Aktuelles in der Parkinson-Therapie - Differenzialdiagnose und Therapie des idiopathischen Parkinson-Syndroms

Zusammenfassung

Die präzise klinische Differenzierung des idiopathischen Parkinson-Syndrom (IPS) von anderen Parkinson-Syndromen ist Grundvoraussetzung für eine rationale, sichere und gesundheitsökonomisch sinnvolle Therapie. Nur ein Teil der Patienten mit Parkinson-Symptomen leidet an dem gut behandelbaren IPS im engeren Sinne. Heute sind acht Dopaminagonisten einschließlich des Apomorphins zur subkutanen Injektion, verschiedene L-Dopa-Darreichungsformen, COMT- und MAO-Hemmer, Amantadin, mit Einschränkungen das Budipin, das Clozapin und die tiefe Hirnstimulation für die Therapie dieser Erkrankung zugelassen. In Situationen, in denen auch eine optimierte medikamentöse Feineinstellung keinen Behandlungserfolg mehr bringt, hat bei Patienten mit schweren Dopa-Wirkungsschwankungen (On-off-Phänomen), Dyskinesien und Tremor inzwischen die tiefe Hirnstimulation („Hirnschrittmacher”) einen festen Platz erobert. Anticholinergika sollten auch bei Tremor-Dominanz nur noch in Ausnahmefällen eingesetzt werden. Cholinesterasehemmer sind hilfreich bei nicht kognitiven Demenz-Symptomen ohne die Parkinson-Symptomatik zu verschlechtern. Kurz vor der europäischen Zulassung stehen momentan spezifische Medikamente gegen Dopa-Dyskinesien. Und mit der Implantation dopaminerger Retinazellen besteht eine weitere Perspektive zur Therapie des idiopthischen Parkinson-Syndroms, die sich bereits in einer fortgeschrittenen Phase der klinischen Prüfung befindet.

Summary

The precise differentiation of Parkinson's disease (PD) from other forms of parkinsonism is the basis for a rationale, safe and pharmacoeconomically sound therapy. Drugs are usually unsatisfactory in other parkinsonian syndromes besides Parkinson's disease proper. Parkinson's disease is a well characterised syndrome which represents only a part of the various causes of parkinsonism. Eight dopamine agonists including apomorphine for subcutaneous injections, various distinct levodopa preparations, amantadine, COMT- and MAO-inhibitors, with restrictions also budipine, clozapine, and deep brain stimulation represent approved therapies for Parkinson's disease. Deep brain stimulation is emerging as treatment strategy for patients with severe on-off fluctuations, levodopa dyskinesias and tremor otherwise refractory to medical therapy. Anticholinergics should be only prescribed exceptionally even in tremor dominant Parkinson's disease. Cholinesterase-inhibitors are effective in non-cognitive symptoms of dementia without worsening parkinsonism. Specific compounds for the management of levodopa induced dyskinesias may gain approval shortly. The implantation of dopaminergic retinal cells represents a new perspective which is already in an advanced stage of clinical trial.

Parkinson's disease - levodopa - dopamine agonists - deep brain stimulation - cholinesterase inhibitors - cell implantation

Literatur

• 1 Baezner H, Oster M, Henning O. et al. . Amantadine increases gait steadiness in frontal gait disorder due to subcortical vascular encephalopathy: a double-blind randomized placebo-controlled trial based on quantitative gait analysis.  Cerebrovasc Dis. 2001;  11 235-244
• 2 Ceballos-Baumann AO, Boecker H, Bartenstein P. et al. . A positron emission tomographic study of subthalamic nucleus stimulation in Parkinson disease: enhanced movement-related activity of motor-association cortex and decreased motor cortex resting activity.  Arch Neurol. 1999;  56 997-1003
• 3 Ceballos-Baumann AO. Dopaminergic agents, COMT inhibitors or amantadine? Proper treatment for your Parkinson patient.  MMW Fortschr Med. 2002;  37-43
• 4 Charles PD, Van Blercom N, Krack P. et al. . Predictors of effective bilateral subthalamic nucleus stimulation for PD.  Neurology. 2002;  59 932-934
• 5 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
• 6 Krack P, Batir A, Van N Blercom. 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
• 7 Kuehler A, Henrich G, Schroeder U. et al. . A novel quality of life instrument for deep brain stimulation in movement disorders.  J Neurol Neurosurg Psychiatry. 2003;  74 1023-1030
• 8 Mancini F, Zangaglia R, Cristina S. et al. . Double-blind, placebo-controlled study to evaluate the efficacy and safety of botulinum toxin type A in the treatment of drooling in parkinsonism.  Mov Disord. 2003;  18 685-688
• 9 McKeith I, Del T Ser, Spano P. et al. . Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study.  Lancet. 2000;  356 2031-2036
• 10 Olanow CW, Goetz CG, Kordower JH. et al. . A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease.  Ann Neurol. 2003;  54 403-414
• 11 Parkinson Study Group . Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression.  JAMA. 2002;  287 1653-1361
• 12 Parkinson Study Group . Pramipexole vs levodopa as initial treatment for Parkinson disease: A randomized controlled trial.  JAMA. 2000;  284 1931-1938
• 13 Rascol O, Brooks DJ, Korczyn AD. et al. . A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa.  056 Study Group. N Engl J Med. 2000;  342 1484-1491
• 14 Schroeder U, Kuehler A, Haslinger B. et al. . Subthalamic nucleus stimulation affects striato-anterior cingulate cortex circuit in a response conflict task: a PET study.  Brain. 2002;  125 1995-2004
• 15 Schroeder U, Kuehler A, Lange KW. et al. . Subthalamic nucleus stimulation affects a frontotemporal network: a PET study.  Ann Neurol. 2003;  54 445-450

1 Deutsche-Parkinson-Vereinigung e.V., Moselstr. 31, 41464 Neuss

2 deprenyl and tocopherol antioxidative therapy of parkinsonism

Anschrift des Verfassers