Unraveling the Mysteries of Restless Leg Syndrome

Abstract

Restless leg syndrome (RLS) or Willis-Ekbom disease (WED) is an under-diagnosed, chronic, and progressive primary sensory-motor disorder. It is characterized by an uncontrollable urge to move the legs due to uncomfortable and sometimes painful sensations, with a diurnal variation. RLS can lead to severe sleep disturbances, a usual cause of consultation. The pathophysiology is known partially, and it is believed that there is an association between the different variants of genetic mutations combined with dopaminergic and brain iron dysregulation, which plays an important role. The data used for this study were extracted from the articles found in the PubMed database that discuss different gene variants, pathophysiology, and various methods of treatment. They also highlight the role of iron in the pathogenesis of RLS as it is required for the synthesis of tyrosine hydroxylase, which is the rate-limiting step for dopamine synthesis. This review article provides a clinically useful overview of RLS in terms of pathophysiological findings, its genetic associations, and therapeutic options by using the currently available literature. Because RLS presents with vague symptoms and shares similarities with many other diseases, it might be overlooked by many physicians resulting in underdiagnosis and under-treatment. While these discoveries provide a breakthrough in understanding the details of RLS, further studies are recommended as these studies are limited to animal models and provide a limited representation of the general population.

Ironing out mechanisms of iron homeostasis and disorders of iron deficiency

“…The exact mechanism for RLS in BID is not well understood; however, impaired striatal dopamine production is widely seen in animal models of ID displaying symptoms characterized as RLS. Tyrosine hydroxylase, the rate-limiting enzyme in dopamine production, requires iron as a cofactor, and its activity is shown to be impaired in animal models of RLS due to BID (96). Although iron administration is not recommended empirically, trials of oral ferrous sulfate with vitamin C can be considered for RLS patients with FTN levels ≤75 ng/mL (97).…”

Prevalence and Associated Factors of Restless Leg Syndrome

“…Our findings are consistent with research sourced from articles obtained from the PubMed database, which covered various aspects of RLS including gene variants, pathophysiology, and treatment methods, indicating that roughly 15% of the global population suffers from RLS. (Memon, 2020). Additionally, a study conducted on the correlation between RLS and sleep quality among the general population in Mangalore, India, revealed a prevalence of 11.9% among 202 participants, with 5 individuals already diagnosed with RLS.…”

Restless Legs Syndrome; Inflammation, Electroneuromyography Findings, and Disease Severity

“…Secondary RLS may be in response to some existing neurological or nutrient-de cient disease or may be a symptom of a disease or disorder other than neurology. However, we also know that the secondary causes of RLS are associated with increased in ammation (15). Neuroimaging and humoral studies have shown that brain iron de ciency plays a role in the pathophysiology of RLS.…”