SLEEP 2026 | Updates in the understanding and treatment of RLS from SLEEP 2026

Well, there are updates in two very different directions. One of them is in our knowledge of the pathophysiology of RLS. We are getting to know more about the mechanisms leading to RLS, about the dysfunction of the basal ganglia, the functional dysfunction – I don’t know where you can say it’s – it’s not a nice word, but I mean the dysfunction, really, in the sense that there is not a structural change in the basal ganglia, unlike Parkinson’s disease. In RLS, there is no anatomic abnormality in the basal ganglia, but it’s just a dysfunction. That dysfunction is being caused ultimately by decreased brain iron levels, and that will lead ultimately to a reduction of adenosine levels in the striatum, and that will… Adenosine is a substance that normally reduces glutamatergic hyperfunction. Once adenosine is decreased, extracellular adenosine is decreased, and this is part of the result of the decreased iron levels in the brain. That will give way to corticostriatal pathways, which are glutamatergic, being unleashed, being hyperfunctioning, and that will lead to the symptoms. So, knowledge in that direction is increasing year by year. We are starting also to know about the genetics, about this kind of how the genes play a role in that, and we believe that in a few years from now, this will also be the basis for new therapeutic options in RLS treatment. For now, what we know, it was published a few years ago, is that a substance that increases adenosine, extracellular adenosine, like dipyridamole, is an agent – it’s a substance that improves RLS symptoms. This is a proof-of-concept study that is already out there in the literature, and what we are considering is new agents that do something similar but in a more perfect way than the dipyridamole. The other treatment innovation comes from neural stimulation. Devices like the TOMAC, which is peroneal nerve stimulation, provide a way of treating very severe patients and, in that way, making them able, putting them in a position in which they can afford reducing the dose of dopaminergic treatment, well, not only of dopaminergics, also of opioids, if they are taking any opioids. So, these very severe patients, while using peroneal nerve stimulation, are going to be able to reduce the doses of pharmacological treatment in general.

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