Dataset Information

In vivo histopathological staging in C9orf72-associated ALS: A tract of interest DTI study.

ABSTRACT:

Background

Diffusion tensor imaging (DTI) can identify amyotrophic lateral sclerosis (ALS)-associated patterns of brain alterations at the group level according to a neuropathological staging system.

Objective

The study was designed to investigate the in vivo staging in ALS patients with the C9orf72 expansion and potential differences to ALS patients with the SOD1 mutation.

Methods

DTI-based white matter mapping was performed both by an unbiased voxel-wise statistical comparison and by a hypothesis-guided tract-wise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 27 ALS patients with C9orf72 expansion vs 15 ALS patients with SOD1 mutation vs 32 matched healthy controls. Clinical and neuropsychological data were acquired and correlated to DTI data.

Results

The analysis of white matter integrity demonstrated regional FA reductions along the CST and also in frontal and prefrontal brain areas according to the proposed propagation pattern for the ALS patients with C9orf72 expansion and sporadic patients. This pattern could not be identified for the SOD1 mutation at the group level. In contrast, in the tract-specific analysis according to the neuropathological ALS-staging pattern, C9orf72 expansion ALS patients showed significant alterations of ALS-related tract systems similar to sporadic patients.

Conclusions

The DTI study including the tract-of-interest-based analysis showed a microstructural corticoefferent involvement pattern according to the staging scheme in C9orf72-associated ALS patients but not in the SOD1 mutation.

SUBMITTER: Muller HP

PROVIDER: S-EPMC7270604 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

In vivo histopathological staging in C9orf72-associated ALS: A tract of interest DTI study.

Müller Hans-Peter HP Del Tredici Kelly K Lulé Dorothée D Müller Kathrin K Weishaupt Jochen H JH Ludolph Albert C AC Kassubek Jan J

NeuroImage. Clinical 20200526

<h4>Background</h4>Diffusion tensor imaging (DTI) can identify amyotrophic lateral sclerosis (ALS)-associated patterns of brain alterations at the group level according to a neuropathological staging system.<h4>Objective</h4>The study was designed to investigate the in vivo staging in ALS patients with the C9orf72 expansion and potential differences to ALS patients with the SOD1 mutation.<h4>Methods</h4>DTI-based white matter mapping was performed both by an unbiased voxel-wise statistical compa ...[more]

PMID: 32505118

Similar Datasets

Project description:BackgroundALS patients with hexanucleotide expansion in C9orf72 are characterized by a specific clinical phenotype, including more aggressive disease course and cognitive decline. Computerized multiparametric MRI with gray matter volumetry and diffusion tensor imaging (DTI) to analyze white matter structural connectivity is a potential in vivo biomarker.ObjectiveThe objective of this study was to develop a multiparametric MRI signature in a large cohort of ALS patients with C9orf72 mutations. The aim was to investigate how morphological features of C9orf72-associated ALS differ in structural MRI and DTI compared to healthy controls and ALS patients without C9orf72 mutations.MethodsAtlas-based volumetry (ABV) and whole brain-based DTI-based analyses were performed in a cohort of n = 51 ALS patients with C9orf72 mutations and compared with both n = 51 matched healthy controls and n = 51 C9orf72 negative ALS patients, respectively. Subsequently, Spearman correlation analysis of C9orf72 ALS patients' data with clinical parameters (age of onset, sex, ALS-FRS-R, progression rate, survival) as well as ECAS and p-NfH in CSF was performed.ResultsThe whole brain voxel-by-voxel comparison of fractional anisotropy (FA) maps between C9orf72 ALS patients and controls showed significant bilateral alterations in axonal structures of the white matter at group level, primarily along the corticospinal tracts and in fibers projecting to the frontal lobes. For the frontal lobes, these alterations were also significant between C9orf72 positive and C9orf72 negative ALS patients. In ABV, patients with C9orf72 mutations showed lower volumes of the frontal, temporal, and parietal lobe, with the lowest values in the gray matter of the superior frontal and the precentral gyrus, but also in hippocampi and amygdala. Compared to C9orf72 negative ALS, the differences were shown to be significant for cerebral gray matter (p = 0.04), especially in the frontal (p = 0.01) and parietal lobe (p = 0.01), and in the thalamus (p = 0.004). A correlation analysis between ECAS and averaged regional FA values revealed significant correlations between cognitive performance in ECAS and frontal association fibers. Lower FA values in the frontal lobes were associated with worse performance in all cognitive domains measured (language, verbal fluency, executive functions, memory and spatial perception). In addition, there were significant negative correlations between age of onset and atlas-based volumetry results for gray matter.ConclusionsThis study demonstrates a distinct pattern of DTI alterations of the white matter and ubiquitous volume reductions of the gray matter early in the disease course of C9orf72-associated ALS. Alterations were closely linked to a more aggressive cognitive phenotype. These results are in line with an expected pTDP43 propagation pattern of cortical affection and thus strengthen the hypothesis that an underlying developmental disorder is present in ALS with C9orf72 expansions. Thus, multiparametric MRI could contribute to the assessment of the disease as an in vivo biomarker even in the early phase of the disease.

Dataset Information

In vivo histopathological staging in C9orf72-associated ALS: A tract of interest DTI study.

Background

Objective

Methods

Results

Conclusions

Publications

In vivo histopathological staging in C9orf72-associated ALS: A tract of interest DTI study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets