Neurological and medical disorders associated with restless legs syndrome

Abstract

The pathophysiology of RLS is still uncertain, but a low brain iron accumulation, an altered dopamine system with disinhibition phenomenons on the spinal levels and metabolic changes may influence the manifestation of RLS symptoms. Genetic findings using whole genome association studies identified several genes associated with a risk to develop RLS, most important the MEIS1 (Winkelmann et al 2007,Spieler et al 2015). Recent metaanalyses have also revealed an important role of environmental, i.e. comorbid factors which manifest RLS symptoms. Following a systematic literature search of RLS associated with comorbidities an increased prevalence of RLS was identified for iron deficiency anemia and kidney disease. In cardiovascular disease, arterial hypertension, diabetes, migraine, and Parkinson’s disease the methodology of studies was still inadequate, but an association might be possible. There is insufficient evidence for conditions such as chronic obstructive pulmonary disease, multiple sclerosis, headache, stroke, narcolepsy, and ataxias. Further diseases are depression and anxiety disorders and pregnancy, which leads to major treatment obstacles due to a lack of data, but consensus recommendations for therapy are available (Picchietti et al 2015). Based on possible gene-microenvironmental interaction the classification “primary” and “secondary” RLS may suggest an inappropriate causal relation and should be avoided. We recognize that in some conditions, treatment of the underlying disease should be achieved as far as possible to reduce or even eliminate RLS symptoms. RLS might be seen as a continuous spectrum with a major genetic contribution at one end and a major environmental or comorbid disease contribution at the other.