Download PDF
Klinische Neurophysiologie 2007; 38(3): 169-178
DOI: 10.1055/s-2007-980183
Originalia

© Georg Thieme Verlag KG Stuttgart · New York

Einfluss der repetitiven transkraniellen Magnetstimulation (rTMS) auf motorische Störungen bei Patienten mit Morbus Parkinson und Morbus Wilson

Influence of Repetitive Transcranial Magnetic Stimulation (rTMS) on Motor Disturbances in Patients with Parkinson's Disease and Wilson's DiseaseAnnegret Wagner 1 , Wieland Hermann 2 , Sven Hesse 3 , Osama Sabri 3 , Armin Wagner 1
  • 1Klinik und Poliklinik für Neurologie, Universität Leipzig
  • 2Klinik für Neurologie, Paracelsus-Klinik Zwickau
  • 3Klinik und Poliklinik für Nuklearmedizin, Universität Leipzig
Further Information

Publication History

Publication Date:
20 September 2007 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Einleitung: Die repetitive transkranielle Magnetstimulation (rTMS) ist ein nichtinvasives Stimulationsverfahren, das in der klinischen Forschung und zur experimentellen Behandlung neurologischer und psychiatrischer Erkrankungen eingesetzt wird. Anliegen der Studie ist es, die Wirksamkeit der rTMS auf motorische Störungen bei Morbus Parkinson und Morbus Wilson zu untersuchen und zu prüfen, ob es eine Beziehung zwischen den motorischen rTMS-Effekten und dem dopaminergen nigrostriatalen System gibt.

Methodik: Wir behandelten 15 Patienten mit Morbus Parkinson (Hoehn & Yahr Stadium I oder II) und 15 Patienten mit Morbus Wilson (neurologische Verlaufsform) mit einer unterschwelligen 5 Hz-rTMS bihemisphäriell über dem primär-motorischen Handareal. Die motorischen Störungen wurden mit dem motorischen Teil der UPDRS, dem „CS“-Schreibtest und einer Schriftprobe bewertet. Die Beurteilung des dopaminergen nigrostriatalen Systems erfolgte mittels [123I]-β-CIT- bzw. [123I]-FP-CIT- und [123I]-IBZM-SPECT.

Ergebnisse: Die Patienten mit Morbus Parkinson profitierten in der UPDRS signifikant von der rTMS. Im „CS“-Schreibtest besserte sich die Symptomatik nur tendenziell. In der Schriftprobe sank die Mikrographie von 40% auf durchschnittlich 19%. Die nuklearmedizinischen Befunde weisen daraufhin, dass vor allem die Patienten mit Morbus Parkinson von der rTMS profitierten, bei denen die Störungen im dopaminergen nigrostriatalen System nicht so stark ausgeprägt waren. Die Patienten mit Morbus Wilson zeigten nach rTMS in keinem Untersuchungstest eine signifikante Verbesserung ihrer motorischen Symptomatik. Das traf nur für Einzelfälle zu.

Diskussion: Wir konnten die Wirksamkeit der rTMS auf motorische Störungen bei Morbus Parkinson bestätigen. Bei Morbus Wilson kann die rTMS nur als individueller Heilversuch empfohlen werden. Obwohl der Wirkungsmechanismus der rTMS im Einzelnen noch nicht bekannt ist, unterstützen unsere Ergebnisse die Annahme, dass an den funktionsverbessernden Effekten der rTMS das dopaminerge System beteiligt ist.

Abstract

Introduction: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive stimulation technique used in clinical research and for the experimental treatment of neurological and psychiatric disorders. The aim of this study was to examine how effective rTMS is for Parkinson's disease (PD) and Wilson's disease (WD), and to ascertain whether a link exists between the motor rTMS effects and the state of the dopaminergic nigrostriatal system.

Methods: We examined 15 patients with PD (Hoehn & Yahr stage I or II) and 15 patients with WD (neurological form) with a single subthreshold 5 Hz-rTMS. The motor disturbances were evaluated using the motor section of the UPDRS, the “CS”-writing test and a handwriting sample. The dopaminergic nigrostriatal system was assessed using [123I]-β-CIT-, [123I]-FP-CIT- and [123I]-IBZM-SPECT.

