Journal of Neurology

, Volume 257, Issue 12, pp 1979–1985 | Cite as

Impairment of sensory-motor integration in patients affected by RLS

  • Vincenzo Rizzo
  • I. Aricò
  • G. Liotta
  • L. Ricciardi
  • C. Mastroeni
  • F. Morgante
  • R. Allegra
  • R. Condurso
  • P. Girlanda
  • R. Silvestri
  • A. Quartarone
Original Communication


Much evidence suggests that restless legs syndrome (RLS) is a disorder characterized by an unsuppressed response to sensory urges due to abnormalities in inhibitory pathways that specifically link sensory input and motor output. Therefore, in the present study, we tested sensory-motor integration in patients with RLS, measured by short latency afferent inhibition (SAI) and long latency afferent inhibition (LAI). SAI and LAI were determined using transcranial magnetic stimulation before and after 1month of dopaminergic treatment in RLS patients. Ten naïve patients with idiopathic RLS and ten healthy age-matched controls were recruited. Patients with secondary causes for RLS (e.g. renal failure, anaemia, low iron and ferritin) were excluded, as well as those with other sleep disorders. Untreated RLS patients demonstrated deficient SAI in the human motor cortex, which proved revertible toward normal values after dopaminergic treatment. We demonstrated an alteration of sensory-motor integration, which is normalized by dopaminergic treatment, in patients affected by RLS. It is likely that the reduction of SAI might contribute significantly to the release of the involuntary movements and might account for the sensory urge typical of this condition.


Restless legs syndrome Sensory-motor integration Transcranial magnetic stimulation 


