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        How predictive are temporal lobe changes of underlying TDP-43 pathology in the ALS-FTD continuum?

        Ana Paula Arantes Bueno,Maxime Bertoux,Leonardo Cruz de Souza,Michael Hornberger 대한임상신경생리학회 2017 Annals of Clinical Neurophysiology Vol.19 No.2

        Detection of underling proteinopathies is becoming increasingly important across neurodegenerative conditions due to upcoming disease intervention trials. In this review, we explored how temporal lobe changes in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) can potentially predict underlying TDP-43 pathology subtypes in FTD. To date, emphasis has been given to frontal lobe changes in the study of the cognitive and behavioural impairments in both syndromes but an increasing number of pathological, imaging and neuropsychological studies suggest how temporal lobe changes could critically affect the cognition and behaviour of these conditions. In this current article, we reviewed pathological, imaging as well as clinical/neuropsychological findings of temporal involvement in the ALS-FTD continuum, how they relate to temporal lobe changes and the underlying TDP-43 pathology in FTD. Findings across studies show that TDP-43 pathology occurs and coincides in many structures in ALS and FTD, but especially in the temporal lobes. In particular, anterior and medial temporal lobes atrophy is consistently found in ALS and FTD. In addition, memory and language impairment as well as emotional and Theory of Mind processing deficits that are characteristics of the two diseases are highly correlated to temporal lobe dysfunction. We conclude by showing that temporal lobe changes due to TDP-43 type B might be particular predictive of TDP-43 type B pathology in behavioural variant FTD, which clearly needs to be investigated further in the future.

      • KCI등재

        How predictive are temporal lobe changes of underlying TDP-43 pathology in the ALS-FTD continuum?

        Bueno, Ana Paula Arantes,Bertoux, Maxime,de Souza, Leonardo Cruz,Hornberger, Michael The Korean Society of Clinical Neurophysiology 2017 Annals of Clinical Neurophysiology Vol.19 No.2

        Detection of underling proteinopathies is becoming increasingly important across neurodegenerative conditions due to upcoming disease intervention trials. In this review, we explored how temporal lobe changes in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) can potentially predict underlying TDP-43 pathology subtypes in FTD. To date, emphasis has been given to frontal lobe changes in the study of the cognitive and behavioural impairments in both syndromes but an increasing number of pathological, imaging and neuropsychological studies suggest how temporal lobe changes could critically affect the cognition and behaviour of these conditions. In this current article, we reviewed pathological, imaging as well as clinical/neuropsychological findings of temporal involvement in the ALS-FTD continuum, how they relate to temporal lobe changes and the underlying TDP-43 pathology in FTD. Findings across studies show that TDP-43 pathology occurs and coincides in many structures in ALS and FTD, but especially in the temporal lobes. In particular, anterior and medial temporal lobes atrophy is consistently found in ALS and FTD. In addition, memory and language impairment as well as emotional and Theory of Mind processing deficits that are characteristics of the two diseases are highly correlated to temporal lobe dysfunction. We conclude by showing that temporal lobe changes due to TDP-43 type B might be particular predictive of TDP-43 type B pathology in behavioural variant FTD, which clearly needs to be investigated further in the future.

      • KCI등재

        Dissociation of Structural and Functional Integrities of the Motor System in Amyotrophic Lateral Sclerosis and Behavioral-Variant Frontotemporal Dementia

        배종석,Michele Ferguson,Rachel Tan,Eneida Mioshi,Neil Simon,James Burrell,Steve Vucic,John R. Hodges,Matthew C Kiernan,Michael Hornberger 대한신경과학회 2016 Journal of Clinical Neurology Vol.12 No.2

        Background and Purpose Tis study investigated the structural and functional changes in the motor system in amyotrophic lateral sclerosis (ALS; n=25) and behavioral-variant frontotemporal dementia (bvFTD; n=17) relative to healthy controls (n=37). Methods Structural changes were examined using a region-of-interest approach, applying voxel-based morphometry for gray-matter changes and difusion tensor imaging for white-matter changes. Functional changes in the motor system were elucidated using threshold-tracking transcranial magnetic stimulation (TMS) measurements of upper motor-neuron excitability. Results The structural analyses showed that in ALS there were more white-matter changes in the corticospinal and motor-cortex regions and more gray-matter changes in the cerebellum in comparison to controls. bvFTD showed substantial gray- and white-matter changes across virtually all motor-system regions compared to controls, although the brainstem was afected less than the other regions. Direct comparisons across patient groups showed that the gray- and white-matter motor-system changes inclusive of the motor cortex were greater in bvFTD than in ALS. By contrast, the functional integrity of the motor system was more adversely afected in ALS than in bvFTD, with both patient groups showing increased excitability of upper motor neurons compared to controls. Conclusions Cross-correlation of structural and functional data further revealed a neural dissociation of diferent motor-system regions and tracts covarying with the TMS excitability across both patient groups. Te structural and functional motor-system integrities appear to be dissociated between ALS and bvFTD, which represents useful information for the diagnosis of motor-system changes in these two disorders.

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