PDF herunterladen
Fortschr Neurol Psychiatr 2007; 75(7): 387-396
DOI: 10.1055/s-2006-944314
Übersicht
© Georg Thieme Verlag Stuttgart · New York

Dyskinesien bei Morbus Parkinson - Klinik, Ätiologie, Therapie

Dyskinesia in Parkinson's Disease - Major Clinical Features, Aetiology, TherapyG.  Ellrichmann1 , H.  Russ1 , T.  Müller1
  • 1Neurologische Klinik im St. Josef-Hospital, Ruhr Universität Bochum (Direktor: Professor Dr. R. Gold)
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
17. November 2006 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Zusammenfassung

Morbus Parkinson als langsam fortschreitende, neurodegenerative Erkrankung des Zentralnervensystems, die weltweit etwa 10 Millionen Menschen betrifft, wird zurzeit rein symptomatisch behandelt. Hierbei besteht das Ziel vorwiegend darin, den herabgesetzten Dopaminstoffwechsel in striatalen Neuronen auszugleichen. Eine chronische Einnahme dopaminerger Substanzen, wie z. B. Levodopa, verstärkt auf lange Sicht jedoch das Auftreten motorischer Komplikationen und Dyskinesien. Dyskinesien präsentieren sich am häufigsten als Chorea, Athetose, Dystonie, Stereotypie, Ballismus oder eine Kombination. Häufig basieren diese unwillkürlichen Bewegungen des Gesichts, des Rumpfes und der Extremitäten auf der Gesamtmenge der dopaminergen Substitution. Therapiestrategien basieren daher auf einer Reduktion der Gesamtdosis von Dopamin. Alternativ bzw. ergänzend eingesetzt werden Apomorphin, Amantadin oder Clozapin. Neuere Behandlungsmöglichkeiten entstehen durch Substanzen wie Sarizotan, Istradefylline, Fipampezol oder Talampanel. Trotzdem resultieren Beeinträchtigungen und reduzierte Lebensqualität der Patienten und deren Angehörigen. Diese Übersicht beschreibt die klinischen Hauptmerkmale sowie Ätiologie und Demografie therapieassoziierter Dyskinesien beim Morbus Parkinson.

Abstract

Parkinson's disease (PD), a slowly, progressive degenerative disorder of the central nervous system, which affects about ten million people world-wide, is currently treated symptomatically. Current treatment aim i. e. to balance the decreased dopamine turnover in striatal neurons. Chronic exposure to dopaminergic agents, however, supports onset of motor complications and dyskinesia in the long term. Dyskinesia appear mainly as chorea, athetosis, dystonia, stereotypia, ballism or a combination. Sometimes excessive abnormal facial, body and limb movements depend on the overall dosage of dopaminergic substitution. This is why the main therapy is based on reducing the total dosage of dopaminergic substances. Either alternative or additional well-tried substances like apomorphine, amantadine or clozapine are used. New possibilities in treatment emerge from substances like sarizotan, istradefylline, fipampezol or talampanel. Even so disability and reduced quality of life in PD patients and their caregivers may exist. This survey describes the major clinical features, aetiology and demographics of treatment-associated dyskinesia in PD.

