FCD Type II and mTOR pathway: Evidence for different mechanisms involved in the pathogenesis of dysmorphic neurons

Laura Rossini, Flavio Villani, Tiziana Granata, Laura Tassi, Giovanni Tringali, Francesco Cardinale, Eleonora Aronica, Roberto Spreafico, Rita Garbelli

Research output: Contribution to journalArticlepeer-review


Type II focal cortical dysplasia (FCD II) is a malformation of cortical development, frequently associated with intractable epilepsy, characterised by cortical dyslamination, dysmorphic neurons (DNs) and balloon cells (BCs). We investigated the expression of pS6 (downstream target) and pPDK1-pAkt (upstream targets) as evidence for mTOR pathway activation and their co-expression with Interleukin-1β in FCD II surgical specimens and compared the findings with control non-epileptic tissue, non-malformed epileptic tissue or acquired epilepsy-Rasmussen's Encephalitis (RE) occasionally presenting pS6 and Interleukin-1β positive abnormal neurons. Downstream mTOR activation was demonstrated in almost all abnormal cells in both FCD II and RE. Conversely, upstream activation in FCD II was observed in the majority of BCs, in a proportion of DNs, not presenting Interleukin-1β expression, but not at all in RE scattered abnormal neurons. Based on these findings we suggest that the presence of BCs and DNs in FCD II could be due to a first upstream mTOR pathway PI3K-Akt-mediate event occurring very early during cortical development in the large proportion of abnormal cells; followed by the appearance of additional pS6 positive DNs promoted by the presence of a later inflammatory processes.

Original languageEnglish
Pages (from-to)146-156
Number of pages11
JournalEpilepsy Research
Publication statusPublished - Jan 1 2017


  • Epilepsy surgery
  • Focal cortical dysplasia
  • inflammation
  • mTOR pathway
  • pI3K-Akt pathway
  • pS6

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


Dive into the research topics of 'FCD Type II and mTOR pathway: Evidence for different mechanisms involved in the pathogenesis of dysmorphic neurons'. Together they form a unique fingerprint.

Cite this