PMID- 26758984
OWN - NLM
STAT- MEDLINE
DCOM- 20160926
LR  - 20220915
IS  - 1532-2130 (Electronic)
IS  - 1090-3798 (Linking)
VI  - 20
IP  - 2
DP  - 2016 Mar
TI  - Early onset epileptic encephalopathy or genetically determined encephalopathy 
      with early onset epilepsy? Lessons learned from TSC.
PG  - 203-211
LID - S1090-3798(15)00216-0 [pii]
LID - 10.1016/j.ejpn.2015.12.005 [doi]
AB  - BACKGROUND: In tuberous sclerosis complex (TSC) a relationship has been shown 
      between early and refractory seizures and intellectual disability. However, it is 
      uncertain whether epilepsy in TSC is simply a marker in infants who are destined 
      to develop an encephalopathic process or if seizures play a causal role in 
      developing an encephalopathy. METHODS: This paper summarizes the key points 
      discussed during a European TSC workshop held in Rome, and reviews the 
      experimental and clinical evidence in support of the two theories. 
      RESULTS/CONCLUSION: There are many factors that influence the appearance of both 
      early seizure onset and the encephalopathy resulting in neurodevelopmental 
      deficits. Experimental studies show that as a consequence of the TSC genes 
      mutation, mammalian target of Rapamycin (mTOR) overactivation determines an 
      alteration in cellular morphology with cytomegalic neurons, altered 
      synaptogenesis and an imbalance between excitation/inhibition, thus providing a 
      likely neuroanatomical substrate for the early appearance of refractory seizures 
      and for the encephalopathic process. At the clinical level, early signs of 
      altered developmental trajectories are often unrecognized before 12 months of 
      age. Evidence from experimental research shows that encephalopathy in TSC might 
      have a genetic cause, and mTOR activation caused by TSC gene mutation can be 
      directly responsible for the early appearance of seizures and encephalopathy.
CI  - Copyright (c) 2015 European Paediatric Neurology Society. Published by Elsevier 
      Ltd. All rights reserved.
FAU - Curatolo, Paolo
AU  - Curatolo P
AD  - Systems Medicine Department, Child Neurology and Psychiatry Unit, Tor Vergata 
      University Hospital of Rome, Italy. Electronic address: curatolo@uniroma2.it.
FAU - Aronica, Eleonora
AU  - Aronica E
AD  - Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, 
      Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands; SEIN - Stichting Epilepsie 
      Instellingen Nederland, Heemstede, The Netherlands; Swammerdam Institute for Life 
      Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The 
      Netherlands. Electronic address: e.aronica@amc.uva.nl.
FAU - Jansen, Anna
AU  - Jansen A
AD  - Pediatric Neurology Unit - UZ Brussel, Brussels, Belgium. Electronic address: 
      anna.jansen@uzbrussel.be.
FAU - Jansen, Floor
AU  - Jansen F
AD  - Department of Child Neurology, Brain Center Rudolf Magnus, University Medical 
      Center Utrecht, The Netherlands. Electronic address: F.E.Jansen@umcutrecht.nl.
FAU - Kotulska, Katarzyna
AU  - Kotulska K
AD  - Department of Neurology and Epileptology, The Children's Memorial Health 
      Institute, Warsaw, Poland. Electronic address: kotulska.jozwiak@gmail.com.
FAU - Lagae, Lieven
AU  - Lagae L
AD  - Department of Development and Regeneration-Section Pediatric Neurology, 
      University Hospitals KU Leuven, Leuven, Belgium. Electronic address: 
      lieven.lagae@uzleuven.be.
FAU - Moavero, Romina
AU  - Moavero R
AD  - Systems Medicine Department, Child Neurology and Psychiatry Unit, Tor Vergata 
      University Hospital of Rome, Italy; Department of Neuroscience and 
      Neurorehabilitation, Pediatric Neurology Unit, Bambino Gesu Children's Hospital, 
      IRCCS, Rome, Italy. Electronic address: rominamoavero@hotmail.com.
FAU - Jozwiak, Sergiusz
AU  - Jozwiak S
AD  - Department of Child Neurology, Medical University of Warsaw, Warsaw, Poland. 
      Electronic address: sergiusz.jozwiak@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20151223
PL  - England
TA  - Eur J Paediatr Neurol
JT  - European journal of paediatric neurology : EJPN : official journal of the 
      European Paediatric Neurology Society
JID - 9715169
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
EIN - Eur J Paediatr Neurol. 2022 Nov;41:109. PMID: 36109305
MH  - Animals
MH  - Brain Diseases/*etiology
MH  - Epilepsy/*genetics
MH  - Female
MH  - Humans
MH  - Infant
MH  - Male
MH  - Seizures/*complications
MH  - TOR Serine-Threonine Kinases
MH  - Tuberous Sclerosis/*complications
OTO - NOTNLM
OT  - Epileptic encephalopathy
OT  - Genetics
OT  - Tuberous sclerosis
OT  - Vigabatrin
OT  - mTOR
EDAT- 2016/01/14 06:00
MHDA- 2016/09/27 06:00
CRDT- 2016/01/14 06:00
PHST- 2015/07/14 00:00 [received]
PHST- 2015/12/01 00:00 [revised]
PHST- 2015/12/13 00:00 [accepted]
PHST- 2016/01/14 06:00 [entrez]
PHST- 2016/01/14 06:00 [pubmed]
PHST- 2016/09/27 06:00 [medline]
AID - S1090-3798(15)00216-0 [pii]
AID - 10.1016/j.ejpn.2015.12.005 [doi]
PST - ppublish
SO  - Eur J Paediatr Neurol. 2016 Mar;20(2):203-211. doi: 10.1016/j.ejpn.2015.12.005. 
      Epub 2015 Dec 23.