Nancy A. Melville

October 14, 2015

Restless legs syndrome (RLS) disease duration of more than 10 years is an independent predictor of silent cerebral microvascular ischemic disease (MVD), new research suggests.

"The implications of our study are that RLS that has gone on for many years is a risk factor for silent cerebral microvascular disease," lead author Arthur S. Walters, MD, a professor of neurology at Vanderbilt University School of Medicine in Nashville, Tennessee, told Medscape Medical News.

"Although age was also a predictor of the microvascular disease, the duration of RLS had an independent effect upon the burden of the microvascular disease."

Their findings were presented here at the American Neurological Association (ANA) 2015 Annual Meeting.

For the study, Dr Walters and his team enrolled 53 patients with a history of RLS for less than 10 years (mean age, 53.7 years; 42 women) and compared them with 44 patients with RLS for more than 10 years. Those patients had a mean age of 54.8 years, and 30 were female.

A control group of 74 persons without RLS (mean age, 53 years; 53 women) was also studied.

None of the participants had a history of stroke or any previous stroke risk factors, such as diabetes, high blood pressure, high cholesterol, or sleep apnea.

MRI of all participants showed that among those with RLS duration greater than 10 years, MVD area and volume decreased significantly compared with those who had had RLS for less than 10 years (P < .0016 for area and P < .016 for volume).

In addition, the RLS group as a whole showed a significantly higher area of MVD compared with controls (P = .036).

Dr Walters said severity of RLS did not differ between those who had had RLS for less than 10 years and those who had had RLS for more than 10 years, according to the International RLS Study Group RLS severity rating scale.

However, he noted that the scale looks only at severity over the past week. Given an equal level of RLS severity between the RLS subgroups, "the findings show that it is the duration of the RLS itself, or the probable cumulative impact of RLS severity over many years, that is linked to the level of cerebral microvascular disease," Dr Walters said.

While only a small percentage of patients were receiving medications for RLS, a subanalysis of the group excluding such patients showed similar results.

In considering the key issue of mechanisms that could link RLS to MVD, one hypothesis suggests a role of high blood pressure in sleep, Dr Walters explained.

"RLS patients have marked increases in blood pressure around the time of the repetitive intermittent involuntary kicking movements (periodic limb movements in sleep or PLMS) that they commonly have in sleep," he said.

"In addition, RLS patients do not have the normal drops in blood pressure during the night, as seen in the general population. In other words, RLS patients are 'nondippers' as opposed to 'dippers.'" 

In possible support of that theory is research that has not yet been published indicating that dopaminergic drugs, which are well known treatments for RLS, also normalize the blood pressure elevations seen around the time of the PLMS, Dr Walters said. 

"The implication is that control of the blood pressure around the time of the PLMS might prevent stroke. However, this obviously needs to be proven."

The study is an investigator-initiated study funded by UCB Pharma. Dr Walters has received grant funding and served on the Medical Advisory Board for UCB Pharma for restless legs syndrome.

American Neurological Association (ANA) 2015 Annual Meeting. Abstract S613. Presented September 27, 2015.

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