Schlüsselwörter

Morbus Parkinson - Dyskinesien - Therapie des M. Parkinson

Key words

parkinson's disease - dyskinesias - therapy of parkinson's disease

Literatur

  • 1 Olanow C W, Watts R L, Koller W C. An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines.  Neurology. 2001;  56 S1-S88
    PubMedGoogle Scholar
  • 2 Reichmann H, Sommer U, Fuchs G. et al . Workshop IV: drug treatment guidelines for the long-term management of Parkinson's disease.  J Neurol. 2000;  247 Suppl 4 IV/40-IV/41
    PubMedGoogle Scholar
  • 3 Ferreira J J, Galitzky M, Montastruc J L, Rascol O. Sleep attacks and Parkinson's disease treatment.  Lancet. 2000;  355 1333-1334
    CrossrefPubMedGoogle Scholar
  • 4 Camp G van, Flamez A, Cosyns B, Goldstein J, Perdaens C, Schoors D. Heart valvular disease in patients with Parkinson's disease treated with high-dose pergolide.  Neurology. 2003;  61 859-861
    PubMedGoogle Scholar
  • 5 Dodd M L, Klos K J, Bower J H, Geda Y E, Josephs K A, Ahlskog J E. Pathological gambling caused by drugs used to treat Parkinson disease.  Arch Neurol. 2005;  62 1377-1381
    CrossrefPubMedGoogle Scholar
  • 6 Klos K J, Bower J H, Josephs K A, Matsumoto J Y, Ahlskog J E. Pathological hypersexuality predominantly linked to adjuvant dopamine agonist therapy in Parkinson's disease and multiple system atrophy.  Parkinsonism Relat Disord. 2005;  11 381-386
    CrossrefPubMedGoogle Scholar
  • 7 Dewey Jr R B. Management of motor complications in Parkinson's disease.  Neurology. 2004;  62 (Suppl 4) S3-S7
    PubMedGoogle Scholar
  • 8 Muenter M D, Sharpless N S, Tyce G M, Darley F L. Patterns of dystonia („I-D-I” and „D-I-D-”) in response to l-dopa therapy for Parkinson's disease.  Mayo Clin Proc. 1977;  52 163-174
    PubMedGoogle Scholar
  • 9 Fahn S. The spectrum of levodopa-induced dyskinesias.  Ann Neurol. 2000;  47 S2-S9
    CrossrefPubMedGoogle Scholar
  • 10 Luquin M R, Scipioni O, Vaamonde J, Gershanik O, Obeso J A. Levodopa-induced dyskinesias in Parkinson's disease: clinical and pharmacological classification.  Mov Disord. 1992;  7 117-124
    CrossrefPubMedGoogle Scholar
  • 11 Marconi R, Lefebvre-Caparros D, Bonnet A M, Vidailhet M, Dubois B, Agid Y. Levodopa-induced dyskinesias in Parkinson's disease phenomenology and pathophysiology.  Mov Disord. 1994;  9 2-12
    CrossrefPubMedGoogle Scholar
  • 12 Adler C H. Relevance of motor complications in Parkinson's disease.  Neurology. 2002;  58 S51-S56
    PubMedGoogle Scholar
  • 13 Jankovic J. Motor fluctuations and dyskinesias in Parkinson's disease: clinical manifestations.  Mov Disord. 2005;  20 Suppl 11 S11-S16
    PubMedGoogle Scholar
  • 14 Melamed E. Early-morning dystonia. A late side effect of long-term levodopa therapy in Parkinson's disease.  Arch Neurol. 1979;  36 308-310
    PubMedGoogle Scholar
  • 15 Cubo E, Gracies J M, Benabou R, Olanow C W, Raman R, Leurgans S, Goetz C G. Early morning off-medication dyskinesias, dystonia, and choreic subtypes.  Arch Neurol. 2001;  58 1379-1382
    CrossrefPubMedGoogle Scholar
  • 16 Nutt J G. Levodopa-induced dyskinesia: review, observations, and speculations.  Neurology. 1990;  40 340-345
    PubMedGoogle Scholar
  • 17 Rice J E, Antic R, Thompson P D. Disordered respiration as a levodopa-induced dyskinesia in Parkinson's disease.  Mov Disord. 2002;  17 524-527
