Restless Legs Syndrome: A Review

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an irresistible urge to move the limbs accompanied by uncomfortable sensations, leading to sleep disturbances. It is associated with psychiatric comorbidities and a decreased quality of life. RLS is common and most severe among females and the elderly. It may be primary or secondary to other conditions and may be familial. Linkage to several chromosomal loci have been demonstrated. The pathogenesis of RLS involves dopaminergic dysfunction, iron metabolism, and abnormalities in supraspinal inhibition. The mainstay of RLS therapy are dopamine agonists or levodopa. This article reviews the clinical characteristics, epidemiology, diagnosis, pathogenesis, and treatment of RLS.

[1]  J. Jankovic,et al.  Exploring the relationship between Parkinson disease and restless legs syndrome. , 2002, Archives of neurology.

[2]  Sanjiv Patel Restless legs syndrome and periodic limb movements of sleep: fact, fad, and fiction , 2002, Current opinion in pulmonary medicine.

[3]  L. Ferini-Strambi,et al.  Genetics in restless legs syndrome. , 2004, Sleep medicine.

[4]  C Trenkwalder,et al.  Clinical symptoms and possible anticipation in a large kindred of familial restless legs syndrome , 1996, Movement disorders : official journal of the Movement Disorder Society.

[5]  Michael Schröder,et al.  Bilateral thalamic gray matter changes in patients with restless legs syndrome , 2005, NeuroImage.

[6]  U. John,et al.  Sex and the risk of restless legs syndrome in the general population. , 2004, Archives of internal medicine.

[7]  R. Allen,et al.  Validation of the Johns Hopkins restless legs severity scale. , 2001, Sleep medicine.

[8]  D J Brooks,et al.  Striatal dopaminergic function in restless legs syndrome , 1999, Neurology.

[9]  W. Hening,et al.  The treatment of restless legs syndrome and periodic limb movement disorder. An American Academy of Sleep Medicine Review. , 1999, Sleep.

[10]  Alexander Hammers,et al.  The role of opioids in restless legs syndrome: an [11C]diprenorphine PET study. , 2005, Brain : a journal of neurology.

[11]  A. Walters Is there a subpopulation of children with growing pains who really have Restless Legs Syndrome? A review of the literature. , 2002, Sleep medicine.

[12]  G Klösch,et al.  Normal IPT and IBZM SPECT in drug naive and levodopa-treated idiopathic restless legs syndrome. , 2001, Neurology.

[13]  Richard P Allen,et al.  Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. , 2003, Sleep medicine.

[14]  J. Connor,et al.  Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome , 2000, Neurology.

[15]  E. Granieri,et al.  Pregnancy as a risk factor for restless legs syndrome. , 2004, Sleep medicine.

[16]  W. Paulus,et al.  Motor system excitability in patients with restless legs syndrome , 1999, Neurology.

[17]  J. McArthur,et al.  Subclinical sensory neuropathy in late-onset restless legs syndrome , 2000, Neurology.

[18]  Giorgio Casari,et al.  Autosomal dominant restless legs syndrome maps on chromosome 14q. , 2003, Brain : a journal of neurology.

[19]  W. Oertel,et al.  Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome. , 2004, Brain : a journal of neurology.

[20]  J. Montplaisir,et al.  Circadian rhythm of restless legs syndrome: Relationship with biological markers , 2004, Annals of neurology.

[21]  D. Garcia-Borreguero Augmentation: understanding a key feature of RLS. , 2004, Sleep medicine.

[22]  J. Connor,et al.  Iron status and neural functioning. , 2003, Annual review of nutrition.

[23]  P. Rompré,et al.  Immobilization tests and periodic leg movements in sleep for the diagnosis of restless leg syndrome , 1998, Movement disorders : official journal of the Movement Disorder Society.

[24]  G. Plazzi,et al.  Motor pattern of periodic limb movements during sleep , 2001, Neurology.

[25]  W. Hening,et al.  Restless legs syndrome (RLS): the continuing development of diagnostic standards and severity measures. , 2003, Sleep medicine.

[26]  M. Kryger,et al.  Restless legs syndrome in 218 patients: associated disorders. , 2000, Sleep medicine.

[27]  J. Matheson,et al.  Restless legs syndrome in patients with polyneuropathy , 1996, Muscle & nerve.

[28]  M. Ohayon,et al.  Prevalence of restless legs syndrome and periodic limb movement disorder in the general population. , 2002, Journal of psychosomatic research.

[29]  R P Allen,et al.  MRI measurement of brain iron in patients with restless legs syndrome , 2001, Neurology.

[30]  E. Tan,et al.  Restless legs syndrome in an Asian population: A study in Singapore , 2001, Movement disorders : official journal of the Movement Disorder Society.

