Restless legs syndrome - Wikipedia

Restless legs syndrome (RLS), now known as Willis-Ekbom Disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. Restlesslegssyndrome FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch Long-termdisorderthatcausesastrongurgetomoveone'slegs Forthesong"RestlessLegs"byHalfManHalfBiscuit,seeAchtungBono. MedicalconditionRestlesslegssyndromeOthernamesWillis–Ekbomdisease(WED),[1]Wittmaack–EkbomsyndromeSleeppatternofapersonwithrestlesslegssyndrome(red)comparedtoahealthysleeppattern(blue)SpecialtySleepmedicineSymptomsUnpleasantfeelinginthelegsthatbrieflyimproveswithmovingthem[2]ComplicationsDaytimesleepiness,lowenergy,irritability,sadness[2]UsualonsetMorecommonwitholderage[3]RiskfactorsLowironlevels,kidneyfailure,Parkinson'sdisease,diabetesmellitus,rheumatoidarthritis,pregnancy,certainmedications[2][4][5]DiagnosticmethodBasedonsymptomsafterrulingoutotherpossiblecauses[6]TreatmentLifestylechanges,medication[2]MedicationLevodopa,dopamineagonists,gabapentin[4]Frequency2.5–15%(US)[4] Restlesslegssyndrome(RLS),nowknownasWillis-EkbomDisease(WED),isgenerallyalong-termdisorderthatcausesastrongurgetomoveone'slegs.[2][7]Thereisoftenanunpleasantfeelinginthelegsthatimprovessomewhatbymovingthem.[2]Thisisoftendescribedasaching,tingling,orcrawlinginnature.[2]Occasionally,armsmayalsobeaffected.[2]Thefeelingsgenerallyhappenwhenatrestandthereforecanmakeithardtosleep.[2]Duetothedisturbanceinsleep,peoplewithRLSmayhavedaytimesleepiness,lowenergy,irritabilityandadepressedmood.[2]Additionally,manyhavelimbtwitchingduringsleep.[8]RLSisnotthesameashabitualfoottappingorlegrocking.[9] RiskfactorsforRLSincludelowironlevels,kidneyfailure,Parkinson'sdisease,diabetesmellitus,rheumatoidarthritis,pregnancyandceliacdisease.[2][4][10]Anumberofmedicationsmayalsotriggerthedisorderincludingantidepressants,antipsychotics,antihistamines,andcalciumchannelblockers.[5]Therearetwomaintypes.[2]OneisearlyonsetRLSwhichstartsbeforeage45,runsinfamiliesandworsensovertime.[2]TheotherislateonsetRLSwhichbeginsafterage45,startssuddenly,anddoesnotworsen.[2]Diagnosisisgenerallybasedonaperson'ssymptomsafterrulingoutotherpotentialcauses.[6] Restlesslegssyndromemayresolveiftheunderlyingproblemisaddressed.[11]Otherwisetreatmentincludeslifestylechangesandmedication.[2]Lifestylechangesthatmayhelpincludestoppingalcoholandtobaccouse,andsleephygiene.[11]Medicationsusedincludelevodopaoradopamineagonistsuchaspramipexole.[4]RLSaffectsanestimated2.5–15%oftheAmericanpopulation.[4]Femalesaremorecommonlyaffectedthanmales,anditbecomesincreasinglycommonwithage.[3][1] Contents 1Signsandsymptoms 1.1Primaryandsecondary 2Causes 2.1ADHD 2.2Medications 2.3Genetics 3Mechanism 4Diagnosis 4.1Differentialdiagnosis 5Treatment 5.1Physicalmeasures 5.2Iron 5.3Medications 6Prognosis 7Epidemiology 8History 8.1Nomenclature 9Controversy 10Research 11Seealso 12References 13Externallinks Signsandsymptoms[edit] RLSsensationsrangefrompainoranachinginthemuscles,to"anitchyoucan'tscratch",a"buzzingsensation",anunpleasant"ticklethatwon'tstop",a"crawling"feeling,orlimbsjerkingwhileawake.Thesensationstypicallybeginorintensifyduringquietwakefulness,suchaswhenrelaxing,reading,studying,ortryingtosleep.[12] Itisa"spectrum"diseasewithsomepeopleexperiencingonlyaminorannoyanceandothershavingmajordisruptionofsleepandimpairmentsinqualityoflife.[13] Thesensations—andtheneedtomove—mayreturnimmediatelyafterceasingmovementoratalatertime.RLSmaystartatanyage,includingchildhood,andisaprogressivediseaseforsome,whilethesymptomsmayremitinothers.[14]InasurveyamongmembersoftherestlesslegsSyndromeFoundation,[15]itwasfoundthatupto45%ofpatientshadtheirfirstsymptomsbeforetheageof20years.[16] "Anurgetomove,usuallyduetouncomfortablesensationsthatoccurprimarilyinthelegs,butoccasionallyinthearmsorelsewhere." Thesensationsareunusualandunlikeothercommonsensations.ThosewithRLShaveahardtimedescribingthem,usingwordsorphrasessuchasuncomfortable,painful,'antsy',electrical,creeping,itching,pinsandneedles,pulling,crawling,buzzing,andnumbness.Itissometimesdescribedsimilartoalimb'fallingasleep'oranexaggeratedsenseofpositionalawarenessoftheaffectedarea.Thesensationandtheurgecanoccurinanybodypart;themostcitedlocationislegs,followedbyarms.Somepeoplehavelittleornosensation,yetstill,haveastrongurgetomove. "Motorrestlessness,expressedasactivity,whichrelievestheurgetomove." Movementusuallybringsimmediaterelief,althoughtemporaryandpartial.Walkingismostcommon;however,stretching,yoga,biking,orotherphysicalactivitymayrelievethesymptoms.Continuous,fastup-and-downmovementsoftheleg,and/orrapidlymovingthelegstowardthenawayfromeachother,maykeepsensationsatbaywithouthavingtowalk.Specificmovementsmaybeuniquetoeachperson. "Worseningofsymptomsbyrelaxation." Sittingorlyingdown(reading,planeride,watchingTV)cantriggerthesensationsandurgetomove.Severitydependsontheseverityoftheperson'sRLS,thedegreeofrestfulness,durationoftheinactivity,etc. "Variabilityoverthecourseoftheday-nightcycle,withsymptomsworseintheeveningandearlyinthenight." SomeexperienceRLSonlyatbedtime,whileothersexperienceitthroughoutthedayandnight.Mostpeopleexperiencetheworstsymptomsintheeveningandtheleastinthemorning. "restlesslegsfeelsimilartotheurgetoyawn,situatedinthelegsorarms." ThesesymptomsofRLScanmakesleepingdifficultformanypatientsandarecentpollshowsthepresenceofsignificantdaytimedifficultiesresultingfromthiscondition.Theseproblemsrangefrombeinglateforworktomissingworkoreventsbecauseofdrowsiness.PatientswithRLSwhorespondedreporteddrivingwhiledrowsymorethanpatientswithoutRLS.Thesedaytimedifficultiescantranslateintosafety,socialandeconomicissuesforthepatientandforsociety. RLSmaycontributetohigherratesofdepressionandanxietydisordersinRLSpatients.[17] Primaryandsecondary[edit] RLSiscategorizedaseitherprimaryorsecondary. PrimaryRLSisconsideredidiopathicorwithnoknowncause.PrimaryRLSusuallybeginsslowly,beforeapproximately40–45yearsofageandmaydisappearformonthsorevenyears.Itisoftenprogressiveandgetsworsewithage.RLSinchildrenisoftenmisdiagnosedasgrowingpains. SecondaryRLSoftenhasasuddenonsetafterage40,andmaybedailyfromthebeginning.Itismostassociatedwithspecificmedicalconditionsortheuseofcertaindrugs(seebelow). Causes[edit] Whilethecauseisgenerallyunknown,itisbelievedtobecausedbychangesinthenervetransmitterdopamine[18]resultinginanabnormaluseofironbythebrain.