Thalamic nuclei in frontotemporal dementia: Mediodorsal nucleus involvement is universal but pulvinar atrophy is unique to C9orf72

Thalamic atrophy is a common feature across all forms of FTD but little is known about specific nuclei involvement. We aimed to investigate in vivo atrophy of the thalamic nuclei across the FTD spectrum. A cohort of 402 FTD patients (age: mean(SD) 64.3(8.2) years; disease duration: 4.8(2.8) years) was compared with 104 age‐matched controls (age: 62.5(10.4) years), using an automated segmentation of T1‐weighted MRIs to extract volumes of 14 thalamic nuclei. Stratification was performed by clinical diagnosis (180 behavioural variant FTD (bvFTD), 85 semantic variant primary progressive aphasia (svPPA), 114 nonfluent variant PPA (nfvPPA), 15 PPA not otherwise specified (PPA‐NOS), and 8 with associated motor neurone disease (FTD‐MND), genetic diagnosis (27 MAPT, 28 C9orf72, 18 GRN), and pathological confirmation (37 tauopathy, 38 TDP‐43opathy, 4 FUSopathy). The mediodorsal nucleus (MD) was the only nucleus affected in all FTD subgroups (16–33% smaller than controls). The laterodorsal nucleus was also particularly affected in genetic cases (28–38%), TDP‐43 type A (47%), tau‐CBD (44%), and FTD‐MND (53%). The pulvinar was affected only in the C9orf72 group (16%). Both the lateral and medial geniculate nuclei were also affected in the genetic cases (10–20%), particularly the LGN in C9orf72 expansion carriers. Use of individual thalamic nuclei volumes provided higher accuracy in discriminating between FTD groups than the whole thalamic volume. The MD is the only structure affected across all FTD groups. Differential involvement of the thalamic nuclei among FTD forms is seen, with a unique pattern of atrophy in the pulvinar in C9orf72 expansion carriers.

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New MRI visual rating scales

Six visual rating scales, three alreary described: medial temporal, posterior, anterior temporal and three new/addapted: orbito-frontal, anterior cingulate and fronto-insula) were assessed in this study

Time to perform visual rating
Mean time to perform and record all six visual rating scales based on three raters assessing the subset study population ( n = 80) was 2.9 ± 1.3 min. Individual rater means and standard deviations were 2.7 ± 1.1, 2.4 ± 1.0 and 3.6 ± 1.6 min.

Inter-rater reliability of visual rating scores
Single measure and average measure ICC results for each scale are shown in Supplementary Table 1 . For the single measures ICC values, representing the reliability of each scale at the level of the individual rater, the MTA scale performed best overall, with very similar results achieved with two raters assessing all 257 scans, and four raters scoring 80 scans [ICC(2,1) ≥ 0.79]. The PA, OF and FI scales also demonstrated good reliability [ICC(2,1) ≥0.71] based on two raters assessing the total study population; reliability was slightly reduced when performed by four raters in the subset population [ICC(2,1) ≥ 0.58]. The reliability of the AC scale was lowest overall [ICC(2,1) range = 0.49–0.62]. As expected, the reliability based on mean rater scores was consistently greater for all scales [ICC(2,k) ≥ 0.73]. There were no material differences in reliability based on the larger or smaller population samples for any scale with the exception of the AT and AC scales, which were less reliable in the larger population sample.

Correlation of grey matter volume with visual rating scores
Voxel-based morphometry analysis revealed a negative partial correlation of higher visual rating score with lower grey matter density for all visual rating scales. 

Reference:

Lorna Harper, Giorgio G. Fumagalli, Frederik Barkhof, Philip Scheltens, John T. O’Brien, Femke Bouwman, Emma J. Burton, Jonathan D. Rohrer, Nick C. Fox, Gerard R. Ridgway, Jonathan M. Schott; MRI visual rating scales in the diagnosis of dementia: evaluation in 184 post-mortem confirmed cases. Brain 2016; 139 (4): 1211-1225. doi: 10.1093/brain/aww005https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/aww005