Rationale Epilepsiebehandlung bei tuberöser Sklerose

Zusammenfassung

Die tuberöse Sklerose (tuberous sclerosis complex, TSC) ist eine Systemerkrankung aufgrund eines Defekts der Tumorsuppressorgene TSC1 (Hamartin) und TSC2 (Tuberin) und der damit verbundenen reduzierten Hemmung des mTOR-Stoffwechsel (mammilian target of rapamycin). Etwa 85% der Patienten leiden an einer Epilepsie, die meist im ersten Lebensjahr und nicht selten als WestSyndrom beginnt und häufig pharmakorefraktär verläuft. Mindestens 60% der Patienten entwickeln kognitive Defizite, Verhaltensstörungen und/oder einen Autismus. Ein früher Epilepsiebeginn korreliert mit diesen Entwicklungsstörungen. Vigabatrin ist bei Säuglingen die Therapie der ersten Wahl. Bei älteren Patienten gibt es keine sicheren Hinweise auf eine höhere Wirksamkeit gegenüber anderen Standardantiepileptika. Die Therapie erfolgt syndromspezifisch nach den Leitlinien. Nach Versagen von zwei Standardtherapien sollte eine prächirurgische Epilepsiediagnostik an einem erfahrenen Zentrum erfolgen, auch bei multiplen Läsionen oder (scheinbar) generalisierten Anfällen. Patienten mit TSC sprechen sehr gut auf ketogene Diäten an. Auch die Vagusnervstimulation zeigt bemerkenswerte Effekte. Erste Berichte legen einen antiepileptischen Effekt von mTOR-Inhibitoren bei TSC nahe.

Summary

Tuberous sclerosis complex (TSC) is a disorder resulting from defects of the tumorsuppressor genes TSC1 (hamartin) and TSC2 (tuberin) and consecutively reduced inhibition of the mTOR pathway. About 85% of the patients suffer from epilepsy. The onset is typically in the first year of life and many patients present with infantile spasms. Epilepsies are frequently pharmacorefractory. At least 60% of the patients present with cognitive deficits, behavioral problems and/or autism. An early epilepsy onset correlates with the degree of the developmental impairment. Vigabatrin is the first line drug in infants. However, there is no evidence of a higher efficacy compared to other standard antiepileptic drugs in older patients. Therefore, epilepsy should be treated according to general guidelines taking into account the electro-clinical syndrome. Presurgical evaluation at an experienced centre is indicated after failure of two standard therapies, even in cases with multiple lesions and (apparently) generalized seizures. Because of apparently good response, ketogenic diets play an important role in TSC-related epilepsy. In addition, remarkable responder rates were reported for vagus nerve stimulation. First studies in a few patients indicate antiepileptic effects of mTOR inhibitors in TSC.

Schlüsselwörter

West-Syndrom - pharmakorefraktär - ketogene Diät - mTOR

Keywords

Infantile spasms - refractory epilepsy - ketogenic diet - mTOR inhibition

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