Neuropediatrics 2013; 44 - FV14_07
DOI: 10.1055/s-0033-1337737

Does the mTOR inhibitor everolimus influence the course of epilepsy in children with tuberous sclerosis complex?

F Mackel 1, B Fiedler 1, A Hahn 2, H Hartmann 3, P Hernaiz-Driever 4, C Hertzberg 5, AK Kolb 6, K Marquard 7, O Witt 8, G Wiegand 9, A Wiemer-Kruel 10, G Kurlemann 1
  • 1Klinik für Kinder-und Jugendmedizin-Allgemeine Pädiatrie-, Münster, Germany
  • 2Universitäts Kinderklinik Gießen, Gießen, Germany
  • 3Medizinische Hochschule Hannover, Hannover, Germany
  • 4Kinderklinik Charite, Berlin, Germany
  • 5Kinderklinik Neukölln, Berlin, Germany
  • 6Klinikum Kassel, Kassel, Germany
  • 7Klinikum Stuttgart, Stuttgart, Germany
  • 8Universitäts-Klinik, Heidelberg, Germany
  • 9Universitäts Kinderklinik Kiel, Kiel, Germany
  • 10Diakonie Kork, Kehl-Kork, Germany

Aims: Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome affecting the skin, brain, kidneys, and heart. The recently approved mTOR inhibitor everolimus acts directly on the pathomechanism of the disorder. Studies documenting the effectiveness of everolimus in treating the subependymal giant cell astrocytoma (SEGA) also indicate an improvement in frequently therapy-resistant epilepsy.

Methods: In a retrospective analysis, 19 children (11 girls) on everolimus from German TSC centers were recorded: 17 SEGA; 1 angiomyolipoma; and 1 lymphedema. Evaluation was conducted for genetics, age at therapy onset, everolimus dosage, number of previous and current antiepileptic drugs, course of epilepsy on everolimus, duration of everolimus therapy, side effects, and tests of affected organs (SEGA, kidneys, angiofibroma, cognition, and behavior).

Results: The boys averaged 8.1 years of age, and the girls averaged 10.7 years of age.

Genetics: 2x TSC1, 9x TSC2, 8x unknown. In all cases, epilepsy therapy was difficult involving extensive previous treatment with a large number of antiepileptic drugs in monotherapy and combined therapy.

The following antiepileptic drugs were administered with add-on dosages of everolimus: 3 mono (2 × VPA, 1 × CBZ). Under polytherapy, 11 out of 17 children received VPA and 6 out of 17 children received OXC/CBZ. The everolimus dosage was 2.5 to 14 mg/d, and the serum concentration varied between 1.9 µg/L and 13 µg/L.

Results: 10/17: relapse SEGA; 4/19: improvement of angiomyolipoma; 5/19: fading of angiofibroma. Epilepsy: 7/17: significant improvement of seizures; 1/17 therapy termination due to a status epilepticus on everolimus; 9/17: to date no change in course of epilepsy. 6/19: improvement of behavior disorders; 1/19: also cognitive function.

Conclusion: Our data on improvements in the epileptic situation in children with TSC on everolimus showed a clinically relevant reduction of the epileptic seizures in 41% of children (7 out of 17). Everolimus was tolerated well with no serious side effects. Part of the data collection was supported by Novartis.