Results: The patients with PD benefited significantly in the UPDRS. In the “CS”-writing test, the symptom improvement trend was less pronounced. In the handwriting sample, micrography sank from 40% to an average of 19%. Judging by the nuclear medicine findings, above all those patients with PD in whom the dopaminergic nigrostriatal system was not as pronounced profited from rTMS. Following rTMS, the patients with WD did not show significant improvement in their motor symptoms. Improvement was only observed in individual cases.

Discussion: We verified the effectiveness of rTMS in PD. However, in connection with WD, rTMS can only be recommended as a course of treatment in individual cases. Although exactly how rTMS works in detail is still unknown, our findings indicate that the function-enhancing effects of rTMS are linked to the dopaminergic system.

Schlüsselwörter

Repetitive transkranielle Magnetstimulation (rTMS) - Morbus Parkinson - Morbus Wilson - SPECT - dopaminerges nigrostriatales System

Key words

repetitive transcranial magnetic stimulation (rTMS) - Parkinson's disease - Wilson's disease - SPECT - dopaminergic nigrostriatal system

Literatur

  • 1 Siebner HR, Rothwell J. Transcranial magnetic stimulation: new insights into representational cortical plasticity.  Exp Brain Res. 2003;  148 1-16
    CrossrefPubMedGoogle Scholar
  • 2 Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation. Electroenceph.  Clin Neurophysiol. 1998;  108 1-16
    PubMedGoogle Scholar
  • 3 Pötter M, Peller M, Siebner HR. Therapeutische Anwendung der repetitiven transkraniellen Magnetstimulation in der Neurologie - Möglichkeiten und Grenzen.  Klin Neurophysiol. 2005;  36 186-201
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Maeda F, Keenan JP, Tormos JM, Topka H, Pascual-Leone A. Interindividual variability of the modulatory effects of repetitive transcranial magnetic stimulation on cortical excitability.  Exp Brain Res. 2000;  133 425-430
    CrossrefPubMedGoogle Scholar
  • 5 Pascual-Leone A, Tormos JM, Keenan J, Tarazona F, Canete C, Catala MD. Study and modulation of human cortical excitability with transcranial magnetic stimulation.  J Clin Neurophysiol. 1998;  15 333-343
    PubMedGoogle Scholar
  • 6 Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M, Cohen LG. Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation.  Neurology. 1997;  48 1398-1403
    CrossrefPubMedGoogle Scholar
  • 7 Muelbacher W, Ziemann U, Boroojerdi B, Hallett M. Effects of low-frequency transcranial magnetic stimulation on motor excitability and basic motor behavior.  Clin Neurophysiol. 2000;  111 1002-1007
    CrossrefPubMedGoogle Scholar
  • 8 Burt T, Lisanby SH, Sackheim HA. Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis.  Int J Neuropsychopharmacol. 2002;  5 73-103
    PubMedGoogle Scholar
  • 9 Kozel FA, George MS. Meta-analysis of left prefrontal repetitive transcranial magnetic stimulation (rTMS) to treat depression.  J Psychiatric Practice. 2002;  8 270-275
    CrossrefPubMedGoogle Scholar
  • 10 Martin JL, Barbanoj MJ, Schlaepfer TE, Thompson E, Perez V, Kulisevsky J. Repetitive transcranial magnetic stimulation for the treatment of depression. Systematic review and meta-analysis.  Br J Psychiatry. 2003;  182 480-491
