Widespread temporo-occipital lobe dysfunction in amyotrophic lateral sclerosis

Loewe, Kristian; Machts, Judith; Kaufmann, Jörn; Petri, Susanne; Heinze, Hans‐Jochen; Borgelt, Christian; Harris, Joseph A.; Vielhaber, Stefan; Schoenfeld, Mircea Ariel

doi:10.1038/srep40252

Cited by 34 publications

(37 citation statements)

References 57 publications

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“…5 also shows substantial involvement in the posterior corpus callosum that connects to the occipital lobe. Although there is no clinical presentation here supporting our finding, subclinical callosal damage for ALS patients is not uncommon 23 , and there are also studies suggested subclinical involvement of occipital lobe in the ALS patients 24, 25 . The ability to capture subclinical findings has a profound clinical implication.…”

Section: Discussionsupporting

confidence: 44%

Differential Tractography as a Track-Based Biomarker for Neuronal Injury

Yeh

Zaydan

Suski

et al. 2019

Preprint

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One Sentence Summary:Differential tractography utilizes repeat diffusion MRI scans of the same subject to identify tracks with neurodegeneration. AbstractDiffusion MRI tractography has been used to map the axonal structure of human brain, but its ability to detect neurodegeneration is yet to be explored. Here we report differential tractography, a new type of tractography that utilizes a novel tracking strategy to map the exact segment of fiber pathways with neurodegeneration. It utilizes voxel-wise differences from repeat scans and aggregates them as track-based biomarkers for neurodegeneration. We examined differential tractography on multiple sclerosis, Huntington disease, amyotrophic lateral sclerosis, and epileptic patients. The results showed that the affected pathways shown by differential tractography matched well with the unique clinical symptoms of the patients, and the false discovery rate of the findings could be estimated using a sham setting to provide a reliability measurement. This novel approach enables a quantitative and objective method to monitor neurodegeneration in individuals, allowing for diagnostic and prognostic evaluation of brain diseases.

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Section: Discussionsupporting

confidence: 44%

Differential Tractography as a Track-Based Biomarker for Neuronal Injury

Yeh

Zaydan

Suski

et al. 2019

Preprint

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“…Posterior cingulate and precuneus are important nodes of the DMN and were found with decreased fALFF and ReHo in the present study. Abnormal activity in the posterior cingulate is documented in rs-fMRI and PET-FDG studies in ALS (Mohammadi et al, 2009;Bueno et al, 2018;Matías-Guiu et al, 2016) as well as functional changes in the precuneus Loewe et al, 2017).…”

Section: Discussionmentioning

confidence: 97%

Regional Dynamics of the Resting Brain in Amyotrophic Lateral Sclerosis Using Fractional Amplitude of Low-Frequency Fluctuations and Regional Homogeneity Analyses

et al. 2019

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Resting state functional magnetic resonance imaging (rs-fMRI) has been playing an important role in the study of amyotrophic lateral sclerosis (ALS). Although functional connectivity is widely studied, the patterns of spontaneous neural activity of the resting brain are important mechanisms that have been used recently to study a variety of conditions but remain less explored in ALS. Here we have used fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) to study the regional dynamics of the resting brain of non-demented ALS patients compared with healthy controls. As expected, we found the sensorimotor network (SMN) with changes in fALFF and ReHo but also found the default mode (DMN), frontoparietal (FPN), salience (SN) networks altered and the cerebellum, although no structural changes between ALS patients and controls were reported in the regions with fALFF and ReHo changes. We show an altered pattern in the spontaneous low frequency oscillations that is not confined to the motor areas and reveal a more widespread involvement of nonmotor regions, including those responsible for cognition.

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“…The visual cortex and forceps major are regions where ALS associated degenerative changes are not anticipated; they have been used previously as internal controls or reference regions [ 10 , 28 , 112 ]. Conversely, some in vivo imaging studies have reported changes in functional connectivity [ 113 , 114 ], grey matter atrophy, cortical thinning and altered glucose metabolism in occipital cortex of individuals with ALS independent of visual impairment [ 115 – 117 ]. These findings have not been validated ex vivo, although it has been reported that pTDP-43 pathology may propagate into occipital lobe in the final stages of bvFTD [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Dissecting the pathobiology of altered MRI signal in amyotrophic lateral sclerosis: A post mortem whole brain sampling strategy for the integration of ultra-high-field MRI and quantitative neuropathology

Pallebage-Gamarallage

et al. 2018

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BackgroundAmyotrophic lateral sclerosis (ALS) is a clinically and histopathologically heterogeneous neurodegenerative disorder, in which therapy is hindered by the rapid progression of disease and lack of biomarkers. Magnetic resonance imaging (MRI) has demonstrated its potential for detecting the pathological signature and tracking disease progression in ALS. However, the microstructural and molecular pathological substrate is poorly understood and generally defined histologically. One route to understanding and validating the pathophysiological correlates of MRI signal changes in ALS is to directly compare MRI to histology in post mortem human brains.ResultsThe article delineates a universal whole brain sampling strategy of pathologically relevant grey matter (cortical and subcortical) and white matter tracts of interest suitable for histological evaluation and direct correlation with MRI. A standardised systematic sampling strategy that was compatible with co-registration of images across modalities was established for regions representing phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) patterns that were topographically recognisable with defined neuroanatomical landmarks. Moreover, tractography-guided sampling facilitated accurate delineation of white matter tracts of interest. A digital photography pipeline at various stages of sampling and histological processing was established to account for structural deformations that might impact alignment and registration of histological images to MRI volumes. Combined with quantitative digital histology image analysis, the proposed sampling strategy is suitable for routine implementation in a high-throughput manner for acquisition of large-scale histology datasets. Proof of concept was determined in the spinal cord of an ALS patient where multiple MRI modalities (T1, T2, FA and MD) demonstrated sensitivity to axonal degeneration and associated heightened inflammatory changes in the lateral corticospinal tract. Furthermore, qualitative comparison of R2* and susceptibility maps in the motor cortex of 2 ALS patients demonstrated varying degrees of hyperintense signal changes compared to a control. Upon histological evaluation of the same region, intensity of signal changes in both modalities appeared to correspond primarily to the degree of microglial activation.ConclusionThe proposed post mortem whole brain sampling methodology enables the accurate intraindividual study of pathological propagation and comparison with quantitative MRI data, to more fully understand the relationship of imaging signal changes with underlying pathophysiology in ALS.Electronic supplementary materialThe online version of this article (10.1186/s12868-018-0416-1) contains supplementary material, which is available to authorized users.

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Widespread temporo-occipital lobe dysfunction in amyotrophic lateral sclerosis

Cited by 34 publications

References 57 publications

Differential Tractography as a Track-Based Biomarker for Neuronal Injury

Differential Tractography as a Track-Based Biomarker for Neuronal Injury

Regional Dynamics of the Resting Brain in Amyotrophic Lateral Sclerosis Using Fractional Amplitude of Low-Frequency Fluctuations and Regional Homogeneity Analyses

Dissecting the pathobiology of altered MRI signal in amyotrophic lateral sclerosis: A post mortem whole brain sampling strategy for the integration of ultra-high-field MRI and quantitative neuropathology

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