    CrossrefPubMedGoogle Scholar
  • 18 Rascol O, Fabre N. Dyskinesia: L-dopa-induced and tardive dyskinesia.  Clin Neuropharmacol. 2001;  24 313-323
    PubMedGoogle Scholar
  • 19 Obeso J A, Rodriguez-Oroz M C, Chana P, Lera G, Rodriguez M, Olanow C W. The evolution and origin of motor complications in Parkinson's disease.  Neurology. 2000;  55 S13-S20
    PubMedGoogle Scholar
  • 20 Bezard E, Brotchie J M, Gross C E. Pathophysiology of levodopa-induced dyskinesia: potential for new therapies.  Nat Rev Neurosci. 2001;  2 577-588
    CrossrefPubMedGoogle Scholar
  • 21 Jenner P. Avoidance of dyskinesia: preclinical evidence for continuous dopaminergic stimulation.  Neurology. 2004;  62 S47-S55
    PubMedGoogle Scholar
  • 22 Stocchi F, Olanow C W. Continuous dopaminergic stimulation in early and advanced Parkinson's disease.  Neurology. 2004;  62 S56-S63
    CrossrefPubMedGoogle Scholar
  • 23 Boraud T, Bezard E, Bioulac B, Gross C E. Dopamine agonist-induced dyskinesias are correlated to both firing pattern and frequency alterations of pallidal neurones in the MPTP-treated monkey.  Brain. 2001;  124 546-557
    CrossrefPubMedGoogle Scholar
  • 24 Widnell K. Pathophysiology of motor fluctuations in Parkinson's disease.  Mov Disord. 2005;  20 Suppl 11 S17-S22
    CrossrefPubMedGoogle Scholar
  • 25 Bonnet A M. Involvement of non-dopaminergic pathways in Parkinson's disease: pathophysiology and therapeutic implications.  CNS Drugs. 2000;  13 351-364
    CrossrefPubMedGoogle Scholar
  • 26 Nicholson S L, Brotchie J M. 5-hydroxytryptamine (5-HT, serotonin) and Parkinson's disease - opportunities for novel therapeutics to reduce the problems of levodopa therapy.  Eur J Neurol. 2002;  9 Suppl 3 1-6
    PubMedGoogle Scholar
  • 27 Deogaonkar M, Subramanian T. Pathophysiological basis of drug-induced dyskinesias in Parkinson's disease.  Brain Res Brain Res Rev. 2005;  50 156-168
    CrossrefPubMedGoogle Scholar
  • 28 Brotchie J M. Nondopaminergic mechanisms in levodopa-induced dyskinesia.  Mov Disord. 2005;  20 919-931
    CrossrefPubMedGoogle Scholar
  • 29 Chase T N, Bibbiani F, Oh J D. Striatal glutamatergic mechanisms and extrapyramidal movement disorders.  Neurotox Res. 2003;  5 139-146
    PubMedGoogle Scholar
  • 30 Calon F, Morissette M, Goulet M, Grondin R, Blanchet P J, Bedard P J, Paolo T Di. Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys: effects on basal ganglia GABA(A)/benzodiazepine receptor complex and GABA content.  Neurochem Int. 1999;  35 81-91
    CrossrefPubMedGoogle Scholar
  • 31 Calon F, Paolo T Di. Levodopa response motor complications - GABA receptors and preproenkephalin expression in human brain.  Parkinsonism Relat Disord. 2002;  8 449-454
    CrossrefPubMedGoogle Scholar
  • 32 Rascol O, Brooks D J, Korczyn A D, Deyn P P De, Clarke C E, Lang A E. for the 056 Study Group . A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa.  N Engl J Med. 2000;  342 1484-1491
    CrossrefPubMedGoogle Scholar
  • 33 Rascol O, Korczyn A D, Deyn P P De, Lang A. Incidence of dyskinesias in a 10-year naturalistic follow-up of patients with early Parkinson's disease (PD) initially receiving ropinirole compared with L-dopa.  Mov Disord. 2005;  20 (Suppl. 10) S57
    PubMedGoogle Scholar
