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Ordinal scales, such as ALSFRS-R, where total sum scores are compared within participants, sometimes under- or over-value changes (i.e., the difference in scores in patients who go from walking up stairs to using a handrail is considered equivalent to the difference between feeding oneself and relying on others for all feeds)

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Accumulation of cytosolic succinate results the inhibition of the 2-oxoglutarate and Fe 2+ -dependent dioxygenases [prolyl hydroxylase domain (PDH) enzymes] responsible for the hydroxylation of the -subunit (HIF-1) of HIF-1

Couto, N., Wood, J