Hippocampal connectivity in Amyotrophic Lateral Sclerosis (ALS): more than Papez circuit impairment

Trojsi, Francesca; Nardo, Federica Di; Caiazzo, Giuseppina; Siciliano, Mattia; D’Alvano, Giulia; Ferrantino, Teresa; Passaniti, Carla; Ricciardi, Dario; Esposito, Sabrina; Lavorgna, Luigi; Russo, Antonio; Cirillo, Mario; Santangelo, Gabriella; Esposito, Fabrizio; Tedeschi, Gioacchino

doi:10.1007/s11682-020-00408-1

Cited by 25 publications

(21 citation statements)

References 75 publications

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“…The significant role of the hippocampus and amygdala in the discrimination between ALS and HC is also not surprising, given the multi‐systemic nature of this disorder that usually presents a variety of clinical frontotemporal manifestations as extra‐motor signatures 52–54 . As for caudate, putamen and pallidum, in our analysis both hippocampus and amygdala did not show any significant atrophy, perfusion alteration, nor a significant variation of iron content, in the analyzed ALS patients, albeit, when all these parameters were concurrently included in a multiparametric discriminative analysis, this led to a significant discrimination from HCs.…”

Section: Discussionsupporting

confidence: 48%

Combining structural and metabolic markers in a quantitative MRI study of motor neuron diseases

Canna

Trojsi

Nardo

et al. 2021

Ann Clin Transl Neurol

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Objective To assess the performance of a combination of three quantitative MRI markers (iron deposition, basal neuronal metabolism, and regional atrophy) for differential diagnosis between amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Methods In total, 33 ALS, 12 PLS, and 28 healthy control (HC) subjects underwent a 3T MRI study including single‐ and multi‐echo sequences for gray matter (GM) volumetry and quantitative susceptibility mapping (QSM) and a pseudo‐continuous arterial spin labeling (ASL) sequence for cerebral blood flow (CBF) measurement. Mean values of QSM, CBF, and GM volumes were extracted in the motor cortex, basal ganglia, thalamus, amygdala, and hippocampus. A generalized linear model was applied to the three measures to binary discriminate between groups. The diagnostic performances were evaluated via receiver operating characteristic analyses. Results A significant discrimination was obtained: between ALS and HCs in the left and right motor cortex, where QSM increases were respectively associated with disability scores and disease duration; between PLS and ALS in the left motor cortex, where PLS patients resulted significantly more atrophic; between ALS and HC in the right motor cortex, where GM volumes were associated with upper motor neuron scores. Significant discrimination between ALS and HC was achieved in subcortical structures only combining all three parameters. Interpretation While increased QSM values in the motor cortex of ALS patients is a consolidated finding, combining QSM, CBF, and GM volumetry shows higher diagnostic potential for differentiating ALS patients from HC subjects and, in the motor cortex, between ALS and PLS.

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Section: Discussionsupporting

confidence: 48%

Combining structural and metabolic markers in a quantitative MRI study of motor neuron diseases

Canna

Trojsi

Nardo

et al. 2021

Ann Clin Transl Neurol

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“…The nfvPPA cohort exhibits widespread degeneration of both commissural and long association fibers with slight left hemispheric predominance in addition to thalamic and striatal projections. The C9orf72 negative ALS‐FTD cohort not only exhibits widespread WM pathology in core ALS‐associated regions such as the corticospinal tracts and corpus callosum, but in line with more recent studies, in the cerebellar peduncles, long association fibers, arcuate fasciculus, uncinate and cingulum (Bede, Chipika, et al., 2021 ; McKenna, Chipika, et al., 2021 ; Trojsi, Di Nardo, Caiazzo, et al., 2020 ) (Table 2 ). WM degeneration in ALS‐FTD patients carrying the GGGGCC hexanucleotide expansion is comparable to the anatomical patterns observed in C9orf72 ‐negative patients, but is more readily detected by FA reductions (Table 2 ).…”