  • 34 Stocchi F, Vacca L, Ruggieri S, Olanow C W. Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study.  Arch Neurol. 2005;  62 905-910
    CrossrefPubMedGoogle Scholar
  • 35 Lozano A M, Lang A E, Galvez-Jimenez N. et al . Effect of GPi pallidotomy on motor function in Parkinson's disease.  Lancet. 1995;  346 1383-1387
    CrossrefPubMedGoogle Scholar
  • 36 Krack P, Pollak P, Limousin P, Hoffmann D, Xie J, Benazzouz A, Benabid A L. Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson's disease.  Brain. 1998;  121 (Pt 3) 451-457
    CrossrefPubMedGoogle Scholar
  • 37 Müller T, Hock K. Dyskinesia can first occur at any stage of Parkinson's disease and at any point during L-dopa treatment.  Parkinsonism Relat Disord. 2005;  11 (Suppl. 2) 131
    PubMedGoogle Scholar
  • 38 Ahlskog J E, Muenter M D. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature.  Mov Disord. 2001;  16 448-458
    CrossrefPubMedGoogle Scholar
  • 39 The Parkinson Study Group . Levodopa and the progression of Parkinson's disease.  N Engl J Med. 2004;  351 2498-2508
    CrossrefPubMedGoogle Scholar
  • 40 Fahn S. Does levodopa slow or hasten the rate of progression of Parkinson's disease?.  J Neurol. 2005;  252 Suppl 4 iv37-iv42
    PubMedGoogle Scholar
  • 41 Golbe L I. Young-onset Parkinson's disease: a clinical review.  Neurology. 1991;  41 168-173
    PubMedGoogle Scholar
  • 42 Kostic V, Przedborski S, Flaster E, Sternic N. Early development of levodopa-induced dyskinesias and response fluctuations in young-onset Parkinson's disease.  Neurology. 1991;  41 202-205
    CrossrefPubMedGoogle Scholar
  • 43 Kumar N, Gerpen J A Van, Bower J H, Ahlskog J E. Levodopa-dyskinesia incidence by age of Parkinson's disease onset.  Mov Disord. 2005;  20 342-344
    CrossrefPubMedGoogle Scholar
  • 44 Müller T, Russ H, Haeger D A. Dyskinesia occurs in 34 % of Parkinson's disease patients receiving dopaminergic treatment: findings from a recent retrospective international survey.  Mov Disord. 2005;  20 (Suppl. 10) S17
    CrossrefPubMedGoogle Scholar
  • 45 Goetz C G. Rating scales for dyskinesias in Parkinson's disease.  Mov Disord. 1999;  14 48-53
    PubMedGoogle Scholar
  • 46 Fahn S, Elton R L. UPDRS Development Committee .Unified Parkinson's Disease Rating Scale. In: Fahn S, Marsden CD, Calne DB, eds. Recent developments in Parkinson's disease. Florham Park: MacMillan Healthcare Information 1987: 153-163
    Google Scholar
  • 47 Abnormal Involuntary Movement Scale .ECDEU Assessment Manual for Psychopharmacology. Washington: US Government Printing Office 1976: 534-537
    Google Scholar
  • 48 Goetz C G, Stebbins G T, Shale H M. et al . Utility of an objective dyskinesia rating scale for Parkinson's disease: inter- and intrarater reliability assessment.  Mov Disord. 1994;  9 390-394
    CrossrefPubMedGoogle Scholar
  • 49 Hauser R A, Friedlander J, Zesiewicz T A. et al . A home diary to assess functional status in patients with Parkinson's disease with motor fluctuations and dyskinesia.  Clin Neuropharmacol. 2000;  23 75-81
    PubMedGoogle Scholar
  • 50 Parkinson Study Group . Evaluation of dyskinesias in a pilot, randomized, placebo-controlled trial of remacemide in advanced Parkinson disease.  Arch Neurol. 2001;  58 1660-1668
    CrossrefPubMedGoogle Scholar