[1]RLSisoftenduetoirondeficiency(lowtotalbodyironstatus).[1]Otherassociatedconditionsmayincludeend-stagekidneydiseaseandhemodialysis,folatedeficiency,magnesiumdeficiency,sleepapnea,diabetes,peripheralneuropathy,Parkinson'sdisease,andcertainautoimmunediseases,suchasmultiplesclerosis.[19]RLScanworseninpregnancy,possiblyduetoelevatedestrogenlevels.[1][20]Useofalcohol,nicotineproducts,andcaffeinemaybeassociatedwithRLS.[1]A2014studyfromtheAmericanAcademyofNeurologyalsofoundthatreducedlegoxygenlevelswerestronglyassociatedwithrestlesslegsSyndromesymptomseverityinuntreatedpatients.[21] ADHD[edit] Anassociationhasbeenobservedbetweenattentiondeficithyperactivitydisorder(ADHD)andRLSorperiodiclimbmovementdisorder.[22]Bothconditionsappeartohavelinkstodysfunctionsrelatedtotheneurotransmitterdopamine,andcommonmedicationsforbothconditionsamongothersystems,affectdopaminelevelsinthebrain.[23]A2005studysuggestedthatupto44%ofpeoplewithADHDhadcomorbid(i.e.coexisting)RLS,andupto26%ofpeoplewithRLShadconfirmedADHDorsymptomsofthecondition.[24] Medications[edit] CertainmedicationsmaycauseorworsenRLS,orcauseitsecondarily,including:[1] certainantiemetics(antidopaminergicones)[25] certainantihistamines(especiallythesedating,firstgenerationH1antihistaminesofteninover-the-countercoldmedications)[25] manyantidepressants(botholderTCAsandnewerSSRIs)[1][25] antipsychoticsandcertainanticonvulsants[1] areboundeffectofsedative-hypnoticdrugssuchasabenzodiazepinewithdrawalsyndromefromdiscontinuingbenzodiazepinetranquilizersorsleepingpills[1] alcoholwithdrawalcanalsocauserestlesslegssyndromeandothermovementdisorderssuchasakathisiaandparkinsonismusuallyassociatedwithantipsychotics[26] opioidwithdrawalisassociatedwithcausingandworseningRLS[27] BothprimaryandsecondaryRLScanbeworsenedbysurgeryofanykind;however,backsurgeryorinjurycanbeassociatedwithcausingRLS.[28] Thecausevs.effectofcertainconditionsandbehaviorsobservedinsomepatients(ex.excessweight,lackofexercise,depressionorothermentalillnesses)isnotwellestablished.LossofsleepduetoRLScouldcausetheconditions,ormedicationusedtotreataconditioncouldcauseRLS.[29][30] Genetics[edit] Morethan60%ofcasesofRLSarefamilialandareinheritedinanautosomaldominantfashionwithvariablepenetrance.[31] Researchandbrainautopsieshaveimplicatedbothdopaminergicsystemandironinsufficiencyinthesubstantianigra.[32]IroniswellunderstoodtobeanessentialcofactorfortheformationofL-dopa,theprecursorofdopamine. Sixgeneticlocifoundbylinkageareknownandlistedbelow.Otherthanthefirstone,allofthelinkagelociwerediscoveredusinganautosomaldominantmodelofinheritance. ThefirstgeneticlocuswasdiscoveredinonelargeFrenchCanadianfamilyandmapstochromosome12q.[33][34]Thislocuswasdiscoveredusinganautosomalrecessiveinheritancemodel.Evidenceforthislocuswasalsofoundusingatransmissiondisequilibriumtest(TDT)in12Bavarianfamilies.[35] ThesecondRLSlocusmapstochromosome14qandwasdiscoveredinoneItalianfamily.[36]EvidenceforthislocuswasfoundinoneFrenchCanadianfamily.[37]Also,anassociationstudyinalargesample159triosofEuropeandescentshowedsomeevidenceforthislocus.[38] Thislocusmapstochromosome9pandwasdiscoveredintwounrelatedAmericanfamilies.[39]EvidenceforthislocuswasalsofoundbytheTDTinalargeBavarianfamily,[40]inwhichsignificantlinkagetothislocuswasfound.[41] Thislocusmapstochromosome20pandwasdiscoveredinalargeFrenchCanadianfamilywithRLS.[42] Thislocusmapstochromosome2pandwasfoundinthreerelatedfamiliesfrompopulationisolatedinSouthTyrol.[43] Thesixthlocusislocatedonchromosome16p12.1andwasdiscoveredbyLevchenkoetal.in2008.[44] Threegenes,MEIS1,BTBD9andMAP2K5,werefoundtobeassociatedtoRLS.[45] TheirroleinRLSpathogenesisisstillunclear.Morerecently,afourthgene,PTPRDwasfoundtobeassociatedwithRLS.[46] Thereisalsosomeevidencethatperiodiclimbmovementsinsleep(PLMS)areassociatedwithBTBD9onchromosome6p21.2,[47][48]MEIS1,MAP2K5/SKOR1,andPTPRD.[48]ThepresenceofapositivefamilyhistorysuggeststhattheremaybeageneticinvolvementintheetiologyofRLS. Mechanism[edit] Althoughitisonlypartlyunderstood,pathophysiologyofrestlesslegssyndromemayinvolvedopamineandironsystemanomalies.[49][50]Thereisalsoacommonlyacknowledgedcircadianrhythmexplanatorymechanismassociatedwithit,clinicallyshownsimplybybiomarkersofcircadianrhythm,suchasbodytemperature.[51]Theinteractionsbetweenimpairedneuronalironuptakeandthefunctionsoftheneuromelanin-containinganddopamine-producingcellshaverolesinRLSdevelopment,indicatingthatirondeficiencymightaffectthebraindopaminergictransmissionsindifferentways.[52] MedialthalamicnucleimayalsohavearoleinRLSaspartasthelimbicsystemmodulatedbythedopaminergicsystem[53]whichmayaffectpainperception.[54]ImprovementofRLSsymptomsoccursinpeoplereceivinglow-dosedopamineagonists.[55] Diagnosis[edit] TherearenospecifictestsforRLS,butnon-specificlaboratorytestsareusedtoruleoutothercausessuchasvitamindeficiencies.Fivesymptomsareusedtoconfirmthediagnosis:[1] Astrongurgetomovethelimbs,usuallyassociatedwithunpleasantoruncomfortablesensations. Itstartsorworsensduringinactivityorrest. Itimprovesordisappears(atleasttemporarily)withactivity. Itworsensintheeveningornight. Thesesymptomsarenotcausedbyanymedicalorbehavioralcondition. Thesesymptomsarenotessential,liketheonesabove,butoccurcommonlyinRLSpatients:[1][56] geneticcomponentorfamilyhistorywithRLS goodresponsetodopaminergictherapy periodiclegmovementsduringdayorsleep moststronglyaffectedarepeoplewhoaremiddle-agedorolder othersleepdisturbancesareexperienced decreasedironstorescanbeariskfactorandshouldbeassessed AccordingtotheInternationalClassificationofSleepDisorders(ICSD-3),themainsymptomshavetobeassociatedwithasleepdisturbanceorimpairmentinordertosupportRLSdiagnosis.[57]Asstatedbythisclassification,RLSsymptomsshouldbeginorworsenwhenbeinginactive,berelievedwhenmoving,shouldhappenexclusivelyormostlyintheeveningandatnight,notbetriggeredbyothermedicalorbehavioralconditions,andshouldimpairone'squalityoflife.[57][58]Generally,bothlegsareaffected,butinsomecasesthereisanasymmetry. Differentialdiagnosis[edit] ThemostcommonconditionsthatshouldbedifferentiatedwithRLSincludelegcramps,positionaldiscomfort,localleginjury,arthritis,legedema,venousstasis,peripheralneuropathy,radiculopathy,habitualfoottapping/legrocking,anxiety,myalgia,anddrug-inducedakathisia.