Therapeutic effectiveness of thalidomide in a patient with treatment-resistant restless legs syndrome

Recent developments in the genetics of restless legs syndrome (RLS) revealed associations of disease risk with genetic loci containing the genes coding cereblon, the protein bound by thalidomide, and its endogenous substrate MEIS2, whose degradation is inhibited by the thalidomide-cereblon interaction. Therefore it was hypothesized that thalidomide may be a potential treatment option for RLS. Here we report on the therapeutic effect of thalidomide in a patient with otherwise treatment-resistant RLS who received 100 mg thalidomide off-label for 3 weeks. The female patient, severely affected by RLS before treatment, experienced significant amelioration of the symptoms, increased self-reported sleep quality, and better daytime functioning during thalidomide treatment. This therapeutic success warrants larger studies investigating the efficacy of drugs of the thalidomide class in RLS.