The Efficacy of Botulinum Toxin in the Management of Restless Leg Syndrome: A Systematic Review of Randomized Control Trials
Maryam RA Altuhafy, Ravi Yadav, Sandeep Talluri, Luay Jabr, Mythili Kalladka, Junad Khan
Citation Information :
Altuhafy MR, Yadav R, Talluri S, Jabr L, Kalladka M, Khan J. The Efficacy of Botulinum Toxin in the Management of Restless Leg Syndrome: A Systematic Review of Randomized Control Trials. Indian Sleep Med 2022; 17 (1):15-21.
Background: Restless legs syndrome (RLS) is a sleep-related movement disorder characterized by an irresistible urge to move the legs, occasionally associated with unpleasant sensations in the leg. Emerging evidence suggests that botulinum neurotoxin may be effective in reducing the symptoms of RLS.
Objective: The objective of the present review was to assess the effectiveness of botulinum toxin in patients with RLS.
Methods: The focused question was “Is botulinum neurotoxin effective in reducing the severity of RLS?” Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) model, indexed databases were searched up to and including February 2021. Joanna Brigg's critical appraisal tool was used to evaluate the risk of bias (ROB) for the included studies.
Result: Four clinical studies were included in the systematic review and processed for data extraction. Three studies reported that the botulinum neurotoxin type A (BoNT/A) had an impact in reducing the severity and improving RLS. One study reported that BoNT/A provides no effectiveness in managing RLS. Overall risk of bias was low in two and moderate in two studies.
Conclusion: The present review suggests the need of more robust high-quality evidence for recommending the management of RLS with BoNT/A on reducing the severity and improving the overall symptoms of RLS.
Mittal SO, Machado D, Richardson D, et al. Botulinum toxin in restless legs syndrome–a randomized double-blind placebo-controlled crossover study. Toxins (Basel) 2018;10(10). DOI: 10.3390/toxins10100401.
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.
Phillips B, Young T, Finn L, et al. Epidemiology of restless legs symptoms in adults. Arch Intern Med 2000;160(14):2137–2141. DOI: 10.1001/archinte.160.14.2137.
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.
Becker PM, Novak M. Diagnosis, comorbidities, and management of restless legs syndrome. Curr Med Res Opin 2014;30(8):1441–1460. DOI: 10.1185/03007995.2014.918029.
Japaridze G, Kasradze S, Maisuradze L, et al. The restless legs syndrome (Review). Georgian Med News 2018;(285):74–81. PMID: 30702074.
Ferre S, Garcia-Borreguero D, Allen RP, et al. New Insights into the Neurobiology of Restless Legs Syndrome. Neuroscientist 2019;25(2):113–125. DOI: 10.1177/1073858418791763.
Ghorayeb I, Benard A, Vivot A, et al. 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.
Harrison EG, Keating JL, Morgan PE. Non-pharmacological interventions for restless legs syndrome: a systematic review of randomised controlled trials. Disabil Rehabil 2019;41(17):2006–2014. DOI: 10.1080/09638288.2018.1453875.
Anguelova GV, Vlak MHM, Kurvers AGY, et al. Pharmacologic and nonpharmacologic treatment of restless legs syndrome. Sleep Med Clin 2018;13(2):219–230. DOI: 10.1016/j.jsmc.2018.02.005.
Limousin N, Flamand M, Schroder C, et al. French consensus: treatment of newly diagnosed restless legs syndrome. Rev Neurol (Paris) 2018;174(7–8):515–521. DOI: 10.1016/j.neurol.2018.06.002.
Earley CJ, Silber MH. Restless legs syndrome: understanding its consequences and the need for better treatment. Sleep Med 2010;11(9):807–815. DOI: 10.1016/j.sleep.2010.07.007.
Borovac JA. Side effects of a dopamine agonist therapy for Parkinson's disease: a mini-review of clinical pharmacology. Yale J Biol Med 2016;89(1):37–47. PMID: 27505015.
Agarwal P, Sia C, Vaish N, et al. Pilot trial of onabotulinumtoxina (Botox) in moderate to severe restless legs syndrome. Int J Neurosci 2011;121(11):622–625. DOI: 10.3109/00207454.2011.602774.
Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2016;354:i4086. DOI: 10.1136/bmj.i4086.
Ekbom K, Ulfberg J. Restless legs syndrome. J Intern Med 2009;266(5):419–431. DOI: 10.1111/j.1365-2796.2009.02159.x.
Torii Y, Kiyota N, Sugimoto N, et al. Comparison of effects of botulinum toxin subtype A1 and A2 using twitch tension assay and rat grip strength test. Toxicon 2011;57(1):93–99. DOI: 10.1016/j.toxicon.2010.10.009.
Go EJ, Ji J, Kim YH, et al. Transient receptor potential channels and botulinum neurotoxins in chronic pain. Front Mol Neurosci 2021;14:772719. DOI: 10.3389/fnmol.2021.772719.
Paterson K, Lolignier S, Wood JN, et al. Botulinum toxin–a treatment reduces human mechanical pain sensitivity and mechanotransduction. Ann Neurol 2014;75(4):591–596. DOI: 10.1002/ana.24122.