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Restless Legs Syndrome: From Diagnosis to Treatment

Year 2023, Volume: 25 Issue: 3, 212 - 217, 30.12.2023
https://doi.org/10.18678/dtfd.1391450

Abstract

Restless legs syndrome (RLS) can be described by an urge to move limbs that typically coincides with an uncomfortable sensation. When at rest or inactivity, signs may start or develop worse; they usually go away when one moves or gets up for a walk. RLS can be both idiopathic or secondary to many kinds of health conditions, such as deficiency of iron, diabetes, obesity, hypothyroidism, and chronic renal failure. At the admission, secondary causes and iron tests, such as transferrin saturation and ferritin, must be evaluated. Assessments should be repeated when symptoms worsen, or when augmentation develops. Augmentation is a significant adverse effect of therapy by levodopa and dopamine agonists. More severe signs, early appearance of symptoms, and spreading of symptoms from the legs to other body parts are indicative of augmentation. Non-pharmacological treatments help some RLS patients control their symptoms. Iron-replacement therapy is a first-line treatment option for patients with indications of low body iron stores. The use of α2δ ligands as initial treatments instead of dopamine agonists has been recommended recently.

References

  • Kouri I, Junna MR, Lipford MC. Restless legs syndrome and periodic limb movements of sleep: from neurophysiology to clinical practice. J Clin Neurophysiol. 2023;40(3):215-23.
  • Liu Z, Guan R, Pan L. Exploration of restless legs syndrome under the new concept: A review. Medicine (Baltimore). 2022;101(50):e32324.
  • Dezube AR, Rauh J, Dezube M, Iafrati M, Rigo J, Muto P. Correlation between restless leg syndrome and superficial venous reflux. Int J Angiol. 2021;30(4):285-91.
  • O’Regan D, Anderson KN. Restless legs syndrome and periodic limb movements of sleep. Br J Hosp Med (Lond). 2020;81(1):1-8.
  • Karroum EG, Leu-Semenescu S, Arnulf I. Topography of the sensations in primary restless legs syndrome. J Neurol Sci. 2012;320(1-2):26-31.
  • Xu Y, Wen H, Li J, Yang J, Luo K, Chang L. The relationship between sleep disorders, anxiety, depression, and cognitive function with restless legs syndrome (RLS) in the elderly. Sleep Breath. 2022;26(3):1309-18.
  • Miranda M, Venegas P. Restless legs syndrome: A clinical update. Rev Chil Neuro-Psiquiat. 2001;39(2):140-8. Spanish.
  • Ulfberg J, Bjorvatn B, Leissner L, Gyring J, Karlsborg M, Regeur L, et al. Comorbidity in restless legs syndrome among a sample of Swedish adults. Sleep Med. 2007;8(7-8):768-72.
  • Phillips B, Hening W, Britz P, Mannino D. Prevalence and correlates of restless legs syndrome: results from the 2005 National Sleep Foundation Poll. Chest. 2006;129(1):76-80.
  • Berger K, Luedemann J, Trenkwalder C, John U, Kessler C. Sex and the risk of restless legs syndrome in the general population. Arch Intern Med. 2004;164(2):196-202.
  • Gossard TR, Trotti LM, Videnovic A, St Louis EK. Restless legs syndrome: contemporary diagnosis and treatment. Neurotherapeutics. 2021;18(1):140-55.
  • Pantaleo NP, Hening WA, Allen RP, Earley CJ. Pregnancy accounts for most of the gender difference in prevalence of familial RLS. Sleep Med. 2010;11(3):310-3.
  • Yilmaz K, Kilincaslan A, Aydin N, Kor D. Prevalence and correlates of restless legs syndrome in adolescents. Dev Med Child Neurol. 2010;53(1):40-7.
  • Gonzalez-Latapi P, Malkani R. Update on restless legs syndrome: from mechanisms to treatment. Curr Neurol Neurosci Rep. 2019;19(8):54.
  • Tuovinen N, Stefani A, Mitterling T, Heidbreder A, Frauscher B, Gizewski ER, et al. Functional connectivity and topology in patients with restless legs syndrome: a case-control resting-state functional magnetic resonance imaging study. Eur J Neurol. 2021;28(2):448-58.
  • Earley CJ, Connor JR, Beard JL, Malecki EA, Epstein DK, Allen RP. Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology. 2000;54(8):1698–700.
  • Allen RP, Auerbach S, Bahrain H, Auerbach M, Earley CJ. The prevalence and impact of restless legs syndrome on patients with iron deficiency anemia. Am J Hematol. 2013;88(4):261-4.
  • Connor JR, Patton SM, Oexle K, Allen RP. Iron and restless legs syndrome: treatment, genetics and pathophysiology. Sleep Med. 2017;31:61-70.
