Zespół niespokojnych nóg – Rokowania, prognozy i postęp choroby

Zespół niespokojnych nóg
Rokowania, prognozy i postęp choroby

Zespół niespokojnych nóg (RLS) to przewlekłe zaburzenie neurologiczne charakteryzujące się nieprzyjemnymi doznaniami w kończynach dolnych oraz nieodpartą potrzebą ich ruchu, nasilającymi się w spoczynku i w nocy. RLS wiąże się ze znacznym pogorszeniem jakości życia, zaburzeniami snu, lękiem i depresją, a także z funkcjonalnymi ograniczeniami, takimi jak trudności w wstawaniu, pochylaniu się czy przenoszeniu ciężarów (np. trudności z wstawaniem z krzesła – HR=2,54, 95% CI 1,62-3,99). Epidemiologiczne dane wskazują na istotny wzrost ryzyka całkowitej śmiertelności (HR=1,92, 95% CI 1,03-3,56) oraz chorób współistniejących, w tym choroby wieńcowej serca, udaru mózgu i przewlekłej choroby nerek (obniżony eGFR), nawet po wykluczeniu innych poważnych schorzeń. Przebieg RLS jest zmienny, z okresami remisji, jednak ciężkie postacie wymagają długoterminowego leczenia, które jest utrudnione przez ryzyko augmentacji przy stosowaniu leków dopaminergicznych oraz ograniczone dane dotyczące terapii u dzieci i osób starszych.

Nowoczesne badania genetyczne, obejmujące metaanalizę GWAS na ponad 116 tysiącach pacjentów z RLS i 1,5 mln kontrolach, zidentyfikowały potencjalne cele terapeutyczne oraz czynniki ryzyka, co otwiera perspektywy dla spersonalizowanych interwencji i zapobiegania chorobie. Zaawansowane modele uczenia maszynowego osiągnęły wysoką skuteczność predykcji ryzyka RLS (AUC do 91% dla 5-letniego okna), co może umożliwić wczesną diagnostykę i interwencję. W świetle poważnych konsekwencji zdrowotnych i funkcjonalnych RLS, wczesne rozpoznanie oraz optymalizacja leczenia są kluczowe dla poprawy rokowania i jakości życia pacjentów, a dalsze badania nad nowymi terapiami celowanymi są niezbędne.

Prognoza Zespołu Niespokojnych Nóg (Restless Legs Syndrome)

Wpływ na umieralność
Ryzyko chorób współistniejących
Progresja choroby i ograniczenia funkcjonalne
Specyficzne ograniczenia funkcjonalne
Wyzwania w długoterminowym leczeniu

Postępy w prognozowaniu i leczeniu

Odkrycia genetyczne i ich implikacje
Nowe możliwości w przewidywaniu ryzyka

Wnioski końcowe

Kolejne rozdziały

Prognoza Zespołu Niespokojnych Nóg (Restless Legs Syndrome)

Zespół niespokojnych nóg (RLS, Restless Legs Syndrome) to zaburzenie neurologiczne, które charakteryzuje się nieprzyjemnymi lub bolesnymi odczuciami w nogach oraz nieodpartą potrzebą poruszania kończynami. Symptomy nasilają się podczas bezczynności i w nocy, a częściowa lub całkowita ulga może nastąpić podczas ruchu, jak chodzenie czy rozciąganie nóg. Jednakże ulga jest tymczasowa, a objawy powracają po zaprzestaniu ruchu.¹ Przebieg kliniczny RLS jest zróżnicowany, a okresy remisji są częste, szczególnie u młodszych pacjentów i osób z łagodniejszą postacią choroby. Jednak ciężka postać RLS jest przewlekłym, postępującym zaburzeniem, które może wymagać długoterminowego leczenia.²

Wpływ na umieralność

Badania wykazały istotny związek między RLS a zwiększoną śmiertelnością. W dużej grupie amerykańskich weteranów zaobserwowano, że pacjenci z nowo zdiagnozowanym RLS mieli o 88% wyższe ryzyko zgonu podczas 8-letniego okresu obserwacji.³ Podobnie, w prospektywnym badaniu przeprowadzonym wśród mężczyzn, RLS był związany z wyższą ogólną śmiertelnością, a związek ten był niezależny od znanych czynników ryzyka. Zwiększona śmiertelność u osób z RLS była częściej związana z chorobami układu oddechowego, chorobami endokrynologicznymi, zaburzeniami odżywiania/metabolicznymi oraz zaburzeniami immunologicznymi.⁴

Skorygowany współczynnik ryzyka (HR) całkowitej śmiertelności wynosił 1,92 (95% CI 1,03-3,56) nawet wśród stosunkowo zdrowej grupy, po wykluczeniu mężczyzn z rakiem, chorobą Parkinsona, nadciśnieniem, chorobami układu sercowo-naczyniowego, cukrzycą, zapaleniem stawów, otyłością oraz innymi poważnymi schorzeniami.⁵ Wyniki te podkreślają kliniczne znaczenie RLS jako powszechnego, ale często nierozpoznawanego zaburzenia o poważnych konsekwencjach zdrowotnych.⁶

Ryzyko chorób współistniejących

RLS wiąże się ze zwiększonym ryzykiem rozwoju istotnych chorób współistniejących. Badania wykazały, że pacjenci z nowo zdiagnozowanym RLS mają czterokrotnie wyższe ryzyko wystąpienia choroby wieńcowej serca (CHD) i udaru mózgu w porównaniu do pacjentów bez RLS.⁷ Związek ten został potwierdzony przez liczne obserwacje wskazujące na powiązanie RLS z incydentami CHD i udaru.⁸

Ponadto, badania wykazały silny związek między nowo zdiagnozowanym RLS a wystąpieniem obniżonego współczynnika filtracji kłębuszkowej (eGFR), co wskazuje na zwiększone ryzyko rozwoju przewlekłej choroby nerek (CKD) u pacjentów z RLS, nawet przy prawidłowej wyjściowej funkcji nerek.⁹ W dużej i współczesnej kohorcie amerykańskich weteranów, nowo zdiagnozowany RLS był związany z wyższym ryzykiem śmiertelności, incydentów CHD, udaru mózgu i CKD.¹⁰

