REVIEW PAPER
Systematic review of neuromuscular diurnal activity in restless legs syndrome
 
More details
Hide details
1
School of Health Sciences, Orebro University, Orebro, Sweden
 
2
Department of Physical Education and Sport Science, ErgoMech-Lab, University of Thessaly, Trikala, Greece
 
3
Department of Molecular Medicine and Surgery, Karolinska Institute, Solna, Sweden
 
4
Centre of Orthopaedics and Regenerative Medicine, C.O.R.E.-C.I.R.I., Aristotle University of Thessaloniki, Thessaloniki, Greece
 
 
Submission date: 2021-05-01
 
 
Acceptance date: 2021-11-15
 
 
Publication date: 2022-02-07
 
 
Hum Mov. 2023;24(1):21-31
 
KEYWORDS
TOPICS
ABSTRACT
Purpose:
The aim of this review was to systematically summarize the current literature on corticospinal excitation and muscle activity in restless legs syndrome (RLS) patients during daytime and diurnal activities. Three models of muscle activation in RLS directed this review: (i) evoked neuromuscular activation; (ii) sensory reflex responsiveness; (iii) voluntary muscle activation.

Methods:
A literature search was conducted in PubMed and Google Scholar, and 51 articles met the primary inclusion criteria. After a quality analysis, a total 13 articles were deemed of sufficient quality for data extraction.

Results:
Three studies on evoked neuromuscular activation demonstrated increased motor excitability associated with RLS. Sensory reflex responsiveness studies in RLS patients revealed increased reflex responsiveness, indicating increased spinal excitability and a possible dysfunction in afferent inhibition. Voluntary muscle activation studies showed both diurnal muscle electromyography abnormalities and an increased circadian variation in the musculature of the lower leg in RLS patients.

Conclusions:
Although a number of mechanisms have been evaluated increasing the understanding of RLS, few studies have evaluated RLS during daytime and diurnal muscle activity in patients with RLS. Furthermore, potential associations with the circadian rhythm have not been thoroughly investigated, nor have methodologies been combined. Future research should aim to establish differences in muscle activity of RLS patients and associate these differences with the duration and severity of symptoms. Suggestions for further studies are provided.

 
REFERENCES (49)
1.
Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, Bell TJ, 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.
 
2.
Hening W, Walters AS, Allen RP, Montplaisir J, Myers A, Ferini-Strambi L. Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study. Sleep Med. 2004;5(3):237–246; doi: 10.1016/j.sleep.2004.03.006.
 
3.
Walters AS. Toward a better definition of the restless legs syndrome. The International Restless Legs Syndrome Study Group. Mov Disord. 1995;10(5):634–642; doi: 10.1002/mds.870100517.
 
4.
Plazzi G, Vetrugno R, Meletti S, Provini F. Motor pattern of periodic limb movements in sleep in idiopathic RLS patients. Sleep Med. 2002;3(Suppl.):31–34; doi: 10.1016/S1389-9457(02)00146-6.
 
5.
Provini F, Vetrugno R, Meletti S, Plazzi G, Solieri L, Lugaresi E, et al. Motor pattern of periodic limb movements during sleep. Neurology. 2001;57(2):300–304; doi: 10.1212/wnl.57.2.300.
 
6.
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):860–873; doi: 10.1016/j.sleep.2014.03.025.
 
7.
Trenkwalder C, Paulus W. Why do restless legs occur at rest? Pathophysiology of neuronal structures in RLS. Neurophysiology of RLS (part 2). Clin Neurophysiol. 2004;115(9):1975–1988; doi: 10.1016/j.clinph.2004.01.031.
 
8.
Barrière G, Cazalets JR, Bioulac B, Tison F, Ghorayeb I. The restless legs syndrome. Prog Neurobiol. 2005;77(3):139–165; doi: 10.1016/j.pneurobio.2005.10.007.
 
9.
Comella CL. Restless legs syndrome: treatment with dopaminergic agents. Neurology. 2002;58(4 Suppl. 1):87–92; doi: 10.1212/wnl.58.suppl_1.s87.
 
10.
Paci D, Lanuzza B, Cosentino FII, Belfiore A, Papotto M, Cocilovo A, et al. Subclinical abnormal EMG activation of the gastrocnemii during gait analysis in restless legs syndrome: a preliminary report in 13 patients. Sleep Med. 2009;10(3):312–316; doi: 10.1016/j.sleep.2008.04.007.
 
11.
Lanza G, Lanuzza B, Aricò D, Cantone M, Cosentino FII, Pennisi M, et al. Direct comparison of cortical excitability to transcranial magnetic stimulation in obstructive sleep apnea syndrome and restless legs syndrome. Sleep Med. 2015;16(1):138–142; doi: 10.1016/j.sleep.2014.08.016.
 
12.
Lanza G, Bachmann CG, Ghorayeb I, Wang Y, Ferri R, Paulus W. Central and peripheral nervous system excitability in restless legs syndrome. Sleep Med. 2017;31:49–60; doi: 10.1016/j.sleep.2016.05.010.
 