[9] Peripheralarterydiseaseandarthritiscanalsocauselegpainbutthisusuallygetsworsewithmovement.[8] Therearelesscommondifferentialdiagnosticconditionsincludedmyelopathy,myopathy,vascularorneurogenicclaudication,hypotensiveakathisia,orthostatictremor,painfullegs,andmovingtoes.[9] Treatment[edit] IfRLSisnotlinkedtoanunderlyingcause,itsfrequencymaybereducedbylifestylemodificationssuchasadoptingimprovingsleephygiene,regularexercise,andstoppingsmoking.[59]Medicationsusedmayincludedopamineagonistsorgabapentininthosewithdailyrestlesslegssyndrome,andopioidsfortreatmentofresistantcases.[1][27] TreatmentofRLSshouldnotbeconsidereduntilpossiblemedicalcausesareruledout.SecondaryRLSmaybecuredifprecipitatingmedicalconditions(anemia)aremanagedeffectively.[1] Physicalmeasures[edit] Stretchingthelegmusclescanbringtemporaryrelief.[12][60]Walkingandmovingthelegs,asthename"restlesslegs"implies,bringstemporaryrelief.Infact,thosewithRLSoftenhaveanalmostuncontrollableneedtowalkandthereforerelievethesymptomswhiletheyaremoving.Unfortunately,thesymptomsusuallyreturnimmediatelyafterthemovingandwalkingceases.Avibratorycounter-stimulationdevicehasbeenfoundtohelpsomepeoplewithprimaryRLStoimprovetheirsleep.[61] Iron[edit] ThereissomeevidencethatintravenousironsupplementationmoderatelyimprovesrestlessnessforpeoplewithRLS.[62] Medications[edit] ForthosewhoseRLSdisruptsorpreventssleeporregulardailyactivities,medicationmaybeuseful.Evidencesupportstheuseofdopamineagonistsincluding:pramipexole,ropinirole,rotigotine,andcabergoline.[63][64]Theyreducesymptoms,improvesleepqualityandqualityoflife.[65]Levodopaisalsoeffective.[66]However,pergolideandcabergolinearelessrecommendedduetotheirassociationwithincreasedriskofvalvularheartdisease.[67]Ropinirolehasafasteronsetwithshorterduration.[68]Rotigotineiscommonlyusedasatransdermalpatchwhichcontinuouslyprovidesstableplasmadrugconcentrations,resultinginitsparticulartherapeuticeffectonpatientswithsymptomsthroughouttheday.[68]Onereviewfoundpramipexoletobebetterthanropinirole.[69][needsupdate] Thereare,however,issueswiththeuseofdopamineagonistsincludingaugmentation.Thisisamedicalconditionwherethedrugitselfcausessymptomstoincreaseinseverityand/oroccurearlierintheday.Dopamineagonistsmayalsocausereboundwhensymptomsincreaseasthedrugwearsoff.Inmanycases,thelongerdopamineagonistshavebeenusedthehighertheriskofaugmentationandreboundaswellastheseverityofthesymptoms.Also,arecentstudyindicatedthatdopamineagonistsusedinrestlesslegssyndromecanleadtoanincreaseincompulsivegambling.[70] Gabapentinorpregabalin,anon-dopaminergictreatmentformoderatetosevereprimaryRLS[71] Opioidsareonlyindicatedinseverecasesthatdonotrespondtoothermeasuresduetotheirhighrateofsideeffects,whichmayincludeconstipation,fatigueandheadache.[72][27] OnepossibletreatmentforRLSisdopamineagonists,unfortunatelypatientscandevelopdopaminedysregulationsyndrome,meaningthattheycanexperienceanaddictivepatternofdopaminereplacementtherapy.Additionally,theycanexhibitsomebehavioraldisturbancessuchasimpulsecontroldisorderslikepathologicgambling,compulsivepurchasingandcompulsiveeating.[73]Therearesomeindicationsthatstoppingthedopamineagonisttreatmenthasanimpactontheresolutionoratleastimprovementoftheimpulsecontroldisorder,eventhoughsomepeoplecanbeparticularlyexposedtodopamineagonistwithdrawalsyndrome.[74] Benzodiazepines,suchasdiazepamorclonazepam,arenotgenerallyrecommended,[75]andtheireffectivenessisunknown.[76]Theyhoweveraresometimesstillusedasasecondline,[77]asaddonagents.[76]Quinineisnotrecommendedduetoitsriskofserioussideeffectsinvolvingtheblood.[78] Prognosis[edit] RLSsymptomsmaygraduallyworsenwithage,althoughmoreslowlyforthosewiththeidiopathicformofRLSthanforpeoplewhoalsohaveanassociatedmedicalcondition.[79]Currenttherapiescancontrolthedisorder,minimizingsymptomsandincreasingperiodsofrestfulsleep.Inaddition,somepeoplehaveremissions,periodsinwhichsymptomsdecreaseordisappearfordays,weeks,ormonths,althoughsymptomsusuallyeventuallyreappear.[79]BeingdiagnosedwithRLSdoesnotindicateorforeshadowanotherneurologicaldisease,suchasParkinson'sdisease.[79]RLSsymptomscanworsenovertimewhendopamine-relateddrugsareusedfortherapy,aneffectcalled"augmentation"whichmayrepresentsymptomsoccurringthroughoutthedayandaffectmovementsofalllimbs.[79]ThereisnocureforRLS.[79] Epidemiology[edit] RLSaffectsanestimated2.5–15%oftheAmericanpopulation.[4][80]Aminority(around2.7%ofthepopulation)experiencedailyorseveresymptoms.[81]RLSistwiceascommoninwomenasinmen,[82]andCaucasiansaremorepronetoRLSthanpeopleofAfricandescent.[80]RLSoccursin3%ofindividualsfromtheMediterraneanorMiddleEasternregions,andin1–5%ofthosefromEastAsia,indicatingthatdifferentgeneticorenvironmentalfactors,includingdiet,mayplayaroleintheprevalenceofthissyndrome.[80][83]RLSdiagnosedatanolderagerunsamoreseverecourse.[60]RLSisevenmorecommoninindividualswithirondeficiency,pregnancy,orend-stagekidneydisease.[84][85]TheNationalSleepFoundation's1998SleepinAmericapollshowedthatupto25percentofpregnantwomendevelopedRLSduringthethirdtrimester.[86]Poorgeneralhealthisalsolinked.[87] ThereareseveralriskfactorsforRLS,includingoldage,familyhistory,anduremia.TheprevalenceofRLStendstoincreasewithage,aswellasitsseverityandlongerdurationofsymptoms.Peoplewithuremiareceivingrenaldialysishaveaprevalencefrom20%to57%,whilethosehavingkidneytransplantimprovecomparedtothosetreatedwithdialysis.[88] RLScanoccuratallages,althoughittypicallybeginsinthethirdorfourthdecade.[58] Genome‐wideassociationstudieshavenowidentified19risklociassociatedwithRLS.[89]NeurologicalconditionslinkedtoRLSincludeParkinson'sdisease,spinalcerebellaratrophy,spinalstenosis,[specify]lumbosacralradiculopathyandCharcot–Marie–Toothdiseasetype2.[80] History[edit] ThefirstknownmedicaldescriptionofRLSwasbySirThomasWillisin1672.[90]WillisemphasizedthesleepdisruptionandlimbmovementsexperiencedbypeoplewithRLS.InitiallypublishedinLatin(DeAnimaBrutorum,1672)butlatertranslatedtoEnglish(TheLondonPracticeofPhysick,1685),Williswrote: Whereforetosome,whenbeingabedtheybetakethemselvestosleep,presentlyinthearmsandlegs,leapingsandcontractionsonthetendons,andsogreatarestlessnessandtossingsofothermembersensue,thatthediseasedarenomoreabletosleep,thaniftheywereinaplaceofthegreatesttorture. Theterm"fidgetsinthelegs"hasalsobeenusedasearlyastheearlynineteenthcentury.