Progresja choroby i ograniczenia funkcjonalne

Jeśli choroba postępuje, objawy mogą pojawiać się wcześniej w ciągu dnia i nasilać jeszcze bardziej w nocy i/lub rozszerzać się poza nogi na ramiona lub tułów.¹¹ RLS ma szerokie spektrum nasilenia choroby. Pacjenci z łagodnym RLS mogą odczuwać jego objawy jako jedynie niewielką niedogodność. Jednak ciężki RLS może mieć paraliżujący wpływ na jakość życia. Może uniemożliwiać uczestnictwo w aktywnościach zawodowych lub społecznych oraz obniżać funkcjonowanie i dobrostan emocjonalny.¹²

Zaburzenia snu wywołane przez RLS mogą prowadzić do słabego funkcjonowania w ciągu dnia, lęku i depresji. Faktycznie, deprywacja snu i zmęczenie w ciągu dnia są najczęstszymi powodami, dla których pacjenci z RLS poszukują leczenia.¹³ Badania wykazały, że osoby cierpiące na RLS częściej doświadczają niepełnosprawności funkcjonalnej, nawet po uwzględnieniu stanu zdrowia i korelacji z zespołami bólowymi.¹⁴

Specyficzne ograniczenia funkcjonalne

RLS prognozuje pogorszenie funkcji w wielu domenach, co sugeruje wpływ na zdolność osób do pracy i samodzielnego życia. Osoby z RLS mają zwiększone ryzyko wystąpienia konkretnych ograniczeń funkcjonalnych, takich jak:¹⁵¹⁶

Trudności we wspinaniu się po kilku piętrach schodów (skorygowany współczynnik ryzyka = 2,38, 95% CI 1,39-4,06)
Problemy z długotrwałym siedzeniem (2,17, 1,25-3,75)
Trudności z wstawaniem z krzesła (2,54, 1,62-3,99)
Problemy z pochylaniem się (2,66, 1,71-4,15)
Trudności z przesuwaniem ciężkich przedmiotów (1,79, 1,08-2,99)
Problemy z przenoszeniem dziesięciu funtów (1,61, 1,05-2,97)
Trudności z podnoszeniem ramion (1,76, 1,05-2,97)
Problemy z podnoszeniem drobnych przedmiotów, np. monety (1,97, 1,12-3,46)

¹⁷

Jeśli obserwowane ograniczenia są odwracalne po zastosowaniu odpowiedniego leczenia, wczesne wykrycie i leczenie RLS może pomóc w złagodzeniu funkcjonalnego pogorszenia związanego z RLS.¹⁸

Wyzwania w długoterminowym leczeniu

Głównym celem leczenia RLS jest zarządzanie objawami i poprawa funkcjonowania pacjenta oraz jakości życia.¹⁹ Istnieje jednak znaczna niepewność co do długoterminowych korzyści i szkód związanych z leczeniem RLS. Większość naszej wiedzy na temat skuteczności farmakologicznych metod leczenia RLS pochodzi z krótkoterminowych badań klinicznych. Jednakże choroba ma charakter przewlekły, często wymagający leczenia przez całe życie.²⁰

Długoterminowe opcje leczenia są ograniczone i wymagają częstych dostosowań ze względu na działania niepożądane.²¹ Długotrwałe leczenie środkami dopaminergicznymi może prowadzić do paradoksalnego nasilenia objawów znanego jako augmentacja, która jest istotnym powikłaniem.²² Augmentacja może wystąpić w ciągu pierwszych 2 lat leczenia, a czasem wiele lat po rozpoczęciu terapii.²³

Dla pacjentów cierpiących na ciężką postać RLS, kluczową kwestią jest identyfikacja opcji leczenia o największych długoterminowych korzyściach i najmniejszych szkodach. Leczenie dzieci i osób starszych z RLS stanowi szczególne wyzwanie. Nie znamy wpływu długotrwałego stosowania tych leków u dzieci. Nie znamy również stosunku ryzyka do korzyści tych leków dla osób starszych, które przyjmują kilka leków z powodu współwystępowania wielu chorób.²⁴

Postępy w prognozowaniu i leczeniu

Odkrycia genetyczne i ich implikacje

Zespół niespokojnych nóg dotyka do 10% osób starszych. Ich opieka zdrowotna jest utrudniona przez opóźnioną diagnozę i niewystarczające leczenie.²⁵ Najnowsze badania genetyczne oferują nową nadzieję dla pacjentów z RLS. Naukowcy z Helmholtz Munich i Uniwersytetu Technicznego w Monachium, wraz z międzynarodowymi współpracownikami, przeprowadzili największe dotychczas badanie genetyczne zespołu niespokojnych nóg.²⁶

W ramach metaanaliz badań asocjacji całego genomu przeprowadzonych na 116 647 osobach z RLS (przypadki) i 1 546 466 kontrolach pochodzenia europejskiego, badacze zidentyfikowali cele do opracowania leków i ich ponownego wykorzystania, priorytetowo potraktowali potencjalne związki przyczynowe między RLS a istotnymi chorobami współistniejącymi i czynnikami ryzyka do dalszych badań oraz dostarczyli dowodów, że nieliniowe interakcje są prawdopodobnie istotne dla przewidywania ryzyka RLS.²⁷

Badania podkreślają znaczenie śledzenia ekspozycji środowiskowych u osób genetycznie podatnych i mogą motywować do ponownej interpretacji wcześniejszych obserwacji w RLS, na przykład potencjalnego wpływu rodności na wyższą częstość występowania u kobiet.²⁸ Badacze zidentyfikowali kilka genów, które są potencjalnymi celami leków i w niektórych przypadkach są już celami znanych leków.²⁹

Nowe możliwości w przewidywaniu ryzyka

Przewidywanie prawdopodobieństwa rozwoju RLS ma kluczowe znaczenie dla ukierunkowanych strategii zapobiegania chorobie.³⁰ Odkrycia te mają potencjał znaczącego wpływu na życie milionów pacjentów z RLS, oferując ścieżkę w kierunku opracowania ulepszonych, spersonalizowanych interwencji mających na celu efektywne leczenie, a nawet zapobieganie chorobie.³¹

Najnowsze badania z wykorzystaniem zaawansowanych modeli uczenia maszynowego wykazały doskonałe wyniki w przewidywaniu ryzyka RLS. Modele te pokazały lepszą wydajność w porównaniu do prostych modeli opartych wyłącznie na wieloczynnikowej skali ryzyka (PRS) lub modeli PRS z interakcjami liniowymi.³² Badaczom udało się osiągnąć AUC (obszar pod krzywą) do 91% dla 5-letniego okna predykcyjnego za pomocą podejść uczenia maszynowego. Wyniki te zostały zwalidowane w badaniu INTERVAL, gdzie wydajność była porównywalna, z AUC sięgającym do 87%.³³

