Midbrain lesion-induced disconjugate gaze: a unifying circuit mechanism of ocular misalignment?

Abstract

Abstract Background: Disconjugate eye movements play a crucial role in depth perception for frontal-eyed species. Midbrain lesions cause disconjugate eye movement deficits, such as skew deviation and hemi-seesaw nystagmus in the vertical plane or esodeviation and convergence-retraction nystagmus in the horizontal plane. While the former have been linked to defective visuo-vestibular interaction, the pathophysiology of the latter remains elusive. Methods & Results: We report a patient with a solitary focal midbrain lesion, presenting with both vertically and horizontally disconjugate eye movement disorders. Videooculography showed a strong correlation of vertical and horizontal oscillations during fixation but not in darkness. Oscillation intensities and waveforms were modulated by fixation, illumination and gaze position, hinting at shared visual- and vestibular-related mechanisms. Diffusion MRI, combined with co-registration to a cytoarchitectonic MR-atlas, pinpointed the lesion to a functionally ill-defined area of the dorsal midbrain, adjacent to the posterior commissure and nuclei with known roles in vertical gaze control. Conclusion: A circumscribed region in the dorsal midbrain is a key node for disconjugate eye movements across both vertical and horizontal planes. Lesioning this area produces a unique ocular motor syndrome that mirrors hallmark patterns of developmental strabismus. Further circuit-level studies could offer pivotal insights into shared pathomechanisms.