Everolimus Alleviates Obstructive Hydrocephalus due to Subependymal Giant Cell Astrocytomas

Pediatr Neurol. 2017 Mar:68:59-63. doi: 10.1016/j.pediatrneurol.2016.11.003. Epub 2017 Jan 3.

Abstract

Background: Subependymal giant cell astrocytomas (SEGAs) are low-grade tumors affecting up to 20% of patients with tuberous sclerosis complex (TSC). Early neurosurgical resection has been the only standard treatment until few years ago when a better understanding of the molecular pathogenesis of TSC led to the use of mammalian target of rapamycin (mTOR) inhibitors. Surgical resection of SEGAs is still considered as the first line treatment in individuals with symptomatic hydrocephalus and intratumoral hemorrhage. We describe four patients with symptomatic or asymptomatic hydrocephalus who were successfully treated with the mTOR inhibitor everolimus.

Methods: We collected the clinical data of four consecutive patients presenting with symptomatic or asymptomatic hydrocephalus due to a growth of subependymal giant cell atrocytomas and who could not undergo surgery for different reasons.

Results: All patients experienced a clinically significant response to everolimus and an early shrinkage of the SEGA with improvement in ventricular dilatation. Everolimus was well tolerated by all individuals.

Conclusions: Our clinical series demonstrate a possible expanding indication for mTOR inhibition in TSC, which can be considered in patients with asymptomatic hydrocephalus or even when the symptoms already appeared. It offers a significant therapeutic alternative to individuals that once would have undergone immediate surgery. Everolimus might also allow postponement of a neurosurgical resection, making it elective with an overall lower risk.

Keywords: SEGA; everolimus; hydrocephalus; mTOR inhibitors; treatment; tuberous sclerosis complex.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Antineoplastic Agents / therapeutic use*
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain Neoplasms / complications
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / physiopathology
  • Everolimus / therapeutic use*
  • Female
  • Glioma, Subependymal / complications
  • Glioma, Subependymal / drug therapy*
  • Glioma, Subependymal / physiopathology
  • Humans
  • Hydrocephalus / drug therapy*
  • Hydrocephalus / etiology
  • Hydrocephalus / physiopathology
  • Male
  • Randomized Controlled Trials as Topic
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Burden
  • Young Adult

Substances

  • Antineoplastic Agents
  • Everolimus
  • MTOR protein, human
  • TOR Serine-Threonine Kinases