Profesor Juliane Winkelmann, kluczowa naukowiec prowadząca badania nad genetyką RLS od ponad 25 lat, stwierdza: „Po raz pierwszy osiągnęliśmy zdolność do wystarczającej oceny ryzyka RLS. To była długa podróż, ale teraz mamy możliwość nie tylko leczyć, ale także uczyć się, jak zapobiegać temu schorzeniu”.³⁴

Wnioski końcowe

Zespół niespokojnych nóg (RLS) ma istotny wpływ na długoterminowe rokowanie pacjentów. Badania konsekwentnie wykazują związek RLS ze zwiększoną śmiertelnością, wyższym ryzykiem chorób sercowo-naczyniowych, udarów i przewlekłej choroby nerek. RLS wpływa również na funkcjonalne zdolności pacjentów, przyczyniając się do różnorodnych ograniczeń fizycznych, które mogą wpływać na ich zdolność do niezależnego życia i pracy.³⁵³⁶³⁷

Wyzwania związane z długoterminowym leczeniem, w tym ryzyko augmentacji przy stosowaniu leków dopaminergicznych, podkreślają potrzebę ciągłych badań nad nowymi opcjami terapeutycznymi. Niedawne odkrycia genetyczne oferują obiecujące perspektywy, zarówno w zakresie przewidywania ryzyka, jak i opracowywania nowych terapii celowanych.³⁸³⁹

Wczesne wykrycie i odpowiednie leczenie RLS jest kluczowe, ponieważ obserwowane ograniczenia funkcjonalne mogą być odwracalne przy właściwej interwencji. Biorąc pod uwagę przewlekły charakter choroby i jej wpływ na jakość życia, zrozumienie długoterminowego rokowania RLS ma zasadnicze znaczenie dla poprawy opieki nad pacjentami i potencjalnie zapobiegania niekorzystnym wynikom zdrowotnym.⁴⁰⁴¹