13.
Bucher SF, Trenkwalder C, Oertel WH. Reflex studies and MRI in the restless legs syndrome. Acta Neurol Scand. 1996;94(2):145–150; doi: 10.1111/j.1600-0404.1996.tb07045.x.
 
14.
Unger EL, Bianco LE, Jones BC, Allen RP, Earley CJ. Low brain iron effects and reversibility on striatal dopaminę dynamics. Exp Neurol. 2014;261:462–468; doi: 10.1016/j.expneurol.2014.06.023.
 
15.
Hyacinthe C, De Deurwaerdere P, Thiollier T, Li Q, Bezard E, Ghorayeb I. Blood withdrawal affects iron store dynamics in primates with consequences on monoaminergic system function. Neuroscience. 2015;290:621–635; doi: 10.1016/j.neuroscience.2015.01.057.
 
16.
Dafkin C, Green A, Olivier B, McKinon W, Kerr S. Circadian variation of flexor withdrawal and crossed extensor reflexes in patients with restless legs syndrome. J Sleep Res. 2018;27(5):e12645; doi: 10.1111/jsr.12645.
 
17.
Garcia-Borreguero D, Larrosa O, Granizo JJ, de la Llave Y, Hening WA. Circadian variation in neuroendocrine response to L-dopa in patients with restless legs syndrome. Sleep. 2004;27(4):669–673; doi: 10.1093/sleep/27.4.669.
 
18.
Bartlett SE, Enquist J, Hopf FW, Lee JH, Gladher F, Kharazia V, et al. Dopamine responsiveness is regulated by targeted sorting of D2 receptors. Proc Natl Acad Sci U S A. 2005;102(32):11521–11526; doi: 10.1073/pnas.0502418102.
 
19.
Paulus W, Trenkwalder C. Less is more: pathophysiology of dopaminergic-therapy-related augmentation in restless legs syndrome. Lancet Neurol. 2006;5(10):878–886; doi: 10.1016/S1474-4422(06)70576-2.
 
20.
Connor JR, Wang X-S, Allen RP, Beard JL, Wiesinger JA, Felt BT, et al. Altered dopaminergic profile in the putamen and substantia nigra in restless leg syndrome. Brain. 2009;132(Pt 9):2403–2412; doi: 10.1093/brain/awp125.
 
21.
Tergau F, Wanshura V, Canelo M, Wisher S, Wassermann EM, Ziemann U, et al. Complete suppression of voluntary motor drive during the silent period after transcranial magnetic stimulation. Exp Brain Res. 1999;124(4):447–454; doi: 10.1007/s002210050640.
 
22.
Czesnik D, Howells J, Bartl M, Veiz E, Ketzler R, Kemmet O, et al. Ih contributes to increased motoneuron excitability in restless legs syndrome. J Physiol. 2019;597(2):599–609; doi: 10.1113/JP275341.
 
23.
Lin Y, Wang Y, Zhan S, Ding Y, Hou Y, Wang L, et al. Impaired sensorimotor integration in restless legs syndrome. Front Neurol. 2018;9:568; doi: 10.3389/fneur.2018.00568.
 
24.
Gold JE, Hallman DM, Hellström F, Björklund M, Crenshaw AG, Djupsjobacka M, et al. Systematic review of biochemical biomarkers for neck and upper-extremity musculoskeletal disorders. Scand J Work Environ Health. 2016;42(2):103–124; doi: 10.5271/sjweh.3533.
 
25.
Floeter MK. Cutaneous silent periods. Muscle Nerve. 2003;28(4):391–401; doi: 10.1002/mus.10447.
 
26.
Côté M-P, Murray LM, Knikou M. Spinal control of locomotion: individual neurons, their circuits and functions. Front Physiol. 2018;9:784; doi: 10.3389/fphys.2018.00784.
 
27.
Toyokura M. F-wave-duration in diabetic polyneuropathy. Muscle Nerve. 1998;21(2):246–249; doi: 10.1002/(sici)1097-4598(199802)21:2<246::aid-mus15>3.0.co;2-#.
 
28.
Isak B, Uluc K, Salcini C, Agan K, Tanridag T, Us O. A neurophysiological approach to the complex organilation sation of the spine: F-wave duration and the cutaneous silent period in restless legs syndrome. Clin Neurophysiol. 2011;122(2):383–390; doi: 10.1016/j.clinph.2010.07.005.
 
29.
Congiu P, Fantini ML, Milioli G, Tacconi P, Figorilli M, Gioi G, et al. F-wave duration as a specific and sensitive tool for the diagnosis of restless legs syndrome/Willis-Ekbom disease. J Clin Sleep Med. 2017;13(3):369–375; doi: 10.5664/jcsm.6482.
 
30.
Özsimsek A, Koyuncuoglu HR. Electrophysiological findings of Turkish patients with restless legs syndrome. Neuropsychiatr Dis Treat. 2017;13:2005–2010; doi: 10.2147/NDT.S132903.
 
