Skip to main content
SpringerLink
Log in

Inhibitory rTMS applied on somatosensory cortex in Wilson’s disease patients with hand dystonia

  • Translational Neurosciences - Original Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

Hand dystonia is a common complication of Wilson’s disease (WD), responsible for handwriting difficulties and disability. Alteration of sensorimotor integration and overactivity of the somatosensory cortex have been demonstrated in dystonia. This study investigated the immediate after effect of an inhibitory repetitive transcranial magnetic stimulation (rTMS) applied over the somatosensory cortex on the writing function in WD patients with hand dystonia. We performed a pilot prospective randomized double-blind sham-controlled crossover rTMS study. A 20-min 1-Hz rTMS session, stereotaxically guided, was applied over the left somatosensory cortex in 13 WD patients with right dystonic writer’s cramp. After 3 days, each patient was crossed-over to the alternative treatment. Patients were clinically evaluated before and immediately after each rTMS session with the Unified Wilson’s Disease rating scale (UWDRS), the Writers’ Cramp Rating Scale (WCRS), a specifically designed scale for handwriting difficulties in Wilson’s disease patients (FAR, flow, accuracy, and rhythmicity evaluation), and a visual analog scale (VAS) for handwriting discomfort. No significant change in UWDRS, WCRS, VAS, or FAR scores was observed in patients treated with somatosensory inhibitory rTMS compared to the sham protocol. The FAR negatively correlated with UWDRS (r = −0.6; P = 0.02), but not with the WCRS score, disease duration, MRI diffusion lesions, or with atrophy scores. In our experimental conditions, a single inhibitory rTMS session applied over somatosensory cortex did not improve dystonic writer cramp in WD patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Bäumer T, Demiralay C, Hidding U, Bikmullina T, Helmich RC, Wunderlich S, Rothwell J, Liepert J, Siebner HR, Münchau A (2007) Abnormal plasticity of the sensorimotor cortex to slow repetitive transcranial magnetic stimulation in patients with writer’s cramp. Mov Disord 22:81–90. doi:10.1002/mds.21219

    Article  PubMed  Google Scholar 

  • Bleton JP, Vidailhet M, Bourdain F, Ducorps A, Schwartz D, Delmaire C, Lehericy S, Renault B, Garnero L, Meunier S (2011) Somatosensory cortical remodeling after rehabilitation and clinical benefit of in writer’s cramp. J Neurol Neurosurg Psychiatry 82:574–577. doi:10.1136/jnnp.2009.192476

    Article  PubMed  Google Scholar 

  • Boecker H, Ceballos-Baumann A, Bartenstein P, Weindl A, Siebner HR, FassbenderT Munz F, Schwaiger M, Conrad B (1999) Sensory processing in Parkinson’s and Huntington’s disease: investigations with 3D H(2)(15)O-PET. Brain 122:1651–1665

    Article  PubMed  Google Scholar 

  • Borich M, Arora S, Kimberley TJ (2009) Lasting effects of repeated rTMS application in focal hand dystonia. Restor Neurol Neurosci 27:55–65. doi:10.3233/RNN-2009-0461

    PubMed  PubMed Central  Google Scholar 

  • Brandmann O, Weiss KH, Kaler SG (2015) Wilson’s disease and other neurological copper disorders. Lancet Neurol 14:103–113. doi:10.1016/S1474-4422(14)70190-5

    Article  Google Scholar 

  • Butterworth S, Francis S, Kelly E, McGlone F, Bowtell R, Sawle GV (2003) Abnormal cortical sensory activation in dystonia: an fMRI study. Mov Disord 18:673–682. doi:10.1002/mds.10416

    Article  PubMed  Google Scholar 

  • Ceballos-Baumann AO, Passingham RE, Marsden CD, Brooks DJ (1995a) Motor reorganization in acquired hemidystonia. Ann Neurol 37:746–757. doi:10.1002/ana.410370608

    Article  CAS  PubMed  Google Scholar 

  • Ceballos-Baumann AO, Passingham RE, Warner T, Playford ED, Marsden CD, Brooks DJ (1995b) Overactive prefrontal and underactive motor cortical areas in idiopathic dystonia. Ann Neurol 37:363–372. doi:10.1002/ana.410370313

    Article  CAS  PubMed  Google Scholar 

  • Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M, Cohen LG (1997) Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology 48:1398–1403