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Materiały źródłowe

#1 Comparative Effectiveness of Treatments for Restless Legs Syndrome | Effective Health Care (EHC) Program
https://effectivehealthcare.ahrq.gov/products/restless-legs/research-protocol
Restless legs syndrome (RLS) or Willis-Ekbom disease is a neurological disorder that causes unpleasant or painful sensations within the legs and a distressing, irresistible urge to move the legs. RLS symptoms worsen during inactivity and at night. Partial or complete relief may result from movement such as walking, stretching, or bending of the legs. Such relief is temporary, however, and symptoms return when movement ceases. If the disease progresses, symptoms may occur earlier in the day and intensify even further at night and/or extend beyond the legs to the arms or trunk. The clinical course of RLS varies; periods of remission are common, particularly in younger patients and those with milder disease. Severe restless legs syndrome, however, is a chronic progressive disorder that may require long-term treatment.
#2 Comparative Effectiveness of Treatments for Restless Legs Syndrome | Effective Health Care (EHC) Program
https://effectivehealthcare.ahrq.gov/products/restless-legs/research-protocol
Restless legs syndrome (RLS) or Willis-Ekbom disease is a neurological disorder that causes unpleasant or painful sensations within the legs and a distressing, irresistible urge to move the legs. RLS symptoms worsen during inactivity and at night. Partial or complete relief may result from movement such as walking, stretching, or bending of the legs. Such relief is temporary, however, and symptoms return when movement ceases. If the disease progresses, symptoms may occur earlier in the day and intensify even further at night and/or extend beyond the legs to the arms or trunk. The clinical course of RLS varies; periods of remission are common, particularly in younger patients and those with milder disease. Severe restless legs syndrome, however, is a chronic progressive disorder that may require long-term treatment.
#3 Association of Incident Restless Legs Syndrome with Outcomes in a Large Cohort of US Veterans
https://pmc.ncbi.nlm.nih.gov/articles/PMC4795990/
Restless Legs Syndrome (RLS) is a common sleep disorder, but there is a paucity of large cohort studies examining the association of RLS with clinical outcomes including all-cause mortality, incident coronary heart disease (CHD), stroke and chronic kidney disease (CKD). […] In this large and contemporary cohort of US veterans, incident RLS was associated with higher risk of mortality, incident CHD, stroke and CKD. […] In a large cohort of US veterans with baseline eGFR 60 ml/min/1.73m2, we examined the association of incident RLS with higher risk of all-cause mortality, incident CHD and stroke, and incident eGFR 60 ml/min/1.73m2. Incident RLS was associated with substantially higher risk of all examined clinical outcomes in this well-balanced propensity-matched cohort. […] In this large cohort study, incident RLS was associated with an 88% higher risk of mortality during a median 8-year follow-up period.
#4 Prospective study of restless legs syndrome and mortality among men
https://pmc.ncbi.nlm.nih.gov/articles/PMC3770202/
We observed that men with RLS had a higher overall mortality and this association was independent of known risk factors. […] The increased mortality in RLS was more frequently associated with respiratory disease, endocrine disease, nutritional/metabolic disease, and immunologic disorders. […] The multivariable adjusted HR of total mortality was 1.92 (95% CI 1.033.56) among a relatively healthy group, after we excluded men with cancer, PD, high blood pressure, CVD, diabetes, arthritis, obesity, snoring every night, cancer, emphysema or chronic bronchitis, chronic obstructive pulmonary disease, pneumonia, asthma, pernicious anemia, ulcerative colitis or Crohn disease, and renal failure. […] The results of this study indicate that men with RLS had a higher overall mortality, which highlights the clinical importance of RLS, a common but underrecognized disorder.
#5 Prospective study of restless legs syndrome and mortality among men
https://pmc.ncbi.nlm.nih.gov/articles/PMC3770202/
We observed that men with RLS had a higher overall mortality and this association was independent of known risk factors. […] The increased mortality in RLS was more frequently associated with respiratory disease, endocrine disease, nutritional/metabolic disease, and immunologic disorders. […] The multivariable adjusted HR of total mortality was 1.92 (95% CI 1.033.56) among a relatively healthy group, after we excluded men with cancer, PD, high blood pressure, CVD, diabetes, arthritis, obesity, snoring every night, cancer, emphysema or chronic bronchitis, chronic obstructive pulmonary disease, pneumonia, asthma, pernicious anemia, ulcerative colitis or Crohn disease, and renal failure. […] The results of this study indicate that men with RLS had a higher overall mortality, which highlights the clinical importance of RLS, a common but underrecognized disorder.
#6 Prospective study of restless legs syndrome and mortality among men
https://pmc.ncbi.nlm.nih.gov/articles/PMC3770202/
We observed that men with RLS had a higher overall mortality and this association was independent of known risk factors. […] The increased mortality in RLS was more frequently associated with respiratory disease, endocrine disease, nutritional/metabolic disease, and immunologic disorders. […] The multivariable adjusted HR of total mortality was 1.92 (95% CI 1.033.56) among a relatively healthy group, after we excluded men with cancer, PD, high blood pressure, CVD, diabetes, arthritis, obesity, snoring every night, cancer, emphysema or chronic bronchitis, chronic obstructive pulmonary disease, pneumonia, asthma, pernicious anemia, ulcerative colitis or Crohn disease, and renal failure. […] The results of this study indicate that men with RLS had a higher overall mortality, which highlights the clinical importance of RLS, a common but underrecognized disorder.
#7 Association of Incident Restless Legs Syndrome with Outcomes in a Large Cohort of US Veterans
https://pmc.ncbi.nlm.nih.gov/articles/PMC4795990/
The incident CHD and stroke risk were 4 times higher in incident RLS patients compared to patients without RLS in our cohort. […] Our results confirm previous observations implicating RLS with incident CHD and stroke. […] We report strong associations of incident RLS with incident low eGFR for the first time in a population with normal eGFR at baseline. […] In our large and contemporary cohort of US veterans, incident RLS was associated with higher risk of mortality, incident CHD, stroke and CKD.
#8 Association of Incident Restless Legs Syndrome with Outcomes in a Large Cohort of US Veterans
https://pmc.ncbi.nlm.nih.gov/articles/PMC4795990/
The incident CHD and stroke risk were 4 times higher in incident RLS patients compared to patients without RLS in our cohort. […] Our results confirm previous observations implicating RLS with incident CHD and stroke. […] We report strong associations of incident RLS with incident low eGFR for the first time in a population with normal eGFR at baseline. […] In our large and contemporary cohort of US veterans, incident RLS was associated with higher risk of mortality, incident CHD, stroke and CKD.
#9 Association of Incident Restless Legs Syndrome with Outcomes in a Large Cohort of US Veterans
https://pmc.ncbi.nlm.nih.gov/articles/PMC4795990/
The incident CHD and stroke risk were 4 times higher in incident RLS patients compared to patients without RLS in our cohort. […] Our results confirm previous observations implicating RLS with incident CHD and stroke. […] We report strong associations of incident RLS with incident low eGFR for the first time in a population with normal eGFR at baseline. […] In our large and contemporary cohort of US veterans, incident RLS was associated with higher risk of mortality, incident CHD, stroke and CKD.
#10 Association of Incident Restless Legs Syndrome with Outcomes in a Large Cohort of US Veterans
https://pmc.ncbi.nlm.nih.gov/articles/PMC4795990/
The incident CHD and stroke risk were 4 times higher in incident RLS patients compared to patients without RLS in our cohort. […] Our results confirm previous observations implicating RLS with incident CHD and stroke. […] We report strong associations of incident RLS with incident low eGFR for the first time in a population with normal eGFR at baseline. […] In our large and contemporary cohort of US veterans, incident RLS was associated with higher risk of mortality, incident CHD, stroke and CKD.
