Hypertrophic olivary degeneration is secondary to trans-synaptic injury along the dentato-rubral-olivary pathway (better known as the triangle of Guillain-Mollaret). It is an unusual type of degeneration because it is associated with enlargement, rather than atrophy, of the inferior olivary neurons. Pathologically, it corresponds to vacuolar degeneration of cytoplasm that results in enlargement.

It is important to recognize this pattern of injury so that the changes in the medulla are not ascribed to a more serious cause, e.g. tumor, demyelination or infarct. The most important clue to the correct diagnosis is the association of a remote lesion along the pathway.