  • 51 Hauser R A, Deckers F, Lehert P. Parkinson's disease home diary: further validation and implications for clinical trials.  Mov Disord. 2004;  19 1409-1413
    CrossrefPubMedGoogle Scholar
  • 52 Hauser R A, Russ H, Hall J, Haeger D A, Muller T. Patient evaluation of a new diary for assessing duration and severity of dyskinesia in patients with Parkinson's disease.  Parkinsonism Relat Disord. 2005;  11 157
    CrossrefPubMedGoogle Scholar
  • 53 Goetz C G, Stebbins G T, Blasucci L M, Grobman M S. Efficacy of a patient-training videotape on motor fluctuations for on-off diaries in Parkinson's disease.  Mov Disord. 1997;  12 1039-1041
    CrossrefPubMedGoogle Scholar
  • 54 Damiano A M, McGrath M M, Willian M K. et al . Evaluation of a measurement strategy for Parkinson's disease: assessing patient health-related quality of life.  Qual Life Res. 2000;  9 87-100
    CrossrefPubMedGoogle Scholar
  • 55 Chapuis S, Ouchchane L, Metz O, Gerbaud L, Durif F. Impact of the motor complications of Parkinson's disease on the quality of life.  Mov Disord. 2005;  20 224-230
    CrossrefPubMedGoogle Scholar
  • 56 Schrag A, Quinn N. Dyskinesias and motor fluctuations in Parkinson's disease. A community-based study.  Brain. 2000;  123 2297-2305
    CrossrefPubMedGoogle Scholar
  • 57 Schrag A, Selai C, Jahanshahi M, Quinn N P. The EQ-5D - a generic quality of life measure-is a useful instrument to measure quality of life in patients with Parkinson's disease.  J Neurol Neurosurg Psychiatry. 2000;  69 67-73
    CrossrefPubMedGoogle Scholar
  • 58 Marras C, Lang A, Krahn M, Tomlinson G, Naglie G. Quality of life in early Parkinson's disease: impact of dyskinesias and motor fluctuations.  Mov Disord. 2004;  19 22-28
    CrossrefPubMedGoogle Scholar
  • 59 Peto V, Jenkinson C, Fitzpatrick R, Greenhall R. The development and validation of a short measure of functioning and well being for individuals with Parkinson's disease.  Qual Life Res. 1995;  4 241-248
    CrossrefPubMedGoogle Scholar
  • 60 Dodel R C, Singer M, Kohn-Volland R. et al . The economic impact of Parkinson's disease. An estimation based on a 3-month prospective anaylsis.  Pharmacoeconomics. 1998;  14 299-312
    CrossrefPubMedGoogle Scholar
  • 61 LePen C, Wait S, Moutard-Martin F, Dujardin M, Ziegler M. Cost of illness and disease severity in a cohort of French patients with Parkinson's disease.  Pharmacoeconomics. 1999;  16 59-69
    CrossrefPubMedGoogle Scholar
  • 62 Dodel R C, Berger K, Oertel W H. Health-related quality of life and healthcare utilisation in patients with Parkinson's disease: impact of motor fluctuations and dyskinesias.  Pharmacoeconomics. 2001;  19 1013-1038
    PubMedGoogle Scholar
  • 63 Maurel F, Lilliu H, Pen C Le. [Social and economic cost of L-dopa-induced dyskinesias in patients with Parkinson's disease].  Rev Neurol (Paris). 2001;  157 507-514
    PubMedGoogle Scholar
  • 64 Fahn S. Is levodopa toxic?.  Neurology. 1996;  47 S184-S195
    PubMedGoogle Scholar
  • 65 Parkinson Study Group . Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression.  JAMA. 2002;  287 1653-1661
    CrossrefPubMedGoogle Scholar
  • 66 Whone A L, Watts R L, Stoessl A J. et al . Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study.  Ann Neurol. 2003;  54 93-101
    CrossrefPubMedGoogle Scholar