#11 Comparative Effectiveness of Treatments for Restless Legs Syndrome | Effective Health Care (EHC) Program
https://effectivehealthcare.ahrq.gov/products/restless-legs/research-protocol
Restless legs syndrome (RLS) or Willis-Ekbom disease is a neurological disorder that causes unpleasant or painful sensations within the legs and a distressing, irresistible urge to move the legs. RLS symptoms worsen during inactivity and at night. Partial or complete relief may result from movement such as walking, stretching, or bending of the legs. Such relief is temporary, however, and symptoms return when movement ceases. If the disease progresses, symptoms may occur earlier in the day and intensify even further at night and/or extend beyond the legs to the arms or trunk. The clinical course of RLS varies; periods of remission are common, particularly in younger patients and those with milder disease. Severe restless legs syndrome, however, is a chronic progressive disorder that may require long-term treatment.
#12 Comparative Effectiveness of Treatments for Restless Legs Syndrome | Effective Health Care (EHC) Program
https://effectivehealthcare.ahrq.gov/products/restless-legs/research-protocol
RLS has a wide spectrum of disease severity. Patients with mild RLS may experience its symptoms as only a minor annoyance. However, severe RLS can have a crippling impact on quality of life. It can prevent participation in occupational or social activities, and reduce function and emotional well-being. RLS-induced sleep disruption may lead to poor daytime functioning, anxiety, and depression. Indeed, sleep deprivation and daytime fatigue are the most common reasons RLS patients seek treatment. […] The primary goal of RLS treatment is to manage symptoms and improve patient function and quality of life. […] Long-term treatment with dopaminergic agents can lead to a paradoxical worsening of symptoms known as augmentation, which is a significant complication. […] Substantial uncertainty exists about the long-term benefits and harms of treatments for RLS. Most of what we know about the effectiveness of pharmacological treatments for RLS comes from short-term clinical trials. Yet, the disease is chronic, often requiring life-long treatment. Furthermore, augmentation, a treatment-induced exacerbation of symptoms in response to dopaminergic therapy, can occur during the first 2 years of treatment and sometimes many years into treatment.
#13 Comparative Effectiveness of Treatments for Restless Legs Syndrome | Effective Health Care (EHC) Program
https://effectivehealthcare.ahrq.gov/products/restless-legs/research-protocol
RLS has a wide spectrum of disease severity. Patients with mild RLS may experience its symptoms as only a minor annoyance. However, severe RLS can have a crippling impact on quality of life. It can prevent participation in occupational or social activities, and reduce function and emotional well-being. RLS-induced sleep disruption may lead to poor daytime functioning, anxiety, and depression. Indeed, sleep deprivation and daytime fatigue are the most common reasons RLS patients seek treatment. […] The primary goal of RLS treatment is to manage symptoms and improve patient function and quality of life. […] Long-term treatment with dopaminergic agents can lead to a paradoxical worsening of symptoms known as augmentation, which is a significant complication. […] Substantial uncertainty exists about the long-term benefits and harms of treatments for RLS. Most of what we know about the effectiveness of pharmacological treatments for RLS comes from short-term clinical trials. Yet, the disease is chronic, often requiring life-long treatment. Furthermore, augmentation, a treatment-induced exacerbation of symptoms in response to dopaminergic therapy, can occur during the first 2 years of treatment and sometimes many years into treatment.
#14 Restless legs syndrome and functional limitations among American elders in the Health and Retirement Study | BMC Geriatrics | Full Text
https://bmcgeriatr.biomedcentral.com/articles/10.1186/1471-2318-12-39
RLS did not predict incident disability for aggregate measures but was associated with increased risk for specific limitations, including: difficulty climbing several stair flights (multivariate-adjusted hazard ratio=2.38, 95% CI 1.39-4.06), prolonged sitting (2.17, 1.25-3.75), rising from a chair (2.54, 1.62-3.99), stooping (2.66, 1.71-4.15), moving heavy objects (1.79, 1.08-2.99), carrying ten pounds (1.61, 1.05-2.97), raising arms (1.76, 1.05-2.97), or picking up a dime (1.97, 1.12-3.46). […] RLS sufferers are more likely to have functional disability, even after adjusting for health status and pain syndrome correlates. […] RLS did predict increases in some specific functions, including difficulties: climbing several stair flights; raising from a chair; sitting prolonged periods; stooping or kneeling; pushing or pulling large objects; picking up a dime; lifting 10lb; or reaching arms up). […] RLS predicted functional decline in multiple domains, which suggests an impact on subjects abilities to work and live independently. If the observed limitations are reversible when appropriate treatment is given, early detection and treatment of RLS may help remediate RLS functional decline.
#15 Restless legs syndrome and functional limitations among American elders in the Health and Retirement Study | BMC Geriatrics | Full Text
https://bmcgeriatr.biomedcentral.com/articles/10.1186/1471-2318-12-39
RLS did not predict incident disability for aggregate measures but was associated with increased risk for specific limitations, including: difficulty climbing several stair flights (multivariate-adjusted hazard ratio=2.38, 95% CI 1.39-4.06), prolonged sitting (2.17, 1.25-3.75), rising from a chair (2.54, 1.62-3.99), stooping (2.66, 1.71-4.15), moving heavy objects (1.79, 1.08-2.99), carrying ten pounds (1.61, 1.05-2.97), raising arms (1.76, 1.05-2.97), or picking up a dime (1.97, 1.12-3.46). […] RLS sufferers are more likely to have functional disability, even after adjusting for health status and pain syndrome correlates. […] RLS did predict increases in some specific functions, including difficulties: climbing several stair flights; raising from a chair; sitting prolonged periods; stooping or kneeling; pushing or pulling large objects; picking up a dime; lifting 10lb; or reaching arms up). […] RLS predicted functional decline in multiple domains, which suggests an impact on subjects abilities to work and live independently. If the observed limitations are reversible when appropriate treatment is given, early detection and treatment of RLS may help remediate RLS functional decline.
#16 Restless legs syndrome and functional limitations among American elders in the Health and Retirement Study | BMC Geriatrics | Full Text
https://bmcgeriatr.biomedcentral.com/articles/10.1186/1471-2318-12-39
RLS did not predict incident disability for aggregate measures but was associated with increased risk for specific limitations, including: difficulty climbing several stair flights (multivariate-adjusted hazard ratio=2.38, 95% CI 1.39-4.06), prolonged sitting (2.17, 1.25-3.75), rising from a chair (2.54, 1.62-3.99), stooping (2.66, 1.71-4.15), moving heavy objects (1.79, 1.08-2.99), carrying ten pounds (1.61, 1.05-2.97), raising arms (1.76, 1.05-2.97), or picking up a dime (1.97, 1.12-3.46). […] RLS sufferers are more likely to have functional disability, even after adjusting for health status and pain syndrome correlates. […] RLS did predict increases in some specific functions, including difficulties: climbing several stair flights; raising from a chair; sitting prolonged periods; stooping or kneeling; pushing or pulling large objects; picking up a dime; lifting 10lb; or reaching arms up). […] RLS predicted functional decline in multiple domains, which suggests an impact on subjects abilities to work and live independently. If the observed limitations are reversible when appropriate treatment is given, early detection and treatment of RLS may help remediate RLS functional decline.
#17 Restless legs syndrome and functional limitations among American elders in the Health and Retirement Study | BMC Geriatrics | Full Text
