Imbalance between thyroid hormones and the dopaminergic system might be central to the pathophysiology of restless legs syndrome: a hypothesis (original) (raw)
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Is Restless Legs Syndrome De Facto Thyroid Disease?
Biomedicines
While a primary role in the pathogenesis of restless legs syndrome (RLS) has been attributed to dysfunction of the dopaminergic system and impaired iron metabolism (particularly in the central nervous system), it has been hypothesized that an imbalance between thyroid hormones and dopaminergic activity may be the starting point for all aspects of RLS. Although this hypothesis was proposed more than a decade ago, it has not yet been verified beyond doubt. The main aim of this study is to compare the prevalence of RLS in a population of patients with the most common thyroid gland diseases with a population of individuals with a healthy thyroid gland. The study included 237 participants divided into smaller groups according to the thyroid disease concerning them. Each participant had a laboratory diagnosis, an ultrasound scan and an assessment of the fulfilment of RLS criteria according to the International Restless Legs Syndrome Study Group (IRLSSG) criteria. The results obtained were...
Hypothyroidism in restless legs syndrome
Journal of Sleep Research, 2020
Restless legs syndrome (RLS) is a chronic sensorimotor disorder characterized by an inescapable urge to move the legs at night, which is aggravated by repose and alleviated with movement (Allen et al., 2014). RLS prevents sleep and rest when it is most desired and its clinical significance is underscored by associations with cardiovascular disease and depression (Koo et al., 2016; Winkelman, Shahar, Sharief, & Gottlieb, 2008). The pathophysiology of RLS is not completely understood, but seems to be associated with low brain iron, abnormal central iron handling and extrasynaptic dopamine excess (Earley et al., 2014). RLS symptoms have variable severity within individuals from day to day and can be triggered by any number of factors, including dopamine blocking or serotonergic medications, or substances such as alcohol and caffeine (Hoque & Chesson, 2010;
Dopamine and iron in the pathophysiology of restless legs syndrome (RLS)
Sleep Medicine, 2004
Background and purpose: The evaluation of the pathophysiology of restless legs syndrome (RLS) stems largely from recognition of the information provided by both pharmacological treatment of the disorder and the secondary forms of the disorder. This article examines the pathophysiological implications of each of these clinical aspects of RLS.
Treating restless legs syndrome: current pathophysiological concepts and clinical trials
Expert Opinion on Investigational Drugs, 2002
Restless legs syndrome is a distinctive clinical syndrome with a prevalence of about 5% in the general population. One of the outstanding characteristics of restless legs syndrome is its extreme responsiveness to dopaminergic agents. Together with the latest pathophysiological and genetic findings, recent epidemiological and clinical data give a new insight into the classification of restless legs syndrome, thus building the theoretical foundation for the development of new pharmacological methods in its treatment. Current efforts within this area focus on establishing dopaminergic substances for therapy. The hypothesis of a disturbed iron metabolism in restless legs syndrome has been revived by recent theoretical considerations. The present review attempts to explain current strategies of treatment for restless legs syndrome in relation to aetiological, genetic and pathophysiological findings.
Restless legs syndrome: pathophysiology and the role of iron and folate
Alternative medicine review : a journal of clinical therapeutic, 2007
Restless Legs Syndrome (RLS) is a common movement disorder characterized by a circadian variation in symptoms involving an urge to move the limbs, usually the legs. Pregnant women, patients with end-stage renal disease or iron-deficiency anemia, and children with attention deficit hyperactivity disorder (AD/HD) have a significantly higher prevalence of RLS. The classic presentation includes the onset or worsening of symptoms when at rest and the circadian pattern of exacerbation of symptoms at night. These symptoms reflect a circadian fluctuation of dopamine in the substantia nigra. Patients with RLS have lower levels of dopamine in the substantia nigra and respond to iron administration. Iron, as a cofactor in dopamine production, plays a central role in the etiology of RLS. Folic acid administration has also been shown to alleviate the symptoms of RLS and may play a role in the treatment of primary (familial) RLS.