  1. 1.
    Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, Bell TJ, Ferini-Strambi L (2005) Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 165:1286–1292CrossRefPubMedGoogle Scholar
  2. 2.
    Hening W (2004) The clinical neurophysiology of the restless legs syndrome and periodic limb movements. Part I: diagnosis, assessment, and characterization. Clin Neurophysiol 115:1965–1974CrossRefPubMedGoogle Scholar
  3. 3.
    Mosko SS, Nudleman KL (1986) Somatosensory and brainstem auditory evoked responses in sleep-related periodic leg movements. Sleep 9:399–404PubMedGoogle Scholar
  4. 4.
    Bucher SF, Seelos KC, Oertel WH, Reiser M, Trenkwalder C (1997) Cerebral generators involved in the pathogenesis of the restless legs syndrome. Ann Neurol 41:639–645CrossRefPubMedGoogle Scholar
  5. 5.
    Tyvaert L, Houdayer E, Devanne H, Bourriez JL, Derambure P, Monaca C (2009) Cortical involvement in the sensory and motor symptoms of primary restless legs syndrome. Sleep Med 10(10):1090–1096CrossRefPubMedGoogle Scholar
  6. 6.
    Entezari-Taher M, Singleton JR, Jones CR, Meekins G, Petajan JH, Smith AG (1999) Changes in excitability of motor cortical circuitry in primary restless legs syndrome. Neurology 53:1201–1205PubMedGoogle Scholar
  7. 7.
    Tergau F, Wischer S, Paulus W (1999) Motor system excitability in patients with restless legs syndrome. Neurology 52:1060–1063PubMedGoogle Scholar
  8. 8.
    Quatrale R, Manconi M, Gastaldo E, Eleopra R, Tugnoli V, Tola MR, Granieri E (2003) Neurophysiological study of corticomotor pathways in restless legs syndrome. Clin Neurophysiol 114:1638–1645CrossRefPubMedGoogle Scholar
  9. 9.
    Scalise A, Cadore IP, Gigli GL (2004) Motor cortex excitability in restless legs syndrome. Sleep Med 5:393–396CrossRefPubMedGoogle Scholar
  10. 10.
    Nardone R, Ausserer H, Bratti A, Covi M, Lochner P, Marth R, Tezzon F (2006) Cabergoline reverses cortical hyperexcitability in patients with restless legs syndrome. Acta Neurol Scand 114:244–249CrossRefPubMedGoogle Scholar
  11. 11.
    Gorsler A, Liepert J (2007) Influence of cabergoline on motor excitability in patients with restless legs syndrome. J Clin Neurophysiol 24:456–460CrossRefPubMedGoogle Scholar
  12. 12.
    Scalise A, Pittaro-Cadore I, Janes F, Marinig R, Gigli GL (2010) Changes of cortical excitability after dopaminergic treatment in restless legs syndrome. Sleep Med 11(1):75–81CrossRefPubMedGoogle Scholar
  13. 13.
    Comella CL (2002) Restless legs syndrome: treatment with dopaminergic agents. Neurology 58:S87–S92PubMedGoogle Scholar
  14. 14.
    Tokimura H, Di Lazzaro V, Tokimura Y, Oliviero A, Profice P, Insola A, Mazzone P, Tonali P, Rothwell JC (2000) Short latency inhibition of human hand motor cortex by somatosensory input from the hand. J Physiol 523(Pt 2):503–513CrossRefPubMedGoogle Scholar
  15. 15.
    Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113CrossRefPubMedGoogle Scholar
  16. 16.
    Walters AS (1995) Toward a better definition of the restless legs syndrome. The International Restless Legs Syndrome Study Group. Mov Disord 10:634–642CrossRefPubMedGoogle Scholar
  17. 17.
    Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J (2003) 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 4:101–119CrossRefPubMedGoogle Scholar
  18. 18.
    Iber C, Ancoli-Israel S, Chesson A, and Quan SF for the American Academy of Sleep Medicine. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications.Google Scholar
  19. 19.
    Sale MV, Ridding MC, Nordstrom MA (2007) Factors influencing the magnitude and reproducibility of corticomotor excitability changes induced by paired associative stimulation. Exp Brain Res 181:615–626CrossRefPubMedGoogle Scholar
  20. 20.
    Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A, Wroe S, Asselman P, Marsden CD (1993) Corticocortical inhibition in human motor cortex. J Physiol 471:501–519PubMedGoogle Scholar
  21. 21.
    Kutukcu Y, Dogruer E, Yetkin S, Ozgen F, Vural O, Aydin H (2006) Evaluation of periodic leg movements and associated transcranial magnetic stimulation parameters in restless legs syndrome. Muscle Nerve 33:133–137CrossRefPubMedGoogle Scholar
  22. 22.
    Ziemann U, Lonnecker S, Steinhoff BJ, Paulus W (1996) The effect of lorazepam on the motor cortical excitability in man. Exp Brain Res 109:127–135CrossRefPubMedGoogle Scholar
  23. 23.
    Hanajima R, Ugawa Y, Terao Y, Ogata K, Kanazawa I (1996) Ipsilateral cortico-cortical inhibition of the motor cortex in various neurological disorders. J Neurol Sci 140:109–116CrossRefPubMedGoogle Scholar
  24. 24.
    Ziemann U, Tergau F, Bruns D, Baudewig J, Paulus W (1997) Changes in human motor cortex excitability induced by dopaminergic and anti-dopaminergic drugs. Electroencephalogr Clin Neurophysiol 105:430–437CrossRefPubMedGoogle Scholar
  25. 25.
    Sanger TD, Garg RR, Chen R (2001) Interactions between two different inhibitory systems in the human motor cortex. J Physiol 530:307–317CrossRefPubMedGoogle Scholar
  26. 26.
    Abbruzzese G, Marchese R, Buccolieri A, Gasparetto B, Trompetto C (2001) Abnormalities of sensorimotor integration in focal dystonia: a transcranial magnetic stimulation study. Brain 124:537–545CrossRefPubMedGoogle Scholar
  27. 27.
    Di Lazzaro V, Oliviero A, Profice P, Pennisi MA, Di Giovanni S, Zito G, Tonali P, Rothwell JC (2000) Muscarinic receptor blockade has differential effects on the excitability of intracortical circuits in the human motor cortex. Exp Brain Res 135:455–461CrossRefPubMedGoogle Scholar
  28. 28.
    Di Lazzaro V, Oliviero A, Saturno E, Dileone M, Pilato F, Nardone R, Ranieri F, Musumeci G, Fiorilla T, Tonali P (2005) Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans. J Physiol 564:661–668CrossRefPubMedGoogle Scholar
  29. 29.
    Di Lazzaro V, Oliviero A, Pilato F, Saturno E, Dileone M, Marra C, Daniele A, Ghirlanda S, Gainotti G, Tonali PA (2004) Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 75:555–559CrossRefPubMedGoogle Scholar
  30. 30.
    Kaji R, Murase N (2001) Sensory function of basal ganglia. Mov Disord 16:593–594CrossRefPubMedGoogle Scholar
  31. 31.
    Lidsky TI, Manetto C, Schneider JS (1985) A consideration of sensory factors involved in motor functions of the basal ganglia. Brain Res 356:133–146PubMedGoogle Scholar
  32. 32.
    Turjanski N, Lees AJ, Brooks DJ (1999) Striatal dopaminergic function in restless legs syndrome: 18F-dopa and 11C-raclopride PET studies. Neurology 52:932–937PubMedGoogle Scholar
  33. 33.
    Cervenka S, Palhagen SE, Comley RA, Panagiotidis G, Cselenyi Z, Matthews JC, Lai RY, Halldin C, Farde L (2006) Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding. Brain 129:2017–2028CrossRefPubMedGoogle Scholar
  34. 34.
    Thierry AM, Blanc G, Sobel A, Stinus L, Golwinski J (1973) Dopaminergic terminals in the rat cortex. Science 182:499–501CrossRefPubMedGoogle Scholar
  35. 35.
    Gaspar P, Stepniewska I, Kaas JH (1992) Topography and collateralization of the dopaminergic projections to motor and lateral prefrontal cortex in owl monkeys. J Comp Neurol 325:1–21CrossRefPubMedGoogle Scholar
  36. 36.
    Huda K, Matsunami K (2003) Influence of dopamine on ventrolateral thalamic inputs in cat motor cortex. Brain Res 963:178–189CrossRefPubMedGoogle Scholar
  37. 37.
    Sailer A, Cunic DI, Paradiso GO, Gunraj CA, Wagle-Shukla A, Moro E, Lozano AM, Lang AE, Chen R (2007) Subthalamic nucleus stimulation modulates afferent inhibition in Parkinson disease. Neurology 68:356–363CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Vincenzo Rizzo
    • 1
  • I. Aricò
    • 1
  • G. Liotta
    • 1
  • L. Ricciardi
    • 1
  • C. Mastroeni
    • 1
  • F. Morgante
    • 1
  • R. Allegra
    • 1
  • R. Condurso
    • 1
  • P. Girlanda
    • 1
  • R. Silvestri
    • 1
  • A. Quartarone
    • 1
    • 2
  1. 1.Department of Neurosciences, Psychiatry and Anaesthesiological SciencesUniversity of MessinaMessinaItaly
  2. 2.Department of NeurologyNYU School of MedicineNew YorkUSA

Personalised recommendations