FDG-PET underscores the key role of the thalamus in frontotemporal lobar degeneration caused by C9ORF72 mutations

• DOI: 10.1038/s41398-019-0381-1
• Publication Date: 2019-01-31T17:04:03Z
• Authors: Janine Diehl-Schmid; Abigail Licata; Oliver Goldhardt; Hans Förstl; Igor Yakushew; Markus Otto; Sarah Anderl-Straub; Ambros Beer; Albert Christian ...; Georg Bernhard La...; Johannes Levin; Adrian Danek; Klaus Fliessbach; Annika Spottke; Klaus Fassbender; Epameinondas Lyros; Johannes Prudlo; Bernd Joachim Krause; Alexander Volk; Dieter Edbauer; Matthias Leopold ...; Alexander Drzezga; Johannes Kornhuber; Martin Lauer; ; Nibal Ackl; Christine v. Arnim; Joachim Brumberg; Florian Gärtner; Holger Jahn; Elisabeth Kasper; Jan Kassubek; Catharina Prix; Lina Riedl; Carola Roßmeier; Sonja Schönecker; Elisa Semler; Stefan Teipel; Christine Westert...; Elisabeth Wlasich; Timo Grimmer
• Keywords: Male; 0301 basic medicine; Sensitivity and Specificity; Article; 03 medical and health sciences; Thalamus; Fluorodeoxyglucose F18; Cerebellum; diagnostic imaging [Frontotemporal Lobar Degeneration]; Humans; ddc:610; genetics [C9orf72 Protein]; Aged; ddc:610; diagnostic imaging [Thalamus]; C9orf72 Protein; metabolism [Cerebellum]; Middle Aged; diagnostic imaging [Cerebellum]; ddc:; metabolism [Frontotemporal Lobar Degeneration]; Positron-Emission Tomography; Mutation; Female; genetics [Frontotemporal Lobar Degeneration]; C9orf72 protein, human; Frontotemporal Lobar Degeneration; metabolism [Thalamus]

AbstractC9ORF72 mutations are the most common cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). MRI studies have investigated structural changes in C9ORF72-associated FTLD (C9FTLD) and provided first insights about a prominent involvement of the thalamus and the cerebellum. Our multicenter, 18F-fluorodeoxyglucose positron-emission tomography study of 22 mutation carriers with FTLD, 22 matched non-carriers with FTLD, and 23 cognitively healthy controls provided valuable insights into functional changes in C9FTLD: compared to non-carriers, mutation carriers showed a significant reduction of glucose metabolism in both thalami, underscoring the key role of the thalamus in C9FTLD. Thalamic metabolism did not correlate with disease severity, duration of disease, or the presence of psychotic symptoms. Against our expectations we could not demonstrate a cerebellar hypometabolism in carriers or non-carriers. Future imaging and neuropathological studies in large patient cohorts are required to further elucidate the central role of the thalamus in C9FTLD.