A 32-year-old female with relapsing-remitting multiple sclerosis (MS) presented with severe new onset ataxia and diplopia. MRI showed a new inflammatory MS lesion that involved the right dorsal pons and extended into the adjacent superior cerebellar peduncle. The patient improved with aggressive immunotherapy; however, repeat MRI 3 months later revealed a new non-enhancing lesion in the left inferior medullary olive. The differential diagnosis for this new lesion included an MS lesion vs hypertrophic olivary degeneration, with infarct or neoplasm as the less likely considerations. We used track density imaging, which provides unprecedented anatomic details based on probabilistic tractography streamlines, to demonstrate apparent changes in the integrity of the dentato-rubro-olivary pathway (Guillain-Mollaret triangle) that were consistent with the diagnosis of hypertrophic olivary degeneration from the antecedent MS lesion involving the right superior cerebellar peduncle. Further medical therapy was avoided, and follow-up MRI 1 year later showed interval involution of the left olivary lesion. This case demonstrates the potential clinical utility of using track density imaging to detect lesion-induced alterations in brainstem connectivity and characterize neurodegeneration in patients.