New Insights Into Restless Legs Syndrome

For the millions who suffer from Restless Legs Syndrome, sleep can be exceedingly difficult and disrupted. RLS is a neurological disorder and a sleep disorder, a condition that causes tingling, twitching, “creepy-crawly” feelings in the legs. These uncomfortable sensations bring about an often-urgent need to move the legs. The symptoms of RLS are most often felt when a person is lying still for a period of time, and are frequently experienced at bedtime. People with RLS commonly experience symptoms of insomnia—difficulty falling asleep and staying asleep. Medications for RLS can be successful in alleviating the twitching and tingling sensations in the lower body, but very often the insomnia symptoms remain, leaving people with RLS coping with chronic sleep problems even after the other RLS symptoms have disappeared.

This is just one of the puzzling aspects of RLS, a condition that has proved mysterious and difficult to understand, diagnose, and treat. But new research may have delivered important new insight into how RLS works in the body, and why sleep problems can stubbornly persist even after successful treatment for tingling, twitching legs.

Researchers at Johns Hopkins University School of Medicine investigated the relationship between brain chemistry and sleep among patients with RLS. They discovered abnormally high levels of a brain chemical involved in stimulating arousal. The brain chemical glutamate is an important neurotransmitter that arouses both the brain and the central nervous system. Researchers found elevated levels of glutamate present in the brains of patients with RLS. Abnormal levels of glutamate may help explain why RLS patients continue to have trouble sleeping, even after other medications have quieted the disruptive sensations in their legs.

Researchers evaluated 48 adults, including 28 patients with RLS and 20 subjects without the condition. Those with RLS had experienced symptoms of the condition for at least 6 months, on 6 or 7 nights per week. Researchers first measured glutamate levels in the brain using MRI. They then spent two days measuring participants’ sleep. They found significantly higher levels of glutamate among RLS patients than in those without the condition. Among the RLS patients in the study, those with higher levels of glutamate experienced more severely disrupted sleep.

This was a small study, and we’ll need to see follow-up research on a larger scale to confirm and further establish the role of glutamate in RLS. But these findings could represent an important step forward in our understanding of RLS. What’s more, this new information could bring about significant changes in treatment of the condition.

Previous research and treatment for RLS has focused on another of the brain’s neurotransmitters: dopamine. Dopamine plays an important role in muscle activity and body movement, and dopamine deficiency can result in involuntary muscle movement. Several drug treatments for RLS involve raising levels of dopamine, in order to soothe the involuntary twinges and intense urges to move the legs. But these drugs have not been successful in improving RLS patients’ sleep.

This new research may deliver an important piece of information to the RLS-sleep puzzle. High levels of glutamate in patients with RLS may be preventing these patients from sleeping well, a problem that is not currently being addressed by the array of dopamine-related medications being used to treat other symptoms of the condition.

As many as 10% of adults in the U.S. suffer from RLS, according to the National Sleep Foundation. RLS is a condition that very often goes undiagnosed or misdiagnosed. RLS can often be misdiagnosed as another sleep disorder or another neurological disorder, or a muscular disorder. Depression is another common misdiagnosis for RLS. Research shows a strong association between depression and RLS. People with RLS appear to be at a significantly elevated risk for depression. The poor sleep experienced by so many RLS patients may play a role in their increased risk for depression. In addition to chronic sleep problems and depression, patients with RLS also appear to be at elevated risk for other serious health conditions, including hypertension and coronary heart disease. The cause of RLS is not known, but the condition does run in families, and recent research has shown evidence of a genetic link.

This latest research is exciting, with the potential to transform our understanding of RLS. There are many steps still to take, and questions to be explored and answered, before we know what changes are best made to the way we treat RLS. But for a condition that has often confounded experts, and caused such discomfort, disruption, and sleeplessness to so many patients, this study brings both welcome and encouraging news.

By Michael Breus, PhD, ABSM