Section: Discussionsupporting

confidence: 82%

White matter microstructure alterations in frontotemporal dementia: Phenotype‐associated signatures and single‐subject interpretation

et al. 2022

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Background: Frontotemporal dementias (FTD) include a genetically heterogeneous group of conditions with distinctive molecular, radiological and clinical features. The majority of radiology studies in FTD compare FTD subgroups to healthy controls to describe phenotype-or genotype-associated imaging signatures. While the characterization of group-specific imaging traits is academically important, the priority of clinical imaging is the meaningful interpretation of individual datasets. Methods:To demonstrate the feasibility of single-subject magnetic resonance imaging (MRI) interpretation, we have evaluated the white matter profile of 60 patients across the clinical spectrum of FTD. A z-score-based approach was implemented, where the diffusivity metrics of individual patients were appraised with reference to demographically matched healthy controls. Fifty white matter tracts were systematically evaluated in each subject with reference to normative data. Results:The z-score-based approach successfully detected white matter pathology in single subjects, and group-level inferences were analogous to the outputs of standard track-based spatial statistics. Conclusions:Our findings suggest that it is possible to meaningfully evaluate the diffusion profile of single FTD patients if large normative datasets are available. In contrast to the visual review of FLAIR and T2-weighted images, computational imaging offers objective, quantitative insights into white matter integrity changes even at singlesubject level.

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“…Moreover, a DTI study has shown that disruption of white matter integrity of the cortico-ponto-cerebellar system in ALS patients was associated with the pseudobulbar syndrome, ( Floeter et al, 2014 ). Further, cortico-ponto-cerebellar system microstructural changes have been related to memory impairment in ALS patients, ( Trojsi et al, 2020 )., Mean FA of the CPT was reduced in ALS patients in a longitudinal multicenter study ( Kalra et al, 2020 ). The CPT is associated with hand dominance-related alterations ( Kim et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Brainstem Involvement in Amyotrophic Lateral Sclerosis: A Combined Structural and Diffusion Tensor MRI Analysis

Zhang

Jin

et al. 2021

Front. Neurosci.

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IntroductionThe brainstem is an important component in the pathology of amyotrophic lateral sclerosis (ALS). Although neuroimaging studies have shown multiple structural changes in ALS patients, few studies have investigated structural alterations in the brainstem. Herein, we compared the brainstem structure between patients with ALS and healthy controls.MethodsA total of 33 patients with ALS and 33 healthy controls were recruited in this study. T1-weighted and diffusion tensor imaging (DTI) were acquired on a 3 Tesla magnetic resonance imaging (3T MRI) scanner. Volumetric and vertex-wised approaches were implemented to assess the differences in the brainstem’s morphological features between the two groups. An atlas-based region of interest (ROI) analysis was performed to compare the white matter integrity of the brainstem between the two groups. Additionally, a correlation analysis was used to evaluate the relationship between ALS clinical characteristics and structural features.ResultsVolumetric analyses showed no significant difference in the subregion volume of the brainstem between ALS patients and healthy controls. In the shape analyses, ALS patients had a local abnormal surface contraction in the ventral medulla oblongata and ventral pons. Compared with healthy controls, ALS patients showed significantly lower fractional anisotropy (FA) in the left corticospinal tract (CST) and bilateral frontopontine tracts (FPT) at the brainstem level, and higher radial diffusivity (RD) in bilateral CST and left FPT at the brainstem level by ROI analysis in DTI. Correlation analysis showed that disease severity was positively associated with FA in left CST and left FPT.ConclusionThese findings suggest that the brainstem in ALS suffers atrophy, and degenerative processes in the brainstem may reflect disease severity in ALS. These findings may be helpful for further understanding of potential neural mechanisms in ALS.

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Hippocampal connectivity in Amyotrophic Lateral Sclerosis (ALS): more than Papez circuit impairment

Cited by 25 publications

References 75 publications

Combining structural and metabolic markers in a quantitative MRI study of motor neuron diseases

Combining structural and metabolic markers in a quantitative MRI study of motor neuron diseases

White matter microstructure alterations in frontotemporal dementia: Phenotype‐associated signatures and single‐subject interpretation

Brainstem Involvement in Amyotrophic Lateral Sclerosis: A Combined Structural and Diffusion Tensor MRI Analysis

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