    Article  CAS  PubMed  Google Scholar 

  • Chung CL, Mak MK (2016) Effect of repetitive transcranial magnetic stimulation on physical function and motor signs in Parkinson’s disease: a systematic review and meta-analysis. Brain Stimul 9:475–487. doi:10.1016/j.brs.2016.03.017

    Article  CAS  PubMed  Google Scholar 

  • Członkowska A, Tarnacka B, Möller JC, Leinweber B, Bandmann O, Woimant F, Oertel WH (2007) Unified Wilson’s Disease Rating Scale—a proposal for the neurological scoring of Wilson’s disease patients. Neurol Neurochir Pol 41:1–12

    PubMed  Google Scholar 

  • Ferenci P, Caca K, Loudianos G, Mieli-Vergani G, Tanner S, Sterlieb Schilsky M, Cox D, Berr F (2003) Diagnosis and phenotypic classification of Wilson disease. Liver Int 23:139–142

    Article  PubMed  Google Scholar 

  • Garraux G, Bauer A, Hanakawa T, Wu T, Kansaku K, Hallett M (2004) Changes in brain anatomy in focal hand dystonia. Ann Neurol 55:736–739. doi:10.1002/ana.20113

    Article  PubMed  Google Scholar 

  • Harlett M (1995) Is dystonia a sensory disorder? Ann Neurol 38:139–140. doi:10.1002/ana.410380203

    Article  Google Scholar 

  • Haslinger B, Altenmüller E, Castrop F, Zimmer C, Dresel C (2010) Sensorimotor overactivity as a pathophysiologic trait of embouchure dystonia. Neurology 74:1790–1797

    Article  CAS  PubMed  Google Scholar 

  • Havrankova P, Jech R, Walker ND, Operto G, Tauchmanova J, Vymazal J, Dusek P, Hromcik M, Ruzicka E (2010) Repetitive TMS of the somatosensory cortex improves writer’s cramp and enhances cortical activity. Neuro Endocrinol Lett 31:73–86

    PubMed  Google Scholar 

  • Hölscher S, Leinweber B, Hefter H, Reuner U, Günther P, Weiss KH, Oertel WH, Möller JC (2010) Evaluation of the symptomatic treatment of residual neurological symptoms in Wilson disease. Eur Neurol 64:83–87. doi:10.1159/000316066

    Article  PubMed  Google Scholar 

  • Huang YZ, Lu CS, Rothwell JC, Lo CC, Chuang WL, Weng YH, Lai SC, Chen RS (2012) Modulation of the disturbed motor network in dystonia by multisession suppression of premotor cortex. PLoS One 7(10):e47574. doi:10.1371/journal.pone.0047574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jinnah HA, Hess EJ (2006) A new twist on the anatomy of dystonia: the basal ganglia and the cerebellum? Neurology 67:1740–1741. doi:10.1212/01.wnl.0000246112.19504.61

    Article  CAS  PubMed  Google Scholar 

  • Kaji R, Rothwell JC, Katayama M, Ikeda T, Kubori T, Kohara N, Mezaki T, Shibasaki H, Kimura J (1995) Tonic vibration reflex and muscle afferent block in writer’s cramp. Ann Neurol 38:155–162. doi:10.1002/ana.410380206

    Article  CAS  PubMed  Google Scholar 

  • Kimberley TJ, Borich MR, Arora S, Siebner HR (2013) Multiple sessions of low-frequency repetitive transcranial magnetic stimulation in focal hand dystonia: clinical and physiological effects. Restor Neurol Neurosci 31:533–542. doi:10.3233/RNN-120259

    PubMed  PubMed Central  Google Scholar 

  • Knecht S, Ellger T, Breitenstein C, Bernd Ringelstein E, Henningsen H (2003) Changing cortical excitability with low-frequency transcranial magnetic stimulation can induce sustained disruption of tactile perception. Biol Psychiatry 53:175–179

    Article  PubMed  Google Scholar 

  • Kruisdijk JJ, Koelman JH, Ongerboer de Visser BW, de Haan RJ, Speelman JD (2007) Botulinum toxin for writer’s cramp: a randomised, placebo-controlled trial and 1-year follow-up. J Neurol Neurosurg Psychiatry 78:264–270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leinweber B, Möller JC, Scherag A, Reuner U, Günther P, Lang CJ, Schmidt HH, Schrader C, Brandmann O, Czlonkowska A, Oertel WH, Hefter H (2008) Evaluation of the Unified Wilson’s Disease Rating Scale (UWDRS) in German patients with treated Wilson’s disease. Mov Disord 23:54–62. doi:10.1002/mds.21761