[91] Subsequently,otherdescriptionsofRLSwerepublished,includingthosebyFrançoisBoissierdeSauvages(1763),MagnusHuss(1849),TheodurWittmaack(1861),GeorgeMillerBeard(1880),GeorgesGillesdelaTourette(1898),HermannOppenheim(1923)andFrederickGerardAllison(1943).[90][92]However,itwasnotuntilalmostthreecenturiesafterWillis,in1945,thatKarl-AxelEkbom(1907–1977)providedadetailedandcomprehensivereportofthisconditioninhisdoctoralthesis,restlesslegs:clinicalstudyofhithertooverlookeddisease.[93]Ekbomcoinedtheterm"restlesslegs"andcontinuedworkonthisdisorderthroughouthiscareer.Hedescribedtheessentialdiagnosticsymptoms,differentialdiagnosisfromotherconditions,prevalence,relationtoanemia,andcommonoccurrenceduringpregnancy.[94][95] Ekbom'sworkwaslargelyignoreduntilitwasrediscoveredbyArthurS.WaltersandWayneA.Heninginthe1980s.Subsequentlandmarkpublicationsinclude1995and2003papers,whichrevisedandupdatedthediagnosticcriteria.[12][96]JournalofParkinsonismandRLSisthefirstpeer-reviewed,online,openaccessjournaldedicatedtopublishingresearchaboutParkinson'sdiseaseandwasfoundedbyaCanadianneurologistDr.AbdulQayyumRana. Nomenclature[edit] Fordecadesthemostwidelyusednameforthediseasewasrestlesslegssyndrome,anditisstillthemostcommonlyused.In2013therestlesslegsSyndromeFoundationrenameditselftheWillis–EkbomDiseaseFoundation,[97]anditencouragestheuseofthenameWillis–Ekbomdisease;itsreasonsarequotedasfollows:[97] ThenameWillis–Ekbomdisease: Eliminatesincorrectdescriptors—theconditionofteninvolvespartsofthebodyotherthanlegs Promotescross-culturaleaseofuse Respondstotrivializationofthediseaseandhumoroustreatmentinthemedia AcknowledgesthefirstknowndescriptionbySirThomasWillisin1672andthefirstdetailedclinicaldescriptionbyDr.KarlAxelEkbomin1945.[97] ApointofconfusionisthatRLSanddelusionalparasitosisareentirelydifferentconditionsthathavebothbeencalled"Ekbomsyndrome",asbothsyndromesweredescribedbythesameperson,Karl-AxelEkbom.[98]Today,callingWED/RLS"Ekbomsyndrome"isoutdatedusage,astheunambiguousnames(WEDorRLS)arepreferredforclarity. Controversy[edit] Somedoctorsexpresstheviewthattheincidenceofrestlesslegssyndromeisexaggeratedbymanufacturersofdrugsusedtotreatit.[99]Othersbelieveitisanunderrecognizedandundertreateddisorder.[80]Further,GlaxoSmithKlineranadvertisementsthat,whilenotpromotingoff-licenceuseoftheirdrug(ropinirole)fortreatmentofRLS,didlinktotheEkbomSupportGroupwebsite.ThatwebsitecontainedstatementsadvocatingtheuseofropiniroletotreatRLS.TheABPIruledagainstGSKinthiscase.[100] Research[edit] DifferentmeasurementshavebeenusedtoevaluatetreatmentsinRLS.Mostofthemarebasedonsubjectiveratingscores,suchasIRLSratingscale(IRLS),ClinicalGlobalImpression(CGI),PatientGlobalImpression(PGI),andQualityoflife(QoL).[101]Thesequestionnairesprovideinformationabouttheseverityandprogressofthedisease,aswellastheperson'squalityoflifeandsleep.[101]Polysomnography(PSG)andactigraphy(bothrelatedtosleepparameters)aremoreobjectiveresourcesthatprovideevidencesofsleepdisturbancesassociatedwithRLSsymptoms.[101] Seealso[edit] Periodiclimbmovementdisorder References[edit] ^abcdefghijklmn"RestlessLegsSyndromeFactSheet|NationalInstituteofNeurologicalDisordersandStroke".Ninds.nih.gov.Retrieved7July2019. ^abcdefghijklmno"WhatIsRestlessLegsSyndrome?".NHLBI.November1,2010.Archivedfromtheoriginalon21August2016.Retrieved19August2016. ^ab"WhoIsatRiskforRestlessLegsSyndrome?".NHLBI.November1,2010.Archivedfromtheoriginalon26August2016.Retrieved19August2016. ^abcdefgRamar,K;Olson,EJ(Aug15,2013)."Managementofcommonsleepdisorders".AmericanFamilyPhysician.88(4):231–8.PMID 23944726. ^ab"WhatCausesRestlessLegsSyndrome?".NHLBI.November1,2010.Archivedfromtheoriginalon20August2016.Retrieved19August2016. ^ab"HowIsRestlessLegsSyndromeDiagnosed?".NHLBI.November1,2010.Archivedfromtheoriginalon27August2016.Retrieved19August2016. ^"RestlessLegsSyndromeInformationPage|NationalInstituteofNeurologicalDisordersandStroke".Ninds.nih.gov.Retrieved7July2019. ^ab"WhatAretheSignsandSymptomsofRestlessLegsSyndrome?".NHLBI.November1,2010.Archivedfromtheoriginalon27August2016.Retrieved19August2016. ^abcAllen,RichardP.;Picchietti,DanielL.;Garcia-Borreguero,Diego;Ondo,WilliamG.;Walters,ArthurS.;Winkelman,JohnW.;Zucconi,Marco;Ferri,Raffaele;Trenkwalder,Claudia(2014-08-01)."Restlesslegssyndrome/Willis–Ekbomdiseasediagnosticcriteria:updatedInternationalRestlessLegsSyndromeStudyGroup(IRLSSG)consensuscriteria–history,rationale,description,andsignificance".SleepMedicine.15(8):860–873.doi:10.1016/j.sleep.2014.03.025.ISSN 1389-9457.PMID 25023924. ^ZisP,HadjivassiliouM(2019)."TreatmentofNeurologicalManifestationsofGlutenSensitivityandCoeliacDisease".CurrTreatOptionsNeurol(Review).21(3):10.doi:10.1007/s11940-019-0552-7.PMID 30806821. ^ab"HowIsRestlessLegsSyndromeTreated?".NHLBI.November1,2010.Archivedfromtheoriginalon27August2016.Retrieved19August2016. ^abcAllen,R;Picchietti,D;Hening,WA;Trenkwalder,C;Walters,AS;Montplaisi,J;RestlessLegsSyndromeDiagnosisEpidemiologyworkshopattheNationalInstitutesofHealth;InternationalRestlessLegsSyndromeStudyGroup(2003)."Restlesslegssyndrome:diagnosticcriteria,specialconsiderations,andepidemiologyAreportfromtherestlesslegssyndromediagnosisandepidemiologyworkshopattheNationalInstitutesofHealth".SleepMedicine.4(2):101–19.doi:10.1016/S1389-9457(03)00010-8.PMID 14592341. ^Earley,ChristopherJ.;Silber,MichaelH.(2010)."Restlesslegssyndrome:Understandingitsconsequencesandtheneedforbettertreatment".SleepMedicine.11(9):807–15.doi:10.1016/j.sleep.2010.07.007.PMID 20817595. ^Xiong,L.;Montplaisir,J.;Desautels,A.;Barhdadi,A.;Turecki,G.;Levchenko,A.;Thibodeau,P.;Dubé,M.P.;Gaspar,C.;Rouleau,GA(2010)."FamilyStudyofRestlessLegsSyndromeinQuebec,Canada:ClinicalCharacterizationof671FamilialCases".ArchivesofNeurology.67(5):617–22.doi:10.1001/archneurol.2010.67.PMID 20457962. ^"Willis–EkbomDiseaseFoundationRevertstoOriginalName"(PDF).2013.Archivedfromtheoriginal(PDF)on2015-09-24. ^Walters,A.S.;Hickey,K.;Maltzman,J.;Verrico,T.;Joseph,D.;Hening,W.;Wilson,V.;Chokroverty,S.(1996)."Aquestionnairestudyof138patientswithrestlesslegssyndrome:The'Night-Walkers'survey".Neurology.46(1):92–5.doi:10.1212/WNL.46.1.92.PMID 8559428.S2CID 25278952. ^Becker,PM;Sharon,D(July2014)."Mooddisordersinrestlesslegssyndrome(Willis–Ekbomdisease)".TheJournalofClinicalPsychiatry.75(7):e679–94.doi:10.4088/jcp.13r08692.PMID 25093484. ^St.LouisE.K.