PMID- 24861491
OWN - NLM
STAT- MEDLINE
DCOM- 20140922
LR  - 20240321
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 55
IP  - 7
DP  - 2014 Jul
TI  - Pathogenetic mechanisms of focal cortical dysplasia.
PG  - 970-8
LID - 10.1111/epi.12650 [doi]
AB  - Focal cortical dysplasias (FCDs) constitute a prevalent cause of intractable 
      epilepsy in children, and is one of the leading conditions requiring epilepsy 
      surgery. Despite recent advances in the cellular and molecular biology of these 
      conditions, the pathogenetic mechanisms of FCDs remain largely unknown. The 
      purpose if this work is to review the molecular underpinnings of FCDs and to 
      highlight potential therapeutic targets. A systematic review of the literature 
      regarding the histologic, molecular, and electrophysiologic aspects of FCDs was 
      conducted. Disruption of the mammalian target of rapamycin (mTOR) signaling 
      comprises a common pathway underlying the structural and electrical disturbances 
      of some FCDs. Other mechanisms such as viral infections, prematurity, head 
      trauma, and brain tumors are also posited. mTOR inhibitors (i.e., rapamycin) have 
      shown positive results on seizure management in animal models and in a small 
      cohort of patients with FCD. Encouraging progress has been achieved on the 
      molecular and electrophysiologic basis of constitutive cells in the dysplastic 
      tissue. Despite the promising results of mTOR inhibitors, large-scale randomized 
      trials are in need to evaluate their efficacy and side effects, along with 
      additional mechanistic studies for the development of novel, molecular-based 
      diagnostic and therapeutic approaches.
CI  - Wiley Periodicals, Inc. (c) 2014 International League Against Epilepsy.
FAU - Marin-Valencia, Isaac
AU  - Marin-Valencia I
AD  - Department of Neurology and Neurotherapeutics, and Pediatrics, University of 
      Texas Southwestern Medical Center, Dallas, Texas, U.S.A.
FAU - Guerrini, Renzo
AU  - Guerrini R
FAU - Gleeson, Joseph G
AU  - Gleeson JG
LA  - eng
GR  - R01NS083823/NS/NINDS NIH HHS/United States
GR  - P01 HD070494/HD/NICHD NIH HHS/United States
GR  - P01HD070494/HD/NICHD NIH HHS/United States
GR  - R01 NS083823/NS/NINDS NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PT  - Systematic Review
DEP - 20140523
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Anticonvulsants)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Anticonvulsants/administration & dosage
MH  - Drug Delivery Systems/methods
MH  - Epilepsy/drug therapy/*epidemiology/*genetics
MH  - Gene Targeting/methods
MH  - Humans
MH  - Malformations of Cortical Development/drug therapy/*epidemiology/*genetics
MH  - Signal Transduction/drug effects/*genetics
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/genetics
PMC - PMC4107035
MID - NIHMS583634
OTO - NOTNLM
OT  - Focal cortical dysplasia
OT  - Giant cell
OT  - Mammalian target of rapamycin
OT  - PMSE syndrome
OT  - mTOR
COIS- CONFLICT OF INTEREST None to declare.
EDAT- 2014/05/28 06:00
MHDA- 2014/09/23 06:00
PMCR- 2015/07/01
CRDT- 2014/05/28 06:00
PHST- 2014/04/04 00:00 [accepted]
PHST- 2014/05/28 06:00 [entrez]
PHST- 2014/05/28 06:00 [pubmed]
PHST- 2014/09/23 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - 10.1111/epi.12650 [doi]
PST - ppublish
SO  - Epilepsia. 2014 Jul;55(7):970-8. doi: 10.1111/epi.12650. Epub 2014 May 23.