Corpus callosum involvement is a consistent feature of amyotrophic lateral sclerosis
Nicola Filippini,Gwenaëlle Douaud,Clare E. Mackay,Steven Knight,Kevin Talbot,Martin R Turner +5 more
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TLDR
Callosal involvement is a consistent feature of ALS, independent of clinical upper motor neuron involvement, and may reflect independent bilateral cortical involvement or interhemispheric spread of pathology.Abstract:
Objective: While the hallmark of amyotrophic lateral sclerosis (ALS) is corticospinal tract in combination with lower motor neuron degeneration, the clinical involvement of both compartments is characteristically variable and the site of onset debated. We sought to establish whether there is a consistent signature of cerebral white matter abnormalities in heterogeneous ALS cases. Methods: In this observational study, diffusion tensor imaging was applied in a whole-brain analysis of 24 heterogeneous patients with ALS and well-matched healthy controls. Tract-based spatial statistics were used, with optimized voxel-based morphometry of T1 images to determine any associated gray matter involvement. Results: A consistent reduction in fractional anisotropy was demonstrated in the corpus callosum of the ALS group, extending rostrally and bilaterally to the region of the primary motor cortices, independent of the degree of clinical upper motor neuron involvement. Matched regional radial diffusivity increase supported the concept of anterograde degeneration of callosal fibers observed pathologically. Gray matter reductions were observed bilaterally in primary motor and supplementary motor regions, and also in the anterior cingulate and temporal lobe regions. A post hoc group comparison model incorporating significant values for fractional anisotropy, radial diffusivity, and gray matter was 92% sensitive, 88% specific, with an accuracy of 90%. Conclusion: Callosal involvement is a consistent feature of ALS, independent of clinical upper motor neuron involvement, and may reflect independent bilateral cortical involvement or interhemispheric spread of pathology. The predominantly rostral corticospinal tract involvement further supports the concept of independent cortical degeneration even in those patients with ALS with predominantly lower motor neuron involvement clinically. Neurology ® 2010;75:1645–1652read more
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Diffusion tensor imaging analysis of sequential spreading of disease in amyotrophic lateral sclerosis confirms patterns of TDP-43 pathology.
Jan Kassubek,Hans-Peter Müller,Kelly Del Tredici,Johannes Brettschneider,Elmar H. Pinkhardt,Dorothée Lulé,Sarah Böhm,Heiko Braak,Albert C. Ludolph +8 more
TL;DR: A new methodological diffusion tensor imaging-based approach to automatically analyse in vivo the fibre tracts that are prone to be involved at each neuropathological stage of amyotrophic lateral sclerosis, enlarges the spectrum of potential non-invasive surrogate markers as a neuroimaging-based read-out for amyotropolitan sclerosis studies within a clinical context.
References
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Current hypotheses for the underlying biology of amyotrophic lateral sclerosis
TL;DR: It is demonstrated that mutations and pathology associated with the TDP‐43 gene and protein may be more common than SOD1 mutations in familial and sporadic ALS, and Convergence of these pathways is likely to mediate disease onset and progression.
Journal ArticleDOI
Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study
Martin R Turner,Annachiara Cagnin,Federico Turkheimer,Federico Turkheimer,Christopher C.J. Miller,Christopher Shaw,David J. Brooks,Peter Leigh,Richard B. Banati,Richard B. Banati +9 more
TL;DR: The findings indicate that cerebral microglial activation can be detected in vivo during the evolution of ALS, and support the previous observations that cerebral pathology is widespread, and argue for the development of therapeutic strategies aimed at inflammatory pathways.
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ALS motor phenotype heterogeneity, focality, and spread: Deconstructing motor neuron degeneration
John Ravits,Albert R. La Spada +1 more
TL;DR: Heterogeneity of motor phenotypes suggests motor neuron degeneration in ALS is in actuality a very orderly and actively propagating process and that fundamental molecular mechanisms may be uniform and their chief properties deduced.
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