Restless legs syndrome: pathophysiology and the role of iron and folate (original) (raw)
Related papers
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.
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.
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.
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.
Update on the management of restless legs syndrome: existing and emerging treatment options
Nature and Science of Sleep, 2010
Restless legs syndrome (RLS) is a sensorimotor disorder, characterized by a circadian variation of symptoms involving an urge to move the limbs (usually the legs) as well as paresthesias. There is a primary (familial) and a secondary (acquired) form, which affects a wide variety of individuals, such as pregnant women, patients with end-stage renal disease, iron deficiency, rheumatic disease, and persons taking medications. The symptoms reflect a circadian fluctuation of dopamine in the substantia nigra. RLS patients have lower dopamine and iron levels in the substantia nigra and respond to both dopaminergic therapy and iron administration. Iron, as a cofactor of dopamine production and a regulator of the expression of dopamine type 2-receptor, has an important role in the RLS etiology. In the management of the disease, the first step is to investigate possible secondary causes and their treatment. Dopaminergic agents are considered as the first-line therapy for moderate to severe RLS. If dopaminergic drugs are contraindicated or not efficacious, or if symptoms are resistant and unremitting, gabapentin or other antiepileptic agents, benzodiazepines, or opioids can be used for RLS therapy. Undiagnosed, wrongly diagnosed, and untreated RLS is associated with a significant impairment of the quality of life.
International Journal of Environmental Research and Public Health
Restless legs syndrome is a common but still underdiagnosed neurologic disorder, characterized by peculiar symptoms typically occurring in the evening and at night, and resulting in sleep disruption and daily functioning impairment. This disease can affect subjects of all age ranges and of both sexes, manifesting itself with a broad spectrum of severity and deserving special attention in certain patient categories, in order to achieve a correct diagnosis and an effective treatment. The diagnosis of restless legs syndrome can be challenging in some patients, especially children and elderly people, and an effective treatment might be far from being easy to achieve after some years of drug therapy, notably when dopaminergic agents are used. Moreover, the pathophysiology of this disorder offers an interesting example of interaction between genetics and the environment, considering strong iron metabolism involvement and its interaction with recognized individual genetic factors. Therefor...
Restless leg syndrome: is it a real problem
2006
Restless legs syndrome (RLS) is a common condition that is frequently unrecognized, misdiagnosed and poorly managed. It is characterized by uncomfortable sensations deep in the legs developing at rest that compel the person to move; symptoms are worst at night and sleep disturbance is common. RLS occurs in 7%-11% of the population in Western countries, and many such people experience troublesome symptoms. Primary RLS is familial in up to two thirds of patients. RLS may also be secondary to a number of conditions including iron deficiency, pregnancy and end-stage renal failure and, perhaps, neuropathy. Secondary RLS is most common in those presenting for the first time in later life. The pathogenesis of RLS probably involves the interplay of systemic or brain iron deficiency and impaired dopaminergic neurotransmission in the subcortex of the brain. RLS is very responsive to dopaminergic therapies. Rebound of RLS symptoms during the early morning and development of severe symptoms earlier in the day (augmentation) are problematic in those treated for a prolonged period with levodopa. Consequently, dopamine agonists have become first line treatment. Anti-convulsant medications and opioids are helpful in some patients. Correction of underlying problem wherever possible is important in the management of secondary 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 leg syndrome: A Narrative Review
2020
The restless leg syndrome is an idiopathic condition typically related to the scarcity of iron or end stage renal infection. It is a notable age-related neurological issue more prevalent among females. Pathophysiology and treatment/management can be approximately linked to the dopaminergic system and iron metabolism. Dopaminergic treatment mutually includes levodopa and dopamine agonists and is usually the first choice in the management of idiopathic Restless leg syndrome (RLS). Apart from medications, physical activity and exercise are compatible with non-pharmacological intervention for decrementing the rigor of RLS. Presently, there is a lack of understanding of this condition often leads to misdiagnosis or under diagnosis. The main objective of this paper is to review the literature about RLS and its veiled management. Key wordsRestless leg syndrome, iron deficiency, dopamine deficiency, physical activity
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.