https://bmcgeriatr.biomedcentral.com/articles/10.1186/1471-2318-12-39
RLS did not predict incident disability for aggregate measures but was associated with increased risk for specific limitations, including: difficulty climbing several stair flights (multivariate-adjusted hazard ratio=2.38, 95% CI 1.39-4.06), prolonged sitting (2.17, 1.25-3.75), rising from a chair (2.54, 1.62-3.99), stooping (2.66, 1.71-4.15), moving heavy objects (1.79, 1.08-2.99), carrying ten pounds (1.61, 1.05-2.97), raising arms (1.76, 1.05-2.97), or picking up a dime (1.97, 1.12-3.46). […] RLS sufferers are more likely to have functional disability, even after adjusting for health status and pain syndrome correlates. […] RLS did predict increases in some specific functions, including difficulties: climbing several stair flights; raising from a chair; sitting prolonged periods; stooping or kneeling; pushing or pulling large objects; picking up a dime; lifting 10lb; or reaching arms up). […] RLS predicted functional decline in multiple domains, which suggests an impact on subjects abilities to work and live independently. If the observed limitations are reversible when appropriate treatment is given, early detection and treatment of RLS may help remediate RLS functional decline.
#18 Restless legs syndrome and functional limitations among American elders in the Health and Retirement Study | BMC Geriatrics | Full Text
https://bmcgeriatr.biomedcentral.com/articles/10.1186/1471-2318-12-39
RLS did not predict incident disability for aggregate measures but was associated with increased risk for specific limitations, including: difficulty climbing several stair flights (multivariate-adjusted hazard ratio=2.38, 95% CI 1.39-4.06), prolonged sitting (2.17, 1.25-3.75), rising from a chair (2.54, 1.62-3.99), stooping (2.66, 1.71-4.15), moving heavy objects (1.79, 1.08-2.99), carrying ten pounds (1.61, 1.05-2.97), raising arms (1.76, 1.05-2.97), or picking up a dime (1.97, 1.12-3.46). […] RLS sufferers are more likely to have functional disability, even after adjusting for health status and pain syndrome correlates. […] RLS did predict increases in some specific functions, including difficulties: climbing several stair flights; raising from a chair; sitting prolonged periods; stooping or kneeling; pushing or pulling large objects; picking up a dime; lifting 10lb; or reaching arms up). […] RLS predicted functional decline in multiple domains, which suggests an impact on subjects abilities to work and live independently. If the observed limitations are reversible when appropriate treatment is given, early detection and treatment of RLS may help remediate RLS functional decline.
#19 Comparative Effectiveness of Treatments for Restless Legs Syndrome | Effective Health Care (EHC) Program
https://effectivehealthcare.ahrq.gov/products/restless-legs/research-protocol
RLS has a wide spectrum of disease severity. Patients with mild RLS may experience its symptoms as only a minor annoyance. However, severe RLS can have a crippling impact on quality of life. It can prevent participation in occupational or social activities, and reduce function and emotional well-being. RLS-induced sleep disruption may lead to poor daytime functioning, anxiety, and depression. Indeed, sleep deprivation and daytime fatigue are the most common reasons RLS patients seek treatment. […] The primary goal of RLS treatment is to manage symptoms and improve patient function and quality of life. […] Long-term treatment with dopaminergic agents can lead to a paradoxical worsening of symptoms known as augmentation, which is a significant complication. […] Substantial uncertainty exists about the long-term benefits and harms of treatments for RLS. Most of what we know about the effectiveness of pharmacological treatments for RLS comes from short-term clinical trials. Yet, the disease is chronic, often requiring life-long treatment. Furthermore, augmentation, a treatment-induced exacerbation of symptoms in response to dopaminergic therapy, can occur during the first 2 years of treatment and sometimes many years into treatment.
#20 Comparative Effectiveness of Treatments for Restless Legs Syndrome | Effective Health Care (EHC) Program
https://effectivehealthcare.ahrq.gov/products/restless-legs/research-protocol
RLS has a wide spectrum of disease severity. Patients with mild RLS may experience its symptoms as only a minor annoyance. However, severe RLS can have a crippling impact on quality of life. It can prevent participation in occupational or social activities, and reduce function and emotional well-being. RLS-induced sleep disruption may lead to poor daytime functioning, anxiety, and depression. Indeed, sleep deprivation and daytime fatigue are the most common reasons RLS patients seek treatment. […] The primary goal of RLS treatment is to manage symptoms and improve patient function and quality of life. […] Long-term treatment with dopaminergic agents can lead to a paradoxical worsening of symptoms known as augmentation, which is a significant complication. […] Substantial uncertainty exists about the long-term benefits and harms of treatments for RLS. Most of what we know about the effectiveness of pharmacological treatments for RLS comes from short-term clinical trials. Yet, the disease is chronic, often requiring life-long treatment. Furthermore, augmentation, a treatment-induced exacerbation of symptoms in response to dopaminergic therapy, can occur during the first 2 years of treatment and sometimes many years into treatment.
#21 Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction | Nature Genetics
https://www.nature.com/articles/s41588-024-01763-1
Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. […] In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction. […] Long-term treatment options are scarce and require frequent adjustment due to side effects. […] Our analyses emphasize the importance of tracking environmental exposures in genetically susceptible individuals and may motivate re-interpretation of previous observations in RLS, for example, of parity potentially driving the higher prevalence observed in women.
#22 Comparative Effectiveness of Treatments for Restless Legs Syndrome | Effective Health Care (EHC) Program
https://effectivehealthcare.ahrq.gov/products/restless-legs/research-protocol
RLS has a wide spectrum of disease severity. Patients with mild RLS may experience its symptoms as only a minor annoyance. However, severe RLS can have a crippling impact on quality of life. It can prevent participation in occupational or social activities, and reduce function and emotional well-being. RLS-induced sleep disruption may lead to poor daytime functioning, anxiety, and depression. Indeed, sleep deprivation and daytime fatigue are the most common reasons RLS patients seek treatment. […] The primary goal of RLS treatment is to manage symptoms and improve patient function and quality of life. […] Long-term treatment with dopaminergic agents can lead to a paradoxical worsening of symptoms known as augmentation, which is a significant complication. […] Substantial uncertainty exists about the long-term benefits and harms of treatments for RLS. Most of what we know about the effectiveness of pharmacological treatments for RLS comes from short-term clinical trials. Yet, the disease is chronic, often requiring life-long treatment. Furthermore, augmentation, a treatment-induced exacerbation of symptoms in response to dopaminergic therapy, can occur during the first 2 years of treatment and sometimes many years into treatment.
#23 Comparative Effectiveness of Treatments for Restless Legs Syndrome | Effective Health Care (EHC) Program
https://effectivehealthcare.ahrq.gov/products/restless-legs/research-protocol
RLS has a wide spectrum of disease severity. Patients with mild RLS may experience its symptoms as only a minor annoyance. However, severe RLS can have a crippling impact on quality of life. It can prevent participation in occupational or social activities, and reduce function and emotional well-being. RLS-induced sleep disruption may lead to poor daytime functioning, anxiety, and depression. Indeed, sleep deprivation and daytime fatigue are the most common reasons RLS patients seek treatment. […] The primary goal of RLS treatment is to manage symptoms and improve patient function and quality of life. […] Long-term treatment with dopaminergic agents can lead to a paradoxical worsening of symptoms known as augmentation, which is a significant complication. […] Substantial uncertainty exists about the long-term benefits and harms of treatments for RLS. Most of what we know about the effectiveness of pharmacological treatments for RLS comes from short-term clinical trials. Yet, the disease is chronic, often requiring life-long treatment. Furthermore, augmentation, a treatment-induced exacerbation of symptoms in response to dopaminergic therapy, can occur during the first 2 years of treatment and sometimes many years into treatment.
