Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.

Tuberous Sclerosis Complex (TSC) is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers) contain...

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Main Authors: Angelika Mühlebner, Jackelien van Scheppingen, Hanna M Hulshof, Theresa Scholl, Anand M Iyer, Jasper J Anink, Ans M W van den Ouweland, Mark D Nellist, Floor E Jansen, Wim G M Spliet, Pavel Krsek, Barbora Benova, Josef Zamecnik, Peter B Crino, Daniela Prayer, Thomas Czech, Adelheid Wöhrer, Jasmin Rahimi, Romana Höftberger, Johannes A Hainfellner, Martha Feucht, Eleonora Aronica
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4905625?pdf=render
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spelling doaj-3b4361f6c3404a0ab17dc4ed6bddecb72020-11-25T02:27:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01116e015739610.1371/journal.pone.0157396Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.Angelika MühlebnerJackelien van ScheppingenHanna M HulshofTheresa SchollAnand M IyerJasper J AninkAns M W van den OuwelandMark D NellistFloor E JansenWim G M SplietPavel KrsekBarbora BenovaJosef ZamecnikPeter B CrinoDaniela PrayerThomas CzechAdelheid WöhrerJasmin RahimiRomana HöftbergerJohannes A HainfellnerMartha FeuchtEleonora AronicaTuberous Sclerosis Complex (TSC) is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers) contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions. However, a histological classification system has not been established for tubers. Therefore, the aim of this study was to define distinct histological patterns within tubers based on semi-automated histological quantification and to find clinically significant correlations. In total, we studied 28 cortical tubers and seven samples of perituberal cortex from 28 TSC patients who had undergone epilepsy surgery. We assessed mammalian target of rapamycin complex 1 (mTORC1) activation, the numbers of giant cells, dysmorphic neurons, neurons, and oligodendrocytes, and calcification, gliosis, angiogenesis, inflammation, and myelin content. Three distinct histological profiles emerged based on the proportion of calcifications, dysmorphic neurons and giant cells designated types A, B, and C. In the latter two types we were able to subsequently associate them with specific features on presurgical MRI. Therefore, these histopathological patterns provide consistent criteria for improved definition of the clinico-pathological features of cortical tubers identified by MRI and provide a basis for further exploration of the functional and molecular features of cortical tubers in TSC.http://europepmc.org/articles/PMC4905625?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Angelika Mühlebner
Jackelien van Scheppingen
Hanna M Hulshof
Theresa Scholl
Anand M Iyer
Jasper J Anink
Ans M W van den Ouweland
Mark D Nellist
Floor E Jansen
Wim G M Spliet
Pavel Krsek
Barbora Benova
Josef Zamecnik
Peter B Crino
Daniela Prayer
Thomas Czech
Adelheid Wöhrer
Jasmin Rahimi
Romana Höftberger
Johannes A Hainfellner
Martha Feucht
Eleonora Aronica
spellingShingle Angelika Mühlebner
Jackelien van Scheppingen
Hanna M Hulshof
Theresa Scholl
Anand M Iyer
Jasper J Anink
Ans M W van den Ouweland
Mark D Nellist
Floor E Jansen
Wim G M Spliet
Pavel Krsek
Barbora Benova
Josef Zamecnik
Peter B Crino
Daniela Prayer
Thomas Czech
Adelheid Wöhrer
Jasmin Rahimi
Romana Höftberger
Johannes A Hainfellner
Martha Feucht
Eleonora Aronica
Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.
PLoS ONE
author_facet Angelika Mühlebner
Jackelien van Scheppingen
Hanna M Hulshof
Theresa Scholl
Anand M Iyer
Jasper J Anink
Ans M W van den Ouweland
Mark D Nellist
Floor E Jansen
Wim G M Spliet
Pavel Krsek
Barbora Benova
Josef Zamecnik
Peter B Crino
Daniela Prayer
Thomas Czech
Adelheid Wöhrer
Jasmin Rahimi
Romana Höftberger
Johannes A Hainfellner
Martha Feucht
Eleonora Aronica
author_sort Angelika Mühlebner
title Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.
title_short Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.
title_full Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.
title_fullStr Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.
title_full_unstemmed Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.
title_sort novel histopathological patterns in cortical tubers of epilepsy surgery patients with tuberous sclerosis complex.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2016-01-01
description Tuberous Sclerosis Complex (TSC) is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers) contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions. However, a histological classification system has not been established for tubers. Therefore, the aim of this study was to define distinct histological patterns within tubers based on semi-automated histological quantification and to find clinically significant correlations. In total, we studied 28 cortical tubers and seven samples of perituberal cortex from 28 TSC patients who had undergone epilepsy surgery. We assessed mammalian target of rapamycin complex 1 (mTORC1) activation, the numbers of giant cells, dysmorphic neurons, neurons, and oligodendrocytes, and calcification, gliosis, angiogenesis, inflammation, and myelin content. Three distinct histological profiles emerged based on the proportion of calcifications, dysmorphic neurons and giant cells designated types A, B, and C. In the latter two types we were able to subsequently associate them with specific features on presurgical MRI. Therefore, these histopathological patterns provide consistent criteria for improved definition of the clinico-pathological features of cortical tubers identified by MRI and provide a basis for further exploration of the functional and molecular features of cortical tubers in TSC.
url http://europepmc.org/articles/PMC4905625?pdf=render
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