Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Petrus de Vries, University of Cape Town, South Africa
- Second opponent: Head of Research Marte Roa Syvertsen, Drammen Hospital, Norway
- Third member and chair of the evaluation committee: Associate Professor Hans Christian Erichsen Landsverk, University of Oslo
Chair of the Defence
Professor Emeritus Leif Ingvald Gjerstad, University of Oslo
Principal Supervisor
Researcher Terje Nærland, University of Oslo
Summary
Tuberous sclerosis complex (TSC) is a rare genetic multisystem disease caused by inactivation of the tumour suppressor genes TSC1 or TSC2 resulting in over activation of the mammalian target of rapamycin pathway and development of benign tumours and lesions in several organs. Epilepsy and renal manifestations are the most common symptoms, with potentially severe symptoms, highlighting the need for regular follow up.
Randomized controlled trials have reported everolimus as an effective preventive treatment for patients with TSC.
The aim of this thesis was to investigate renal manifestations and treatment with everolimus in two study populations.
Study 1 (Norway and France, n = 357) used questionnaires to investigate rates of renal angiomyolipoma (R-AML), renal bleeding, follow up routines, and patients’ and parents’ knowledge about renal manifestations.
Study 2 (Denmark and Norway, n=64) reviewed medical records, magnetic resonance imaging and interviews to investigate effectiveness and safety of everolimus for R-AML, epilepsy and subependymal giant cell astrocytoma (SEGA).
In population 1, R-AML was described in 54% and R-AML related bleeding in 7%; both increased with age. Thirty percent did not receive the recommended renal imaging, and adolescents received the poorest follow-up. Twenty eight percent were unaware of bleeding risk; parents were better informed than patients. Our findings indicate a need for improved renal follow-up and patient education. Our results have been incorporated into clinical practice recommendations.
In Study 2, everolimus was beneficial in reducing seizure frequency in 1/3 of patients and in reducing or stabilizing the tumor size of R-AML and SEGA in all. Adverse effects were reported in 95% and a third experienced grade ≥3 events, more common in children. Our results demonstrate a need for closer monitoring and follow-up of adverse effects, particularly for children and increased focus on the balance between benefits and adverse effects.
Additional information
Contact the research support staff.