Table 1.

Common shortcomings for ALS imaging studies.

Common methodological limitations of individual ALS imaging studies • Technique-driven rather than clinical problem-driven studies • Confirmatory as opposed to original study designs • Small to moderate sample sizes, lack of power calculations • Inadequate discussion or interpretation of unilateral findings • Suboptimal clinical patient characterisation • Lack of comprehensive genotyping i.e. C9orf72 which may contribute to extra-motor changes • Limited imaging methods i.e. white matter only, grey matter only studies, as opposed to multifaceted, multimodal structural/functional, cortical/subcortical characterisation • Lack of disease controls and “ALS-mimic” controls • Correlation of brain changes with clinical measures that also heavily depend on lower motor neuron function (ALSFRS-r, tapping rates) • Lack of post-mortem validation of imaging findings • Lenient statistical models, insufficient correction for demographic factors (education, handedness, age, gender) • Reports of statistical “trends” uncorrected for multiple testing Shortcomings of the current literature of ALS imaging • Paucity of presymptomatic studies • Paucity of classifier (diagnostic) studies • Paucity of meta-analyses • Paucity of high-field MRI studies • Lack of large, cross-platform, multi-centre studies • Lack of post-mortem imaging studies in ALS • Relative paucity of spinal cord studies • Lack of quantitative LMN/plexus/PNS imaging studies • Paucity of muscle imaging studies