Objective: To identify demographic or clinical factors predictive of refractory cases.

Background: Restless Legs Syndrome (RLS), impacting 5-13% of the US population, poses challenges in long-term management. A knowledge gap exists in predicting resistance to first-line therapies.

Method: This retrospective study, conducted at the Parkinson’s Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas (January 2018 to September 2023) identified all patients with RLS evaluated during the pre-specified period and compared clinical and demographic data between medication-refractory group and “benign” group.

Results: Among 132 patients with RLS, 23 (17.4%) were categorized as medication-refractory. This cohort was characterized by a significantly lower mean age at onset (39.3 vs. 53.5 years), longer disease duration (26.7 vs. 14.0 years), and a higher prevalence of a positive family history of RLS among first-degree relatives compared to the “benign” group (56.5% vs. 15.5%). Furthermore, dopamine agonists were initiated as the primary medication at a significantly higher rate (p =0.006).

Conclusion: Our study found that a younger age at disease onset, prolonged disease duration, initial use of dopamine agonists, and a positive family history increased the likelihood of refractory RLS. We caution against the use of dopamine agonists in young patients with RLS. Additionally, our research suggests that botulinum toxin could be a viable second-line treatment for RLS, given its low side effect incidence, pending further confirmation of efficacy and safety through additional studies.