(2014).Newevidenceforreducedlegoxygenlevelsinrestlesslegssyndrome.Neurology,82,e185.https://doi.org/10.1212/WNL.0000000000000513 ^"Restlesslegssyndrome".MedlinePlus,USNationalLibraryofMedicine,NationalInstitutesofHealth.7August2017.Retrieved23June2019. ^Gupta,R.;Dhyani,M.;Kendzerska,T.;Pandi-Perumal,S.R.;BaHammam,A.S.;Srivanitchapoom,P.;Pandey,S.;Hallett,M.(19October2015)."Restlesslegssyndromeandpregnancy:prevalence,possiblepathophysiologicalmechanismsandtreatment".ActaNeurologicaScandinavica.133(5):320–329.doi:10.1111/ane.12520.ISSN 0001-6314.PMC 5562408.PMID 26482928. ^St.LouisE.K.(2014).Newevidenceforreducedlegoxygenlevelsinrestlesslegssyndrome.Neurology,82,e185.https://doi.org/10.1212/WNL.0000000000000513 ^Walters,A.S.;Silvestri,R;Zucconi,M;Chandrashekariah,R;Konofal,E(2008)."ReviewofthePossibleRelationshipandHypotheticalLinksBetweenAttentionDeficitHyperactivityDisorder(ADHD)andtheSimpleSleepRelatedMovementDisorders,Parasomnias,Hypersomnias,andCircadianRhythmDisorders".JournalofClinicalSleepMedicine.4(6):591–600.doi:10.5664/jcsm.27356.PMC 2603539.PMID 19110891. ^"Attentiondeficithyperactivitydisorder–OtherDisordersAssociatedwithADHD".UniversityofMarylandMedicalCenter.2008.Retrieved27October2021.Check|archive-url=value(help) ^Cortese,S;Konofal,E;Lecendreux,M;Arnulf,I;Mouren,MC;Darra,F;DallaBernardina,B(2005)."Restlesslegssyndromeandattention-deficit/hyperactivitydisorder:Areviewoftheliterature".Sleep.28(8):1007–13.doi:10.1093/sleep/28.8.1007.PMID 16218085. ^abcBuchfuhrer,MJ(October2012)."Strategiesforthetreatmentofrestlesslegssyndrome".Neurotherapeutics(Review).9(4):776–90.doi:10.1007/s13311-012-0139-4.PMC 3480566.PMID 22923001. ^Neiman,J;Lang,AE;Fornazzari,L;Carlen,PL(May1990)."Movementdisordersinalcoholism:areview".Neurology.40(5):741–6.doi:10.1212/wnl.40.5.741.PMID 2098000.S2CID 8940680. ^abcTrenkwalder,Claudia;Zieglgänsberger,Walter;Ahmedzai,SamH.;Högl,Birgit(2017)."Pain,opioids,andsleep:implicationsforrestlesslegssyndrometreatment".SleepMedicine.31:78–85.doi:10.1016/j.sleep.2016.09.017.ISSN 1389-9457.PMID 27964861. ^Crotti,FrancescoMaria;Carai,A.;Carai,M.;Sgaramella,E.;Sias,W.(2005)."Entrapmentofcruralbranchesofthecommonperonealnerve".AdvancedPeripheralNerveSurgeryandMinimalInvasiveSpinalSurgery.ActaNeurochirurgica.97.pp. 69–70.doi:10.1007/3-211-27458-8_15.ISBN 978-3-211-23368-9.PMID 15830971. ^"ExerciseandRestlessLegsSyndrome".Archivedfromtheoriginalon2015-08-06.Retrieved2008-05-28. ^Phillips,BarbaraA.;Britz,Pat;Hening,Wayne(October31,2005).TheNSF2005SleepinAmericanpollandthoseatriskforRLS.Chest2005.Laysummary–ScienceDaily(October31,2005). ^Lavigne,GJ;Montplaisir,JY(1994)."Restlesslegssyndromeandsleepbruxism:prevalenceandassociationamongCanadians".Sleep.17(8):739–43.PMID 7701186. ^Connor,J.R.;Boyer,P.J.;Menzies,S.L.;Dellinger,B.;Allen,R.P.;Ondo,W.G.;Earley,C.J.(2003)."Neuropathologicalexaminationsuggestsimpairedbrainironacquisitioninrestlesslegssyndrome".Neurology.61(3):304–9.doi:10.1212/01.WNL.0000078887.16593.12.PMID 12913188.S2CID 44703083. ^Desautels,Alex;Turecki,Gustavo;Montplaisir,Jacques;Sequeira,Adolfo;Verner,Andrei;Rouleau,GuyA.(2001)."IdentificationofaMajorSusceptibilityLocusforRestlessLegsSyndromeonChromosome12q".TheAmericanJournalofHumanGenetics.69(6):1266–70.doi:10.1086/324649.PMC 1235538.PMID 11704926. ^Desautels,A.;Turecki,G;Montplaisir,J;Xiong,L;Walters,AS;Ehrenberg,BL;Brisebois,K;Desautels,AK;Gingras,Y;Johnson,WG;Lugaresi,E;Coccagna,G;Picchietti,DL;Lazzarini,A;Rouleau,GA(2005)."RestlessLegsSyndrome:ConfirmationofLinkagetoChromosome12q,GeneticHeterogeneity,andEvidenceofComplexity".ArchivesofNeurology.62(4):591–6.doi:10.1001/archneur.62.4.591.PMID 15824258. ^Winkelmann,Juliane;Lichtner,Peter;Pütz,Benno;Trenkwalder,Claudia;Hauk,Stephanie;Meitinger,Thomas;Strom,Tim;Muller-Myhsok,Bertram(2006)."EvidenceforfurthergeneticlocusheterogeneityandconfirmationofRLS-1inrestlesslegssyndrome".MovementDisorders.21(1):28–33.doi:10.1002/mds.20627.PMID 16124010.S2CID 25736900. ^Bonati,M.T.(2003)."Autosomaldominantrestlesslegssyndromemapsonchromosome14q".Brain.126(6):1485–92.doi:10.1093/brain/awg137.PMID 12764067. ^Levchenko,Anastasia;Montplaisir,Jacques-Yves;Dubé,Marie-Pierre;Riviere,Jean-Baptiste;St-Onge,Judith;Turecki,Gustavo;Xiong,Lan;Thibodeau,Pascale;Desautels,Alex;Verlaan,DominiqueJ.;Rouleau,GuyA.(2004)."The14qrestlesslegssyndromelocusintheFrenchCanadianpopulation".AnnalsofNeurology.55(6):887–91.doi:10.1002/ana.20140.PMID 15174026.S2CID 31001901. ^Kemlink,David;Polo,Olli;Montagna,Pasquale;Provini,Federica;Stiasny-Kolster,Karin;Oertel,Wolfgang;DeWeerd,Al;Nevsimalova,Sona;Sonka,Karel;Högl,Birgit;Frauscher,Birgit;Poewe,Werner;Trenkwalder,Claudia;Pramstaller,PeterP.;Ferini-Strambi,Luigi;Zucconi,Marco;Konofal,Eric;Arnulf,Isabelle;Hadjigeorgiou,GeorgiosM.;Happe,Svenja;Klein,Christine;Hiller,Anja;Lichtner,Peter;Meitinger,Thomas;Müller-Myshok,Betram;Winkelmann,Juliane(2007)."Family-basedassociationstudyoftherestlesslegssyndromeloci2and3inaEuropeanpopulation".MovementDisorders.22(2):207–12.doi:10.1002/mds.21254.PMID 17133505.S2CID 34801702. ^Chen,Shenghan;Ondo,WilliamG.;Rao,Shaoqi;Li,Lin;Chen,Qiuyun;Wang,Qing(2004)."GenomewideLinkageScanIdentifiesaNovelSusceptibilityLocusforRestlessLegsSyndromeonChromosome9p".TheAmericanJournalofHumanGenetics.74(5):876–885.doi:10.1086/420772.PMC 1181982.PMID 15077200. ^Liebetanz,K.M.;Winkelmann,J;Trenkwalder,C;Pütz,B;Dichgans,M;Gasser,T;Müller-Myhsok,B(2006)."RLS3:Fine-mappingofanautosomaldominantlocusinafamilywithintrafamilialheterogeneity".Neurology.67(2):320–321.doi:10.1212/01.wnl.0000224886.65213.b5.PMID 16864828.S2CID 20796797. ^Lohmann-Hedrich,K.;Neumann,A.;Kleensang,A.;Lohnau,T.;Muhle,H.;Djarmati,A.;König,I.R.;Pramstaller,P.P.;Schwinger,E.;Kramer,P.L.;Ziegler,A.;Stephani,U.;Klein,C.(2008)."Evidenceforlinkageofrestlesslegssyndrometochromosome9p:Aretheretwodistinctloci?".Neurology.70(9):686–694.doi:10.1212/01.wnl.0000282760.07650.ba.PMID 18032746.S2CID 24889954. ^Levchenko,A.;Provost,S;Montplaisir,JY;Xiong,L;St-Onge,J;Thibodeau,P;Rivière,JB;Desautels,A;Turecki,G;Dubé,M.P.;Rouleau,G.A.