Caudate atrophy on MRI is a characteristic feature of FTLD-FUS

Abstract

Background and purpose: Frontotemporal lobar degeneration (FTLD) can be subdivided into those in which the abnormal protein is tau (FTLD-TAU), the TAR DNA binding protein 43 (FTLD-TDP) and the fused in sarcoma protein (FTLD-FUS). We have observed severe caudate atrophy at autopsy in FTLD-FUS, and hence, we aimed to determine whether caudate atrophy on MRI is a feature that can distinguish FTLD-FUS from FTLD-TDP and FTLD-TAU.

Methods: From a cohort of 207 cases of FTLD, we identified all cases of FTLD-FUS that had a volumetric antemortem head MRI (n = 3). Caudate and frontal lobe volumes were measured in all three cases using atlas-based parcellation and SPM5 and were compared to 10 randomly selected cases of FTLD-TDP and 10 randomly selected cases of FTLD-TAU. Total grey matter volumes were also calculated for all cases.

Results: The FTLD-FUS cases had significantly smaller caudate volumes (P = 0.02) yet similar frontal lobe grey matter volumes (P = 0.12) compared to FTLD-TDP and FTLD-TAU. Caudate volumes when corrected for total grey matter volume (P = 0.01) or frontal lobe grey matter volume (P = 0.01) were significantly smaller in FTLD-FUS than in FTLD-TDP and FTLD-TAU and showed no overlap with the other two groups.

Conclusions: Caudate atrophy on MRI appears to be significantly greater in FTLD-FUS compared with FTLD-TDP and FTLD-TAU, suggesting that severe caudate atrophy may be a useful clinical feature to predict FTLD-FUS pathology.

Figure 1

Diagram illustrating the subclassification of frontotemporal lobar degeneration (FTLD). FTLD-TAU = FTLD with tau immunoreactive inclusions; FTLD-U = FTLD with ubiquitin immunoreactive inclusions; FTLD-TDP = FTLD with TAR DNA binding protein 43 immunoreactive inclusions; FTLD-FUS = FTLD with fused in sarcoma immunoreactive inclusions; aFTLD-U = atypical FTLD-U (FTLD-U without TDP-43 immunoreactive inclusions); NIBD = neurofilament inclusion body disease (also known as NIFID, neuronal intermediate filament inclusion body disease); BIBD = basophilic inclusion body disease.

Figure 2

FUS immunoreactive neuronal cytoplasmic inclusions (arrows) in the dentate granule cells of the hippocampus in a representative FTLD-FUS case (Case 1).

Figure 3

Axial T1-weighted MRI scans show that the caudate in our three FTLD-FUS cases (left panel) are visually smaller than the caudate in two representative FTLD-TDP cases (right panel); in spite of the times from onset to MRI scan. Note one of the FTLD-TDP cases was six years from onset at the time of the MRI scan with relatively preserved caudate volume.

Figure 4

Scatter plots demonstrating caudate (A), frontal grey matter (B), total grey matter (C), caudate/total grey matter (D), frontal grey matter/total grey matter (E), and caudate/frontal grey matter (F) volumes in FTLD-FUS cases compared to FTLD-TDP and FTLD-TAU cases. There was no overlap in caudate, caudate/total grey matter and caudate/frontal grey matter volumes between FTLD-FUS and the other groups, with smaller volumes observed in FTLD-FUS. The mean value for each group is shown using a red line.