  • 67 Goetz C G, Poewe W, Rascol O, Sampaio C. Evidence-based medical review update: pharmacological and surgical treatments of Parkinson's disease: 2001 to 2004.  Mov Disord. 2005;  20 523-539
    CrossrefPubMedGoogle Scholar
  • 68 Rinne U K, Bracco F, Chouza C. et al . Early treatment of Parkinson's disease with cabergoline delays the onset of motor complications. Results of a double-blind levodopa controlled trial. The PKDS009 Study Group.  Drugs. 1998;  55 Suppl 1 23-30
    CrossrefPubMedGoogle Scholar
  • 69 Parkinson Study Group . Pramipexole vs levodopa as initial treatment for Parkinson disease: A randomized controlled trial.  JAMA. 2000;  284 1931-1938
    CrossrefPubMedGoogle Scholar
  • 70 Smith L A, Jackson M J, Al Barghouthy G. et al . Multiple small doses of levodopa plus entacapone produce continuous dopaminergic stimulation and reduce dyskinesia induction in MPTP-treated drug-naive primates.  Mov Disord. 2005;  20 306-314
    CrossrefPubMedGoogle Scholar
  • 71 Heindl M, Scheller D, Lebsanft H, Schmidt W J. Continuous versus discontinuous administration of rotigotine in a rat model of dyskinesia.  Parkinsonism Relat Disord. 2005;  11 (Suppl. 2) 103
    CrossrefPubMedGoogle Scholar
  • 72 Blanchet P J, Calon F, Martel J C. et al . Continuous administration decreases and pulsatile administration increases behavioral sensitivity to a novel dopamine D2 agonist (U-91356A) in MPTP-exposed monkeys.  J Pharmacol Exp Ther. 1995;  272 854-859
    PubMedGoogle Scholar
  • 73 Marin C, Aguilar E, Obeso J A. Entacapone, a COMT inhibitor, attenates the severity of levodopa-induced dyskinesias in hemiparkinsonian rats.  Neurology. 2004;  19 S257
    PubMedGoogle Scholar
  • 74 Scheller D, Kehr J. Evidence for continuous dopamine receptor stimulation by rotigotine in freely moving rats using a continuous delivery system.  Parkinsonism Relat Disord. 2005;  11 (Suppl. 2) 103
    CrossrefPubMedGoogle Scholar
  • 75 Watts R L, Wendt J, Nausieda P A, Poole K, Sommerville K W, Bovbjerg V E. Efficacy, safety, and tolerability of the rotigotine transdermal patch in patients with early-stage, idiopathic Parkinson's disease. A multicenter, multinational, randomized, double-blind, placebo-controlled trial.  Mov Disord. 2004;  19 (Suppl. 9) 258
    PubMedGoogle Scholar
  • 76 Cristina S, Zangaglia R, Mancini F, Martignoni E, Nappi G, Pacchetti C. High-dose ropinirole in advanced Parkinson's disease with severe dyskinesias.  Clin Neuropharmacol. 2003;  26 146-150
    PubMedGoogle Scholar
  • 77 Colzi A, Turner K, Lees A J. Continuous subcutaneous waking day apomorphine in the long term treatment of levodopa induced interdose dyskinesias in Parkinson's disease.  J Neurol Neurosurg Psychiatry. 1998;  64 573-576
    CrossrefPubMedGoogle Scholar
  • 78 Verhagen M L, Dotto P Del, van den Munckhof P, Fang J, Mouradian M M, Chase T N. Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease.  Neurology. 1998;  50 1323-1326
    CrossrefPubMedGoogle Scholar
  • 79 Crosby N J, Deane K H, Clarke C E. Amantadine for dyskinesia in Parkinson's disease. Cochrane Database Syst Rev 2003 CD003467
    Google Scholar
  • 80 Paci C, Thomas A, Onofrj M. Amantadine for dyskinesia in patients affected by severe Parkinson's disease.  Neurol Sci. 2001;  22 75-76
