Idiopathisches Parkinson-Syndrom - Update: Pharmaka, aktivierende Therapien und tiefe Hirnstimulation

Zwei Non-Ergot-Dopaminagonisten - Rotigotin als erstes „Parkinson-Pflaster” und Piribedil - sind seit 2007 sowohl zur Mono- als auch zur Kombinationstherapie mit L-Dopa zugelassen. Hinzu kommt Ropinirol in einer neuen, retardierten Darreichungsform, das nur einmal täglich eingenommen werden muss. Der Einsatz des parenteralen Non-Ergot-Dopaminagonisten Apomorphin als Penject zum bedarfsorientierten Einsatz oder über eine Mikropumpe zur kontinuierlichen subkutanen Infusion bei Off-Phasen wächst und eignet sich auch für Patienten in Warteposition für die tiefe Hirnstimulation. L-Dopa gilt weiterhin als die Referenz in der Parkinsontherapie. Die COMT-Hemmer Entacapon (als Einzel- oder Kombinationspräparat mit L-Dopa/Carbidopa) und Tolcapon wirken nur über eine L-Dopa-Potenzierung und sind für Wearing-off-Phänomene hilfreich. Außerdem etabliert sich ein L-Dopa/Carbidopa-Gel zur kontinuierlichen duodenalen Infusion via perkutaner endoskopischer Gastroektomie für ausgewählte Patienten mit schweren Off-Phasen. Ferner wurde 2005 ein neuer MAO-B-Hemmer, Rasagilin, für alle Phasen des idiopathischen Parkinson-Syndroms (IPS) und 2007 der Cholinesterasehemmer Rivastigimin für die Demenz bei IPS zugelassen. Wesentliche lebensqualitätsbestimmende Symptome wie Sturzneigung, Sprech- und Schluckstörungen lassen sich trotz der vielen Medikamente und der tiefen Hirnstimulation in späten Stadien der Krankheit schlecht behandeln. Hier spielen neue, symptomorientierte aktivierende Therapien eine wesentliche Rolle, deren Konzepte wie z.B. die Stimmtherapie nach Lee Silverman und das Training von Ausgleichsschritten wissenschaftlich etabliert sind. Bei der tiefen Hirnstimulation, deren Ergebnis mit der positiven Wirkung von L-Dopa korreliert, zeichnet sich der Trend ab, eher jüngere Patienten zu operieren.

Two non-ergot dopamine agonists, rotigotine (Neupro®) the first transdermal patch in Parkinson's disease (PD), and piribedil (Clarium®) have been licensed in Germany since 2007 for mono- and levodopa combination therapy. Ropinirole 24-hour prolonged release (Requip® Monotab), another non-ergot dopamine agonist, will be introduced and allow once daily dosing of ropinirol. The non-ergot parenteral dopamine agonist apomorphine available as penject for on demand use or for continuous subcutaneous infusion in patients with off-phases has an important role in patients with in complex motor fluctuations, also for those waiting for deep brain stimulation. Levodopa is still the gold standard in PD therapy. The COMT inhibitors entacapone (Comtess® or in Stalevo® as triple combination with levodopa/carbidopa) and tolcapone (Tasmar®) work only by increasing the bioavailability of levodopa and are helpful for wearing-off phenomena. Levodopa/carbidopa as a gel (Duodopa®) for continuous dudodenal infusion via PEG represents an alternative to the apomorphine pump for seleceted patients. Furthermore, in 2005 a new MAO-B inhibitor, rasagiline (Azilect®), was licensed for all PD stages and in 2007 a cholinesterase inhibitor rivastigimin (Exelon®) for PD associated dementia. However, essential quality of life determining parkinsonian symptoms such as falls, voice and swallowing symptoms are difficult to treat despite the many new drugs and deep brain stimulation (DBS). New activating therapy concepts are emerging for medication and DBS refractory symptoms, which will be increasingly evidence based such as the Lee Silverman Voice Treatment (LSVT®) and the repetitive training of compensatory steps. In DBS of the subthalamic nucleus there is a trend to operate in earlier stages of the disease course than before as the magnitude of postoperative quality of life improvement occurs mainly in young patients.