    CrossrefPubMedGoogle Scholar
  • 11 McNamara B, Ray JL, Arthurs OJ, Boniface S. Transcranial magnetic stimulation for depression and other psychiatric disorders.  Psychol Med. 2001;  31 1141-1146
    CrossrefPubMedGoogle Scholar
  • 12 Pascual-Leone A, Valls-Solé J, Brasil-Neto JP, Cammarota A, Grafman J, Hallett M. Akinesia in Parkinson's disease. II. Effects of subthreshold repetitive transcranial motor cortex stimulation.  Neurology. 1994;  44 892-898
    PubMedGoogle Scholar
  • 13 Pascual-Leone A, Catala D. Lasting beneficial effect of rapid-rate transcranial magnetic stimulation on slowness in Parkinson's disease.  Neurology. 1995;  45 A315
    PubMedGoogle Scholar
  • 14 Mally J, Stone TW. Improvement in Parkinsonian symptoms after repetitive transcranial magnetic stimulation.  J Neurol Sci. 1999;  162 179-184
    CrossrefPubMedGoogle Scholar
  • 15 Siebner HR, Mentschel C, Auer C, Conrad B. Repetitive transcranial magnetic stimulation has a beneficial effect on bradykinesia in Parkinson's disease.  NeuroReport. 1999;  10 589-594
    PubMedGoogle Scholar
  • 16 Siebner HR, Rossmeier C, Mentschel C, Peinemann A, Conrad B. Short-term motor improvement after sub-threshold 5-Hz repetitive transcranial magnetic stimulation of the primary motor hand area in Parkinson`s disease.  J Neurol Sci. 2000;  178 91-94
    CrossrefPubMedGoogle Scholar
  • 17 Groot M De, Hermann W, Steffen J, Wagner A, Grahmann F. Kontralaterale und ipsilaterale repetitive transkranielle Magnetstimulation bei Parkinson-Patienten.  Nervenarzt. 2001;  72 932-938
    CrossrefPubMedGoogle Scholar
  • 18 Shimamoto H, Takasaki K, Shigemori M, Imaizumi T, Ayabe M, Shoji H. Therapeutic effect and mechanism of repetitive transcranial magnetic stimulation in Parkinson's disease.  J Neurol. 2001;  248 48-52
    PubMedGoogle Scholar
  • 19 Siebner HR, Löer C, Mentschel C, Weindl D, Conrad B. Repetitive transcranial magnetic stimulation in Parkinson's disease and focal dystonia.  Clin Neurophysiol. 2002;  54 399-409
    PubMedGoogle Scholar
  • 20 Sommer M, Kamm T, Tergau F, Ulm G, Paulus W. Repetitive paired-pulse transcranial magnetic stimulation affects corticospinal excitability and finger tapping in Parkinson's disease.  Clin Neurophysiol. 2002;  113 944-950
    CrossrefPubMedGoogle Scholar
  • 21 Ikeguchi M, Touge T, Nishiyama Y, Takeuchi H, Kuriyama S, Ohkawa M. Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson's disease.  J Neurol Sci. 2003;  209 41-46
    CrossrefPubMedGoogle Scholar
  • 22 Khedr EM, Farweez HM, Islam H. Therapeutic effect of repetitive transcranial magnetic stimulation on motor function in Parkinson's disease patients.  Eur J Neurol. 2003;  10 567-572
    CrossrefPubMedGoogle Scholar
  • 23 Lefaucheur JP, Drouot X, Raison F Von, Menard-Lefaucheur I, Cesaro P, Nguyen JP. Improvement of motor performance and modulation of cortical excitability by repetitive transcranial magnetic stimulation of the motor cortex in Parkinson's disease.  Clin Neurophysiol. 2004;  115 2530-2541
    CrossrefPubMedGoogle Scholar
  • 24 Steffen J, Hermann W, Groot M De, Eggers B, Grahmann F, Kühn HJ, Wagner A. Repetitive transcranial magnetic stimulation in Wilson's disease.  Z Gastroenterol. 2001;  39 P23
    PubMedGoogle Scholar
