While gaze-evoked nystagmus (GEN) is a common manifestation of MS, it is seldom evaluated specifically in dedicated imaging studies. Nystagmus has considerable quality of life implications, it impacts on rehabilitation efforts, ability to work, reading, using computers, watching television, driving and operating machinery. GEN is widely regarded as a specific manifestation of neuronal integrator dysfunction, which provides insufficient discharge to fixate at an eccentric position, resulting in a drift to the primary gaze position and triggering a corrective saccade.

Patients were recruited from a specialist MS clinic and underwent standardised clinical evaluation and multimodal neuroimaging including high-resolution structural and diffusion tensor data acquisitions. Morphometric analyses were carried out to evaluate patterns of cortical, subcortical, brainstem and cerebellar grey matter pathology. Volumetric analyses were also performed to further characterise subcortical grey matter degeneration. White matter integrity was evaluated using axial-, mean-, and radial diffusivity as well as fractional anisotropy.

Whole-brain and region-of-interest morphometry highlighted considerable brainstem and cerebellar grey matter atrophy. Nystagmus-associated grey matter degeneration was identified in medial cerebellar, posterior medullar, central pontine and superior collicular regions. Volume reductions were identified in the putamen, thalamus and hippocampus. The tract-wise evaluation of white matter metrics revealed widespread pathology in frontotemporal and parietal regions.