Restless Legs Syndrome and Parkinson Disease: A Causal Relationship Between the Two Disorders?

Abstract

Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) is a common sleep related movement disorder that can be idiopathic or occurs in comorbidity with other medical conditions such as polyneuropathy, iron deficiency anemia, multiple sclerosis, hypertension and cardiovascular diseases. In recent years, a growing body of literature investigated the association between RLS/WED and Parkinson's Disease (PD). Several questions regarding the comorbidity between these two disorders are still unanswered. If the insurgence of RLS/WED may precede the onset of PD, or if RLS/WED could represent a secondary condition of PD and if impaired dopaminergic pathway may represent a bridge between these two conditions are still debatable issues. In this review, we critically discuss the relationship between RLS/WED and PD by reviewing cross sectional and longitudinal studies, as well as the role of dopamine in these disorders. A twofold interpretation have to be taken into account: dopaminergic therapy may have a crucial role in the development of RLS/WED in PD patients or RLS/WED can be conceived as an early manifestation of PD rather than a risk factor. Several studies showed a high prevalence of RLS/WED in PD patients and several findings related to dopaminergic and iron alterations in both disorders, however up to now it is difficult to find a point of agreement between studies. A greater number of systematic and strongly controlled longitudinal studies as well as basic pathophysiological investigations particularly in RLS/WED are needed to clarify this complex relationship.

Nigral iron deposition in common tremor disorders

“…Previous MRI studies have shown reduced nigral iron in patients with RLS. 15 We investigated if an association of RLS and PD may explain normal R2* values in some patients with PD. Contrary to this assumption, all patients with PD and RLS (n = 10) had abnormal R2* values.…”

Practical Evaluation and Management of Insomnia in Parkinson's Disease: A Review

“…As the estimated prevalence of moderate to severe SDB in those older than age 60 is elevated (men, 24%–65%; women, 16%–35%), all individuals with PD and DMS should be screened for SDB . In addition, restless legs syndrome (RLS) may be more common in those with PD, with the majority of studies finding increased rates among those with PD (3%–52%) relative to controls (0%–10%) . The uncomfortable sensations of RLS that occur during periods of immobility often prevent sleep, and because they are typically improved with voluntary movement, commonly result in the individual getting out of bed to walk about.…”

“…The uncomfortable sensations of RLS that occur during periods of immobility often prevent sleep, and because they are typically improved with voluntary movement, commonly result in the individual getting out of bed to walk about. Furthermore, up to 90% of individuals with RLS also experience periodic limb movements of sleep, rhythmic limb jerks, which can disrupt sleep continuity . Another common sleep disturbance in PD is RBD, a parasomnia wherein individuals appear to “act out their dreams,” often manifesting violent movements (eg, punching, kicking) and vocalizations associated with vivid dreams .…”

“…43 In addition, restless legs syndrome (RLS) may be more common in those with PD, with the majority of studies finding increased rates among those with PD (3%-52%) relative to controls (0%-10%). 44 The uncomfortable sensations of RLS that occur during periods of immobility often prevent sleep, and because they are typically improved with voluntary movement, commonly result in the individual getting out of bed to walk about. Furthermore, up to 90% of individuals with RLS also experience periodic limb movements of sleep, rhythmic limb jerks, which can disrupt sleep continuity.…”

“…Furthermore, up to 90% of individuals with RLS also experience periodic limb movements of sleep, rhythmic limb jerks, which can disrupt sleep continuity. 5,44 Another common sleep disturbance in PD is RBD, a parasomnia wherein individuals appear to "act out their dreams," often manifesting violent movements (eg, punching, kicking) and vocalizations associated with vivid dreams. 5,45 A confirmed diagnosis of RBD requires PSG demonstrating pathologically preserved muscle tone during rapid eye movement sleep (rapid eye movement without atonia).…”