Neue Entwicklungen der Epileptogenese und therapeutische Perspektiven

Der Nervenarzt (Impact Factor: 0.79). 08/2011; 82(8):978-985. DOI: 10.1007/s00115-011-3260-4

ABSTRACT Die Epileptogenese beschreibt die Entstehungsmechanismen von Epilepsien. Wir haben 4Gebiete ausgewählt, auf denen entscheidende
Fortschritte für das Verständnis der Epileptogenese erzielt wurden. Dies betrifft im Einzelnen (1) inflammatorische Prozesse,
denen bei der Entstehung von Temporallappenepilepsien mit Hippokampussklerose (TLE mit HS) eine zunehmende Bedeutung zukommt,
(2) Störungen intrinsischer Eigenschaften von neuronalen Kompartimenten, v.a. erworbene Störungen von Ionenkanälen, von denen
hier bei der TLE mit HS solche in Dendriten beschrieben werden sollen, (3) epigenetische Effekte, die z.B. die Methylierung
von Promotoren betreffen und dadurch sekundär die Expression bestimmter Gene verändern und die auch bei der TLE mit HS gefunden
werden, und schließlich (4) die Epileptogenese der idiopathischen Epilepsien, die durch angeborene genetische Veränderungen
verursacht werden und überwiegend Ionenkanäle betreffen. Neben grundlagenwissenschaftlichen Aspekten wird auf klinische Konsequenzen
und therapeutische Perspektiven eingegangen.

Epileptogenesis describes the mechanisms of how epilepsies are generated. We have chosen four areas in which significant progress
has been achieved in understanding epileptogenesis. Those are (1) inflammatory processes which play an increasingly important
role for the generation of temporal lobe epilepsy with hippocampal sclerosis (TLE with HS), (2) disturbances of intrinsic
properties of neuronal compartments, in particular acquired defects of ion channels of which those in dendrites are described
here for TLE with HS, (3) epigenetic effects, which affect for example the methylation of promoters and secondarily can change
the expression of specific genes in TLE with HS, and finally (4) the epileptogenesis of idiopathic epilepsies which are caused
by inborn genetic alterations affecting mainly ion channels. Apart from aspects of basic research, we will describe clinical
consequences and therapeutic perspectives.

KeywordsEpilepsy–Inflammation–Ion channel–Epigenetics–Genetics

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