  • Allen RP. Restless leg syndrome/Willis-Ekbom disease pathophysiology. Sleep Med Clin. 2015;10(3):207-14.
  • Ruppert E. Restless arms syndrome: Prevalence, impact, and management strategies. Neuropsychiatr Dis Treat. 2019;15:1737-50.
  • Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, et al. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria--history, rationale, description, and significance. Sleep Med. 2014;15(8):860-73.
  • Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J, et al. Restless legs syndrome: Diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003;4(2):101-19.
  • Montplaisir J, Boucher S, Nicolas A, Lesperance P, Gosselin A, Rompré P, et al. Immobilization tests and periodic leg movements in sleep for the diagnosis of restless leg syndrome. Mov Disord. 1998;13(2):324-9.
  • Prakash S, Ahuja S, Rathod C. Dopa responsive burning mouth syndrome: Restless mouth syndrome or oral variant of restless legs syndrome? J Neurol Sci. 2012;320(1-2):156-60.
  • Pérez-Díaz H, Iranzo A, Rye DB, Santamaría J. Restless abdomen: A phenotypic variant of restless legs syndrome. Neurology. 2011;77(13):1283-6.
  • Jung Y, Hassan A, St Louis EK, Robertson CE. Restless mouth syndrome. Neurol Clin Pract. 2017;7(3):e29-30.
  • Horvath J, Landis T, Burkhard PR. Restless arms. Lancet. 2008;371(9611):530.
  • Koo YS, Lee GT, Lee SY, Cho YW, Jung KY. Topography of sensory symptoms in patients with drug-naïve restless legs syndrome. Sleep Med. 2013;14(12):1369-74.
  • Michaud M, Chabli A, Lavigne G, Montplaisir J. Arm restlessness in patients with restless legs syndrome. Mov Disord. 2000;15(2):289-93.
  • Raggi A, Ferri R. Phantom restless legs syndrome. Eur Neurol. 2019;81(5-6):302-8.
  • Silber MH, Becker PM, Earley C, Garcia-Borreguero D, Ondo WG; Medical Advisory Board of the Willis-Ekbom Disease Foundation. Willis-Ekbom Disease Foundation revised consensus statement on the management of restless legs syndrome. Mayo Clin Proc. 2013;88(9):977-86.
  • Allen RP, Earley CJ. Defining the phenotype of the restless legs syndrome (RLS) using age-of-symptom-onset. Sleep Med. 2000;1(1):11-9.
  • Trenkwalder C, Allen R, Högl B, Paulus W, Winkelmann J. Restless legs syndrome associated with major diseases: A systematic review and new concept. Neurology. 2016;86(14):1336-43.
  • Becker PM, Novak M. Diagnosis, comorbidities, and management of restless legs syndrome. Curr Med Res Opin. 2014;30(8):1441-60.
  • Sarberg M, Josefsson A, Wiréhn AB, Svanborg E. Restless legs syndrome during and after pregnancy and its relation to snoring. Acta Obstet Gynecol Scand. 2012;91(7):850-5.
  • Chokroverty S. Differential diagnoses of restless legs syndrome/Willis-Ekbom disease: mimics and comorbidities. Sleep Med Clin. 2015;10(3):249-62.
  • Lesage S, Hening WA. The restless legs syndrome and periodic limb movement disorder: A review of management. Semin Neurol. 2004;24(3):249-59.
  • Silber MH, Buchfuhrer MJ, Earley CJ, Koo BB, Manconi M, Winkelman JW, et al. The management of restless legs syndrome: an updated algorithm. Mayo Clin Proc. 2021;96(7):1921-37.
  • Winkelmann J, Allen RP, Högl B, Inoue Y, Oertel W, Salminen AV. Treatment of restless legs syndrome: Evidence-based review and implications for clinical practice (Revised 2017)§. Mov Disord. 2018;33(7):1077-91.
  • Anguelova GV, Vlak MHM, Kurvers AGY, Rijsman RM. Pharmacologic and nonpharmacologic treatment of restless legs syndrome. Sleep Med Clin. 2020;15(2):277-88.
  • Allen RP, Earley CJ. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep. 1996;19(3):205-13.
  • García-Borreguero D, Allen RP, Kohnen R, Högl B, Trenkwalder C, Oertel W, et al. Diagnostic standards for dopaminergic augmentation of restless legs syndrome: report from a World Association of Sleep Medicine-International Restless Legs Syndrome Study Group consensus conference at the Max Planck Institute. Sleep Med. 2007;8(5):520-30.
  • Leu-Semenescu S, Petiau C, Charley Monaca C, Dauvilliers Y. French consensus: Augmentation syndrome in restless legs syndrome. Rev Neurol (Paris). 2018;174(7-8):532-9.
  • Williams AM, Garcia-Borreguero D. Management of restless legs syndrome augmentation. Curr Treat Options Neurol. 2009;11(5):327-32.
  • García-Borreguero D, Williams AM. Dopaminergic augmentation of restless legs syndrome. Sleep Med Rev. 2010;14(5):339-46.