31.
Dafkin C, Green A, Olivier B, McKinon W, Kerr S. Plantar reflex excitability is increased in the evening in restless legs syndrome patients. Neurosci Lett. 2017;660:74–78; doi: 10.1016/j.neulet.2017.09.027.
 
32.
Shahani BT, Young RR. Human flexor reflexes. J Neurol Neurosurg Psychiatry. 1971;34(5):616–627; doi: 10.1136/jnnp.34.5.616.
 
33.
McArdle WD, Katch FI, Katch VL. Exercise physiology: nutrition, energy, and human performance. Philadelphia: Lippincott Williams & Wilkins; 2015.
 
34.
Palmieri RM, Ingersoll CD, Hoffman MA. The Hoffmann reflex: methodologic considerations and applications for use in sports medicine and athletic training research. J Athl Train. 2004;39(3):268–277.
 
35.
Aksu M, Bara-Jimenez W. State dependent excitability changes of spinal flexor reflex in patients with restless legs syndrome secondary to chronic renal failure. Sleep Med. 2002;3(5):427–430; doi: 10.1016/s1389-9457(02)00073-4.
 
36.
Gunduz A, Metin B, Metin SZ, Poyraz BC, Karadeniz D, Kiziltan G, et al. Lower limb flexor reflex: comparisons between drug-induced akathisia and restless legs syndrome. Neurosci Lett. 2017;641:40–44; doi: 10.1016/j.neulet.2017.01.042.
 
37.
Scaglione C, Vetrugno R, Plazzi G, Rizzo G, Provini F, Montagna P, et al. Group I nonreciprocal inhibition in primary restless legs syndrome. Mov Disord. 2008;23(1):96–100; doi: 10.1002/mds.21794.
 
38.
Marconi B, Filippi GM, Koch G, Giacobbe V, Pecchioli C, Versace V, et al. Long-term effects on cortical excitability and motor recovery induced by repeated muscle vibration in chronic stroke patients. Neurorehabil Neural Repair. 2011;25(1):48–60; doi: 10.1177/1545968310376757.
 
39.
Moore JC. The Golgi tendon organ: a review and update. Am J Occup Ther. 1984;38(4):227–236; doi: 10.5014/ajot.38.4.227.
 
40.
Dafkin C, Green A, Olivier B, McKinon W, Kerr S. Distal muscle activity alterations during the stance phase of gait in restless leg syndrome (RLS) patients. Sleep Med. 2018;45:89–93; doi: 10.1016/j.sleep.2018.01.013.
 
41.
Spiegelhalder K, Feige B, Paul D, Riemann D, van Elst LT, Seifritz E, et al. Cerebral correlates of muscle tone fluctuations in restless legs syndrome: a pilot study with combined functional magnetic resonance imaging and anterior tibial muscle electromyography. Sleep Med. 2008;9(2):177–183; doi: 10.1016/j.sleep.2007.03.021.
 
42.
Manto M, Bower JM, Conforto AB, Delgado-García JM, da Guarda SNF, Gerwig M, et al. Consensus paper: roles of the cerebellum in motor control – the diversity of ideas on cerebellar involvement in movement. Cerebellum. 2012;11(2):457–487; doi: 10.1007/s12311-011-0331-9.
 
43.
Akazawa K, Kato K. Neural network model for control of muscle force based on the size principle of motor unit. Proc IEEE. 1990;78(9):1531–1535; doi: 10.1109/5.58328.
 
44.
Uchiyama T, Akazawa K. Neural network model for muscle force control based on the size principle and recurrent inhibition of Renshaw cells. In: Malmgren H, Borga M, Niklasson L (eds.), Artificial neural networks in medicine and biology. London: Springer; 2000;289–294.
 
45.
Friedman WA, Sypert GW, Munson JB, Fleshman JW. Recurrent inhibition in type-identified motoneurons. J Neurophysiol. 1981;46(6):1349–1359; doi: 10.1152/jn.1981.46.6.1349.
 
46.
Ter Haar Romeny BM, Denier van der Gon JJ, Gielen CCAM. Changes in recruitment order of motor units in the human biceps muscle. Exp Neurol. 1982;78(2):360–368; doi: 10.1016/0014-4886(82)90054-1.
 
47.
Nardone A, Romanò C, Schieppati M. Selective recruitment of high-threshold human motor units during voluntary isotonic lengthening of active muscles. J Physiol. 1989;409:451–471; doi: 10.1113/jphysiol.1989.sp017507.
 
48.
Oskarsson E, Wåhlin-Larsson B, Ulfberg J. Reduced daytime intramuscular blood flow in patients with restless legs syndrome/Willis-Ekbom disease. Psychiatry Clin Neurosci. 2014;68(8):640–643; doi: 10.1111/pcn.12170.
 
49.
Wåhlin-Larsson B, Ulfberg J, Aulin KP, Kadi F. The expression of vascular endothelial growth factor in skeletal muscle of patients with sleep disorders. Muscle Nerve. 2009;40(4):556–561; doi: 10.1002/mus.21357.
 
eISSN:1899-1955
Journals System - logo
Scroll to top