    Article  PubMed  Google Scholar 

  • Litwin T, Dusek P, Czlonkowska A (2016) Neurological manifestations in Wilson’s disease—possible treatment options for symptoms. Expert Opin Orphan Drugs. doi:10.1080/21678707.2016.1188003

    Google Scholar 

  • Lozeron P, Poujois A, Richard A, Masmoudi S, Meppiel E, Woimant F, Kubis N (2016) Contribution of TMS and rTMS in the understanding of the pathophysiology and in the treatment of dystonia. Front Neural Circuits 10:90. doi:10.3389/fncir.2016.00090

    Article  PubMed  PubMed Central  Google Scholar 

  • Machado A, Chien HF, Deguti MM, Cancado E, Azevedo RS, Scaff M, Barbosa ER (2006) Neurological manifestations in Wilson’s disease: report of 119 cases. Mov Disord 21:2192–2196. doi:10.1002/mds.21170

    Article  PubMed  Google Scholar 

  • Murase N, Rothwell JC, Kaji R, Urushihara R, Nakamura K, Murayama N, Igasaki T, Sakata-Igasaki M, Mima T, Ikeda A, Shibasaki H (2005) Subthreshold low-frequency repetitive transcranial magnetic stimulation over the premotor cortex modulates writer’s cramp. Brain 128:104–115

    Article  PubMed  Google Scholar 

  • Obeso I, Cerasa A, Quattrone A (2016) The effectiveness of transcranial brain stimulation in improving clinical signs of hyperkinetic movement disorders. Front Neurosci 9:486. doi:10.3389/fnins.2015.00486

    Article  PubMed  PubMed Central  Google Scholar 

  • Poujois A, Devedjian JC, Moreau C, Devos D, Chaine P, Woimant F, Duce JA (2016) Bioavailable trace metals in neurological diseases. Curr Treat Options Neurol 10:46. doi:10.1007/s11940-016-0426-1

    Article  Google Scholar 

  • Schneider SA, Pleger B, Draganski B, Cordivari C, Rothwell JC, Bathia KP, Dolan RG (2010) Modulatory effects of 5 Hz rTMS over the primary somatosensory cortex in focal dystonia—an fMRI–TMS study. Mov Disord 25:76–83. doi:10.1002/mds.22825

    Article  PubMed  PubMed Central  Google Scholar 

  • Siebner HR, Tormos JM, Ceballos-Baumann AO, Auer C, Catala MD, Conrad B, Pascual-Leone A (1999) Low-frequency repetitive transcranial magnetic stimulation of the motor cortex in writer’s cramp. Neurology 52:529–537

    Article  CAS  PubMed  Google Scholar 

  • Sinha S, Taly AB, Ravishankar S, Prashanth LK, Venugopal KS, Arunodaya GR, Vasudev MK, Swamy HS (2006) Wilson’s disease: cranial MRI observations and clinical correlation. Neuroradiology 48:613–621. doi:10.1007/s00234-006-0101-4

    Article  CAS  PubMed  Google Scholar 

  • Svetel M, Kozić D, Stefanova E, Semnic R, Dragasevic N, Kostic VS (2001) Dystonia in Wilson’s disease. Mov Disord 16:719–723

    Article  CAS  PubMed  Google Scholar 

  • Taly AB, Meenakshi SS, Sinha S (2007) Wilson disease: description of 282 patients evaluated over 3 decades. Medicine 82:112–121

    Article  Google Scholar 

  • Tyvaert L, Houdayer E, Devanne H, Monaca C, Cassim F, Derambure P (2006) The effect of repetitive transcranial magnetic stimulation on dystonia: a clinical and pathophysiological approach. Neurophysiol Clin 36:135–143. doi:10.1016/j.neucli.2006.08.007

    Article  CAS  PubMed  Google Scholar 

  • Weiss KH, Stremmel W (2014) Clinical considerations for an effective medical therapy in Wilson’s disease. In: Kaler SG, Lutsenko S, Schilsky ML, Thiele DJ, Huster D (eds) Ann N Y Acad Sci 1315:81–85