Huzursuz Bacaklar Sendromu: Tanıdan Tedaviye

Year 2023, Volume: 25 Issue: 3, 212 - 217, 30.12.2023
https://doi.org/10.18678/dtfd.1391450

Abstract

Huzursuz bacaklar sendromu (HBS), uzuvları hareket ettirme dürtüsünün tipik olarak rahatsız edici bir hisle örtüşmesiyle tanımlanabilir. Dinlenme veya hareketsizlik sırasında belirtiler başlayabilir veya daha kötü gelişebilir; genellikle kişi hareket ettiğinde veya yürüyüşe çıktığında kaybolurlar. HBS hem idiyopatik hem de demir eksikliği, diyabet, obezite, hipotiroidizm ve kronik böbrek yetmezliği gibi birçok sağlık durumuna sekonder olabilir. İlk başvuruda ikincil nedenler ve transferrin saturasyonu, ferritin gibi demir testleri değerlendirilmelidir. Semptomlar kötüleştiğinde veya augmentasyon geliştiğinde değerlendirmeler tekrarlanmalıdır. Augmentasyon, levodopa ve dopamin agonistleriyle yapılan tedavinin önemli bir olumsuz etkisidir. Belirtilerin daha şiddetli olması, belirtilerin erken ortaya çıkması ve belirtilerin bacaklardan diğer vücut bölgelerine yayılması augmentasyonun göstergesidir. Farmakolojik olmayan tedaviler bazı HBS hastalarının semptomlarını kontrol altına almasına yardımcı olur. Demir replasman tedavisi, vücut demir depolarının düşük olduğu belirtileri olan hastalar için birinci basamak tedavi seçeneğidir. Son zamanlarda dopamin agonistleri yerine başlangıç tedavileri olarak α2δ ligandlarının kullanılması önerilmiştir.

