Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients - An Atlas-Based Volumetric MRI Study

Background: The neuropathology of patients with frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS) due to a C9orf72 mutation is characterized by two distinct types of characteristic protein depositions containing either TDP-43 or so-called dipeptide repeat proteins that extend beyo...

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Authors: Schonecker, S, Neuhofer, C, Otto, M, Ludolph, A, Kassubek, J, Landwehrmeyer, B, Anderl-Straub, S, Semler, E, Diehl-Schmid, J, Prix, C, Vollmar, C, Fortea, J, Huppertz, HJ, Arzberger, T, Edbauer, D, Feddersen, B, Dieterich, M, Schroeter, ML, Volk, AE, Fliessbach, K, Schneider, A, Kornhuber, J, Maler, M, Prudlo, J, Jahn, H, Boeckh-Behrens, T, Danek, A, Klopstock, T, Levin, J, Deutsches FTLD-Konsortium
Format: article
Status:Published version
Publication Date:2018
Country:España
Institution:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repository:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p3838
Online Access:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3838
Access Level:Open access
Keyword:C9orf72
frontotemporal dementia
amyotrophic lateral sclerosis
atlas based volumetric MRI analysis
thalamus
cerebellum
salience network
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spelling Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients - An Atlas-Based Volumetric MRI StudySchonecker, SNeuhofer, COtto, MLudolph, AKassubek, JLandwehrmeyer, BAnderl-Straub, SSemler, EDiehl-Schmid, JPrix, CVollmar, CFortea, JHuppertz, HJArzberger, TEdbauer, DFeddersen, BDieterich, MSchroeter, MLVolk, AEFliessbach, KSchneider, AKornhuber, JMaler, MPrudlo, JJahn, HBoeckh-Behrens, TDanek, AKlopstock, TLevin, JDeutsches FTLD-KonsortiumC9orf72frontotemporal dementiaamyotrophic lateral sclerosisatlas based volumetric MRI analysisthalamuscerebellumsalience networkBackground: The neuropathology of patients with frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS) due to a C9orf72 mutation is characterized by two distinct types of characteristic protein depositions containing either TDP-43 or so-called dipeptide repeat proteins that extend beyond frontal and temporal regions. Thalamus and cerebellum seem to be preferentially affected by the dipeptide repeat pathology unique to C9orf72 mutation carriers. Objective: This study aimed to determine if mutation carriers showed an enhanced degree of thalamic and cerebellar atrophy compared to sporadic patients or healthy controls. Methods: Atlas-based volumetry was performed in 13 affected C9orf72 FTD, ALS and FTD/ALS patients, 45 sporadic FTD and FTD/ALS patients and 19 healthy controls. Volumes and laterality indices showing significant differences between mutation carriers and sporadic patients were subjected to binary logistic regression to determine the best predictor of mutation carrier status. Results: Compared to sporadic patients, mutation carriers showed a significant volume reduction of the thalamus, which was most striking in the occipital, temporal and prefrontal subregion of the thalamus. Disease severity measured by mini mental status examination (MMSE) and FTD modified Clinical Dementia Rating Scale Sum of Boxes (FTD-CDR-SOB) significantly correlated with volume reduction in the aforementioned thalamic subregions. No significant atrophy of cerebellar regions could be detected. A logistic regression model using the volume of the prefrontal and the laterality index of the occipital subregion of the thalamus as predictor variables resulted in an area under the curve (AUC) of 0.88 while a model using overall thalamic volume still resulted in an AUC of 0.82. Conclusion: Our data show that thalamic atrophy in C9orf72 mutation carriers goes beyond the expected atrophy in the prefrontal and temporal subregion and is in good agreement with the cortical atrophy pattern described in C9orf72 mutation carriers, indicating a retrograde degeneration of functionally connected regions. Clinical relevance of the detected thalamic atrophy is illustrated by a correlation with disease severity. Furthermore, the findings suggest MRI volumetry of the thalamus to be of high predictive value in differentiating C9orf72 mutation carriers from patients with sporadic FTD.FRONTIERS MEDIA SA2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3838Frontiers in Aging NeuroscienceISSN: 16634365reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p38382026-06-14T12:41:47Z
dc.title.none.fl_str_mv Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients - An Atlas-Based Volumetric MRI Study
title Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients - An Atlas-Based Volumetric MRI Study
spellingShingle Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients - An Atlas-Based Volumetric MRI Study
Schonecker, S
C9orf72
frontotemporal dementia
amyotrophic lateral sclerosis
