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  Atrophy in the thalamus but not cerebellum is specific for C9orf72 FTD and ALS patients: An atlas-based volumetric MRI study

Schönecker, S., Neuhofer, C., Otto, M., Ludolph, A., Kassubek, J., Landwehrmeyer, B., et al. (2018). Atrophy in the thalamus but not cerebellum is specific for C9orf72 FTD and ALS patients: An atlas-based volumetric MRI study. Frontiers in Aging Neuroscience, 10: 45. doi:10.3389/fnagi.2018.00045.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-F477-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-A35B-F
Genre: Journal Article


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Schönecker, Sonja1, Author
Neuhofer, Christiane1, Author
Otto, Markus2, Author
Ludolph, Albert2, Author
Kassubek, Jan2, Author
Landwehrmeyer, Bernhard2, Author
Anderl-Straub, Sarah2, Author
Semler, Elisa2, Author
Diehl-Schmid, Janine3, Author
Prix, Catharina1, Author
Vollmar, Christian1, Author
Fortea, Juan4, Author
Deutsches FTLD-Konsortium, Author              
Huppertz, Hans-Jürgen5, Author
Arzberger, Thomas6, Author
Edbauer, Dieter7, 8, 9, Author
Feddersen, Berend10, Author
Dieterich, Marianne1, 7, 9, Author
Schroeter, Matthias L.11, 12, Author              
Volk, Alexander E.13, Author
Fließbach, Klaus14, 15, AuthorSchneider, Anja14, 15, AuthorKornhuber, Johannes16, AuthorMaler, Manuel16, AuthorPrudlo, Johannes17, 18, AuthorJahn, Holger19, 20, AuthorBoeckh-Behrens, Tobias21, AuthorDanek, Adrian1, AuthorKlopstock, Thomas7, 9, 22, AuthorLevin, Johannes1, 7, Author more..
1Department of Neurology, Ludwig Maximilians University Munich, Germany, ou_persistent22              
2Department of Neurology, Ulm University, Germany, ou_persistent22              
3Departments of Psychiatry and Psychotherapy, TU Munich, Germany, ou_persistent22              
4Hospital San Pau Barcelona, Spain, ou_persistent22              
5Swiss Epilepsy Centre, Zurich, Switzerland, ou_persistent22              
6Center for Neuropathology and Prion Research, Ludwig Maximilians University Munich, Germany, ou_persistent22              
7German Center for Neurodegenerative Diseases, Munich, Germany, ou_persistent22              
8Institute for Metabolic Biochemistry, Ludwig Maximilians University Munich, Germany, ou_persistent22              
9Munich Cluster for Systems Neurology (SyNergy), Germany, ou_persistent22              
10Department of Palliative Medicine, Ludwig Maximilians University Munich, Germany, ou_persistent22              
11Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
12Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              
13Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Germany, ou_persistent22              
14German Center for Neurodegenerative Diseases, Bonn, Germany, ou_persistent22              
15Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Germany, ou_persistent22              
16Department of Psychology and Psychotherapy, Friedrich Alexander University Erlangen, Germany, ou_persistent22              
17Department of Neurology, University Medicine Rostock, Germany, ou_persistent22              
18German Center for Neurodegenerative Diseases, Rostock, Germany, ou_persistent22              
19Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Germany, ou_persistent22              
20AMEOS Klinikum Heiligenhafen, Germany, ou_persistent22              
21Department of Neuroradiology, TU Munich, Germany, ou_persistent22              
22Friedrich Baur Institute, Department of Neurology, Ludwig Maximilians University Munich, Germany, ou_persistent22              


Free keywords: C9orf72; Frontotemporal dementia; Amyotrophic lateral sclerosis; Atlas based volumetric MRI analysis; Thalamus; Cerebellum; Salience network
 Abstract: 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.


Language(s): eng - English
 Dates: 2017-09-292018-02-122018-03-15
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.3389/fnagi.2018.00045
PMID: 29599716
PMC: PMC5863593
Other: eCollection 2018
 Degree: -



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Project information

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Project name : German Consortium for Frontotemporal Lobar Degeneration
Grant ID : O1GI1007A
Funding program : -
Funding organization : German Federal Ministry of Education and Research (BMBF)
Project name : -
Grant ID : -
Funding program : -
Funding organization : Munich Cluster for Systems Neurology (SyNergy)
Project name : -
Grant ID : -
Funding program : -
Funding organization : Lüneburg Foundation
Project name : -
Grant ID : 11362
Funding program : -
Funding organization : Michael J. Fox Foundation
Project name : -
Grant ID : VO 2028(1-1)
Funding program : -
Funding organization : Deutsche Forschungsgemeinschaft (DFG)
Project name : C9orf72 repeat expansion in FTD/ALS - from mechanisms to therapeutic approaches / DPR-MODELS
Grant ID : 617198
Funding program : Funding Programme 7
Funding organization : European Commission (EC)

Source 1

Title: Frontiers in Aging Neuroscience
  Abbreviation : Front Aging Neurosci
Source Genre: Journal
Publ. Info: Lausanne : Frontiers Research Foundation
Pages: - Volume / Issue: 10 Sequence Number: 45 Start / End Page: - Identifier: ISSN: 1663-4365
CoNE: https://pure.mpg.de/cone/journals/resource/1663-4365