[31]  T. Young,et al.  Epidemiology of restless legs symptoms in adults. , 2000, Archives of internal medicine.

[32]  S. Chokroverty,et al.  Frequent occurrence of myoclonus while awake and at rest, body rocking and marching in place in a subpopulation of patients with restless legs syndrome , 1988, Acta neurologica Scandinavica.

[33]  J. R. Young,et al.  Restless leg syndrome. , 1969, Geriatrics.

[34]  C. Gerloff,et al.  Cortical involvement in the generation of “involuntary” movements in restless legs syndrome , 2004, Neurology.

[35]  A. Walters,et al.  Periodic Limb Movement Disorder and Restless Legs Syndrome in Children With Attention-deficit Hyperactivity Disorder , 1998, Journal of child neurology.

[36]  S. O’Keeffe Restless legs syndrome. A review. , 1996, Archives of internal medicine.

[37]  D. Garcia-Borreguero,et al.  Restless legs syndrome and PD , 2003, Neurology.

[38]  E. Tan,et al.  Restless legs symptoms in thyroid disorders. , 2004, Parkinsonism & related disorders.

[39]  S. Chokroverty,et al.  Positron emission tomographic studies in restless legs syndrome , 1999, Movement disorders : official journal of the Movement Disorder Society.

[40]  C Trenkwalder,et al.  Cerebral generators involved in the pathogenesis of the restless legs syndrome , 1997, Annals of neurology.

[41]  J. Connor,et al.  Thy1 expression in the brain is affected by iron and is decreased in Restless Legs Syndrome , 2004, Journal of the Neurological Sciences.

[42]  G. Ayida,et al.  Restless leg syndrome in pregnancy. , 1988, BMJ.

[43]  C. Trenkwalder,et al.  Reflex studies and MRI in the restless legs syndrome , 1996, Acta neurologica Scandinavica.

[44]  M. Nangaku,et al.  Clinical and psychological aspects of restless legs syndrome in uremic patients on hemodialysis. , 2003, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[45]  D. Garcia-Borreguero,et al.  Restless legs syndrome: an overview of the current understanding and management , 2004, Acta neurologica Scandinavica.

[46]  Clete Kushida,et al.  Practice parameters for the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder. , 2004, Sleep.

[47]  W. Hening Subjective and objective criteria in the diagnosis of the restless legs syndrome. , 2004, Sleep medicine.

[48]  J. Sowers,et al.  Circadian variation in plasma dopamine levels in man , 1984, Journal of endocrinological investigation.

[49]  C Trenkwalder,et al.  Periodic limb movements and restless legs syndrome. , 1996, Neurologic clinics.

[50]  C Trenkwalder,et al.  Circadian rhythm of periodic limb movements and sensory symptoms of restless legs syndrome , 1999, Movement disorders : official journal of the Movement Disorder Society.

[51]  H. Bastuji,et al.  Sleep/wake abnormalities in patients with periodic leg movements during sleep: Factor analysis on data from 24‐h ambulatory polygraphy , 1999, Journal of sleep research.

[52]  U. Keil,et al.  Prevalence and risk factors of RLS in an elderly population , 2000, Neurology.

[53]  M. Michaud,et al.  Arm restlessness in patients with restless legs syndrome , 2000, Movement disorders : official journal of the Movement Disorder Society.

[54]  Richard P Allen,et al.  An update on the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder. , 2004, Sleep.

[55]  W. Ondo,et al.  Restless legs syndrome in monozygotic twins: Clinical correlates , 2000, Neurology.

[56]  M. Behari,et al.  Restless legs syndrome in Parkinson's disease: A case‐controlled study , 2003, Movement disorders : official journal of the Movement Disorder Society.

[57]  Shaoqi Rao,et al.  Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p. , 2004, American journal of human genetics.

[58]  G. Deuschl,et al.  Idiopathic restless legs syndrome: , 2004, Journal of Neurology.

[59]  B. Phillips Movement disorders , 2004, Neurology.

[60]  A. Desautels,et al.  Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q. , 2001, American journal of human genetics.

[61]  J. Jankovic,et al.  Restless legs syndrome , 1996, Neurology.

[62]  J. Connor,et al.  Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome , 2003, Neurology.

[63]  N. Kıylıoğlu,et al.  Iron deficiency anemia and restless legs syndrome: is there an electrophysiological abnormality? , 2003, Clinical Neurology and Neurosurgery.

[64]  J. Mountifield Restless leg syndrome relieved by cessation of smoking. , 1985, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[65]  B. Karp,et al.  Restless legs syndrome due to interferon‐α , 2004 .

