Zeitschrift für Epileptologie

, Volume 27, Issue 2, pp 132–138 | Cite as

Ethosuximid bei strukturellen und läsionellen Epilepsien

Leitthema
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Zusammenfassung

Ethosuximid ist als Antiepileptikum zur Behandlung von kindlichen Absencen und einigen weiteren idiopathischen Epilepsien etabliert. Sein Hauptwirkungsmechanismus ist die Hemmung von Kalzium(Ca-)Kanälen des T-Typs. Neuere Untersuchungen zeigen weitere Wirkungsmechanismen, wie die Beeinflussung von rezeptorgesteuerten Kaliumkanälen („G protein activated inwardly rectifying K+ channel“, GIRK). Tierexperimentell lassen sich antikonvulsive Effekte an oszillatorischen thalamischen Neuronen, aber auch an neokortikalen Strukturen belegen. Diese Wirkungsmechanismen sind bei zur Therapie struktureller, fokaler Epilepsien angewendeten Antiepileptika nicht vorhanden. (Zonisamid hat eine schwache Wirkung auf T-Typ-Ca-Kanäle.) Daher bringt Ethosuximid (und das ähnliche Mesuximid) neue Angriffspunkte in eine Kombinationstherapie therapierefraktärer Epilepsien ein. Anhand von 3 Kasuistiken (2 jugendliche Patienten mit hypothalamischen Hamartomen, ein 3 Jahre alter Junge mit Miller-Dieker-Syndrom) wird gezeigt, dass die Kombination eines Succinimids mit einem Natrium(Na)-Kanal-Hemmer (Lamotrigin, Rufinamid) zur lange anhaltenden, deutlichen Besserung (> 90 % Anfallsreduktion) einer therapierefraktären strukturellen Epilepsie führen kann. Die klinische Wirkung war von dem Sistieren epilepsietypischer Potenziale im EEG begleitet. Diese Beispiele zeigen, dass Ethosuximid nicht nur bei idiopathischen Epilepsien, sondern auch bei schwer therapierbaren strukturellen Epilepsien einen Versuch wert ist. Der Stellenwert der Substanz bei dieser Indikation kann anhand der vorhandenen Datenlage nicht abgeschätzt werden.

Schlüsselwörter

Succinimide T-Typ-Kalzium-Kanäle Wirkungsmechanismus Hypothalamische Hamartome Lissenzephalie 

Ethosuximide in structural-metabolic epilepsy syndromes

Abstract

Ethosuximide is a well-established drug for the treatment of childhood absence epilepsies. In some reports it was also successfully used in other, mostly idiopathic epilepsy syndromes. Its main mechanism of action is blockade of T-type calcium channels but it also exhibits inhibitory effects on G protein-activated inwardly rectifying K+ (GIRK) channels. Animal experiments have shown that anticonvulsant effects are generated in thalamic oscillatory neurons and in some neocortical structures. Moreover, the substance shows antiepileptogenic effects in mouse models of genetic epilepsies. Due to the nearly unique effects (zonisamide shows a weak inhibition of T-type channels too) this drug is an interesting compound in antiepileptic combination therapies. This article presents three cases of severe, pharmacoresistant structural epilepsy where the list of unsuccessfully tried medications showed a gap with regard to T-type calcium channels. Two were adolescents with hypothalamic hamartoma where a long lasting seizure reduction of > 90 % could be achieved by combining lamotrigine and ethosuximide. A third case was a 3-year-old boy with Miller-Dieker syndrome. In this case a massive remission of seizures could be achieved for at least 2 years. In all three cases the effect was accompanied by the disappearance of electroencephalogram (EEG) spike discharges. These case studies show that ethosuximide is a potentially effective agent also in epilepsies with structural etiologies. Its specific mechanisms of action can contribute to polytherapy in highly phramacoresistant epilepsies besides its established indications. Further studies are needed to estimate the chance of a successful treatment under such conditions.

Keywords

Succinimides T-type calcium channel Mechanism of action Hypothalamic hamartomas Lissencephaly 

Notes

Einhaltung der ethischen Richtlinien

Interessenkonflikt. U. Brandl erhält Honorare für Vorträge von verschiedenen Antiepileptikaherstellern (Desitin, Eisai, UCB, Viropharma). Keines dieser Honorare steht im Zusammenhang mit der in diesem Beitrag behandelten Substanz. Der Beitrag enthält keine Studien an Menschen oder Tieren.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Klinik für Kinder- und JugendmedizinUniversitätsklinikum JenaJenaDeutschland

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