Linking restless legs syndrome with Parkinson's disease: clinical, imaging and genetic evidence

The common features of dopaminergic dysfunction and response to dopaminergic agents in RLS and PD, together with comorbidity in some patients has fuelled the concept that these two diseases may share the same pathophysiology [1]. We review the clinical, imaging and genetic evidence, exploring the link between RLS (restless legs syndrome) and PD (Parkinson's disease).PD is a progressive neurodegenerative disorder characterised by pathologic intraneuronal alpha-synuclein-positive Lewy bodies and neuronal cell loss. In particular, involvement of dopaminergic cells in the substantia nigra pars compacta is associated with development of the motor features of the disease. The cardinal clinical symptoms and signs of PD are bradykinesia, rigidity, tremor, postural instability and freezing attacks [2]. The prevalence of PD increases with age, affecting 1-2% of the population over the age of 65 years, and 3% of those over 85 years [3]. Several monogenic forms of PD and numerous genetic susceptibility factors have been identified [4,5]. Sleep disturbances have been widely reported in PD, although an increased incidence of periodic leg movements of sleep (PLMS) is debatable, with polysomnography studies revealing mixed findings [6-10].Restless legs syndrome (RLS) was initially described by Ekbom [11] in 1945. It tends to present in mid to later life and has a prevalence of 2.7-10% in Western populations [12,13]. It is reportedly much less common amongst Asians [14]. Four essential diagnostic criteria were proposed by the International Restless Legs Syndrome Study Group (IRLSSG) in 1995; 1. An urge to move the legs associated with paresthesias, 2. motor restlessness, 3. worsening at rest with at least partial relief by activity, and 4. worsening at night [15,16]. In 2003, at a consensus conference at National Institute of Health, USA, these criteria were modified and new criteria developed for the diagnosis of RLS in the cognitively impaired elderly and in children [17]. Additio