Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients - An Atlas-Based Volumetric MRI Study
Por:
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
Publicada:
15 mar 2018
Resumen:
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.
Filiaciones:
Schonecker, S:
Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany
Neuhofer, C:
Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany
Otto, M:
Univ Ulm, Dept Neurol, Ulm, Germany
Ludolph, A:
Univ Ulm, Dept Neurol, Ulm, Germany
Kassubek, J:
Univ Ulm, Dept Neurol, Ulm, Germany
Landwehrmeyer, B:
Univ Ulm, Dept Neurol, Ulm, Germany
Anderl-Straub, S:
Univ Ulm, Dept Neurol, Ulm, Germany
Semler, E:
Univ Ulm, Dept Neurol, Ulm, Germany
Diehl-Schmid, J:
Tech Univ Munich, Dept Psychiat & Psychotherapy, Munich, Germany
Prix, C:
Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany
Vollmar, C:
Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany
Fortea, J:
Hosp San Pau Barcelona, Barcelona, Spain
Huppertz, HJ:
Swiss Epilepsy Clin, Klin Lengg, Zurich, Switzerland
Arzberger, T:
Ludwig Maximilians Univ Munchen, Ctr Neuropathol & Prion Res, Munich, Germany
Edbauer, D:
German Ctr Neurodegenerat Dis DZNE, Munich, Germany
Ludwig Maximilians Univ Munchen, Inst Metab Biochem, Munich, Germany
Munich Cluster Syst Neurol SyNergy, Munich, Germany
Feddersen, B:
Ludwig Maximilians Univ Munchen, Dept Palliat Med, Munich, Germany
Dieterich, M:
Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany
German Ctr Neurodegenerat Dis DZNE, Munich, Germany
Munich Cluster Syst Neurol SyNergy, Munich, Germany
Schroeter, ML:
Max Planck Inst Human Cognit & Brain Sci MPG, Leipzig, Germany
Univ Hosp Leipzig, Clin Cognit Neurol, Leipzig, Germany
Volk, AE:
Univ Med Ctr Hamburg Eppendorf, Inst Human Genet, Hamburg, Germany
Fliessbach, K:
German Ctr Neurodegenerat Dis DZNE, Bonn, Germany
Univ Hosp Bonn, Dept Neurodegenerat Dis & Geriatr Psychiat, Bonn, Germany
Schneider, A:
German Ctr Neurodegenerat Dis DZNE, Bonn, Germany
Univ Hosp Bonn, Dept Neurodegenerat Dis & Geriatr Psychiat, Bonn, Germany
Kornhuber, J:
Friedrich Alexander Univ Erlangen Nurnberg, Dept Psychiat & Psychotherapy, Erlangen, Germany
Maler, M:
Friedrich Alexander Univ Erlangen Nurnberg, Dept Psychiat & Psychotherapy, Erlangen, Germany
Prudlo, J:
Univ Rostock, Med Ctr, Dept Neurol, Rostock, Germany
German Ctr Neurodegenerat Dis DZNE, Rostock, Germany
Jahn, H:
Univ Med Ctr Hamburg Eppendorf, Dept Psychiat & Psychotherapy, Hamburg, Germany
AMEOS Klinikum Heiligenhafen, Heiligenhafen, Germany
Boeckh-Behrens, T:
Tech Univ Munich, Dept Diagnost & Intervent Neuroradiol, Munich, Germany
Danek, A:
Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany
Klopstock, T:
German Ctr Neurodegenerat Dis DZNE, Munich, Germany
Munich Cluster Syst Neurol SyNergy, Munich, Germany
Ludwig Maximilians Univ Munchen, Friedrich Baur Inst, Dept Neurol, Munich, Germany
Levin, J:
Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany
German Ctr Neurodegenerat Dis DZNE, Munich, Germany
Gold, Green Published
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