Prevalence of Restless Legs and Association with Patient-reported Outcome Measures in Myasthenia Gravis

Overview

Journal J Clin Sleep Med

Specialties Neurology
Psychiatry

Date 2024 Sep 27

PMID 39329188

Authors

Mohanad AlGaeed

Tarrant McPherson

Ikjae Lee

Michelle Feese

Inmaculada Aban

Gary Cutter

Henry J Kaminski

Elias G Karroum

Affiliations

Soon will be listed here.

Abstract

Study Objectives: Inflammatory and immune mechanisms are considered in restless legs syndrome (RLS) pathophysiology with several autoimmune diseases associated with RLS. There is a paucity of studies examining RLS prevalence in myasthenia gravis (MG), an autoimmune neuromuscular disease. This study investigated RLS prevalence and association with patient-reported measures in a large registry of participants with MG using a validated RLS diagnostic questionnaire.

Methods: The Myasthenia Gravis Foundation of America MG Patient Registry is used on a semiannual basis to survey participants with MG. Patients aged ≥ 18 years, living in the United States, and answering "yes" to physician diagnosed MG were invited by email to enroll in an RLS-customized web-based survey. Collection of data included demographics, disease variables, patient-reported measures with a simple depression scale, MG-quality of life-15 revised, MG-activities of daily living instruments, and 13-item short-form Cambridge-Hopkins diagnostic questionnaire for RLS. Multivariable logistic regression models explored the association between RLS and MG variables of interest.

Results: A total of 630 eligible participants with MG (age: 62.8 ± 13.2; 54.9% female; 91.6% White) completed the survey. The overall prevalence of RLS was 14.8%. The prevalence of clinically significant RLS was 8.4%. The odds of having RLS were increased with higher (worse) MG-activities of daily living, MG-quality of life-15 revised, and depression scores. History of "thymic tumor with thymectomy" and "continuous positive airway pressure therapy" were also independent predictors of RLS.

Conclusions: RLS is common in patients with MG and is associated with worse functional status, quality of life, and depression. The thymus could play a key role in an autoimmune process associating MG with RLS.

Citation: AlGaeed M, McPherson T, Lee I, et al. Prevalence of restless legs and association with patient-reported outcome measures in myasthenia gravis. . 2025;21(2):269-276.

References

Sieminski M, Bilinska M, Nyka W . Increased frequency of restless legs syndrome in myasthenia gravis. Eur Neurol. 2012; 68(3):166-70. DOI: 10.1159/000339485. View

Winkelman J, Redline S, Baldwin C, Resnick H, Newman A, Gottlieb D . Polysomnographic and health-related quality of life correlates of restless legs syndrome in the Sleep Heart Health Study. Sleep. 2009; 32(6):772-8. PMC: 2690565. DOI: 10.1093/sleep/32.6.772. View

Stevens M . Restless Legs Syndrome/Willis-Ekbom Disease Morbidity: Burden, Quality of Life, Cardiovascular Aspects, and Sleep. Sleep Med Clin. 2015; 10(3):369-73, xv-xvi. DOI: 10.1016/j.jsmc.2015.05.017. View

Whittom S, Dauvilliers Y, Pennestri M, Vercauteren F, Molinari N, Petit D . Age-at-onset in restless legs syndrome: a clinical and polysomnographic study. Sleep Med. 2007; 9(1):54-9. DOI: 10.1016/j.sleep.2007.01.017. View

Ruiter A, Strijbos E, de Meel R, Lipka A, Raadsheer W, Tannemaat M . Accuracy of patient-reported data for an online patient registry of autoimmune myasthenia gravis and Lambert-Eaton myasthenic syndrome. Neuromuscul Disord. 2021; 31(7):622-632. DOI: 10.1016/j.nmd.2021.05.006. View

Walters A, Paueksakon P, Adler C, Moussouttas M, Weinstock L, Spruyt K . Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis. J Am Heart Assoc. 2021; 10(11):e019627. PMC: 8483539. DOI: 10.1161/JAHA.120.019627. View

