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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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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