Structural MRI Signatures in Genetic Presentations of the Frontotemporal Dementia-Motor Neuron Disease Spectrum

Objective.To assess cortical, subcortical and cerebellar grey matter (GM) atrophy using magnetic resonance imaging (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. A whole-brain voxel-based morphometry (VBM) analysis was performed. GM volumes of subcortical and cerebellar structures were obtained.Results.Compared with controls, GM atrophy on VBM was greater and more diffuse in genetic FTD, followed by sporadic FTD and genetic MND cases, 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, in particular comparing C9-MND with sMND cases. 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 the clinical presentation within the FTLD spectrum.

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016 One disease or three: is frontotemporal dementia – motor neuron disease a distinct entity?

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-anzan.16 ◽

2019 ◽

Vol 90 (e7) ◽

pp. A6.2-A6

Author(s):

Zhe (Jill) Long ◽

Muireann Irish ◽

David Foxe ◽

John Hodges ◽

Olivier Piguet ◽

...

Keyword(s):

Cluster Analysis ◽

Motor Neuron ◽

Motor Neuron Disease ◽

Frontotemporal Dementia ◽

Cortical Atrophy ◽

Voxel Based Morphometry ◽

Disease Group ◽

Cognitive Behavioural ◽

Data Driven Approach ◽

Patient Subgroups

IntroductionFrontotemporal dementia-motor neuron disease (FTD-MND) is diagnosed when patients meet criteria for the diagnosis of both FTD and MND, but the mode presentation of this disorder is currently unknown. This study aimed to compare the mode of presentation, and profiles of behavioural and language disturbances, of FTD-MND with that of other FTD phenotypes using a data-driven approach.Methods31 FTD-MND, 119 bvFTD, 47 PNFA, 42 SD patients and 127 controls underwent comprehensive clinical, neuropsychological and neuroimaging assessments. Z-transformed scores were used to compare the severity of behavioural and language domains in each disease group. Two-step cluster analysis profiled patient subgroups. Voxel-based morphometry investigated differential patterns of cortical atrophy between groups.ResultsOverall, FTD-MND patients presented with behavioural or language disturbances less frequently than FTD phenotypes, but mixed behavioural-language presentations were more common. FTD-MND patients demonstrated less severe disinhibition, apathy and semantic deficits relative to bvFTD and SD respectively.Behavioural and language deficits were of comparable severity in FTD-MND, unlike other FTD phenotypes where behaviour was worse than language (bvFTD) or language worse than behaviour (PNFA, SD).In cluster analysis, FTD-MND patients were evenly distributed across three subgroups designated as ‘mild mixed’, ‘language dominant’ and ‘behavioural dominant’. Relative to the ‘mild mixed’ group, ‘language dominant’ patients demonstarted more atrophy of the anterior temporal lobe and peri-insular regions, while ‘behavioural dominant’ patients displayed more prefrontal atrophy.ConclusionFTD-MND does not present as a uniform syndrome. Rather, there may be at least three subgroups that demonstrate distinctive cognitive, behavioural, and neuroanatomical characteristics.

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