atlas based volumetric MRI analysis
thalamus
cerebellum
salience network
title_short Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients - An Atlas-Based Volumetric MRI Study
title_full Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients - An Atlas-Based Volumetric MRI Study
title_fullStr Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients - An Atlas-Based Volumetric MRI Study
title_full_unstemmed Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients - An Atlas-Based Volumetric MRI Study
title_sort Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients - An Atlas-Based Volumetric MRI Study
dc.creator.none.fl_str_mv Schonecker, S
Neuhofer, C
Otto, M
Ludolph, A
Kassubek, J
Landwehrmeyer, B
Anderl-Straub, S
Semler, E
Diehl-Schmid, J
Prix, C
Vollmar, C
Fortea, J
Huppertz, HJ
Arzberger, T
Edbauer, D
Feddersen, B
Dieterich, M
Schroeter, ML
Volk, AE
Fliessbach, K
Schneider, A
Kornhuber, J
Maler, M
Prudlo, J
Jahn, H
Boeckh-Behrens, T
Danek, A
Klopstock, T
Levin, J
Deutsches FTLD-Konsortium
author Schonecker, S
author_facet Schonecker, S
Neuhofer, C
Otto, M
Ludolph, A
Kassubek, J
Landwehrmeyer, B
Anderl-Straub, S
Semler, E
Diehl-Schmid, J
Prix, C
Vollmar, C
Fortea, J
Huppertz, HJ
Arzberger, T
Edbauer, D
Feddersen, B
Dieterich, M
Schroeter, ML
Volk, AE
Fliessbach, K
Schneider, A
Kornhuber, J
Maler, M
Prudlo, J
Jahn, H
Boeckh-Behrens, T
Danek, A
Klopstock, T
Levin, J
Deutsches FTLD-Konsortium
author_role author
author2 Neuhofer, C
Otto, M
Ludolph, A
Kassubek, J
Landwehrmeyer, B
Anderl-Straub, S
Semler, E
Diehl-Schmid, J
Prix, C
Vollmar, C
Fortea, J
Huppertz, HJ
Arzberger, T
Edbauer, D
Feddersen, B
Dieterich, M
Schroeter, ML
Volk, AE
Fliessbach, K
Schneider, A
Kornhuber, J
Maler, M
Prudlo, J
Jahn, H
Boeckh-Behrens, T
Danek, A
Klopstock, T
Levin, J
Deutsches FTLD-Konsortium
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv C9orf72
frontotemporal dementia
amyotrophic lateral sclerosis
atlas based volumetric MRI analysis
thalamus
cerebellum
salience network
topic C9orf72
frontotemporal dementia
amyotrophic lateral sclerosis
atlas based volumetric MRI analysis
thalamus
cerebellum
salience network
description Background: The neuropathology of patients with frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS) due to a C9orf72 mutation is characterized by two distinct types of characteristic protein depositions containing either TDP-43 or so-called dipeptide repeat proteins that extend beyond frontal and temporal regions. Thalamus and cerebellum seem to be preferentially affected by the dipeptide repeat pathology unique to C9orf72 mutation carriers. Objective: This study aimed to determine if mutation carriers showed an enhanced degree of thalamic and cerebellar atrophy compared to sporadic patients or healthy controls. Methods: Atlas-based volumetry was performed in 13 affected C9orf72 FTD, ALS and FTD/ALS patients, 45 sporadic FTD and FTD/ALS patients and 19 healthy controls. Volumes and laterality indices showing significant differences between mutation carriers and sporadic patients were subjected to binary logistic regression to determine the best predictor of mutation carrier status. Results: Compared to sporadic patients, mutation carriers showed a significant volume reduction of the thalamus, which was most striking in the occipital, temporal and prefrontal subregion of the thalamus. Disease severity measured by mini mental status examination (MMSE) and FTD modified Clinical Dementia Rating Scale Sum of Boxes (FTD-CDR-SOB) significantly correlated with volume reduction in the aforementioned thalamic subregions. No significant atrophy of cerebellar regions could be detected. A logistic regression model using the volume of the prefrontal and the laterality index of the occipital subregion of the thalamus as predictor variables resulted in an area under the curve (AUC) of 0.88 while a model using overall thalamic volume still resulted in an AUC of 0.82. Conclusion: Our data show that thalamic atrophy in C9orf72 mutation carriers goes beyond the expected atrophy in the prefrontal and temporal subregion and is in good agreement with the cortical atrophy pattern described in C9orf72 mutation carriers, indicating a retrograde degeneration of functionally connected regions. Clinical relevance of the detected thalamic atrophy is illustrated by a correlation with disease severity. Furthermore, the findings suggest MRI volumetry of the thalamus to be of high predictive value in differentiating C9orf72 mutation carriers from patients with sporadic FTD.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3838
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3838
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv FRONTIERS MEDIA SA
publisher.none.fl_str_mv FRONTIERS MEDIA SA
dc.source.none.fl_str_mv Frontiers in Aging Neuroscience
ISSN: 16634365
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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