Multicenter case-control study on restless legs syndrome in multiple sclerosis: the REMS study

Abstract

Study objectives: To verify the existence of a symptomatic form of restless legs syndrome (RLS) secondary to multiple sclerosis (MS) and to identify possible associated risk factors.

Design: Prospective, multicenter, case-control epidemiologic survey.

Settings: Twenty sleep centers certified by the Italian Association of Sleep Medicine.

Patients: Eight hundred and sixty-one patients affected by MS and 649 control subjects.

Interventions: N/A.

Measures and results: Data regarding demographic and clinical factors, presence and severity of RLS, the results of hematologic tests, and visual analysis of cerebrospinal magnetic resonance imaging studies were collected. The prevalence of RLS was 19% in MS and 4.2% in control subjects, with a risk to be affected by RLS of 5.4 (95%confidence interval: 3.56-8.26) times greater for patients with MS than for control subjects. In patients with MS, the following risk factors for RLS were significant: older age; longer MS duration; the primary progressive MS form; higher global, pyramidal, and sensory disability; and the presence of leg jerks before sleep onset. Patients with MS and RLS more often had sleep complaints and a higher intake of hypnotic medications than patients with MS without RLS. RLS associated with MS was more severe than that of control subjects.

Conclusions: RLS is significantly associated with MS, especially in patients with severe pyramidal and sensory disability. These results strengthen the idea that the inflammatory damage correlated with MS may induce a secondary form of RLS. As it does in idiopathic cases, RLS has a significant impact on sleep quality in patients with MS; therefore, it should be always searched for, particularly in the presence of insomnia unresponsive to treatment with common hypnotic drugs.

Figures

Figure 1

Likelihood of prevalence rate of restless legs syndrome (RLS), in both control subjects and patients with RLS, based on the frequency of RLS symptom occurrence chosen as a threshold for the diagnosis of RLS.

Figure 2

Prevalence of each restless legs syndrome (RLS) diagnostic criterion in patients with multiple sclerosis and control subjects classified as RLS negative (MS/RLS− and CS/RLS−, respectively).

Figure 3

Distribution of the frequency of the 3 clinical courses of multiple sclerosis (MS) in patients with and without RLS. RR refers to relapsing remitting; SP secondary progressive; PP, primary progressive.

Figure 4

Comparison of Expanded Disability Status Scale (EDSS) scores found in MS/RLS+ and MS/RLS− patients. MS refers to multiple sclerosis; RLS, restless legs syndrome. *mean ± SD

Figure 5

Anatomic distribution of symptoms of restless legs syndrome (RLS) in RLS patients with and without multiple sclerosis (MS).