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Multicenter Study
. 2019 Jan 31;9(1):54.
doi: 10.1038/s41398-019-0381-1.

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

Janine Diehl-Schmid  1 , Abigail Licata  2 , Oliver Goldhardt  2 , Hans Förstl  2 , Igor Yakushew  3 , Markus Otto  4 , Sarah Anderl-Straub  4 , Ambros Beer  4 , Albert Christian Ludolph  4 , Georg Bernhard Landwehrmeyer  4 , Johannes Levin  5   6 , Adrian Danek  5 , Klaus Fliessbach  7   8 , Annika Spottke  8   9 , Klaus Fassbender  10 , Epameinondas Lyros  10 , Johannes Prudlo  11 , Bernd Joachim Krause  12 , Alexander Volk  13 , Dieter Edbauer  6   14 , Matthias Leopold Schroeter  15   16 , Alexander Drzezga  17   18 , Johannes Kornhuber  19 , Martin Lauer  20 ; FTLDc Study Group; Timo Grimmer  2
Collaborators, Affiliations
Multicenter Study

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

Janine Diehl-Schmid et al. Transl Psychiatry. .

Abstract

C9ORF72 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.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. C9+ patients compared with controls.
C9+ < healthy control; voxel-based comparison, p < 0.05 family-wise error corrected; clusters rendered to a three-dimensional brain within Statistical Parametric Mapping, views from mesial left, mesial right, back, front, lateral right, lateral left, bottom, above
Fig. 2
Fig. 2. C9- patients compared with controls.
C9− < healthy control; voxel based comparison, p < 0.05 family-wise error corrected; clusters rendered to a three-dimensional brain within Statistical Parametric Mapping; views from mesial left, mesial right, back, front, lateral right, lateral left, bottom, above
Fig. 3
Fig. 3. C9+ patients compared with C9− patients.
Clusters overlaid on a mean of 152 T1 MRIs within Statistical Parametric Mapping; each slice is separated by 5 mm
Fig. 4
Fig. 4. Thalamus-Pons FDG uptake ratios for patients and controls.
a Global thalamic 18F-fluorodeoxyglucose (FDG) uptake in C9+, C9−, and healthy controls (HC): scatterplots. b Right thalamic FDG uptake in C9+, C9−, and HC: scatterplots. c Left thalamic FDG uptake in C9+, C9−, and HC: scatterplots
Fig. 5
Fig. 5. ROC curve analyses.
Receiver-operating characteristic (ROC) curve plots for global and hemispheric thalamus/pons ratios including reference line; a whole patient group (C9+ and C9−) vs. healthy controls (HCs); b C9+ vs. C9−; c C9+ vs. HC; d C9– vs. HC. ThalR right thalamus, ThalL left thalamus
See this image and copyright information in PMC

References

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