References

  • Kouri I, Junna MR, Lipford MC. Restless legs syndrome and periodic limb movements of sleep: from neurophysiology to clinical practice. J Clin Neurophysiol. 2023;40(3):215-23.
  • Liu Z, Guan R, Pan L. Exploration of restless legs syndrome under the new concept: A review. Medicine (Baltimore). 2022;101(50):e32324.
  • Dezube AR, Rauh J, Dezube M, Iafrati M, Rigo J, Muto P. Correlation between restless leg syndrome and superficial venous reflux. Int J Angiol. 2021;30(4):285-91.
  • O’Regan D, Anderson KN. Restless legs syndrome and periodic limb movements of sleep. Br J Hosp Med (Lond). 2020;81(1):1-8.
  • Karroum EG, Leu-Semenescu S, Arnulf I. Topography of the sensations in primary restless legs syndrome. J Neurol Sci. 2012;320(1-2):26-31.
  • Xu Y, Wen H, Li J, Yang J, Luo K, Chang L. The relationship between sleep disorders, anxiety, depression, and cognitive function with restless legs syndrome (RLS) in the elderly. Sleep Breath. 2022;26(3):1309-18.
  • Miranda M, Venegas P. Restless legs syndrome: A clinical update. Rev Chil Neuro-Psiquiat. 2001;39(2):140-8. Spanish.
  • Ulfberg J, Bjorvatn B, Leissner L, Gyring J, Karlsborg M, Regeur L, et al. Comorbidity in restless legs syndrome among a sample of Swedish adults. Sleep Med. 2007;8(7-8):768-72.
  • Phillips B, Hening W, Britz P, Mannino D. Prevalence and correlates of restless legs syndrome: results from the 2005 National Sleep Foundation Poll. Chest. 2006;129(1):76-80.
  • Berger K, Luedemann J, Trenkwalder C, John U, Kessler C. Sex and the risk of restless legs syndrome in the general population. Arch Intern Med. 2004;164(2):196-202.
  • Gossard TR, Trotti LM, Videnovic A, St Louis EK. Restless legs syndrome: contemporary diagnosis and treatment. Neurotherapeutics. 2021;18(1):140-55.
  • Pantaleo NP, Hening WA, Allen RP, Earley CJ. Pregnancy accounts for most of the gender difference in prevalence of familial RLS. Sleep Med. 2010;11(3):310-3.
  • Yilmaz K, Kilincaslan A, Aydin N, Kor D. Prevalence and correlates of restless legs syndrome in adolescents. Dev Med Child Neurol. 2010;53(1):40-7.
  • Gonzalez-Latapi P, Malkani R. Update on restless legs syndrome: from mechanisms to treatment. Curr Neurol Neurosci Rep. 2019;19(8):54.
  • Tuovinen N, Stefani A, Mitterling T, Heidbreder A, Frauscher B, Gizewski ER, et al. Functional connectivity and topology in patients with restless legs syndrome: a case-control resting-state functional magnetic resonance imaging study. Eur J Neurol. 2021;28(2):448-58.
  • Earley CJ, Connor JR, Beard JL, Malecki EA, Epstein DK, Allen RP. Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology. 2000;54(8):1698–700.
  • Allen RP, Auerbach S, Bahrain H, Auerbach M, Earley CJ. The prevalence and impact of restless legs syndrome on patients with iron deficiency anemia. Am J Hematol. 2013;88(4):261-4.
  • Connor JR, Patton SM, Oexle K, Allen RP. Iron and restless legs syndrome: treatment, genetics and pathophysiology. Sleep Med. 2017;31:61-70.
  • Allen RP. Restless leg syndrome/Willis-Ekbom disease pathophysiology. Sleep Med Clin. 2015;10(3):207-14.
  • Ruppert E. Restless arms syndrome: Prevalence, impact, and management strategies. Neuropsychiatr Dis Treat. 2019;15:1737-50.
  • Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, et al. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria--history, rationale, description, and significance. Sleep Med. 2014;15(8):860-73.
  • Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J, et al. Restless legs syndrome: Diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003;4(2):101-19.
  • Montplaisir J, Boucher S, Nicolas A, Lesperance P, Gosselin A, Rompré P, et al. Immobilization tests and periodic leg movements in sleep for the diagnosis of restless leg syndrome. Mov Disord. 1998;13(2):324-9.
  • Prakash S, Ahuja S, Rathod C. Dopa responsive burning mouth syndrome: Restless mouth syndrome or oral variant of restless legs syndrome? J Neurol Sci. 2012;320(1-2):156-60.
  • Pérez-Díaz H, Iranzo A, Rye DB, Santamaría J. Restless abdomen: A phenotypic variant of restless legs syndrome. Neurology. 2011;77(13):1283-6.
  • Jung Y, Hassan A, St Louis EK, Robertson CE. Restless mouth syndrome. Neurol Clin Pract. 2017;7(3):e29-30.
  • Horvath J, Landis T, Burkhard PR. Restless arms. Lancet. 2008;371(9611):530.
  • Koo YS, Lee GT, Lee SY, Cho YW, Jung KY. Topography of sensory symptoms in patients with drug-naïve restless legs syndrome. Sleep Med. 2013;14(12):1369-74.
  • Michaud M, Chabli A, Lavigne G, Montplaisir J. Arm restlessness in patients with restless legs syndrome. Mov Disord. 2000;15(2):289-93.
  • Raggi A, Ferri R. Phantom restless legs syndrome. Eur Neurol. 2019;81(5-6):302-8.
  • Silber MH, Becker PM, Earley C, Garcia-Borreguero D, Ondo WG; Medical Advisory Board of the Willis-Ekbom Disease Foundation. Willis-Ekbom Disease Foundation revised consensus statement on the management of restless legs syndrome. Mayo Clin Proc. 2013;88(9):977-86.
  • Allen RP, Earley CJ. Defining the phenotype of the restless legs syndrome (RLS) using age-of-symptom-onset. Sleep Med. 2000;1(1):11-9.
  • Trenkwalder C, Allen R, Högl B, Paulus W, Winkelmann J. Restless legs syndrome associated with major diseases: A systematic review and new concept. Neurology. 2016;86(14):1336-43.
  • Becker PM, Novak M. Diagnosis, comorbidities, and management of restless legs syndrome. Curr Med Res Opin. 2014;30(8):1441-60.
  • Sarberg M, Josefsson A, Wiréhn AB, Svanborg E. Restless legs syndrome during and after pregnancy and its relation to snoring. Acta Obstet Gynecol Scand. 2012;91(7):850-5.
  • Chokroverty S. Differential diagnoses of restless legs syndrome/Willis-Ekbom disease: mimics and comorbidities. Sleep Med Clin. 2015;10(3):249-62.
  • Lesage S, Hening WA. The restless legs syndrome and periodic limb movement disorder: A review of management. Semin Neurol. 2004;24(3):249-59.
  • Silber MH, Buchfuhrer MJ, Earley CJ, Koo BB, Manconi M, Winkelman JW, et al. The management of restless legs syndrome: an updated algorithm. Mayo Clin Proc. 2021;96(7):1921-37.
  • Winkelmann J, Allen RP, Högl B, Inoue Y, Oertel W, Salminen AV. Treatment of restless legs syndrome: Evidence-based review and implications for clinical practice (Revised 2017)§. Mov Disord. 2018;33(7):1077-91.
  • Anguelova GV, Vlak MHM, Kurvers AGY, Rijsman RM. Pharmacologic and nonpharmacologic treatment of restless legs syndrome. Sleep Med Clin. 2020;15(2):277-88.
  • Allen RP, Earley CJ. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep. 1996;19(3):205-13.
  • García-Borreguero D, Allen RP, Kohnen R, Högl B, Trenkwalder C, Oertel W, et al. Diagnostic standards for dopaminergic augmentation of restless legs syndrome: report from a World Association of Sleep Medicine-International Restless Legs Syndrome Study Group consensus conference at the Max Planck Institute. Sleep Med. 2007;8(5):520-30.
  • Leu-Semenescu S, Petiau C, Charley Monaca C, Dauvilliers Y. French consensus: Augmentation syndrome in restless legs syndrome. Rev Neurol (Paris). 2018;174(7-8):532-9.
  • Williams AM, Garcia-Borreguero D. Management of restless legs syndrome augmentation. Curr Treat Options Neurol. 2009;11(5):327-32.
  • García-Borreguero D, Williams AM. Dopaminergic augmentation of restless legs syndrome. Sleep Med Rev. 2010;14(5):339-46.
There are 45 citations in total.

