Neuroprotektion: Eine neue therapeutische Option in der Epilepsietherapie?

Zusammenfassung

Primäres Ziel bei der Behandlung von Epilepsiepatienten ist die Anfallsfreiheit. Neben diesem palliativ symptomatischen Therapieansatz gibt es im klinischen Alltag bisher keine Möglichkeit auf medikamentösem Wege den Verlauf der Erkrankung zu beeinflussen oder diese gar zu heilen („Disease Modification”). Evidenzen aus klinischen und präklinischen Studien belegen, dass es im Verlauf der Erkrankung häufig zu einem neuronalen Zellverlust und einer Einschränkung der kognitiven Funktion kommt. Vor diesem Hintergrund erhält der Aspekt der Neuroprotektion, d. h. der Schutz vor einer zunehmenden Degeneration des neuronalen Gewebes durch den zugrunde liegenden Krankheitsprozess oder wiederkehrender epileptischer Anfälle bei nicht erreichter Anfallsfreiheit einen besonderen Stellenwert. Daten bezüglich der neuroprotektiven Wirkung von Antikonvulsiva gibt es bisher fast ausschließlich auf tierexperimenteller Basis. Die vier wesentlichen Mechanismen, die bei der Schädigung des Nervengewebes eine Rolle spielen sind (1) vermehrter Na⁺-Einstrom in die Zelle, (2) exzessiver Ca²⁺-Influx, (3) Verminderung der GABAergen Inhibition und (4) eine verstärkte glutamaterge Exzitotoxizität durch die massive Stimulation von ionotropen Glutamat-Rezeptoren (insbesondere des non-NMDA-Rezeptors). Diese Übersichtsarbeit stellt den derzeitigen Forschungsstand bezüglich einer schützenden Wirkung der in Deutschland zugelassenen Antiepileptika dar und beurteilt das Potenzial ihrer neuroprotektiven Eigenschaften.

Neuroprotection: A New Therapeutic Option in the Treatment of Epilepsy?

The primary aim in treating patients with epilepsy is the suppression of seizures. Apart from this symptomatic treatment so far no pharmacological approach exists to alter the natural course of the disease („disease modification”). There is clinical, as well as pre-clinical evidence that neuronal damage and an impairment of cognitive function frequently occurs during the course of epilepsy. It seems logical to investigate the feasibility of new therapeutic approaches in which neuroprotection plays a major role. The prevention of neuronal damage induced either by the pathophysiological cellular alterations generated by the disease itself, by repetetive seizures, or a status epilepticus is of major interest. Unfortunately so far data concerning the neuroprotective potential of anticonvulsive drugs is only available in preclinical studies. The four basic mechanisms by which neuronal damage usually occurs are (1) increased Na⁺-influx, (2) increased Ca²⁺-influx, (3) diminished GABA-ergic activity and (4) increased glutamatergic excitotoxicity through massive stimulation of ionotropic Glutamat-receptors (especially non-NMDA-receptors). This review reflects the current literature regarding the protective effects of anticonvulsive drugs.

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