Key words

Parkinson's disease - pharmacotherapy - activating therapy - deep brain stimulation - L-Dopa

Literatur

• 1 Biglan KM. et al. . Parkinson Study Group CALM-PD Investigators. Risk factors for somnolence, edema, and hallucinations in early Parkinson disease.  Neurology. 2007;  69 187-195
• 2 Biglan KM. et al. . Rasagiline improves quality of life in patients with early Parkinson's disease.  Mov Disord. 2006;  21 616-623
• 3 Burkhard PR. et al. . Suicide after successful deep brain stimulation for movement disorders.  Neurology. 2004;  63 2170-2172
• 4 Castro-Caldas A. et al. . The Parkinson-Control study: a 1-year randomized, double-blind trial comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson's disease.  Mov Disord. 2006;  21 500-509
• 5 Ceballos-Bauman AO.. Apomorphin bei idiopathischem Parkinson-Syndrom.  Akt Neurol. 2005;  32
• 6 Ceballos-Bauman A, Ebersbach G.. Aktivierende Therapien bei Parkinson-Syndromen. Stuttgart: Thieme 2008
• 7 Chan PL. et al. . Levodopa slows progression of Parkinson's disease: external validation by clinical trial simulation.  Pharm Res. 2007;  24 791-802
• 8 Derost PP. et al. . Is DBS-STN appropriate to treat severe Parkinson disease in an elderly population?.  Neurology. 2007;  68 1345-1355
• 9 Deutschl G. et al. . A randomized trial of deep-brain stimulation for Parkinson's disease.  N Engl J Med. 2006;  355 896-908
• 10 Dodd ML. et al. . Pathological gambling caused by drugs used to treat Parkinson disease.  Arch Neurol. 2005;  62 1377-1381
• 11 Eggert K. et al. . Herzklappenerkrankungen und andere fibrotische Reaktionen als Nebenwirkung von Dopamin-Agonisten: Klinische Konsequenzen beim jetzigen Stand (8/2004) der Erkenntnisse.  DÄB. 2005;  102
• 12 Emre M. et al. . Rivastigmine for dementia associatied with Parkinson's disease.  N Engl J Med. 2004;  351 2509-2518
• 13 The Entacapone to Tolcapone Switch Study Investigators. . Entacapone to tolcapone switch: Multicenter double-blind, randomized, active-controlled trial in advanced Parkinson's disease.  Mov Disord. 2007;  22 14-19
• 14 Fahn S. et al. . Levodopa and the progression of Parkinson's disease.  N Engl J Med. 2004;  351 2498-2508
• 15 Farley BG, Koshland GF.. Training BIG to move faster: the application of the speed-amplitude relation as a rehabilitation strategy for people with Parkinson's disease.  Exp Brain Res. 2005;  167 462-467
• 16 Fisher BE. et al. . Exercise-induced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse basal ganglia.  J Neurosci Res. 2004;  77
• 17 Fox CM. et al. . The science and practice of LSVT/LOUD: neural plasticity-principled approach to treating individuals with Parkinson disease and other neurological disorders.  Semin Speech Lang. 2006;  27 283-299
• 18 Funkiewiez A. et al. . Long term effects of bilateral subthalamic nucleus stimulation on cognitive function, mood, and behaviour in Parkinson's disease.  J Neurol Neurosurg Psychiatry. 2004;  75 834-839
• 19 Grazko MA. et al. . Botulinum toxin A for spasticity, muscle spasms, and rigidity.  Neurology. 1995;  45 712-717
• 20 Henningsen P. et al. .Neuro-Psychosomatik. Stuttgart: Schattauer Verlag 2006
• 21 Jobges M. et al. . Repetitive training of compensatory steps: a therapeutic approach for postural instability in Parkinson's disease.  J Neurol Neurosurg Psychiatry. 2004;  75 1682-1687
• 22 Katzenschlager R. et al. . Continuous subcutaneous apomorphine therapy improves dyskinesias in Parkinson's disease: a prospective study using single-dose challenges.  Mov Disord. 2005;  20 151-157