    CrossrefPubMedGoogle Scholar
  • 81 Thomas A, Iacono D, Luciano A L, Armellino K, Iorio A Di, Onofrj M. Duration of amantadine benefit on dyskinesia of severe Parkinson's disease.  J Neurol Neurosurg Psychiatry. 2004;  75 141-143
    PubMedGoogle Scholar
  • 82 Verhagen Metman L, Dotto P Del, LePoole K, Konitsiotis S, Fang J, Chase T N. Amantadine for levodopa-induced dyskinesias: a 1-year follow-up study.  Arch Neurol. 1999;  56 1383-1386
    CrossrefPubMedGoogle Scholar
  • 83 Durif F, Debilly B, Galitzky M. et al . Clozapine improves dyskinesias in Parkinson disease: a double-blind, placebo-controlled study.  Neurology. 2004;  62 381-388
    PubMedGoogle Scholar
  • 84 Lang A E, Lozano A M, Montgomery E, Duff J, Tasker R, Hutchinson W. Posteroventral medial pallidotomy in advanced Parkinson's disease.  N Engl J Med. 1997;  337 1036-1042
    CrossrefPubMedGoogle Scholar
  • 85 Vitek J L, Bakay R A, Freeman A. et al . Randomized trial of pallidotomy versus medical therapy for Parkinson's disease.  Ann Neurol. 2003;  53 558-569
    CrossrefPubMedGoogle Scholar
  • 86 The Deep-Brain Stimulation for Parkinson's Disease Study Group . Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson's disease.  N Engl J Med. 2001;  345 956-963
    CrossrefPubMedGoogle Scholar
  • 87 Vitek J L. Deep brain stimulation for Parkinson's disease. A critical re-evaluation of STN versus GPi DBS.  Stereotact Funct Neurosurg. 2002;  78 119-131
    CrossrefPubMedGoogle Scholar
  • 88 Krack P, Batir A, Blercom N Van. et al . Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease.  N Engl J Med. 2003;  349 1925-1934
    CrossrefPubMedGoogle Scholar
  • 89 Bartoszyk G D, Amsterdam C Van, Greiner H E. et al . Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile.  J Neural Transm. 2004;  111 113-126
    CrossrefPubMedGoogle Scholar
  • 90 Bibbiani F, Oh J D, Chase T N. Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models.  Neurology. 2001;  57 1829-1834
    PubMedGoogle Scholar
  • 91 Olanow C W, Damier P, Goetz C G. et al . Multicenter, open-label, trial of sarizotan in Parkinson disease patients with levodopa-induced dyskinesias (the SPLENDID Study).  Clin Neuropharmacol. 2004;  27 58-62
    PubMedGoogle Scholar
  • 92 Jenner P. Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinson's disease.  Expert Opin Investig Drugs. 2005;  14 729-738
    CrossrefPubMedGoogle Scholar
  • 93 Bara-Jimenez W, Sherzai A, Dimitrova T. et al . Adenosine A(2A) receptor antagonist treatment of Parkinson's disease.  Neurology. 2003;  61 293-296
    PubMedGoogle Scholar
  • 94 Hauser R A, Hubble J P, Truong D D. Randomized trial of the adenosine A(2A) receptor antagonist istradefylline in advanced PD.  Neurology. 2003;  61 297-303
    PubMedGoogle Scholar
  • 95 LeWitt P A. and the 6002-US-005/6002-US-006 Clinical Investigator Group . ‘OFF’ time reduction from adjunctice use of istradefylline (KW-6002) in levodopa-treated patients with advanced Parkinson's disease.  Mov Disord. 2004;  19 (Suppl. 9) 222
    CrossrefPubMedGoogle Scholar
  • 96 Savola J M, Hill M, Engstrom M. et al . Fipamezole (JP-1730) is a potent alpha2 adrenergic receptor antagonist that reduces levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease.  Mov Disord. 2003;  18 872-883
    CrossrefPubMedGoogle Scholar
