Abstract
Restless legs syndrome (RLS)/Willis-Ekbom disease is a neurologic disorder characterized
by a strong desire to move when at rest (usually in the evening) and paraesthesia in their lower
legs. The most widely used therapies for first-line treatment of RLS are dopaminergic drugs; however,
their long-term use can lead to augmentation. α2δ Ligands, opioids, iron, glutamatergic drugs,
adenosine, and sleep aids have been investigated as alternatives. The pathogenesis of RLS is not
well understood. Despite the efficacy of dopaminergic drugs in the treatment of this disorder, unlike
in Parkinson’s disease dopaminergic cell loss in the substantia nigra has not been observed in RLS.
The etiology of RLS is likely complex, involving multiple neural pathways. RLS-related genes
identified in genome-wide association studies can provide insight into the mechanistic basis and
pathophysiology of RLS. Here we review the current treatments and knowledge of the mechanisms
underlying RLS.
Keywords:
Restless legs syndrome, dopaminergic drugs, nondopaminergic drugs, mechanisms, genetic factors, augmentation.
Graphical Abstract
[30]
Schormair, B.; Zhao, C.; Bell, S.; Tilch, E.; Salminen, A.V.; Pütz, B.; Dauvilliers, Y.; Stefani, A.; Högl, B.; Poewe, W.; Kemlink, D.; Sonka, K.; Bachmann, C.G.; Paulus, W.; Trenkwalder, C.; Oertel, W.H.; Hornyak, M.; Teder-Laving, M.; Metspalu, A.; Hadjigeorgiou, G.M.; Polo, O.; Fietze, I.; Ross, O.A.; Wszolek, Z.; Butterworth, A.S.; Soranzo, N.; Ouwehand, W.H.; Roberts, D.J.; Danesh, J.; Allen, R.P.; Earley, C.J.; Ondo, W.G.; Xiong, L.; Montplaisir, J.; Gan-Or, Z.; Perola, M.; Vodicka, P.; Dina, C.; Franke, A.; Tittmann, L.; Stewart, A.F.R.; Shah, S.H.; Gieger, C.; Peters, A.; Rouleau, G.A.; Berger, K.; Oexle, K.; Di Angelantonio, E.; Hinds, D.A.; Müller-Myhsok, B.; Winkelmann, J. 23andMe Research Team; DESIR study group. Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis.
Lancet Neurol., 2017,
16(11), 898-907.
[
http://dx.doi.org/10.1016/S1474-4422(17)30327-7] [PMID:
29029846]
[95]
Burbank, F.; Buchfuhrer, M.J.; Kopjar, B. Sleep improvement for restless legs syndrome patients. Part I: pooled analysis of two prospective, double-blind, sham-controlled, multi-center, randomized clinical studies of the effects of vibrating pads on RLS symptoms. Res. Rev. Parkinsonism, 2013, 3, 1-10.