]

https://www.ajmc.com/view/heat-cold-the ... s-syndrome
https://onlinelibrary.wiley.com/doi/10.1002/nop2.70080

A study published in Nursing Open is summarized at the top link above. The study itself is reported at the second link.

The researchers combed thru the literature and selected 7 studies that were relevant (out of thousands they looked at). After analyzing the results of these studies, they concluded that alternating application of heat and cold for 10 minutes each helps relieve WED/RLS symptoms, especially in younger people and in pregnant women, and the hotter the better up to 42C. As for how the heat and cold were applied, they list the following methods: 'heat or cold wrap (wearable)’, ‘hot or cold water bottles,’ ‘hot or cold stone therapy,’ ‘heat or cold pack (grain),’ ‘hot or cold poultices’, ‘heat lamp,’ ‘electric heat pads,’ ‘hydrotherapy,’ ‘hot or cold water baths’ and ‘stream/sauna’ used between −100°C and +100°C. Presumably, each of the 7 studies did it differently.

[badnights]

https://link.springer.com/article/10.10 ... 24-03230-x

A study title "Urges to move and struggles to breathe: restless legs syndrome/WillisEkbom disease in adult patients with obstructive sleep apnea" found that "RLS/WED was associated with female sex, chronic insomnia symptoms, greater anxiety, and depression ..., and with mild obstructive sleep apnea severity. On the other hand, severe obstructive sleep apnea was negatively associated to RLS/WED."

[ViewsAskew]

Article about France's updates to its treatment algorithm:

https://www.medscape.com/viewarticle/ir ... 25a1000ekh

[Rustsmith]

I just read a manuscript that has been submitted for publication by Stefan Clemans, William Ondo and Walter Paulus that is proposing a new theory about the cause of RLS and augmentation. The paper has not been published yet. I received a copy from Dr Clemans via ResearchGate. However, you can find a few other papers about this theory that Dr Clemans is actively pushing.

They build upon the iron deficiency model and propose that RLS (and Tourette's) symptoms are due to an imbalance in the excitory D3 receptors and the inhibitory D1 receptors. When the ratio of D3/D1 becomes too large, we get symptoms. Treating with a dopamine agonist (which target D3) reduces the number of active D3 receptors and the ration returns to normal. Treating with a DA for too long causes the number of D3 receptors to continue to increase, leading to augmentation.

The authors are studying the use of ecopipam to treat D1 receptors in individuals with augmentation with the goal of returning the D3/D1 ratio to normal. In a very small trial on augmented individuals, ecopipam worked as they expected. They are now moving on to a larger study that will also include RLS patients who have not augmented. If it works, ecopipam could turn out to be a new mode of treating RLS, especially for those who have or are augmented.

On a personal note, I am returning to Dr Ondo in late January and will be interested to see if he asks me to participate in one of these studies.