  • 97 Konitsiotis S, Blanchet P J, Verhagen L, Lamers E, Chase T N. AMPA receptor blockade improves levodopa-induced dyskinesia in MPTP monkeys.  Neurology. 2000;  54 1589-1595
    PubMedGoogle Scholar
  • 98 Johnston T H, Brotchie J M. Drugs in development for Parkinson's disease.  Curr Opin Investig Drugs. 2004;  5 720-726
    PubMedGoogle Scholar
  • 99 Hill M P, Ravenscroft P, Bezard E. et al . Levetiracetam potentiates the antidyskinetic action of amantadine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of Parkinson's disease.  J Pharmacol Exp Ther. 2004;  310 386-394
    CrossrefPubMedGoogle Scholar
  • 100 Bezard E, Hill M P, Crossman A R. et al . Levetiracetam improves choreic levodopa-induced dyskinesia in the MPTP-treated macaque.  Eur J Pharmacol. 2004;  485 159-164
    CrossrefPubMedGoogle Scholar
  • 101 Zesiewicz T A, Sullivan K L, Maldonado J L, Tatum W O, Hauser R A. Open-label pilot study of levetiracetam (Keppra) for the treatment of levodopa-induced dyskinesias in Parkinson's disease.  Mov Disord. 2005;  20 1205-1209
    CrossrefPubMedGoogle Scholar
  • 102 Meco G, Fabrizio E, Epifanio A, Raimondo G Di, Vanacore N, Morgante L. Levetiracetam in l-dopa induced dyskinesia.  Clinical Neuropharmacology. 2005;  28 102-103
    CrossrefPubMedGoogle Scholar
  • 103 Michel A, Ravenscroft P. et al . Seletracetam (UCB 44 212) reduces L-dopa dyskinesia in the MPTP-lesioned marmoset model of Parkinson's disease.  Mov Disord. 2005;  20 (Suppl. 10) S57
    PubMedGoogle Scholar
  • 104 Bezard E, Ferry S, Mach U, Stark H, Leriche L, Boraud T, Gross C, Sokoloff P. Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor function.  Nat Med. 2003;  9 762-767
    PubMedGoogle Scholar
  • 105 Hsu A, Togasaki D M, Bezard E, Sokoloff P, Langston J W, Monte D A Di, Quik M. Effect of the D3 dopamine receptor partial agonist BP897 [N-[4-(4-(2-methoxyphenyl)piperazinyl)butyl]-2-naphthamide] on L-3,4-dihydroxyphenylalanine-induced dyskinesias and parkinsonism in squirrel monkeys.  J Pharmacol Exp Ther. 2004;  311 770-777
    CrossrefPubMedGoogle Scholar
  • 106 Weiner D M, Vanover K E, Hacksell U, Brann M R, Davis R E. The tolerability of ACP-103, a 5-HT2a receptor inverse agonist in Parkinson's disease patients.  Mov Disord. 2005;  20 (Suppl. 10) S241
    PubMedGoogle Scholar
  • 107 Olanow C W. Surgical therapy for Parkinson's disease.  Eur J Neurol. 2002;  9 Suppl 3 31-39
    CrossrefPubMedGoogle Scholar
  • 108 Watts R L, Raiser C D, Stover N P. et al . Stereotaxic intrastriatal implantation of human retinal pigment epithelial (hRPE) cells attached to gelatin microcarriers: a potential new cell therapy for Parkinson's disease.  J Neural Transm Suppl. 2003;  (65) 215-227
    PubMedGoogle Scholar
  • 109 Bakay R A, Raiser C D, Stover N P. et al . Implantation of spheramine in advanced Parkinson's disease (PD).  Front Biosci. 2004;  9 592-602
    PubMedGoogle Scholar
  • 110 Doudet D J, Cornfeldt M L, Honey C R. et al . PET imaging of implanted human retinal pigment epithelial cells in the MPTP-induced primate model of Parkinson's disease.  Exp Neurol. 2004;  189 361-368
    CrossrefPubMedGoogle Scholar

Gisa Ellrichmann

Neurologische Klinik St. Josef-Hospital, Bochum

Gudrunstraße 56

44791 Bochum

eMail: gisa.ellrichmann@rub.de