  • 25 Hermann W, Günther P, Villmann T, Wagner A, Wagner A. Repetitive transcranial magnetic stimulation in Wilson's disease.  J Neurol. 2004;  251 P342
    PubMedGoogle Scholar
  • 26 Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.  J Neurol Neurosurg Psychiatry. 1992;  55 181-184
    CrossrefPubMedGoogle Scholar
  • 27 Mai N, Marquardt C. Schreibtraining in der neurologischen Rehabilitation. In: Mai N, Ziegler W, Kerkhoff G, Troppmann N (Hrsg). EKN - Materialien für die Rehabilitation. Dortmund: Borgmann 1999: 10-32
    Google Scholar
  • 28 Haase HJ. Der standardisierte Handschrifttest. Diagnostische Verwertung bei akuten schizophrenen Psychosen.  Psycho. 1986;  6 620-630
    PubMedGoogle Scholar
  • 29 Barthel H, Müller U, Wächter T, Slomka P, Danneberg C, Murai T, Kahn T, Georgi P. Multimodale SPECT- und MRT-Bilddatenanalyse zur Verbesserung der Diagnostik des idiopathischen Parkinson-Syndroms.  Radiologe. 2000;  40 863-869
    CrossrefPubMedGoogle Scholar
  • 30 Benamer TS, Patterson J, Grosset DG, Booij J, Bruin K De, Royen E, Speelman JD, Horstink MHIM, Sips HJWA, Dierckx RA, Versijpt J, Decoo D, Linden C, Hadley DM, Doder M, Lees AJ, Costa DC, Gacinovic S, Oertel WH, Pogarell O, Hoeffken H, Joseph K, Tatsch K, Schwarz J, Ries V. Accurate differentiation of parkinsonism and essentiell tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group.  Mov Disord. 2000;  15 503-510
    CrossrefPubMedGoogle Scholar
  • 31 Brücke T, Kornhuber J, Angelberger P, Asenbaum S, Frassine H, Podreka I. SPECT imaging of dopamine and serotonin transporters with [123I]β-CIT. Binding kinetics in the human brain.  J Neural Transm. 1993;  94 137-146
    CrossrefPubMedGoogle Scholar
  • 32 Tatsch K, Schwarz J, Oertel WH, Kirsch CM. SPECT imaging of dopamine D2 receptors with 123J-IBZM: initial experience in controls and patients with Parkinson's syndrome and Wilson's disease.  Nucl Med Commun. 1991;  12 699-707
    CrossrefPubMedGoogle Scholar
  • 33 Müller U, Wächter T, Barthel H, Reuter M, Cramon DY von. Striatal [123I]beta-CIT SPECT and prefrontal cognitive functions in Parkinson's disease.  J Neural Transm. 2000;  107 303-319
    CrossrefPubMedGoogle Scholar
  • 34 Hesse S, Oehlwein C, Barthel H, Schwarz J, Polster D, Wagner A, Sabri O. Possible impact of dopamine SPECT on decision-making for drug treatment in Parkinsonian syndrome.  J Neural Transm. 2006;  113 1177-1190
    CrossrefPubMedGoogle Scholar
  • 35 Harms V. Schätzen und Testen. In: Harms V (Hrsg). Biomathematik, Statistik und Dokumentation. Kiel-Mönkeberg: Harms-Verlag 1998: 186-235
    Google Scholar
  • 36 Tergau F, Toromos JM, Paulus W, Pascual-Leone A, Ziemann U. Effects of repetitive transcranial magnetic stimulation (rTMS) on cortico-spinal and cortico-cortical excitability.  Neurology. 1997;  48 A107
    PubMedGoogle Scholar
  • 37 Maeda F, Keenan JP, Tormos JM, Topka H, Pascual-Leone A. Interindividual variability of the modulatory effects of repetitive transcranial magnetic stimulation on cortical excitability.  Exp Brain Res. 2000;  133 425-430
    CrossrefPubMedGoogle Scholar
  • 38 Ghabra MB, Hallett M, Wassermann EM. Simultaneous repetitive transcranial magnetic stimulation does not speed fine movement in PD.  Neurology. 1999;  52 768-770
    PubMedGoogle Scholar