#24 Comparative Effectiveness of Treatments for Restless Legs Syndrome | Effective Health Care (EHC) Program
https://effectivehealthcare.ahrq.gov/products/restless-legs/research-protocol
We will systematically review the literature to assess the benefits and harms of treatment, especially long-term outcomes. We will evaluate methods used to define RLS, assess its severity, and measure treatment benefits and harms. Further, we will identify gaps in the available evidence and develop a future research agenda. […] For patients suffering from severe RLS, the critical issue is how to identify the treatment options with the greatest long-term benefits and the least harms. Treating children and older adults with RLS presents specific challenges. We do not know the impact of long-term use of these drugs in children. Neither do we know the risks/benefits of the drugs for older adults who take several medications for multimorbidities.
#25 Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction | Nature Genetics
https://www.nature.com/articles/s41588-024-01763-1
Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. […] In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction. […] Long-term treatment options are scarce and require frequent adjustment due to side effects. […] Our analyses emphasize the importance of tracking environmental exposures in genetically susceptible individuals and may motivate re-interpretation of previous observations in RLS, for example, of parity potentially driving the higher prevalence observed in women.
#26 Restless Legs Syndrome: Genetic Discoveries Advance Treatment and Risk Prediction
https://www.helmholtz-munich.de/en/newsroom/news-all/artikel/restless-legs-syndrome-genetic-discoveries-advance-treatment-and-risk-prediction
Researchers at Helmholtz Munich and the Technical University of Munich (TUM) together with international collaborators have conducted the largest genetic investigation of the restless legs syndrome to date. […] The findings of this study have the potential to significantly influence the lives of millions of RLS patients, offering a pathway towards the development of enhanced, personalized interventions aimed at effectively treating or even preemptively addressing the disease. […] For the first time, we achieved the ability to sufficiently assess the risk for RLS. It has been a long journey, but now we are empowered to not only treat but to learn how to prevent this condition, says Juliane Winkelmann, who has been a key scientist driving research on the genetics of RLS for more than 25 years.
#27 Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction | Nature Genetics
https://www.nature.com/articles/s41588-024-01763-1
Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. […] In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction. […] Long-term treatment options are scarce and require frequent adjustment due to side effects. […] Our analyses emphasize the importance of tracking environmental exposures in genetically susceptible individuals and may motivate re-interpretation of previous observations in RLS, for example, of parity potentially driving the higher prevalence observed in women.
#28 Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction | Nature Genetics
https://www.nature.com/articles/s41588-024-01763-1
Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. […] In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction. […] Long-term treatment options are scarce and require frequent adjustment due to side effects. […] Our analyses emphasize the importance of tracking environmental exposures in genetically susceptible individuals and may motivate re-interpretation of previous observations in RLS, for example, of parity potentially driving the higher prevalence observed in women.
#29 Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction | Nature Genetics
https://www.nature.com/articles/s41588-024-01763-1
Our study provides discoveries relevant for advancing clinical care in RLS. We identified several genes that are druggable and in some cases targets of known drugs. […] Predicting the likelihood of developing RLS is crucial for targeted disease-prevention strategies. […] The latter showed superior performance compared to simple PRS-only or PRS-plus-linear interactions models. […] We were able to achieve an AUC of up to 91% for the 5-year prediction window with the machine learning approaches and validated our results in the INTERVAL study, where the performance was comparable with an AUC of up to 87%.
#30 Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction | Nature Genetics
https://www.nature.com/articles/s41588-024-01763-1
Our study provides discoveries relevant for advancing clinical care in RLS. We identified several genes that are druggable and in some cases targets of known drugs. […] Predicting the likelihood of developing RLS is crucial for targeted disease-prevention strategies. […] The latter showed superior performance compared to simple PRS-only or PRS-plus-linear interactions models. […] We were able to achieve an AUC of up to 91% for the 5-year prediction window with the machine learning approaches and validated our results in the INTERVAL study, where the performance was comparable with an AUC of up to 87%.
#31 Restless Legs Syndrome: Genetic Discoveries Advance Treatment and Risk Prediction
https://www.helmholtz-munich.de/en/newsroom/news-all/artikel/restless-legs-syndrome-genetic-discoveries-advance-treatment-and-risk-prediction
Researchers at Helmholtz Munich and the Technical University of Munich (TUM) together with international collaborators have conducted the largest genetic investigation of the restless legs syndrome to date. […] The findings of this study have the potential to significantly influence the lives of millions of RLS patients, offering a pathway towards the development of enhanced, personalized interventions aimed at effectively treating or even preemptively addressing the disease. […] For the first time, we achieved the ability to sufficiently assess the risk for RLS. It has been a long journey, but now we are empowered to not only treat but to learn how to prevent this condition, says Juliane Winkelmann, who has been a key scientist driving research on the genetics of RLS for more than 25 years.
#32 Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction | Nature Genetics
https://www.nature.com/articles/s41588-024-01763-1
Our study provides discoveries relevant for advancing clinical care in RLS. We identified several genes that are druggable and in some cases targets of known drugs. […] Predicting the likelihood of developing RLS is crucial for targeted disease-prevention strategies. […] The latter showed superior performance compared to simple PRS-only or PRS-plus-linear interactions models. […] We were able to achieve an AUC of up to 91% for the 5-year prediction window with the machine learning approaches and validated our results in the INTERVAL study, where the performance was comparable with an AUC of up to 87%.
#33 Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction | Nature Genetics
https://www.nature.com/articles/s41588-024-01763-1
Our study provides discoveries relevant for advancing clinical care in RLS. We identified several genes that are druggable and in some cases targets of known drugs. […] Predicting the likelihood of developing RLS is crucial for targeted disease-prevention strategies. […] The latter showed superior performance compared to simple PRS-only or PRS-plus-linear interactions models. […] We were able to achieve an AUC of up to 91% for the 5-year prediction window with the machine learning approaches and validated our results in the INTERVAL study, where the performance was comparable with an AUC of up to 87%.
#34 Restless Legs Syndrome: Genetic Discoveries Advance Treatment and Risk Prediction
