Update zur Pathophysiologie des Restless-Legs-Syndroms

Zusammenfassung

Die Ursachen des Restless-Legs-Syndroms (RLS) sind heterogen. Die sogenannten idiopathischen RLS-Syndrome, die vor allem bei jüngeren Patienten unter 30 Jahren symptomatisch werden, sind häufig familiär bedingt. Die ersten Gene wurden in diesem Jahr im Gen MEIS1, im BTBD9 Gen und in den Genen, die die mitogenaktivierende Proteinkinase MAP2K5 und den Transkriptionsfaktor LBXCOR1 codieren, jeweils auf den Chromosomen 2p, 6p und 15q, identifiziert. Eine Vielzahl symptomatischer Ursachen wie Eisenmangel, Urämie, Polyneuropathie und andere verursachen die sog. sekundären Formen. Von besonderem pathophysiologischem Interesse ist derzeit die Klärung der Frage, warum die dopaminerge Therapie für idiopathische wie symptomatische Formen so effizient ist und das hiermit verbundene Problem der sogenannten Augmentation. Unter Augmentation versteht man eine therapieinduzierte paradoxe Verstärkung der Symptome des RLS durch dopaminerge Therapie, wahrscheinlich dosisabhängig. Sie tritt bei bis zu 60 % der Patienten vorzugsweise unter L-Dopa aber auch unter der Therapie mit Dopaminagonisten auf. Augmentation wird wahrscheinlich durch Verschiebung des Gleichgewichtes zugunsten erregender dopaminerger D1-Rezeptoren und zuungunsten hemmender D2-Rezeptoren wahrscheinlich spinal verursacht. Eisenmangel stellt einen auslösenden oder verstärkenden Faktor dar. Die Therapie mit L-Dopa oder Dopaminagonisten sollte daher wesentlich niedriger als beim Parkinsonsyndrom gehalten werden. Eisensubstitution und Opiate sind die Mittel der Wahl, um das Risiko der Augmentation zu minimieren und ggfs. zu therapieren.

Abstract

The Restless Legs Syndrome (RLS) is a heterogeneous disease. The so-called idiopathic RLS syndromes affect preferentially younger patients before the age of 30 and are with a higher likelihood familial. This year intronic variants in the homeobox gene MEIS1, the BTBD9 gene encoding a BTB(POZ) domain as well as variants in a third locus containing the genes encoding mitogen-activated protein kinase MAP2K5 and the transcription factor LBXCOR1 on chromosomes 2p, 6p and 15q, were identified. Symptomatic or secondary forms encompass iron deficiency, uremia, polyneuropathy and other causes. At present it is of particular interest to unravel why dopaminergic therapy is so efficient in the disease and why it leads to augmentation in some patients. Augmentation can be defined as a therapy induced paradoxical symptom severity increase caused by dopaminergic therapy. Augmentation occurs in about 60 % of patients preferentially on L-Dopa, but also on therapy with dopamine agonists. It is probably caused by a relative shift of the balance between excitatory dopaminergic D1-receptors and inhibitory D2-receptors at a spinal level. Iron deficiency is an initiating or strengthening factor. Therapy with L-Dopa or dopamine agonists should remain at distinctly lower doses than those commonly used in Parkinson's disease. Iron substitution and opiates are drugs of choice to minimize the risk of augmentation.

Schlüsselwörter

RLS - Restless-Legs-Syndrom - Pathophysiologie - Genetik - Dopamin - Opiate

Key words

RLS - restless legs syndrome - pathophysiology - genetics - dopamine - opiate

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