  • 39 Tergau F, Wassermann EM, Paulus W, Ziemann U. Lack of clinical improvement in patients with Parkinson's disease after low and high frequency repetitive transcranial magnetic stimulation. Electroencephalogr.  Clin Neurophysiol. 1999;  51 281-288
    PubMedGoogle Scholar
  • 40 Boylan LS, Pullman SL, Lisanby SH, Spicknall KE, Sackheim HA. Repetitive transcranial magnetic stimulation to SMA worsens complex movements in Parkinson's disease.  Clin Neurophysiol. 2001;  112 259-264
    CrossrefPubMedGoogle Scholar
  • 41 Okabe S, Ugawa Y, Kanazawa I. The Effectiveness of rTMS on Parkinson's Disease Study Group (2003) 0,2 Hz repetitive transcranial magnetic stimulation has no add-on effects as compared to a realistic sham stimulation in Parkinson's disease.  Mov Disord. 2003;  18 382-388
    CrossrefPubMedGoogle Scholar
  • 42 Tatsch K, Schwarz J, Oertel WH, Kirsch CM. Idiopathic Parkinson syndrome: I-123 IBZM SPECT findings in drug naive and treated patients.  Eur J Nucl Med. 1992;  19 609
    PubMedGoogle Scholar
  • 43 Oertel WH, Tatsch K, Schwarz J, Kraft E, Trenkwalder C, Scherer J, Weinzierl M, Vogl T, Kirsch CM. Decrease of D2 receptors indicated by 123J-iodobenzamide single-photon emission computed tomography relates to neurological deficit in treated Wilson's disease.  Ann Neurol. 1992;  32 743-748
    CrossrefPubMedGoogle Scholar
  • 44 Jeon B, Kim JM, Jeong JM, Kim KM, Chang JS, Lee DS, Lee MC. Dopamine transporter imaging with [123J]β-CIT demonstrates presynaptic nigrostriatal dopaminergic damage in Wilson's disease.  J Neurol Neurosurg Psychiatry. 1998;  65 60-64
    PubMedGoogle Scholar
  • 45 Barthel H, Sorger D, Kühn HJ, Wagner A, Kluge R, Hermann W. Differential alteration of the nigrostriatal dopaminergic system in Wilson's disease investigated with [123I]β-CIT and high-resolution SPET.  Eur J Nucl Med. 2001;  28 1656-1663
    CrossrefPubMedGoogle Scholar
  • 46 Hermann W, Eggers B, Barthel H, Clark D, Villmann T, Hesse S, Grahmann F, Kühn HJ, Sabri O, Wagner A. Correlation between automated writing movements and striatal dopaminergic innervation in patients with Wilson's disease.  J Neurol. 2002;  249 1082-1087
    PubMedGoogle Scholar
  • 47 Barthel H, Hermann W, Kluge R, Hesse S, Collingridge DR, Wagner A, Sabri O. Concordant pre- and postsynaptic deficits of dopaminergic neurotransmission in neurologic Wilson's disease.  Am J Neuroradiol. 2003;  24 234-238
    PubMedGoogle Scholar
  • 48 Wang H, Wang X, Schleich H. LTD und LTP induced by transcranial magnetic stimulation in auditory cortex.  Neuroreport. 1996;  7 521-525
    PubMedGoogle Scholar
  • 49 Fitzgerald PB, Fountain S, Daskalakis ZJ. A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition.  Clin Neurophysiol. 2006;  117 2584-2596
    CrossrefPubMedGoogle Scholar
  • 50 Lang N, Siebner HR, Ernst D, Nitsche MA, Paulus W, Lemon RN, Rothwell JC. Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects.  Biol Psychiatr. 2004;  56 634-639
    CrossrefPubMedGoogle Scholar
  • 51 Daskalakis ZJ, Möller B, Christensen B, Fitzgerald PB, Gunraj C, Chen R. The effects of repetitive transcranial magnetic stimulation on cortical inhibition in healthy human subjects.  Exp Brain Res. 2006;  174 403-412
    CrossrefPubMedGoogle Scholar
