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This study complements current understanding of disease progression and patterns of spread in ALS, highlighting several important points for consideration. Firstly, the cross-sectional analysis reaffirms significant CST changes, supporting the primacy of the motor pathway in disease manifestation. White matter involvement in other areas, mainly the frontal, brainstem and hippocampal regions, also correlates well with the four neuropathological disease stages described in separate post-mortem ALS studies, suggesting that DTI may also be able to assess disease staging in vivo<\/em>. Of particular interest, the authors\u2019 use of TOI techniques to map and track axonal loss over time at the level of the individual patient is particularly relevant, as methodological variability in previous DTI studies have cast significant doubt regarding suitability of this technique for individual patient analysis. Given the heterogeneity of ALS, an ability to individualise analysis would clarify intrinsic differences between subgroups, enable more suitable patient stratification for clinical trials and guide personalised therapeutic approaches.<\/p>\n