Trenkwalder C, Allen R, Hogl B, Clemens S, Patton S, Schormair B . Comorbidities, treatment, and pathophysiology in restless legs syndrome. Lancet Neurol. 2018; 17(11):994-1005. DOI: 10.1016/S1474-4422(18)30311-9. View

Weinstock L, Walters A, Paueksakon P . Restless legs syndrome--theoretical roles of inflammatory and immune mechanisms. Sleep Med Rev. 2012; 16(4):341-54. DOI: 10.1016/j.smrv.2011.09.003. View

Ondo W . Restless Legs Syndrome "Patient Odyssey" survey of disease burden on patient and spouses/partners. Sleep Med. 2018; 47:51-53. DOI: 10.1016/j.sleep.2017.12.003. View

10.

Jimenez-Jimenez F, Alonso-Navarro H, Garcia-Martin E, Agundez J . Inflammatory factors and restless legs syndrome: A systematic review and meta-analysis. Sleep Med Rev. 2023; 68:101744. DOI: 10.1016/j.smrv.2022.101744. View

11.

Lee I, Kaminski H, McPherson T, Feese M, Cutter G . Gender differences in prednisone adverse effects: Survey result from the MG registry. Neurol Neuroimmunol Neuroinflamm. 2018; 5(6):e507. PMC: 6192695. DOI: 10.1212/NXI.0000000000000507. View

12.

Marrie R, Cutter G, Tyry T, Campagnolo D, Vollmer T . Validation of the NARCOMS registry: diagnosis. Mult Scler. 2007; 13(6):770-5. DOI: 10.1177/1352458506075031. View

13.

Gilhus N, Tzartos S, Evoli A, Palace J, Burns T, Verschuuren J . Myasthenia gravis. Nat Rev Dis Primers. 2019; 5(1):30. DOI: 10.1038/s41572-019-0079-y. View

14.

Ning P, Hu F, Yang B, Shen Q, Zhao Q, Huang H . Systematic review and meta-analysis of observational studies to understand the prevalence of restless legs syndrome in multiple sclerosis: an update. Sleep Med. 2018; 50:97-104. DOI: 10.1016/j.sleep.2018.05.039. View

15.

Hornyak M, Rupp A, Riemann D, Feige B, Berger M, Voderholzer U . Low-dose hydrocortisone in the evening modulates symptom severity in restless legs syndrome. Neurology. 2008; 70(18):1620-2. DOI: 10.1212/01.wnl.0000310984.45538.89. View

16.

Allen R, Bharmal M, Calloway M . Prevalence and disease burden of primary restless legs syndrome: results of a general population survey in the United States. Mov Disord. 2011; 26(1):114-20. DOI: 10.1002/mds.23430. View

17.

Li K, Hou L, Tan Y, Huang Y, Shi J, Han J . Iron metabolism patterns in non-anemic patients with myasthenia gravis: A cross-sectional and follow-up study. Front Neurol. 2022; 13:1060204. PMC: 9729274. DOI: 10.3389/fneur.2022.1060204. View

18.

Burns T, Sadjadi R, Utsugisawa K, Gwathmey K, Joshi A, Jones S . International clinimetric evaluation of the MG-QOL15, resulting in slight revision and subsequent validation of the MG-QOL15r. Muscle Nerve. 2016; 54(6):1015-1022. DOI: 10.1002/mus.25198. View

19.

Veasey S, Rosen I . Obstructive Sleep Apnea in Adults. N Engl J Med. 2019; 380(15):1442-1449. DOI: 10.1056/NEJMcp1816152. View

20.

Trenkwalder C, Allen R, Hogl B, Paulus W, Winkelmann J . Restless legs syndrome associated with major diseases: A systematic review and new concept. Neurology. 2016; 86(14):1336-1343. PMC: 4826337. DOI: 10.1212/WNL.0000000000002542. View