Journal Article

DZNE-2021-00171

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Abnormal pain perception is associated with thalamo-cortico-striatal atrophy in C9orf72 expansion carriers in the GENFI cohort.

Convery, R. S. ; Bocchetta, M. ; Greaves, C. V. ; Moore, K. M. ; Cash, D. M. ; Van Swieten, J. ; Moreno, F. ; Sánchez-Valle, R. ; Borroni, B. ; Laforce, R. ; Masellis, M. ; Tartaglia, M. C. ; Graff, C. ; Galimberti, D. ; Rowe, J. B. ; Finger, E. ; Synofzik, M.DZNE* ; Vandenberghe, R. ; de Mendonca, A. ; Tagliavini, F. ; Santana, I. ; Ducharme, S. ; Butler, C. ; Gerhard, A. ; Levin, J.DZNE* ; Danek, A. ; Otto, M. ; Warren, J. D. ; Rohrer, J. D. ; Initiative, G. F. (Collaboration Author) ; Rossor, M. N. ; Fox, N. C. ; Woollacott, I. O. C. ; Shafei, R. ; Heller, C. ; Peakman, G. ; Swift, I. ; Todd, E. ; Guerreiro, R. ; Bras, J. ; Thomas, D. L. ; Nicholas, J. ; Mead, S. ; Jiskoot, L. ; Meeter, L. ; Panman, J. ; Papma, J. ; van Minkelen, R. ; Pijnenburg, Y. ; Barandiara, M. ; Indakoetxea, B. ; Gabilondo, A. ; Tainta, M. ; de Arriba, M. ; Gorostidi, A. ; Zulaica, M. ; Villanua, J. ; Diaz, Z. ; Borrego-Ecija, S. ; Olives, J. ; Lladó, A. ; Balasa, M. ; Antonell, A. ; Bargallo, N. ; Premi, E. ; Cosseddu, M. ; Gazzina, S. ; Padovani, A. ; Gasparotti, R. ; Archetti, S. ; Black, S. ; Mitchell, S. ; Rogaeva, E. ; Freedman, M. ; Keren, R. ; Tang-Wai, D. ; Öijerstedt, L. ; Andersson, C. ; Jelic, V. ; Thonberg, H. ; Arighi, A. ; Fenoglio, C. ; Scarpini, E. ; Fumagalli, G. ; Cope, T. ; Timberlake, C. ; Rittman, T. ; Shoesmith, C. ; Bartha, R. ; Rademakers, R. ; Wilke, C. ; Karnarth, H.-O. ; Bender, B. ; Bruffaerts, R. ; Vandamme, P. ; Vandenbulcke, M. ; Ferreira, C. B. ; Miltenberger, G. ; Maruta, C. ; Verdelho, A. ; Afonso, S. ; Taipa, R. ; Caroppo, P. ; Di Fede, G. ; Giaccone, G. ; Prioni, S. ; Redaelli, V. ; Rossi, G. ; Tiraboschi, P. ; Duro, D. ; Almeida, M. R. ; Branco, M. C. ; Leitão, M. J. ; Tabuas-Pereira, M. ; Santiago, B. ; Gauthier, S. ; Rosa-Neto, P. ; Veldsman, M. ; Flanagan, T. ; Prix, C. ; Hoegen, T. ; Wlasich, E. ; Loosli, S. ; Schonecker, S. ; Semler, E. ; Anderl-Straub, S.

2020
BMJ Publishing Group London

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Please use a persistent id in citations: doi:10.1136/jnnp-2020-323279

Abstract: Frontotemporal dementia (FTD) is typically associated with changes in behaviour, language and movement. However, recent studies have shown that patients can also develop an abnormal response to pain, either heightened or diminished. We aimed to investigate this symptom in mutation carriers within the Genetic FTD Initiative (GENFI).Abnormal responsiveness to pain was measured in 462 GENFI participants: 281 mutation carriers and 181 mutation-negative controls. Changes in responsiveness to pain were scored as absent (0), questionable or very mild (0.5), mild (1), moderate (2) or severe (3). Mutation carriers were classified into C9orf72 (104), GRN (128) and MAPT (49) groups, and into presymptomatic and symptomatic stages. An ordinal logistic regression model was used to compare groups, adjusting for age and sex. Voxel-based morphometry was performed to identify neuroanatomical correlates of abnormal pain perception.Altered responsiveness to pain was present to a significantly greater extent in symptomatic C9orf72 expansion carriers than in controls: mean score 0.40 (SD 0.71) vs 0.00 (0.04), reported in 29% vs 1%. No significant differences were seen between the other symptomatic groups and controls, or any of the presymptomatic mutation carriers and controls. Neural correlates of altered pain perception in C9orf72 expansion carriers were the bilateral thalamus and striatum as well as a predominantly right-sided network of regions involving the orbitofrontal cortex, inferomedial temporal lobe and cerebellum.Changes in pain perception are a feature of C9orf72 expansion carriers, likely representing a disruption in somatosensory, homeostatic and semantic processing, underpinned by atrophy in a thalamo-cortico-striatal network.

Keyword(s): Adult (MeSH) ; Aged (MeSH) ; Asymptomatic Diseases (MeSH) ; Atrophy: diagnostic imaging (MeSH) ; Atrophy: genetics (MeSH) ; Atrophy: physiopathology (MeSH) ; C9orf72 Protein: genetics (MeSH) ; Cerebellum: diagnostic imaging (MeSH) ; Cerebellum: pathology (MeSH) ; Cerebral Cortex: diagnostic imaging (MeSH) ; Cerebral Cortex: pathology (MeSH) ; Cohort Studies (MeSH) ; Corpus Striatum: diagnostic imaging (MeSH) ; Corpus Striatum: pathology (MeSH) ; DNA Repeat Expansion (MeSH) ; Female (MeSH) ; Frontotemporal Dementia: diagnostic imaging (MeSH) ; Frontotemporal Dementia: genetics (MeSH) ; Frontotemporal Dementia: physiopathology (MeSH) ; Humans (MeSH) ; Logistic Models (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Mutation (MeSH) ; Pain Perception (MeSH) ; Perceptual Disorders: diagnostic imaging (MeSH) ; Perceptual Disorders: genetics (MeSH) ; Perceptual Disorders: physiopathology (MeSH) ; Prefrontal Cortex: diagnostic imaging (MeSH) ; Prefrontal Cortex: pathology (MeSH) ; Progranulins: genetics (MeSH) ; Temporal Lobe: diagnostic imaging (MeSH) ; Temporal Lobe: pathology (MeSH) ; Thalamus: diagnostic imaging (MeSH) ; Thalamus: pathology (MeSH) ; tau Proteins: genetics (MeSH) ; frontotemporal dementia ; pain ; C9orf72 Protein ; C9orf72 protein, human ; GRN protein, human ; MAPT protein, human ; Progranulins ; tau Proteins

Note: ISSN 1468-330X not unique: **3 hits**.

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Contributing Institute(s):

1. Parkinson Genetics (AG Gasser)
2. Clinical Neurodegeneration (AG Levin)
3. U Clinical Researchers - München (U Clinical Researchers - München)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)
2. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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