Details

Primary Language English
Subjects Neurology and Neuromuscular Diseases
Journal Section Invited Review
Authors

Rashad İsmayılov 0000-0001-5931-9508

Yıldız Değirmenci 0000-0002-8584-5488

Early Pub Date November 30, 2023
Publication Date December 30, 2023
Submission Date August 22, 2023
Published in Issue Year 2023 Volume: 25 Issue: 3

Cite

APA İsmayılov, R., & Değirmenci, Y. (2023). Restless Legs Syndrome: From Diagnosis to Treatment. Duzce Medical Journal, 25(3), 212-217. https://doi.org/10.18678/dtfd.1391450
AMA İsmayılov R, Değirmenci Y. Restless Legs Syndrome: From Diagnosis to Treatment. Duzce Med J. December 2023;25(3):212-217. doi:10.18678/dtfd.1391450
Chicago İsmayılov, Rashad, and Yıldız Değirmenci. “Restless Legs Syndrome: From Diagnosis to Treatment”. Duzce Medical Journal 25, no. 3 (December 2023): 212-17. https://doi.org/10.18678/dtfd.1391450.
EndNote İsmayılov R, Değirmenci Y (December 1, 2023) Restless Legs Syndrome: From Diagnosis to Treatment. Duzce Medical Journal 25 3 212–217.
IEEE R. İsmayılov and Y. Değirmenci, “Restless Legs Syndrome: From Diagnosis to Treatment”, Duzce Med J, vol. 25, no. 3, pp. 212–217, 2023, doi: 10.18678/dtfd.1391450.
ISNAD İsmayılov, Rashad - Değirmenci, Yıldız. “Restless Legs Syndrome: From Diagnosis to Treatment”. Duzce Medical Journal 25/3 (December 2023), 212-217. https://doi.org/10.18678/dtfd.1391450.
JAMA İsmayılov R, Değirmenci Y. Restless Legs Syndrome: From Diagnosis to Treatment. Duzce Med J. 2023;25:212–217.
MLA İsmayılov, Rashad and Yıldız Değirmenci. “Restless Legs Syndrome: From Diagnosis to Treatment”. Duzce Medical Journal, vol. 25, no. 3, 2023, pp. 212-7, doi:10.18678/dtfd.1391450.
Vancouver İsmayılov R, Değirmenci Y. Restless Legs Syndrome: From Diagnosis to Treatment. Duzce Med J. 2023;25(3):212-7.