Neuropediatrics 2016; 47 - P07-07
DOI: 10.1055/s-0036-1583685

Everolimus as Targeted mTOR Inhibition in Neonates and Infants with Tuberous Sclerosis

I. Brösse 1, C. Vogelsang 1, A. Ziegler 1, G. Hoffmann 1
  • 1Centre for Childhood and Adolescent Medicine, Department for Neuropediatrics and Metabolic Disease, University Hospital of Heidelberg, Germany

Background: Tuberous sclerosis complex (TSC) is a multisystem disease with age-dependent development of hamartomas in multiple organic systems. Complications in neonates and infants occur by cardiac rhabdomyomas causing hemodynamic instability, arrhythmias or other complications and by subependymal giant cell astrocytomas (SEGA) causing obstructive hydrocephalus. A targeted therapy with everolimus, a selective mTOR inhibitor is licensed in Europe and USA for the treatment of SEGA and angiomyolipomas at the age of 3 years.

Case Report: We present a late preterm with 34 weeks of gestational age and the clinical diagnosis of TSC with cardiac rhabdomyomas, cortical tubers and subependymal nodules. In neonatal age arrhythmia refractory to medication with consecutive cardiac decompensation led to intensive care unit treatment. Progressive heart failure, significant insufficiency of mitral valve and a high right ventricular pressure resulted. At the adjusted age of 4 weeks we started everolimus for 7 weeks after informed consent of the parents as compassionate use. Rhabdomyoma of the right ventricle completely vanished, arrhythmias stopped under concomitant triple antiarrhythmic treatment. cMRI after everolimus treatment showed a reduction in subependymal nodules of at least 50%. Everolimus was well tolerated, and the patient presented no side effects. Two weeks after the end of the treatment, the patient showed a relapse of arrhythmias and a stop of rhabdomyoma regression. cMRI 6 weeks later showed stable findings.

Conclusion: Under compassionate use of Everolimus, we obtained a relevant therapeutic success regarding the life-threatening arrhythmias with cardiac failure. Additionally, we recognized a significant regression of subependymal nodules. The potential of everolimus on neurological outcome regarding epilepsy and developmental disorder is uncertain. Further prospective randomized clinical trials are needed to evaluate the benefit-risk profile of everolimus in neonates and young infants.