(2006)."Anovelautosomaldominantrestlesslegssyndromelocusmapstochromosome20p13".Neurology.67(5):900–901.doi:10.1212/01.wnl.0000233991.20410.b6.PMID 16966564.S2CID 20555259. ^Pichler,Irene;Marroni,Fabio;BeuVolpato,Claudia;Gusella,JamesF.;Klein,Christine;Casari,Giorgio;DeGrandi,Alessandro;Pramstaller,PeterP.(2006)."LinkageAnalysisIdentifiesaNovelLocusforRestlessLegsSyndromeonChromosome2qinaSouthTyroleanPopulationIsolate".TheAmericanJournalofHumanGenetics.79(4):716–23.doi:10.1086/507875.PMC 1592574.PMID 16960808. ^Levchenko,Anastasia;Montplaisir,Jacques-Yves;Asselin,GéRaldine;Provost,Sylvie;Girard,SimonL.;Xiong,Lan;Lemyre,Emmanuelle;St-Onge,Judith;Thibodeau,Pascale;Desautels,Alex;Turecki,Gustavo;Gaspar,Claudia;Dubé,Marie-Pierre;Rouleau,GuyA.(2009)."Autosomal-dominantlocusforrestlesslegssyndromeinFrench-Canadiansonchromosome16p12.1".MovementDisorders.24(1):40–50.doi:10.1002/mds.22263.PMID 18946881.S2CID 7796597. ^Winkelmann,Juliane;Schormair,Barbara;Lichtner,Peter;Ripke,Stephan;Xiong,Lan;Jalilzadeh,Shapour;Fulda,Stephany;Pütz,Benno;Eckstein,Gertrud;Hauk,Stephanie;Trenkwalder,Claudia;Zimprich,Alexander;Stiasny-Kolster,Karin;Oertel,Wolfgang;Bachmann,CorneliusG;Paulus,Walter;Peglau,Ines;Eisensehr,Ilonka;Montplaisir,Jacques;Turecki,Gustavo;Rouleau,Guy;Gieger,Christian;Illig,Thomas;Wichmann,H-Erich;Holsboer,Florian;Müller-Myhsok,Bertram;Meitinger,Thomas(2007)."Genome-wideassociationstudyofrestlesslegssyndromeidentifiescommonvariantsinthreegenomicregions".NatureGenetics.39(8):1000–6.doi:10.1038/ng2099.PMID 17637780.S2CID 10606410. ^Ding,Li;Getz,Gad;Wheeler,DavidA.;Mardis,ElaineR.;McLellan,MichaelD.;Cibulskis,Kristian;Sougnez,Carrie;Greulich,Heidi;Muzny,DonnaM.;Morgan,MargaretB.;Fulton,Lucinda;Fulton,RobertS.;Zhang,Qunyuan;Wendl,MichaelC.;Lawrence,MichaelS.;Larson,DavidE.;Chen,Ken;Dooling,DavidJ.;Sabo,Aniko;Hawes,AliciaC.;Shen,Hua;Jhangiani,ShaliniN.;Lewis,LoraR.;Hall,Otis;Zhu,Yiming;Mathew,Tittu;Ren,Yanru;Yao,Jiqiang;Scherer,StevenE.;Clerc,Kerstin(2008)."Somaticmutationsaffectkeypathwaysinlungadenocarcinoma".Nature.455(7216):1069–75.Bibcode:2008Natur.455.1069D.doi:10.1038/nature07423.PMC 2694412.PMID 18948947. ^Stefansson,Hreinn;Rye,DavidB.;Hicks,Andrew;Petursson,Hjorvar;Ingason,Andres;Thorgeirsson,ThorgeirE.;Palsson,Stefan;Sigmundsson,Thordur;Sigurdsson,AlbertP.;Eiriksdottir,Ingibjorg;Soebech,Emilia;Bliwise,Donald;Beck,JosephM.;Rosen,Ami;Waddy,Salina;Trotti,LynnM.;Iranzo,Alex;Thambisetty,Madhav;Hardarson,GudmundurA.;Kristjansson,Kristleifur;Gudmundsson,LarusJ.;Thorsteinsdottir,Unnur;Kong,Augustine;Gulcher,JeffreyR.;Gudbjartsson,Daniel;Stefansson,Kari(2007)."AGeneticRiskFactorforPeriodicLimbMovementsinSleep".NewEnglandJournalofMedicine.357(7):639–47.doi:10.1056/NEJMoa072743.PMID 17634447.S2CID 44726156. ^abMoore,H;Winkelmann,J;Lin,L;Finn,L;Peppard,P;Mignot,E(2014)."PeriodiclegmovementsduringsleepareassociatedwithpolymorphismsinBTBD9,TOX3/BC034767,MEIS1,MAP2K5/SKOR1,andPTPRD".Sleep.37(9):1535–1542.doi:10.5665/sleep.4006.PMC 4153066.PMID 25142570. ^Allen,R(2004)."Dopamineandironinthepathophysiologyofrestlesslegssyndrome(RLS)".SleepMedicine.5(4):385–91.doi:10.1016/j.sleep.2004.01.012.PMID 15222997. ^Clemens,S.;Rye,D;Hochman,S(2006)."Restlesslegssyndrome:Revisitingthedopaminehypothesisfromthespinalcordperspective".Neurology.67(1):125–130.doi:10.1212/01.wnl.0000223316.53428.c9.PMID 16832090.S2CID 40963114. ^Barrière,G.;Cazalets,J.R.;Bioulac,B.;Tison,F.;Ghorayeb,I.(2005-10-01)."Therestlesslegssyndrome".ProgressinNeurobiology.77(3):139–165.doi:10.1016/j.pneurobio.2005.10.007.ISSN 0301-0082.PMID 16300874.S2CID 9327680. ^Dauvilliers,Yves;Winkelmann,Juliane(2013-11-01)."Restlesslegssyndrome:updateonpathogenesis".CurrentOpinioninPulmonaryMedicine.19(6):594–600.doi:10.1097/MCP.0b013e328365ab07.ISSN 1070-5287.PMID 24048084.S2CID 20370566. ^Klein,MarianneO.;Battagello,DaniellaS.;Cardoso,ArielR.;Hauser,DavidN.;Bittencourt,JacksonC.;Correa,RicardoG.(2019-01-01)."Dopamine:Functions,Signaling,andAssociationwithNeurologicalDiseases".CellularandMolecularNeurobiology.39(1):31–59.doi:10.1007/s10571-018-0632-3.ISSN 1573-6830.PMID 30446950.S2CID 53567202. ^Garcia-Borreguero,Diego;Williams,Anne-Marie(2014-08-01)."Anupdateonrestlesslegssyndrome(Willis-Ekbomdisease):clinicalfeatures,pathogenesisandtreatment".CurrentOpinioninNeurology.27(4):493–501.doi:10.1097/WCO.0000000000000117.ISSN 1350-7540.PMID 24978636. ^Paulus,Walter;Trenkwalder,Claudia(2006-10-01)."Lessismore:pathophysiologyofdopaminergic-therapy-relatedaugmentationinrestlesslegssyndrome".TheLancetNeurology.5(10):878–886.doi:10.1016/S1474-4422(06)70576-2.ISSN 1474-4422.PMID 16987735.S2CID 43111931. ^Allen,RichardP.;Montplaisir,Jacques;Walters,ArthurScott;Ferini-Strambi,Luigi;Högl,Birgit(2017),"RestlessLegsSyndromeandPeriodicLimbMovementsDuringSleep",PrinciplesandPracticeofSleepMedicine,Elsevier,pp. 923–934.e6,doi:10.1016/b978-0-323-24288-2.00095-7,ISBN 9780323242882 ^abSateia,MichaelJ(November2014)."InternationalClassificationofSleepDisorders-ThirdEdition".Chest.146(5):1387–1394.doi:10.1378/chest.14-0970.PMID 25367475. ^abBreen,DP;Högl,B;Fasano,A;Trenkwalder,C;Lang,AE(July2018)."Sleep-relatedmotorandbehavioraldisorders:Recentadvancesandnewentities".MovementDisorders.33(7):1042–1055.doi:10.1002/mds.27375.PMID 29756278.S2CID 21672153. ^"Restlesslegssyndrome—Treatment".NationalHealthService.6August2018. ^abAllen,RichardP.;Earley,ChristopherJ.(2001)."RestlessLegsSyndrome".JournalofClinicalNeurophysiology.18(2):128–47.doi:10.1097/00004691-200103000-00004.PMID 11435804.S2CID 34082653. ^Foy,Jonette."RegulationName:Vibratorycounter-stimulationdevice"(PDF).FoodandDrugAdministration.Archived(PDF)fromtheoriginalon24October2014.Retrieved17October2014. ^Trotti,LynnM;Becker,LorneA(2019)."Ironforthetreatmentofrestlesslegssyndrome".CochraneDatabaseofSystematicReviews(Systematicreview).1:CD007834.doi:10.1002/14651858.CD007834.pub3.ISSN 1465-1858.PMC 6353229.PMID 30609006. ^Zintzaras,E;Kitsios,GD;Papathanasiou,AA;Konitsiotis,S;Miligkos,M;Rodopoulou,P;Hadjigeorgiou,GM(Feb2010)."Randomizedtrialsofdopamineagonistsinrestlesslegssyndrome:asystematicreview,qualityassessment,andmeta-analysis".ClinicalTherapeutics.32(2):221–37.doi:10.1016/j.clinthera.2010.01.028.PMID 20206780. ^Winkelman,JW;Armstrong,MJ;Allen,RP;Chaudhuri,KR;Ondo,W;Trenkwalder,C;Zee,PC;Gronseth,GS;Gloss,D;Zesiewicz,T(13December2016)."Practiceguidelinesummary:Treatmentofrestlesslegssyndromeinadults:ReportoftheGuidelineDevelopment,Dissemination,andImplementationSubcommitteeoftheAmericanAcademyofNeurology".Neurology.87(24):2585–2593.doi:10.1212/wnl.0000000000003388.PMC 5206998.PMID 27856776. ^Scholz,H.;Trenkwalder,C.;Kohnen,R.;Riemann,D.;Kriston,L.;Hornyak,M.