References: 1. Wijemanne S, Jankovic J. Restless legs syndrome: clinical presentation diagnosis and treatment. Sleep Med. 2015;16(6):678-690. doi:10.1016/j.sleep.2015.03.002
2. Rye DB, Trotti LM. Restless Legs Syndrome and Periodic Leg Movements of Sleep. Neurol Clin. 2012;30(4):1137-1166. doi:10.1016/j.ncl.2012.08.004
3. Allen RP, Walters AS, Montplaisir J, et al. Restless Legs Syndrome Prevalence and Impact: REST General Population Study. Arch Intern Med. 2005;165(11):1286-1292. doi:10.1001/archinte.165.11.1286
4. Picchietti DL, Van Den Eeden SK, Inoue Y, Berger K. Achievements, challenges, and future perspectives of epidemiologic research in restless legs syndrome (RLS). Sleep Med. 2017;31:3-9. doi:10.1016/j.sleep.2016.06.007
5. Koo BB. Restless Leg Syndrome Across the Globe: Epidemiology of the Restless Legs Syndrome/Willis-Ekbom Disease. Sleep Med Clin. 2015;10(3):189-205. doi:10.1016/j.jsmc.2015.05.004
6. Manconi M, Garcia-Borreguero D, Schormair B, et al. Restless legs syndrome. Nat Rev Dis Primer. 2021;7(1):80. doi:10.1038/s41572-021-00311-z
7. Para KS, Chow CA, Nalamada K, et al. Suicidal thought and behavior in individuals with restless legs syndrome. Sleep Med. 2019;54:1-7. doi:10.1016/j.sleep.2018.09.019
8. Rinaldi F, Galbiati A, Marelli S, et al. Defining the phenotype of restless legs syndrome/Willis-Ekbom disease (RLS/WED): a clinical and polysomnographic study. J Neurol. 2016;263(2):396-402. doi:10.1007/s00415-015-7994-y
9. Chenini S, Barateau L, Guiraud L, et al. Depressive Symptoms and Suicidal Thoughts in Restless Legs Syndrome. Mov Disord Off J Mov Disord Soc. 2022;37(4):812-825. doi:10.1002/mds.28903
10. Cesnik E, Casetta I, Turri M, et al. Transient RLS during pregnancy is a risk factor for the chronic idiopathic form. Neurology. 2010;75(23):2117-2120. doi:10.1212/WNL.0b013e318200d779
11. Manconi M, Govoni V, De Vito A, et al. Restless legs syndrome and pregnancy. Neurology. 2004;63(6):1065-1069. doi:10.1212/01.wnl.0000138427.83574.a6
12. Prosperetti C, Manconi M. Restless Legs Syndrome/Willis-Ekbom Disease and Pregnancy. Sleep Med Clin. 2015;10(3):323-329, xiv. doi:10.1016/j.jsmc.2015.05.016
13. Stefani A, Mitterling T, Heidbreder A, et al. Multimodal Magnetic Resonance Imaging reveals alterations of sensorimotor circuits in restless legs syndrome. Sleep. 2019;42(12):zsz171. doi:10.1093/sleep/zsz171
14. Yepes G, Guitart X, Rea W, et al. Targeting hypersensitive corticostriatal terminals in restless legs syndrome. Ann Neurol. 2017;82(6):951-960. doi:10.1002/ana.25104
15. Lin Y, Wang Y, Zhan S, et al. Impaired Sensorimotor Integration in Restless Legs Syndrome. Front Neurol. 2018;9:568. doi:10.3389/fneur.2018.00568
16. Ferré S, García-Borreguero D, Allen RP, Earley CJ. New Insights into the Neurobiology of Restless Legs Syndrome. Neurosci Rev J Bringing Neurobiol Neurol Psychiatry. 2019;25(2):113-125. doi:10.1177/1073858418791763
17. Fulda S, Allen RP, Earley CJ, et al. We need to do better: A systematic review and meta-analysis of diagnostic test accuracy of restless legs syndrome screening instruments. Sleep Med Rev. 2021;58:101461. doi:10.1016/j.smrv.2021.101461
18. Zhou X, Du J, Liang Y, et al. The Efficacy and Safety of Pharmacological Treatments for Restless Legs Syndrome: Systemic Review and Network Meta-Analysis. Front Neurosci. 2021;15:751643. doi:10.3389/fnins.2021.751643
19. Winkelmann J, Allen RP, Högl B, et al. Treatment of restless legs syndrome: Evidence-based review and implications for clinical practice (Revised 2017)§. Mov Disord Off J Mov Disord Soc. 2018;33(7):1077-1091. doi:10.1002/mds.27260
20. Trenkwalder C, Beneš H, Grote L, et al. Prolonged release oxycodone-naloxone for treatment of severe restless legs syndrome after failure of previous treatment: a double-blind, randomised, placebo-controlled trial with an open-label extension. Lancet Neurol. 2013;12(12):1141-1150. doi:10.1016/S1474-4422(13)70239-4
21. Evidente VGH, Evidente DH, Ponce FA, Evidente MH, Lambert M, Garrett R. Thalamic Deep Brain Stimulation May Improve Restless Legs Syndrome in Patients With Essential Tremor. Neuromodulation J Int Neuromodulation Soc. 2022;25(6):911-917. doi:10.1111/ner.13532
22. Ohayon MM, O’Hara R, Vitiello MV. Epidemiology of restless legs syndrome: A synthesis of the literature. Sleep Med Rev. 2012;16(4):283-295. doi:10.1016/j.smrv.2011.05.002
23. Allen RP, Earley CJ. Defining the phenotype of the restless legs syndrome (RLS) using age-of-symptom-onset. Sleep Med. 2000;1(1):11-19. doi:10.1016/s1389-9457(99)00012-x
24. Broström A, Alimoradi Z, Lind J, Ulander M, Lundin F, Pakpour A. Worldwide estimation of restless legs syndrome: a systematic review and meta-analysis of prevalence in the general adult population. J Sleep Res. 2023;32(3):e13783. doi:10.1111/jsr.13783
25. Whittom S, Dauvilliers Y, Pennestri MH, et al. Age-at-onset in restless legs syndrome: a clinical and polysomnographic study. Sleep Med. 2007;9(1):54-59. doi:10.1016/j.sleep.2007.01.017
26. Liu Z, Guan R, Pan L. Exploration of restless legs syndrome under the new concept: A review. Medicine (Baltimore). 2022;101(50):e32324. doi:10.1097/MD.0000000000032324
27. Aurora RN, Kristo DA, Bista SR, et al. The treatment of restless legs syndrome and periodic limb movement disorder in adults–an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine Clinical Practice Guideline. Sleep. 2012;35(8):1039-1062. doi:10.5665/sleep.1988
28. Hornyak M, Trenkwalder C, Kohnen R, Scholz H. Efficacy and safety of dopamine agonists in restless legs syndrome. Sleep Med. 2012;13(3):228-236. doi:10.1016/j.sleep.2011.09.013
29. Khan M. Restless Legs Syndrome and Other Common Sleep-Related Movement Disorders. Contin Minneap Minn. 2023;29(4):1130-1148. doi:10.1212/CON.0000000000001269
30. Manconi M, Ferri R, Zucconi M, et al. Effects of acute dopamine-agonist treatment in restless legs syndrome on heart rate variability during sleep. Sleep Med. 2011;12(1):47-55. doi:10.1016/j.sleep.2010.03.019
31. van der Veen S, Caviness JN, Dreissen YEM, et al. Myoclonus and other jerky movement disorders. Clin Neurophysiol Pract. 2022;7:285-316. doi:10.1016/j.cnp.2022.09.003
32. Silver N, Allen RP, Senerth J, Earley CJ. A 10-year, longitudinal assessment of dopamine agonists and methadone in the treatment of restless legs syndrome. Sleep Med. 2011;12(5):440-444. doi:10.1016/j.sleep.2010.11.002
33. Allen RP, Ondo WG, Ball E, et al. Restless legs syndrome (RLS) augmentation associated with dopamine agonist and levodopa usage in a community sample. Sleep Med. 2011;12(5):431-439. doi:10.1016/j.sleep.2011.03.003
34. Cornelius JR, Tippmann-Peikert M, Slocumb NL, Frerichs CF, Silber MH. Impulse control disorders with the use of dopaminergic agents in restless legs syndrome: a case-control study. Sleep. 2010;33(1):81-87.
35. Zeng P, Wang T, Zhang L, Guo F. Exploring the causes of augmentation in restless legs syndrome. Front Neurol. 2023;14:1160112. doi:10.3389/fneur.2023.1160112
36. Nahab FB, Peckham EL, Hallett M. Double-blind, placebo-controlled, pilot trial of botulinum toxin A in restless legs syndrome. Neurology. 2008;71(12):950-951. doi:10.1212/01.wnl.0000325994.93782.a1
37. Mittal SO, Machado D, Richardson D, Dubey D, Jabbari B. Botulinum Toxin in Restless Legs Syndrome-A Randomized Double-Blind Placebo-Controlled Crossover Study. Toxins. 2018;10(10):401. doi:10.3390/toxins10100401
38. Ghorayeb I, Bénard A, Vivot A, Tison F, Burbaud P. A phase II, open-label, non-comparative study of Botulinum toxin in Restless Legs Syndrome. Sleep Med. 2012;13(10):1313-1316. doi:10.1016/j.sleep.2012.08.019
39. Su YC, Guo YH, Liao CL, Lin YC. Effectiveness and Safety of Botulinum Toxin Type A in Treatment of Restless Legs Syndrome: A Systematic Review and Meta-Analysis. Healthcare. 2021;9(11):1538. doi:10.3390/healthcare9111538

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