• 23 Keus SH. et al. . Practice Recommendations Development Group. Evidence-based analysis of physical therapy in Parkinson's disease with recommendations for practice and research.  Mov Disord. 2007;  22
• 24 Lagalla G. et al. . Botulinum toxin type A for drooling in Parkinson's disease: a double-blind, randomized, placebo-controlled study.  Mov Disord. 2006;  21 704-707
• 25 Lees AJ. et al. . Safety and tolerability of adjunctive tolcapone treatment in patients with early Parkinson's disease.  J Neurol Neurosurg Psychiatry. 2007;  78 944-948
• 26 Maidment I. et al. . Cholinesterase inhibitors for Parkinson's disease dementia.  Cochrane Database Syst Rev. 2006;  1
• 27 de Marcaida JA. et al. . Effects of tyramine administration in Parkinson's disease patients treated with selective MAO-B inhibitor rasagiline.  Mov Disord. 2006;  21 1716-1721
• 28 Müller J. et al. . Botulinum toxin treatment in atypical parkinsonian disorders associated with disabling focal dystonia.  J Neurol. 2002;  249 300-304
• 29 Nyholm D. et al. . Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease.  Neurology. 2005;  64 216-623
• 30 Pacchetti C. et al. . „Off” painful dystonia in Parkinson's disease treated with botulinum toxin.  Mov Disord. 1995;  10 333-336
• 31 Pahwa R. et al. . Ropinirole 24-hour prolonged release: randomized, controlled study in advanced Parkinson disease.  Neurology. 2007;  68 1108-1115
• 32 Parkinson Study Group. . A controlled trial of rotigotine monotherapy in early Parkinson's disease.  Arch Neurol. 2003;  60 1721-1728
• 33 Parkinson Study Group. . A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease.  Arch Neurol. 2004;  61 561-566
• 34 Pinto S. et al. . Treatments for dysarthria in Parkinson's disease.  Lancet Neurol. 2004;  3 547-556
• 35 Poewe WH. et al. . Efficacy of pramipexole and transdermal rotigotine in advanced Parkinson's disease: a double-blind, double-dummy, randomised controlled trial.  Lancet Neurol. 2007;  6 513-520
• 36 Pontone G. et al. . Clinical features associated with impulse control disorders in Parkinson disease.  Neurology. 2006;  67 1258-1261
• 37 Ramig LO. et al. . Intensive voice treatment (LSVT) for patients with Parkinson's disease: a 2 year follow up.  J Neurol Neurosurg Psychiatry. 2001;  71 493-498
• 38 Rascol O. et al. . Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial.  Lancet. 2003;  365 947-954
• 39 Rascol O. et al. . Early piribedil monotherapy of Parkinson's disease: A planned seven-month report of the REGAIN study.  Mov Disord. 2006;  21 2110-2115
• 40 Schade R. et al. . Dopamine agonists and the risk of cardiac-valve regurgitation.  N Engl J Med. 2007;  356 29-38
• 41 Schrag A.. Entacapone in the treatment of Parkinson's disease.  Lancet Neurol. 2005;  4 366-370
• 42 Schüpbach M. et al. . Neurosurgery in Parkinson disease: a distressed mind in a repaired body?.  Neurology. 2006;  66 1811-1816
• 43 Schüpbach WM. et al. . Neurosurgery at an earlier stage of Parkinson disease: a randomized, controlled trial.  Neurology. 2007;  68 267-271
• 44 Smeding HM. et al. . Neuropsychological effects of bilateral STN stimulation in Parkinson disease: a controlled study.  Neurology. 2006;  66 1830-1836
• 45 Voon V. et al. . Factors associated with dopaminergic drug-related pathological gambling in Parkinson disease.  Arch Neurol. 2007;  64 212-216
• 46 Weintraub D. et al. . Association of dopamine agonist use with impulse control disorders in Parkinson disease.  Arch Neurol. 2006;  63 969-973
• 47 Zanettini R. et al. . Valvular heart disease and the use of dopamine agonists for Parkinson's disease.  N Engl J Med. 2007;  356 39-46

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