(2011).Hornyak,Magdolna(ed.)."Dopamineagonistsforrestlesslegssyndrome".CochraneDatabaseSystRev(3):CD006009.doi:10.1002/14651858.CD006009.pub2.PMID 21412893. ^Scholz,H;Trenkwalder,C;Kohnen,R;Riemann,D;Kriston,L;Hornyak,M(Feb16,2011)."Levodopaforrestlesslegssyndrome".TheCochraneDatabaseofSystematicReviews(2):CD005504.doi:10.1002/14651858.CD005504.pub2.PMID 21328278. ^Zanettini,Renzo;Antonini,Angelo;Gatto,Gemma;Gentile,Rosa;Tesei,Silvana;Pezzoli,Gianni(2007-01-04)."ValvularHeartDiseaseandtheUseofDopamineAgonistsforParkinson'sDisease".NewEnglandJournalofMedicine.356(1):39–46.doi:10.1056/NEJMoa054830.ISSN 0028-4793.PMID 17202454. ^abMackie,Susan;Winkelman,JohnW.(2015-05-01)."Long-TermTreatmentofRestlessLegsSyndrome(RLS):AnApproachtoManagementofWorseningSymptoms,LossofEfficacy,andAugmentation".CNSDrugs.29(5):351–357.doi:10.1007/s40263-015-0250-2.ISSN 1179-1934.PMID 26045290. ^Quilici,S;Abrams,KR;Nicolas,A;Martin,M;Petit,C;Lleu,PL;Finnern,HW(Oct2008)."Meta-analysisoftheefficacyandtolerabilityofpramipexoleversusropiniroleinthetreatmentofrestlesslegssyndrome".SleepMedicine.9(7):715–26.doi:10.1016/j.sleep.2007.11.020.PMID 18226947. ^Tippmann-Peikert,M.;Park,J.G.;Boeve,B.F.;Shepard,J.W.;Silber,M.H.(2007)."Pathologicgamblinginpatientswithrestlesslegssyndrometreatedwithdopaminergicagonists".Neurology.68(4):301–3.doi:10.1212/01.wnl.0000252368.25106.b6.PMID 17242339.S2CID 26183000.Laysummary–ScienceDaily(February9,2007). ^Nagandla,K;De,S(July2013)."Restlesslegssyndrome:pathophysiologyandmodernmanagement".PostgraduateMedicalJournal.89(1053):402–10.doi:10.1136/postgradmedj-2012-131634.PMID 23524988. ^deOliveiraCO;CarvalhoLB;CarlosK;ContiC;deOliveiraMM;PradoLB;PradoGF(29June2016)."Opioidsforrestlesslegssyndrome".CochraneDatabaseofSystematicReviews.6(6):CD006941.doi:10.1002/14651858.CD006941.pub2.PMC 6885031.PMID 27355187. ^Rosenberg,RichardS.;Tracy,SharonL.;Lamm,CarinI.;Casey,KennethR.;Zak,RochelleS.;Rowley,JamesA.;Bista,SabinR.;Kristo,DavidA.;Aurora,R.Nisha(2012-08-01)."TheTreatmentofRestlessLegsSyndromeandPeriodicLimbMovementDisorderinAdults—AnUpdatefor2012:PracticeParameterswithanEvidence-BasedSystematicReviewandMeta-AnalysesAnAmericanAcademyofSleepMedicineClinicalPracticeGuideline".Sleep.35(8):1039–1062.doi:10.5665/sleep.1988.ISSN 0161-8105.PMC 3397811.PMID 22851801. ^Rosenberg,RichardS.;Tracy,SharonL.;Lamm,CarinI.;Casey,KennethR.;Zak,RochelleS.;Rowley,JamesA.;Bista,SabinR.;Kristo,DavidA.;Aurora,R.Nisha(2012-08-01)."TheTreatmentofRestlessLegsSyndromeandPeriodicLimbMovementDisorderinAdults—AnUpdatefor2012:PracticeParameterswithanEvidence-BasedSystematicReviewandMeta-AnalysesAnAmericanAcademyofSleepMedicineClinicalPracticeGuideline".Sleep.35(8):1039–1062.doi:10.5665/sleep.1988.ISSN 0161-8105.PMC 3397811.PMID 22851801. ^Trenkwalder,C;Winkelmann,J;Inoue,Y;Paulus,W(August2015)."Restlesslegssyndrome-currenttherapiesandmanagementofaugmentation".NatureReviews.Neurology.11(8):434–45.doi:10.1038/nrneurol.2015.122.PMID 26215616.S2CID 22534190. ^abCarlosK,PradoGF,TeixeiraCD,ContiC,deOliveiraMM,PradoLB,CarvalhoLB(2017)."Benzodiazepinesforrestlesslegssyndrome".CochraneDatabaseSystRev.3:CD006939.doi:10.1002/14651858.CD006939.pub2.PMC 6464545.PMID 28319266. ^Garcia-Borreguero,D;Stillman,P;Benes,H;Buschmann,H;Chaudhuri,KR;GonzalezRodríguez,VM;Högl,B;Kohnen,R;Monti,GC;Stiasny-Kolster,K;Trenkwalder,C;Williams,AM;Zucconi,M(27February2011)."Algorithmsforthediagnosisandtreatmentofrestlesslegssyndromeinprimarycare".BMCNeurology.11:28.doi:10.1186/1471-2377-11-28.PMC 3056753.PMID 21352569. ^"Qualaquin(quininesulfate):NewRiskEvaluationandMitigationStrategy–Riskofserioushematologicalreactions".Archivedfromtheoriginalon2010-07-16. ^abcde"RestlessLegsSyndromeFactsheet".NationalInstitutesofHealth.ArchivedfromtheoriginalonJanuary4,2015.RetrievedJanuary13,2015. ^abcdeGamaldo,C.E.;Earley,C.J.(2006)."RestlessLegsSyndrome:AClinicalUpdate".Chest.130(5):1596–604.doi:10.1378/chest.130.5.1596.PMID 17099042. ^Allen,R.P.;Walters,AS;Montplaisir,J;Hening,W;Myers,A;Bell,TJ;Ferini-Strambi,L(2005)."RestlessLegsSyndromePrevalenceandImpact:RESTGeneralPopulationStudy".ArchivesofInternalMedicine.165(11):1286–92.doi:10.1001/archinte.165.11.1286.PMID 15956009. ^Berger,K.;Luedemann,J;Trenkwalder,C;John,U;Kessler,C(2004)."SexandtheRiskofRestlessLegsSyndromeintheGeneralPopulation".ArchivesofInternalMedicine.164(2):196–202.doi:10.1001/archinte.164.2.196.PMID 14744844. ^"Welcome–NationalSleepFoundation".Archivedfromtheoriginalon2007-07-28.Retrieved2007-07-23. ^Lee,KathrynA.;Zaffke,MaryEllen;Baratte-Beebe,Kathleen(2001)."RestlessLegsSyndromeandSleepDisturbanceduringPregnancy:TheRoleofFolateandIron".JournalofWomen'sHealth&Gender-BasedMedicine.10(4):335–41.doi:10.1089/152460901750269652.PMID 11445024. ^Trenkwalder,C;Allen,R;Högl,B;Paulus,W;Winkelmann,J(5April2016)."Restlesslegssyndromeassociatedwithmajordiseases:Asystematicreviewandnewconcept".Neurology.86(14):1336–1343.doi:10.1212/WNL.0000000000002542.PMC 4826337.PMID 26944272. ^"SleepingByTrimesters:3rdTrimester".NationalSleepFoundation.Archivedfromtheoriginalon2007-05-08. ^Yeh,Paul;Walters,ArthurS.;Tsuang,JohnW.