Zusammenfassung
Wir berichten den Fall einer inzwischen 71 Jahre alten Patientin mit einer idiopathisch generalisierten Epilepsie mit Myoklonien und generalisierten tonisch-klonischen Anfällen bei photoparoxysmaler Reaktion Grad 4 nach Waltz, die trotz der üblichen medikamentösen und expositionsreduzierenden prophylaktischen Maßnahmen über Jahre nicht anfallsfrei geworden war. Sie hatte bei der Proof-of-Concept-Studie teilgenommen, bei der lange vor den Zulassungsstudien der Effekt von Einmaldosen von Brivaracetam (BRV) auf die photoparoxysmale Reaktion (PPR) photosensibler Epilepsiepatienten getestet worden war. In dieser Studie hatte sich ein eindeutig positiver Effekt von BRV auf die PPR in unserem Fall nachweisen lassen. Deshalb behandelten wir sie nach Zulassung von BRV zur Behandlung von Epilepsien mit fokalen und sekundär generalisierten Anfällen im Sinne einer Off-Label-Anwendung mit BRV als Zusatzmedikation bis zu einer Dosishöhe von 200 mg. Leider scheiterte dieser „rationale“ Therapieansatz, weil sich sowohl generalisierte tonisch-klonische Anfälle als auch insbesondere die PPR nicht unterdrücken ließen. Diese kasuistische Erfahrung suggeriert, dass die Übertragbarkeit der Ergebnisse einer Einmaldosisstudie auf die spätere Wirksamkeit unter chronischen Therapiebedingungen fraglich ist.
Abstract
We report the case of a meanwhile 71-year-old female patient with an idiopathic generalized epilepsy syndrome with myoclonic and generalized tonic-clonic seizures and extensive photoparoxysmal response (PPR) grade 4 according to Waltz. The patient did not become seizure-free over many years in spite of the usual antiepileptic drug (AED) regimens and prophylactic protective arrangements to reduce the impact of photic stimulation. The patient had participated in a previous proof-of-concept study in which the effect of a single dose of brivaracetam (BRV) on the PPR of photosensitive epilepsy patients was tested, long before the approval studies. In this study the patient showed a convincing positive effect of a single dose of BRV on the PPR. Therefore, the patient was treated with BRV after its approval for treatment of epilepsy for patients with focal and secondary generalized tonic-clonic seizures in the sense of an off-label approach. The maximum add-on dose was 200 mg per day. Unfortunately, this “rational” therapeutic approach failed because the PPR and the frequency of generalized tonic-clonic seizures were not suppressed. This case experience suggests that results of a single-dose study in patients with PPR do not necessarily predict the long-term potential of a given AED even on an individual basis.
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B.J. Steinhoff war als Referent für die Firmen Desitin, Eisai, GW, Hexal, Novartis und UCB tätig und erhielt Beraterhonorare von B. Braun Melsungen, GW und Idorsia. C. Kurth war als Referent für Desitin tätig. A.M. Staack war als Referentin für Desitin, Eisai und UCB tätig. M. Bacher, I. Fazekas und A.-S. Wendling geben an, dass kein Interessenkonflikt besteht.
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Steinhoff, B.J., Bacher, M., Fazekas, I. et al. „Rationale“ Pharmakotherapie gescheitert. Z. Epileptol. 32, 160–164 (2019). https://doi.org/10.1007/s10309-018-0209-7
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DOI: https://doi.org/10.1007/s10309-018-0209-7