Movement disorders expert William G. Ondo, MD, explains how restless legs syndrome is both under- and over-diagnosed.

People with restless legs syndrome report that their sleep is interrupted multiple nights a week. Almost half, according to one survey, avoid going to the movies and other events where they’ll be expected to sit still for long periods of time. Some bed partners even report that their sleep is disrupted too, with about a third resorting to snoozing in a separate bed.1

With these quality of life issues known, restless legs syndrome (also known as RLS and as Willis-Ekbom Disease or WED) can be especially rewarding for sleep clinicians to identify and treat. Unlike many other sleep disorders, it doesn’t require an in-lab sleep study for diagnosis and it has several treatment options—ranging from well-established pharmaceuticals to newer medical devices—that don’t have the patient adherence concerns frequently raised in tandem with the more commonly discussed sleep disorder of sleep apnea.

But a challenge is identifying all of the suffering and as yet untreated RLS patients. Though diagnosis has improved, sleep clinicians can further impact change by educating primary care physicians on RLS symptoms, as well as screening their own relevant patient populations for the movement disorder.

The symptoms to educate and screen for, according to the International Restless Legs Syndrome Study Group, are: an urge to move the legs usually accompanied by uncomfortable sensations in the legs; the urge/sensations begin or worsen during periods of rest or inactivity; are relieved by movement; and only occur or are worse in the evening or night; and the occurrence of these features is not accounted for as symptoms primary to another condition.2

William G. Ondo, MD, director of the Movement Disorders Clinic at the Houston Methodist Neurological Institute, has been diagnosing, treating, and researching RLS for more than 20 years. Ondo earned his medical degree from the Medical College of Virginia, then completed an internship at the University of North Carolina Hospital, a neurology residency at Duke University, and a movement disorders fellowship at the Baylor College of Medicine. He is board certified in adult neurology and sleep medicine.


William G. Ondo, MD, director of the Movement Disorders Clinic at Neurological Institute, has 20 years of experience diagnosing, treating, and researching restless legs syndrome. Here, he demonstrates how to check a patient’s patellar reflex.

Sleep Review (SR): What sparked your interest in movement disorders?

William G. Ondo, MD: Upon starting residency, I really had no notion there was such a thing as movement disorders. I simply found myself most interested in cases of Parkinson’s disease, tardive dyskinesia, and Huntington’s disease. I very much liked the fact that you could see the problem, examination being the key to the diagnosis, and that relatively good treatments existed.

SR: What sparked your interest in RLS specifically?

Ondo: During my movement disorders fellowship, we first started to use dopaminergic medicines for RLS. The initial benefit of these medicines was the most dramatic treatment effect of any condition that we managed. During that fellowship, I went on to write a single paper on RLS, and back in 1996 that made me an expert.3

SR: What are the consequences for people who do not get a diagnosis of RLS when they have the disorder?

Ondo: I think diagnosis is generally better than in the past. Some of this must be attributed to increased patient awareness. The particular problem with misdiagnosis of RLS is that we have relatively good treatments for this. Every day that the patient is not diagnosed, they are suffering needlessly.

SR: What role can sleep medicine clinicians play in getting more people with RLS correctly diagnosed?

Ondo: The main role for sleep physicians is to educate primary care physicians regarding RLS. For several years, there were several pharmaceutical companies who were advertising about restless leg syndrome, but currently there is fairly minimal marketing, so the onus falls on physicians to continue to educate their peers.

SR: Are there patient populations who sleep clinicians may already be seeing who should be considered at high risk for RLS?

Ondo: Restless leg syndrome often presents with insomnia. It usually just takes a few questions to differentiate this population with insomnia secondary to RLS. Patients may initially state they have something like muscle cramps, but the diagnosis of RLS is simply based on several questions including: an urge to move the legs, transient relief with movement, worsening at rest, and worsening at night.

Restless leg syndrome is very common in people with renal failure, especially those on dialysis, and I think this population is still relatively poorly diagnosed and treated.

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SR: What tips do you have when considering an RLS diagnosis?

Ondo: In all cases, the diagnosis is based on interview. Patients having the 4 cardinal features of RLS, not otherwise explained, have RLS. There actually is no necessary role of a polysomnogram, although the absence of periodic limb movements of sleep in an untreated RLS patient would be a red flag. Keep in mind there are also people diagnosed with RLS who in fact really have poorly differentiated leg pain at night rather than a true urge to move. So the condition is often underdiagnosed but can also be overdiagnosed.

SR: Can you weigh in on how healthcare professionals can distinguish RLS from other disorders? (Disorders we asked about are in bold in Ondo’s responses.)

Ondo: In most cases, a true urge to move the legs without having a whole body sense of restlessness is the differentiating feature between RLS and a variety of potential mimics.

Osteoarthritis certainly may be worse at night, but typically the pain is in the joints rather than deep in the calves or thigh as is seen in restless legs.

Disc lesion with radiculopathy may be very position dependent but results in pain and other paresthesia, rather than a true urge to move, is usually very asymmetric. RLS in the setting of radiculopathy has been reported.

Akathisia is really the closest thing to RLS, but differs in that there is an entire body restlessness and need to move, not just the limbs. Akathisia may be somewhat worse at night but does not have nearly as dramatic a circadian pattern as RLS, and it is usually associated with dopamine-blocking drugs. Mild serotonin syndrome from SSRI [selective serotonin reuptake inhibitor] medicines can also result in a general sense of akathisia.

PLMS (periodic limb movements of sleep) often accompany RLS, but this is a sign observed on a polysomnogram and is not actually part of the diagnostic criteria. That said, we occasionally see people whose only manifestation is leg jerking during the day without any subjective urge to move. By our strict definition, this is not RLS, but it seems to respond similarly from a treatment standpoint.

Varicose veins have occasionally been associated with RLS, but typically are not symptomatic other than from a cosmetic standpoint.

True muscle cramps are a chaotic sudden contraction of muscle. It does improve by stretching the muscle (moving) but typically patients can break the cramp by doing this. There is obvious muscle contracture, and there is not really an urge to move.


Ondo recommends serum ferritin and iron binding percentage studies for patients who have RLS.

SR: Is there anything you’d like to add?

Ondo: Our understanding of RLS has improved tremendously over the past 2 decades. We now have identified a number of genes and neuropathologies associated with RLS. At this point it appears multiple pathophysiologies might result in RLS symptoms, possibly through a final common pathway.

I would say the only evaluation absolutely needed in all RLS cases is serum ferritin and iron binding percentage studies, although this represents only an indirect look at the actual pathology of reduced CNS [central nervous system] iron stores.

Treatment is still extremely rewarding, though long-term management can be more difficult due to augmentation associated with dopaminergic medications. The RLS research community is looking at ways to mitigate this and at other treatment options including high-dose intravenous iron and opioid medications.

Sree Roy is chief editor of Sleep Review.

1. Restless Legs Syndrome Foundation Blog. Lifestyle, emotional and relationship impact of RLS/WED. 2014 Feb.
2. International Restless Legs Syndrome Study Group. Diagnostic Criteria. 2012.
3. Ondo W, Jankovic J. Restless legs syndrome: clinicoetiologic correlates. Neurology. 1996 Dec;47(6):1435-41.