Background and Aims:

We aimed to assess cortical, subcortical and cerebellar grey matter (GM) atrophy using MRI in patients with disorders of the frontotemporal lobar degeneration (FTLD) spectrum with known genetic mutations.

Methods:

Sixty-six patients carrying FTLD-related mutations were enrolled, including 44 with pure motor neuron disease (MND) and 22 with frontotemporal dementia (FTD). Sixty-one patients with sporadic FTLD (sFTLD) matched for age, sex and disease severity with genetic FTLD (gFTLD) were also included, as well as 52 healthy controls. Voxel-based morphometry (VBM) was performed. GM volumes of subcortical and cerebellar structures were obtained.

Results:

Compared with controls, GM atrophy on VBM was greatest in genetic FTD, whereas sporadic MND (sMND) patients showed focal motor cortical atrophy. Patients carrying C9ORF72 and GRN mutations showed the most widespread cortical volume loss, in contrast with GM sparing in SOD1 and TARDBP. Globally, gFTLD patients showed greater atrophy of parietal cortices and thalami compared with sFTLD. In volumetric analysis, gFTLD patients showed volume loss compared with sFTLD in the caudate nuclei and thalami, especially comparing C9-MND with sMND. In the cerebellum, gFTLD patients showed greater atrophy of the right lobule VIIb than sFTLD. Thalamic volumes of gFTLD patients with a C9ORF72 mutation showed an inverse correlation with Frontal Behavioral Inventory scores.

Conclusions:

Measures of deep GM and cerebellar structural involvement may be useful markers of gFTLD, particularly C9ORF72-related disorders, regardless of the clinical presentation within the FTLD spectrum.

Study funding: Italian Ministry of Health (RF-2011-02351193; GR-2011-02351217; GR-2013-02357415) and the European Research Council (StG-2016_714388_NeuroTRACK).

Background and Aims:

To apply mathematical modeling to unravel MRI connectomic signatures among the amyotrophic lateral sclerosis (ALS)-behavioral variant of frontotemporal dementia (bvFTD) spectrum.

Methods:

83 ALS, 35 bvFTD and 61 controls underwent clinical, cognitive evaluations and MRI scan. ALS were divided in 54 ALS with only motor deficits (ALS-cn), 21 ALS cognitively/behaviorally impaired (ALS-ci/bi) and 8 ALS with bvFTD (ALS-FTD).

Mathematical models based on connectomic approach and ROC curve analysis identified the characteristic patterns of damage of ALS-cn and bvFTD. Single-subject analysis was performed on ALS-ci/bi and ALS-FTD to assess shared features with ALS-cn and bvFTD.

Results:

The structural/functional patterns of damage characterizing ALS-cn and bvFTD were identified. ALS-like pattern resulted in a focused structural damage within motor areas. bvFTD-like pattern resulted in widespread structural damage and decreased functional connectivity, mainly in frontotemporoparietal areas. ALS-ci/bi showed structural damage mostly overlapping with the ALS-like pattern, whereas they diverged from ALS-cn in functional connectivity showing enhanced functional connectivity within sensorimotor and decreased functional connectivity in frontotemporal areas. The latter mirrored the bvFTD-like pattern. ALS-FTD patients resembled the bvFTD-like pattern of damage both structurally and functionally, with a frank structural ALS-like damage in motor areas.

Conclusions:

Alterations of the frontotemporoparietal network characterized bvFTD-like pattern, while a focal damage within sensorimotor-basal ganglia areas defined the ALS-like pattern. Commonalities and differences relative to the two ends of ALS-FTD spectrum were found in ALS-ci/bi and ALS-FTD.

Funding: The Italian Ministry of Health (GR-2011-02351217; GR-2013-02357415; RF-2011-02351193), AriSLA (ConnectALS), European Research Council (StG2016_714388_NeuroTRACK).