  • Weiss KH, Thurik F, Gotthardt DN, Schäffer M, Teufel U, Wiegrand F, Merle U, Ferenci-Foerster D, Maieron A, Stauber R, Zoller H, Schmidt HH, Reuner U, Hefter H, Trocello JM, Houwen RH, Ferenci P, Stremmel W, EUROWILSON Consortium (2013) Efficacy and safety of oral chelators in treatment of patients with Wilson disease. Clin Gastroenterol Hepatol 11:1028–1035. doi:10.1016/j.cgh.2013.03.012

    Article  CAS  PubMed  Google Scholar 

  • Wissel J, Kabus C, Wenzel R, Klepsch S, Swartz U, Nebe A, Schelosky L, Scholz U, Poewe W (1996) Botulinum toxin in writer’s cramp: objective response evaluation in 31 patients. J Neurol Neurosurg Psychiatry 61:172–175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Funding sources for the study: French Ministry of Health, Programme Hospitalier de Recherche Clinique, and Assistance Publique des Hôpitaux de Paris (CIRC P121105). We are grateful to Mr. Loïc Bruyser for technical support.

Author information

Author notes

  1. Pierre Lozeron and Aurélia Poujois equally contributed to the manuscript.

Authors and Affiliations

  1. Service de Physiologie Clinique-Explorations Fonctionnelles, AP-HP, Hôpital Lariboisière, 2, rue Ambroise Paré, 75010, Paris, France

    Pierre Lozeron, Elodie Meppiel, Sana Masmoudi & Nathalie Kubis

  2. Université Paris Diderot, Sorbonne Paris Cité, 75475, Paris, France

    Pierre Lozeron, Eric Vicaut, Emmanuel Houdart & Nathalie Kubis

  3. INSERM UMR965, 75475, Paris, France

    Pierre Lozeron & Nathalie Kubis

  4. Service de Neurologie, AP-HP, Hôpital Lariboisière, Paris, France

    Aurélia Poujois, Jean-Marc Trocello & France Woimant

  5. Centre de référence national de la maladie de Wilson, Hôpital Lariboisière, Paris, France

    Aurélia Poujois, Thierry Peron Magnan, Jean-Marc Trocello & France Woimant

  6. Unité de Recherche Clinique, AP-HP, Hôpital Lariboisière, Paris, France

    Eric Vicaut

  7. Service de Neuroradiologie, AP-HP, Hôpital Lariboisière, Paris, France

    Emmanuel Houdart & Jean-Pierre Guichard

Authors
  1. Pierre Lozeron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aurélia Poujois
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elodie Meppiel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sana Masmoudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thierry Peron Magnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eric Vicaut
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Emmanuel Houdart
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jean-Pierre Guichard
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jean-Marc Trocello
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. France Woimant
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Nathalie Kubis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nathalie Kubis.

Ethics declarations

Conflict of interest

PL received consultancies fees from ‘CSL Behring’, travel grants from ‘CSL Behring’, and ‘LFB biomedicaments’ and speaker honoraria from ‘Astellas’. AP received consultancies fees from ‘Univar’, travel grants from ‘Merz’ and ‘Allergan’, and speaker honoraria from ‘Univar’. EM declares that she has no conflict of interest. SM received financial support from ‘humanair medical’ to attend SFRMS meeting, and financial support from ‘Sanofi’ to attend “Les Rencontres de Neurologie” meeting. TPM declares that he has no conflict of interest. EV received consultancies fees and/or speaker honoraria from ‘Bayer Health care’, ‘Bristol-Myers Squibb’, ‘Daiichi-Sankyo’, ‘Johnson&Johnson’, ‘Innothera’, and ‘Pfizer’.AP received consultancies fees from Univar, travel grants from Merz and speaker honoraria from Univar. EH declares that he has no conflict of interest. FW declares that she has no conflict of interest. JMT received consultancies fees from ‘Allergan’ and ‘Aguettant’. JPG declares that he has no conflict of interest. NK received financial support from ‘CSL Behring’ to attend SFN meeting.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 1046 kb)

Supplementary material 2 (DOCX 29 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lozeron, P., Poujois, A., Meppiel, E. et al. Inhibitory rTMS applied on somatosensory cortex in Wilson’s disease patients with hand dystonia. J Neural Transm 124, 1161–1170 (2017). https://doi.org/10.1007/s00702-017-1756-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-017-1756-1

Keywords

Search

Navigation