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

Martina Bocchetta,Jonathan D Rohrer,David M Cash,Juan E Iglesias,Jason D Warren,Mollie Neason

doi:10.1002/hbm.24856

Martina Bocchetta, Jonathan D Rohrer + Show 4 more

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https://doi.org/10.1002/hbm.24856

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Abstract

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.

Highlights

The thalamus is the relay station of the brain, with so many different connections that it is virtually connected to all other brain regions
We reviewed the UCL Dementia Research Centre frontotemporal dementia (FTD) MRI database to identify 402 patients with a volumetric T1-weighted magnetic resonance (MR) scan passing standard quality control protocols and with a diagnosis of behavioural variant FTD (Rascovsky et al, 2011), semantic variant primary progressive aphasia, nonfluent primary progressive aphasia (Gorno-Tempini et al, 2011), a primary progressive aphasia not otherwise specified (PPA-NOS) (Harris et al, 2013), or FTD with associated motor neurone disease (FTD-MND) (Table 2)
In a large cohort of FTD patients we have shown that the MD is the only thalamic nucleus affected across all FTD groups

Summary

Introduction

The thalamus is the relay station of the brain, with so many different connections that it is virtually connected to all other brain regions. It is composed of several nuclei, each of them with specific connections and functional specialization (Table 1) (Behrens et al, 2003; Hale et al, 2015; Herrero et al, 2002; Kim et al, 2013; Lambert et al, 2017; Morel, 2007; Schmahmann, 2003; Zhang et al, 2008, 2010). LD LP VA VLa VLp VPL VM Intralaminar Midline MD LGN MGN.

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