[66]  A. Desautels,et al.  Dopaminergic neurotransmission and restless legs syndrome: A genetic association analysis , 2001, Neurology.

[67]  A. de Weerd,et al.  Sleep disorders and depressive feelings: a global survey with the Beck depression scale. , 2003, Sleep medicine.

[68]  M. Brin,et al.  Studies of penetrance and anticipation in five autosomal‐dominant restless legs syndrome pedigrees , 1999, Movement disorders : official journal of the Movement Disorder Society.

[69]  Christopher J. Earley Restless legs syndrome , 2003 .

[70]  R. Allen Dopamine and iron in the pathophysiology of restless legs syndrome (RLS). , 2004, Sleep medicine.

[71]  P. Dyck,et al.  THE SYMPTOM OF RESTLESS LEGS , 1965, Archives of internal medicine.

[72]  K. Mills,et al.  A clinical, serological and neurophysiological study of restless legs syndrome in rheumatoid arthritis. , 1994, British journal of rheumatology.

[73]  J. Montplaisir,et al.  SPECT imaging of striatal pre- and postsynaptic dopaminergic status in restless legs syndrome with periodic leg movements in sleep , 2002, Journal of Neurology.

[74]  S. O’Keeffe,et al.  Iron status and restless legs syndrome in the elderly. , 1994, Age and ageing.

[75]  N. Carter,et al.  Prevalence of restless legs syndrome among men aged 18 to 64 years: An association with somatic disease and neuropsychiatric symptoms , 2001, Movement disorders : official journal of the Movement Disorder Society.

[76]  Richard P Allen,et al.  Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study. , 2004, Sleep medicine.

[77]  P. Anderer,et al.  EEG mapping, psychometric, and polysomnographic studies in restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) patients as compared with normal controls. , 2002, Sleep medicine.

[78]  M Partinen,et al.  An FDOPA PET study in patients with periodic limb movement disorder and restless legs syndrome , 2000, Neurology.

[79]  C. Guilleminault,et al.  Atlas and scoring rules , 1993 .

[80]  E. Lutz Restless legs, anxiety and caffeinism. , 1978, The Journal of clinical psychiatry.

[81]  M. Zetin,et al.  Self-reported depressive symptomatology, mood ratings, and treatment outcome in sleep disorders patients. , 1989, Journal of clinical psychology.

[82]  A. Desautels,et al.  The 14q restless legs syndrome locus in the French Canadian population , 2004, Annals of neurology.

[83]  S. Agarwal,et al.  Restless legs syndrome in hemodialysis patients in India: a case controlled study. , 2003, Sleep medicine.

[84]  R. Allen,et al.  Evaluating the quality of life of patients with restless legs syndrome. , 2004, Clinical therapeutics.

[85]  A. Walters,et al.  Ropinirole is effective in the treatment of restless legs syndrome. TREAT RLS 2: A 12‐week, double‐blind, randomized, parallel‐group, placebo‐controlled study , 2004, Movement disorders : official journal of the Movement Disorder Society.

[86]  O. Doğu,et al.  Correlation of anxiety and depression symptoms in patients with restless legs syndrome: a population based survey , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[87]  G. Chertow,et al.  Restless legs syndrome in end-stage renal disease. , 1996, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[88]  W. Poewe,et al.  Akathisia, restless legs and periodic limb movements in sleep in Parkinson’s disease , 2004, Neurology.

[89]  S. Chokroverty,et al.  A questionnaire study of 138 patients with restless legs syndrome , 1996, Neurology.

[90]  Richard P. Allen,et al.  Restless Legs Syndrome: A Review of Clinical and Pathophysiologic Features , 2001, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[91]  A. Desautels,et al.  Evidence for a genetic association between monoamine oxidase A and restless legs syndrome , 2002, Neurology.

[92]  M. Dichgans,et al.  Complex segregation analysis of restless legs syndrome provides evidence for an autosomal dominant mode of inheritance in early age at onset families , 2002, Annals of neurology.

[93]  H. Pall,et al.  Restless leg syndrome and rheumatoid arthritis. , 1986, British medical journal.

[94]  Christopher R. Jones,et al.  Changes in excitability of motor cortical circuitry in primary restless legs syndrome , 1999, Neurology.

[95]  E. Lainey,et al.  Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study, a 12 week, randomised, placebo controlled study in 10 European countries. , 2009, Journal of neurology, neurosurgery, and psychiatry.

[96]  W. Poewe,et al.  Transient restless legs syndrome after spinal anesthesia , 2002, Neurology.

[97]  R. Rodnitzky,et al.  The importance of formal serum iron studies in the assessment of restless legs syndrome , 1998, Neurology.