Silent Cerebral Small Vessel Disease in Restless Legs Syndrome

Growing literature suggests that patients with restless legs syndrome (RLS) may be at increased risk for hypertension, heart disease, and stroke. Cerebral small vessel disease (SVD) is a known risk factor for clinical stroke. This study evaluated silent cerebral SVD by MRI in patients with RLS, in the absence of a history of previous clinical stroke or known stroke risk factors and taking into account disease duration. Fifty-three patients with RLS < 10 y were prospectively recruited along with 44 with RLS > 10 y and 74 normal controls. A magnetic resonance imaging study was obtained from all subjects and scans were analyzed for area and volume of SVD. There was a significant increase in SVD area in the entire group of RLS patients compared to controls (P = 0.036); this was almost entirely driven by the group with RLS > 10 y. SVD area and volume were significantly increased in patients with RLS > 10 y with respect to both controls (P < 0.0001 and P < 0.0014, respectively) and RLS < 10 y (P < 0.00022 and P < 0.003, respectively). Age, duration of RLS, and the interaction of age and duration of RLS were independent predictors of SVD disease. Duration of RLS was an independent predictor of the burden of cerebral SVD (area P < 0.00012 and volume P < 0.0025), whereas sex and insomnia were not. RLS duration should be taken into account when analyzing the association between RLS and cerebrovascular disease; our data support the hypothesis that a long-lasting RLS and its accompanying periodic limb movements in sleep are a risk factor for silent SVD and perhaps for the development of clinical stroke. Restless legs syndrome (RLS) has been reported to lead to cerebrovascular disease by some authors, to be an effect of stroke by others and to have no relationship by another group of authors. This study demonstrates that patients with long-lasting RLS are significantly more frequently affected by cerebral small vessel disease than those with short-duration RLS or controls, that cannot be explained by the presence of other known risk factors. This is the first study that demonstrates an increased frequency of cerebral small vessel disease in RLS which might represent a risk factor for the development of clinical stroke later during the chronic disease course.