  • 52 Modugno N, Nakamura Y, MacKinnon CD, Filipovic SR, Bestmann S, Berardelli A, Rothwell JC. Motor cortex excitability following short trains of repetitive magnetic stimulation.  Exp Brain Res. 2001;  140 453-459
    CrossrefPubMedGoogle Scholar
  • 53 Peinemann A, Reimer B, Loer C, Quartarone A, Munchau A, Conrad B, Siebner HR. Long-lasting increase in corticospinal excitability after 1800 pulses of subthreshold 5 Hz repetitive TMS to the primary motor cortex.  Clin Neurophysiol. 2004;  115 1519-1526
    CrossrefPubMedGoogle Scholar
  • 54 Tings T, Lang N, Tergau F, Paulus W, Sommer M. Orientation-specific fast rTMS maximizes corticospinal inhibition and facilitation.  Exp Brain Res. 2005;  124 323-333
    PubMedGoogle Scholar
  • 55 Arai N, Okabe S, Furubayashi T, Terao Y, Yuasa K, Ugawa Y. Comparison between short-train, monophasic and biphasic repetitive transcranial magnetic stimulation (rTMS) of the human motor cortex.  Clin Neurophysiol. 2005;  116 605-613
    CrossrefPubMedGoogle Scholar
  • 56 Fitzgerald PB, Brown TL, Daskalakis ZJ, Chen R, Kulkarni J. Intensity-dependent effects of 1 Hz rTMS on human corticospinal excitability.  Clin Neurophysiol. 2002;  113 1136-1141
    CrossrefPubMedGoogle Scholar
  • 57 Lang N, Harms J, Weyh T, Lemon RN, Paulus W, Rothwell JC, Siebner HR. Stimulus intensity and coil characteristics influence the efficacy of rTMS to suppress cortical excitability.  Clin Neurophysiol. 2006;  117 2292-2301
    CrossrefPubMedGoogle Scholar
  • 58 Taylor JL, Loo CK. Stimulus waveform influences the efficacy of repetitive transcranial magnetic stimulation.  J Affect Disord. 2007;  271-276
    PubMedGoogle Scholar
  • 59 Strafella AP, Paus T, Barett J, Dagher A. Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus.  J Neurosci. 2001;  21 RC157 , (1-4)
    PubMedGoogle Scholar
  • 60 Strafella AP, Paus T, Fraraccio M, Dagher A. Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex.  Brain. 2003;  126 2609-2615
    CrossrefPubMedGoogle Scholar
  • 61 Ikeguchi M, Touge T, Nishiyama Y, Takeuchi H, Kuriyama S, Ohkawa M. Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson's disease.  J Neurol Sci. 2003;  209 41-46
    CrossrefPubMedGoogle Scholar
  • 62 Keck ME, Welt T, Erhardt A, Müller MB, Toschi N, Holsboer F, Sillaber I. Repetitive transcranial magnetic stimulation increases the release of dopamine in the mesolimbic and mesostriatal system.  Neuropharmacol. 2002;  43 101-109
    CrossrefPubMedGoogle Scholar
  • 63 Kanno M, Matsumoto M, Togashi H, Yoshioka M, Mano Y. Effects of acute repetitive transcranial magnetic stimulation on dopamin release in the rat dorsolateral striatum.  J Neurol Sci. 2004;  217 73-81
    CrossrefPubMedGoogle Scholar
  • 64 Ohnishi T, Hayashi T, Okabe S, Nonaka I, Matsuda H, Iida H, Imabayashi E, Watabe H, Miyake Y, Ogawa M, Teramoto N, Ohta Y, Ejima N, Sawada T, Ugawa Y. Endogenous dopamine release induced by repetitive transcranial magnetic stimulation over the primary motor cortex: an [11C]raclopride positron emission tomography study in anesthetized macaque monkeys.  Biol Psychiatry. 2004;  55 484-489
    CrossrefPubMedGoogle Scholar

Korrespondenzadresse

Prof. Dr. med. Armin Wagner

Klinik und Poliklinik für Neurologie

Universität Leipzig

Liebigstraße 22a

04103 Leipzig

Email: armin.wagner@medizin.uni-leipzig.de

      >