SLEEP 2026 | Key recommendations for managing coexisting restless legs syndrome and obstructive sleep apnea

Over the last years, that has been summarized in a meta-analysis that we performed last year, the concurrence of two of the most common sleep disorders, namely obstructive sleep apnea and restless legs syndrome, the comorbidity of the two has been well established. Out of every 100 patients suffering from OSA, approximately between 20 and 32, depending on the different case series and studies, suffer from concomitant RLS. What happens when RLS is occuring in a patient who simultaneously suffers from obstructive sleep apnea? Usually, the presence of RLS leads to an increase in the severity of RLS itself, those patients are usually more severe in terms of their RLS symptoms, but their OSA symptoms are also more severe. So there is a mutual reinforcement, in the worst sense of the word, in the sense that both disorders become more severe. Not only that, there is also a group of patients for which the RLS is so severe that their tolerance towards CPAP is lower. They cannot tolerate CPAP, and for that reason their OSA becomes untreated in a not negligible proportion of patients. This is the other consequence of that, but in general, both disorders become more severe.
We’re showing data at this meeting by which we asked ourselves what the reason is for the increased comorbidity between the two. Why is that association taking place? We come to the conclusion that patients with comorbid OSA and RLS have lower brain iron levels than patients with just OSA, and that their brain iron levels are similar to those of patients with just RLS. So in other words, those patients with OSA, for whatever reason, brain iron levels decrease, and I’m talking not so much about serum iron levels, which are usually very similar to the general population, but brain iron levels, whenever these brain iron levels decreases, if they also have other genetic factors et cetera, they will develop RLS. That is one of the reasons for the increased comorbidity. But there are also several mechanisms that play in the same direction. The chronic inflammation that takes place is a natural thing in OSA tends to mask the serum iron levels in RLS patients. So that misguides the clinician in some way because they artificially increase ferritin levels, making the clinician believe that serum iron levels are normal when they are not. So there is an interplay between hypoxia, inflammation, and decreased brain iron that leads to that comorbidity.

What do we recommend in these cases? Well, first of all, a good diagnosis, being able to identify both conditions. RLS patients can, this is a message mainly to the RLS community, RLS patients can have other sleep disorders besides RLS, so that would be a strong rationale for performing a sleep study in these patients. Likewise, for the sleep-disordered breathing community, whenever you see that an OSA patient has decreased sleep efficiency, you should ask yourself and do a differential diagnosis for RLS. Okay, good diagnosis is always the first step. But on top of that, when it comes to treatment, I would start with an aggressive iron treatment in these patients for two reasons. Because it is very likely the cause of the RLS, and secondly, because if you treat the iron deficiency, it will take some time until things resolve, so the sooner you start, the better. Okay, once that has been done, I would consider an aggressive treatment of the OSA because, if you are able eliminate the hypoxia, the normalized oxygen levels are going to secondarily reduce the chronic inflammatory processes that are leading indirectly to the RLS. So, first treat the iron deficiency, then treat the OSA. For patients that do not tolerate the CPAP because of the severity of the RLS symptoms, of course you can always try short-term pharmacological management of the RLS symptoms to calm them down during the night, giving you the opportunity to initiate CPAP treatment.
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