(1December2012)."Restlesslegssyndrome:acomprehensiveoverviewonitsepidemiology,riskfactors,andtreatment".Sleep&Breathing=Schlaf&Atmung.16(4):987–1007.doi:10.1007/s11325-011-0606-x.ISSN 1522-1709.PMID 22038683.S2CID 24079411. ^Hening,Wayne;Allen,Richard;Earley,Christopher;Kushida,Clete;Picchietti,Daniel;Silber,Michael(1999)."TheTreatmentofRestlessLegsSyndromeandPeriodicLimbMovementDisorder".Sleep.doi:10.1093/sleep/22.7.970. ^Schormair,Barbara(November2017)."Identificationofnovelrisklociforrestlesslegssyndromeingenome-wideassociationstudiesinindividualsofEuropeanancestry:ameta-analysis".TheLancetNeurology.16(11):898–907.doi:10.1016/S1474-4422(17)30327-7.PMC 5755468.PMID 29029846. ^abCoccagna,G;Vetrugno,R;Lombardi,C;Provini,F(2004)."Restlesslegssyndrome:anhistoricalnote".SleepMedicine.5(3):279–83.doi:10.1016/j.sleep.2004.01.002.PMID 15165536. ^CalebHillierPARRY(1815).ElementsofPathologyandTherapeutics.Vol.1...GeneralPathology.pp. 381&397.Archivedfromtheoriginalon2017-09-08. ^Konofal,Eric;Karroum,Elias;Montplaisir,Jacques;Derenne,Jean-Philippe;Arnulf,Isabelle(2009)."TwoearlydescriptionsofrestlesslegssyndromeandperiodiclegmovementsbyBoissierdeSauvages(1763)andGillesdelaTourette(1898)".SleepMedicine.10(5):586–91.doi:10.1016/j.sleep.2008.04.008.PMID 18752999. ^Ekrbom,Karl-Axel(2009)."PREFACE".ActaMedicaScandinavica.121:1–123.doi:10.1111/j.0954-6820.1945.tb11970.x. ^Teive,HélioA.G.;Munhoz,RenatoP.;Barbosa,EgbertoReis(2009)."ProfessorKarl-AxelEkbomandrestlesslegssyndrome".Parkinsonism&RelatedDisorders.15(4):254–7.doi:10.1016/j.parkreldis.2008.07.011.PMID 18829374. ^Ulfberg,J(2004)."ThelegacyofKarl-AxelEkbom".SleepMedicine.5(3):223–4.doi:10.1016/j.sleep.2004.04.002.PMID 15165526. ^Walters,ArthurS.;Aldrich,MichaelS.;Allen,Richard;Ancoli-Israel,Sonia;Buchholz,David;Chokroverty,Sudhansu;Coccagna,Giorgio;Earley,Christopher;Ehrenberg,Bruce;Feest,T.G.;Hening,Wayne;Kavey,Neil;Lavigne,Gilles;Lipinski,Joseph;Lugaresi,Elio;Montagna,Pasquale;Montplaisir,Jacques;Mosko,SarahS.;Oertel,Wolfgang;Picchietti,Daniel;Pollmächer,Thomas;Shafor,Renata;Smith,RobertC.;Telstad,Wenche;Trenkwalder,Claudia;VonScheele,Christian;Walters,ArthurS.;Ware,J.Catesby;Zucconi,Marco(1995)."Towardabetterdefinitionoftherestlesslegssyndrome".MovementDisorders.10(5):634–42.doi:10.1002/mds.870100517.PMID 8552117.S2CID 22970514. ^abc"RestlessLegsSyndromeFoundationisnowtheWillis–EkbomDiseaseFoundation".2013.Archivedfromtheoriginalon2013-09-15. ^Wittmaack–EkbomsyndromeatWhoNamedIt? ^Woloshin,Steven;Schwartz,LisaM.(2006)."GivingLegstoRestlessLegs:ACaseStudyofHowtheMediaHelpsMakePeopleSick".PLOSMedicine.3(4):e170.doi:10.1371/journal.pmed.0030170.PMC 1434499.PMID 16597175. ^Templeton,Sarah-Kate(August6,2006)."Glaxo'scurefor'restlesslegs'wasanunlicenseddrug".TimesOnline.TimesNewspapersLtd.ArchivedfromtheoriginalonFebruary11,2007.Retrieved2009-07-24. ^abcAurora,R.Nisha;Kristo,DavidA.;Bista,SabinR.;Rowley,JamesA.;Zak,RochelleS.;Casey,KennethR.;Lamm,CarinI.;Tracy,SharonL.;Rosenberg,RichardS.(August2012)."UpdatetotheAASMClinicalPracticeGuideline:"TheTreatmentofRestlessLegsSyndromeandPeriodicLimbMovementDisorderinAdults—AnUpdatefor2012:PracticeParameterswithanEvidence-BasedSystematicReviewandMeta-Analyses"".Sleep.35(8):1037.doi:10.5665/sleep.1986.PMC 3397810.PMID 22851800. Externallinks[edit] WikimediaCommonshasmediarelatedtoRestlesslegsyndrome. LookuprestlesslegssyndromeinWiktionary,thefreedictionary. RestlesslegssyndromeatCurlie ClassificationDICD-10:G25.8ICD-10-CM:G25.81ICD-9-CM:333.94OMIM:102300608831MeSH:D012148DiseasesDB:29476ExternalresourcesMedlinePlus:000807eMedicine:neuro/509PatientUK:Restlesslegssyndrome vteDiseasesofthenervoussystem,primarilyCNSInflammationBrain Encephalitis Viralencephalitis Herpesviralencephalitis Limbicencephalitis Encephalitislethargica Cavernoussinusthrombosis Brainabscess Amoebic Brainandspinalcord Encephalomyelitis Acutedisseminated Meningitis Meningoencephalitis Brain/encephalopathyDegenerativeExtrapyramidalandmovementdisorders Basalgangliadisease Parkinsonism PD Postencephalitic NMS PKAN Tauopathy PSP Striatonigraldegeneration Hemiballismus HD OA Dyskinesia Dystonia Statusdystonicus Spasmodictorticollis Meige's Blepharospasm Athetosis Chorea Choreoathetosis Myoclonus Myoclonicepilepsy Akathisia Tremor Essentialtremor Intentiontremor Restlesslegs Stiff-person Dementia Tauopathy Alzheimer's Early-onset Primaryprogressiveaphasia Frontotemporaldementia/Frontotemporallobardegeneration Pick's DementiawithLewybodies Posteriorcorticalatrophy Vasculardementia Mitochondrialdisease Leighsyndrome Demyelinating Autoimmune Inflammatory Multiplesclerosis Formoredetailedcoverage,seeTemplate:DemyelinatingdiseasesofCNS Episodic/paroxysmalSeizuresandepilepsy Focal Generalised Statusepilepticus Formoredetailedcoverage,seeTemplate:Epilepsy Headache Migraine Cluster Tension Formoredetailedcoverage,seeTemplate:Headache Cerebrovascular TIA Stroke Formoredetailedcoverage,seeTemplate:Cerebrovasculardiseases Other Sleepdisorders Formoredetailedcoverage,seeTemplate:Sleep CSF Intracranialhypertension Hydrocephalus Normalpressurehydrocephalus Choroidplexuspapilloma Idiopathicintracranialhypertension Cerebraledema Intracranialhypotension Other Brainherniation Reyesyndrome Hepaticencephalopathy Toxicencephalopathy Hashimoto'sencephalopathy Both/eitherDegenerativeSA Friedreich'sataxia Ataxia–telangiectasia MND UMNonly: Primarylateralsclerosis Pseudobulbarpalsy Hereditaryspasticparaplegia LMNonly: Distalhereditarymotorneuronopathies Spinalmuscularatrophies SMA SMAX1 SMAX2 DSMA1 CongenitalDSMA Spinalmuscularatrophywithlowerextremitypredominance(SMALED) SMALED1 SMALED2A SMALED2B SMA-PCH SMA-PME Progressivemuscularatrophy Progressivebulbarpalsy Fazio–Londe Infantileprogressivebulbarpalsy both: Amyotrophiclateralsclerosis Authoritycontrol:Nationallibraries Japan Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Restless_legs_syndrome&oldid=1052279048" Categories:ExtrapyramidalandmovementdisordersSleepdisordersSyndromesHiddencategories:CS1errors:URLArticleswithshortdescriptionShortdescriptionisdifferentfromWikidataWikipediaarticlesinneedofupdatingfromSeptember2019AllWikipediaarticlesinneedofupdatingArticlesneedingmoredetailedreferencesCommonscategorylinkisonWikidataArticleswithCurlielinksArticleswithNDLidentifiersWikipediamedicinearticlesreadytotranslateWikipedianeurologyarticlesreadytotranslate Navigationmenu Personaltools NotloggedinTalkContributionsCreateaccountLogin Namespaces ArticleTalk Variants expanded collapsed Views ReadEditViewhistory More expanded collapsed Search Navigation MainpageContentsCurrenteventsRandomarticleAboutWikipediaContactusDonate Contribute HelpLearntoeditCommunityportalRecentchangesUploadfile Tools WhatlinkshereRelatedchangesUploadfileSpecialpagesPermanentlinkPageinformationCitethispageWikidataitem Print/export DownloadasPDFPrintableversion Inotherprojects WikimediaCommons Languages AfrikaansالعربيةAzərbaycancaتۆرکجهCatalàDanskDeutschEestiEspañolEuskaraفارسیFrançais한국어ՀայերենItalianoעבריתLietuviųLugandaBahasaMelayuမြန်မာဘာသာNederlands日本語Norskbokmålଓଡ଼ିଆPolskiPortuguêsRomânăРусскийSimpleEnglishSlovenčinaSlovenščinaСрпски/srpskiSuomiSvenskaTürkçeУкраїнськаTiếngViệt中文 Editlinks