The Neurobiology and Treatment of Restless Legs Syndrome
Behavioural Neurology, 2013
Background: Restless legs syndrome (RLS) is a relatively common neurological disorder affecting sleep and healthrelated quality of life. Neuroimaging studies, autopsy investigations and experimental studies using animal models have been conducted to investigate the potential causes of RLS, resulting in the generation of multiple pathophysiological hypotheses. Methods: This paper reviews the neurobiology and pharmacotherapy of RLS, with a critical analysis of the heterogeneity and methodological limitations of the existing scientific literature. Results: Although several neurotransmitter systems dysfunction and neuroanatomical abnormalities have been implicated in RLS pathogenesis, dopamine dysfunction within basal ganglia pathways, iron deficiency and opioid system abnormalities have consistently been found to be involved. Their involvement is further strengthened by the therapeutic effectiveness of dopaminergic agents, iron supplementation and opioid medications. Discussion: Converging evidence from neuroimaging, autoptic and animal studies points towards dopamine dysregulation and iron metabolism alterations as the main contributors to RLS pathophysiology. The possible interactions between different neurotransmitter systems should guide further neuropharmacological research in order to improve therapeutic efficacy for this disabling condition.
Experimental and Therapeutic Medicine, 2021
The aim of this overview was to outline the pathophysiology, common comorbidities and current therapeutic modalities in the treatment/management of restless legs syndrome (RLS) a sensorimotor neurological disorder. The main symptom in RLS is a compelling compulsion to move the legs and a sense of restlessness at rest most commonly occurring during the night and improving with movement. The prevalence of secondary RLS among comorbid conditions such as idiopathic pulmonary fibrosis, end-stage renal disease, irritable bowel syndrome and attention deficit/hyperactivity disorder have further elucidated our understanding of the role of the iron-dopamine hypothesis as an etiopathogenetic hallmark in RLS and the efficacy of therapeutic approaches in milder to more severe forms. Currently, RLS treatment uses only symptomatic agents, since a disease-modifying therapy does not yet exist. The phenomena of rebound and augmentation have become central phenomena in overcoming the pharmacotherapeutic challenges when treating with dopaminergic agents in RLS. Considering alternative nonpharmacological therapies, especially for the treatment of RLS in pregnancy has a significant role and positive clinical outcome for patients in controlling symptoms.
Update in restless legs syndrome
Current Opinion in Neurology, 2010
Purpose of review-Although restless legs syndrome (RLS) is a disorder recognized in the medical literature since the 17th century, there have only recently been significant clinical and scientific advances in diagnosis, epidemiology and understanding the disorder, mainly due to the advent of dopaminergic treatment. Recent findings-Recent discoveries have uncovered the iron-dopamine connection in RLS and the basic dopaminergic pathology related to the RLS symptoms. These have led to new understanding of the morbidity of RLS and the many conditions associated with RLS, which have also supported new approaches to treatment. These developments are each briefly described here. Summary-Although there has been progress in understanding, diagnosing and treating RLS, it remains an underdiagnosed and undertreated condition severely impairing functioning of patients with moderate-to-severe disease. Much work is needed to improve on current, as well as other novel therapies.
Iron in Restless Legs Syndrome
Movement Disorders Clinical Practice, 2014
A link between restless legs syndrome (RLS) and iron has been recognized for several decades. Yet, the precise role that iron or other components of iron metabolism play in bringing about RLS is still a matter of debate. During the last few years, many new pieces of evidence from genetics, pathology, imaging, and clinical studies have surfaced. However, the way this evidence fits into the larger picture of RLS as a disease is not always easily understood. To provide a better understanding of the complex interplay between iron metabolism and RLS and highlight areas that need further elucidation, we systematically and critically review the current literature on the role of iron in RLS pathophysiology and treatment with a special emphasis on genetics, neuropathology, cell and animal models, imaging studies, and therapy.
Restless legs syndrome: A community-based study of prevalence, severity, and risk factors
Neurology, 2005
To assess the prevalence and severity of restless legs syndrome (RLS) in the general community and to investigate its potential relationship with iron metabolism and other potential risk factors. Methods: This was a cross-sectional study of a sex-and age-stratified random sample of the general population (50 to 89 years; n ϭ 701). The diagnosis of RLS was established by face-to-face interviews; severity was graded on the RLS severity scale. Each subject underwent a thorough clinical examination and extensive laboratory testing. Results: The prevalence of RLS was 10.6% (14.2% in women, 6.6% in men); 33.8% of all patients with RLS had mild, 44.6% had moderate, and 21.6% had severe disease expression. None had been previously diagnosed or was on dopaminergic therapy. Free serum iron, transferrin, and ferritin concentrations were similar in subjects with and without RLS. However, soluble transferrin receptor (sTR) concentrations were different in subjects with and without RLS (1.48 vs 1.34 mg/L; p Ͻ 0.001). Female sex and high sTR independently predicted the risk of RLS. Conclusion: This large survey confirms the high prevalence, female preponderance, and underrecognition of restless legs syndrome in the general community. Although two-thirds of patients had moderate to severe disease, none was on current dopaminergic therapy.