https://www.helmholtz-munich.de/en/newsroom/news-all/artikel/restless-legs-syndrome-genetic-discoveries-advance-treatment-and-risk-prediction
Researchers at Helmholtz Munich and the Technical University of Munich (TUM) together with international collaborators have conducted the largest genetic investigation of the restless legs syndrome to date. […] The findings of this study have the potential to significantly influence the lives of millions of RLS patients, offering a pathway towards the development of enhanced, personalized interventions aimed at effectively treating or even preemptively addressing the disease. […] For the first time, we achieved the ability to sufficiently assess the risk for RLS. It has been a long journey, but now we are empowered to not only treat but to learn how to prevent this condition, says Juliane Winkelmann, who has been a key scientist driving research on the genetics of RLS for more than 25 years.
#35 Prospective study of restless legs syndrome and mortality among men
https://pmc.ncbi.nlm.nih.gov/articles/PMC3770202/
We observed that men with RLS had a higher overall mortality and this association was independent of known risk factors. […] The increased mortality in RLS was more frequently associated with respiratory disease, endocrine disease, nutritional/metabolic disease, and immunologic disorders. […] The multivariable adjusted HR of total mortality was 1.92 (95% CI 1.033.56) among a relatively healthy group, after we excluded men with cancer, PD, high blood pressure, CVD, diabetes, arthritis, obesity, snoring every night, cancer, emphysema or chronic bronchitis, chronic obstructive pulmonary disease, pneumonia, asthma, pernicious anemia, ulcerative colitis or Crohn disease, and renal failure. […] The results of this study indicate that men with RLS had a higher overall mortality, which highlights the clinical importance of RLS, a common but underrecognized disorder.
#36 Association of Incident Restless Legs Syndrome with Outcomes in a Large Cohort of US Veterans
https://pmc.ncbi.nlm.nih.gov/articles/PMC4795990/
Restless Legs Syndrome (RLS) is a common sleep disorder, but there is a paucity of large cohort studies examining the association of RLS with clinical outcomes including all-cause mortality, incident coronary heart disease (CHD), stroke and chronic kidney disease (CKD). […] In this large and contemporary cohort of US veterans, incident RLS was associated with higher risk of mortality, incident CHD, stroke and CKD. […] In a large cohort of US veterans with baseline eGFR 60 ml/min/1.73m2, we examined the association of incident RLS with higher risk of all-cause mortality, incident CHD and stroke, and incident eGFR 60 ml/min/1.73m2. Incident RLS was associated with substantially higher risk of all examined clinical outcomes in this well-balanced propensity-matched cohort. […] In this large cohort study, incident RLS was associated with an 88% higher risk of mortality during a median 8-year follow-up period.
#37 Restless legs syndrome and functional limitations among American elders in the Health and Retirement Study | BMC Geriatrics | Full Text
https://bmcgeriatr.biomedcentral.com/articles/10.1186/1471-2318-12-39
RLS did not predict incident disability for aggregate measures but was associated with increased risk for specific limitations, including: difficulty climbing several stair flights (multivariate-adjusted hazard ratio=2.38, 95% CI 1.39-4.06), prolonged sitting (2.17, 1.25-3.75), rising from a chair (2.54, 1.62-3.99), stooping (2.66, 1.71-4.15), moving heavy objects (1.79, 1.08-2.99), carrying ten pounds (1.61, 1.05-2.97), raising arms (1.76, 1.05-2.97), or picking up a dime (1.97, 1.12-3.46). […] RLS sufferers are more likely to have functional disability, even after adjusting for health status and pain syndrome correlates. […] RLS did predict increases in some specific functions, including difficulties: climbing several stair flights; raising from a chair; sitting prolonged periods; stooping or kneeling; pushing or pulling large objects; picking up a dime; lifting 10lb; or reaching arms up). […] RLS predicted functional decline in multiple domains, which suggests an impact on subjects abilities to work and live independently. If the observed limitations are reversible when appropriate treatment is given, early detection and treatment of RLS may help remediate RLS functional decline.
#38 Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction | Nature Genetics
https://www.nature.com/articles/s41588-024-01763-1
Our study provides discoveries relevant for advancing clinical care in RLS. We identified several genes that are druggable and in some cases targets of known drugs. […] Predicting the likelihood of developing RLS is crucial for targeted disease-prevention strategies. […] The latter showed superior performance compared to simple PRS-only or PRS-plus-linear interactions models. […] We were able to achieve an AUC of up to 91% for the 5-year prediction window with the machine learning approaches and validated our results in the INTERVAL study, where the performance was comparable with an AUC of up to 87%.
#39 Restless Legs Syndrome: Genetic Discoveries Advance Treatment and Risk Prediction
https://www.helmholtz-munich.de/en/newsroom/news-all/artikel/restless-legs-syndrome-genetic-discoveries-advance-treatment-and-risk-prediction
Researchers at Helmholtz Munich and the Technical University of Munich (TUM) together with international collaborators have conducted the largest genetic investigation of the restless legs syndrome to date. […] The findings of this study have the potential to significantly influence the lives of millions of RLS patients, offering a pathway towards the development of enhanced, personalized interventions aimed at effectively treating or even preemptively addressing the disease. […] For the first time, we achieved the ability to sufficiently assess the risk for RLS. It has been a long journey, but now we are empowered to not only treat but to learn how to prevent this condition, says Juliane Winkelmann, who has been a key scientist driving research on the genetics of RLS for more than 25 years.
#40 Restless legs syndrome and functional limitations among American elders in the Health and Retirement Study | BMC Geriatrics | Full Text
https://bmcgeriatr.biomedcentral.com/articles/10.1186/1471-2318-12-39
RLS did not predict incident disability for aggregate measures but was associated with increased risk for specific limitations, including: difficulty climbing several stair flights (multivariate-adjusted hazard ratio=2.38, 95% CI 1.39-4.06), prolonged sitting (2.17, 1.25-3.75), rising from a chair (2.54, 1.62-3.99), stooping (2.66, 1.71-4.15), moving heavy objects (1.79, 1.08-2.99), carrying ten pounds (1.61, 1.05-2.97), raising arms (1.76, 1.05-2.97), or picking up a dime (1.97, 1.12-3.46). […] RLS sufferers are more likely to have functional disability, even after adjusting for health status and pain syndrome correlates. […] RLS did predict increases in some specific functions, including difficulties: climbing several stair flights; raising from a chair; sitting prolonged periods; stooping or kneeling; pushing or pulling large objects; picking up a dime; lifting 10lb; or reaching arms up). […] RLS predicted functional decline in multiple domains, which suggests an impact on subjects abilities to work and live independently. If the observed limitations are reversible when appropriate treatment is given, early detection and treatment of RLS may help remediate RLS functional decline.
#41 Comparative Effectiveness of Treatments for Restless Legs Syndrome | Effective Health Care (EHC) Program
https://effectivehealthcare.ahrq.gov/products/restless-legs/research-protocol
We will systematically review the literature to assess the benefits and harms of treatment, especially long-term outcomes. We will evaluate methods used to define RLS, assess its severity, and measure treatment benefits and harms. Further, we will identify gaps in the available evidence and develop a future research agenda. […] For patients suffering from severe RLS, the critical issue is how to identify the treatment options with the greatest long-term benefits and the least harms. Treating children and older adults with RLS presents specific challenges. We do not know the impact of long-term use of these drugs in children. Neither do we know the risks/benefits of the drugs for older adults who take several medications for multimorbidities.