Evolution of white matter damage in amyotrophic lateral sclerosis

Matt C. Gabel, Rebecca J. Broad, Alexandra L. Young, Sharon Abrahams, Mark Bastin, Ricarda A.L. Menke , Ammar Al Chalabi, Laura H. Goldstein, Stella Tsermentseli, Daniel C. Alexander, Martin R. Turner, Nigel Leigh, Mara Cercignani

Research output: Contribution to journalArticlepeer-review

Abstract

Objective
To characterize disease evolution in amyotrophic lateral sclerosis using an event-based model designed to extract temporal information from cross-sectional data. Conventional methods for understanding mechanisms of rapidly progressive neurodegenerative disorders are limited by the subjectivity inherent in the selection of a limited range of measurements, and the need to acquire longitudinal data.
Methods
The event-based model characterizes a disease as a series of events, each comprising a significant change in subject state. The model was applied to data from 154 patients and 128 healthy controls selected from five independent diffusion MRI data sets acquired in four different imaging laboratories between 1999 and 2016. The biomarkers modelled were mean fractional anisotropy values of white matter tracts implicated in amyotrophic lateral sclerosis. The cerebral portion of the corticospinal tracts was divided into 3 segments.
Results
Application of the model to the pooled datasets revealed that the corticospinal tracts were involved before other white matter tracts. Distal corticospinal tract segments were involved earlier than more proximal (i.e. cephalad) segments. In addition, the model revealed early ordering of fractional anisotropy change in the corpus callosum and subsequently in long association fibers.
Interpretation
These findings represent data-driven evidence for early involvement of the corticospinal tracts and body of the corpus callosum in keeping with conventional approaches to image analysis, while providing new evidence to inform directional degeneration of the corticospinal tracts. This data-driven model provides new insight into the dynamics of neuronal damage in amyotrophic lateral sclerosis.
Original languageEnglish
JournalAnnals of Clinical and Translational Neurology
Early online date4 May 2020
DOIs
Publication statusE-pub ahead of print - 4 May 2020

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