Stages of oculomotor dysfunctions confirms the model of axonal spread of pTDP-43 pathology in amyotrophic lateral sclerosis

Objective To see whether the sequential corticofugal spreading of pTDP-43 pathology in amyotrophic lateral sclerosis (ALS) (Brettschneider et al., Ann Neurol 2013) permit the categorization of eye movement disturbances in a corresponding oculomotor staging scheme. Methods Saccadic and smooth pursuit eye movements were video-oculographically recorded from 68 ALS patients and 31 matched healthy controls in order to compute parameters for executive oculomotor functions and brainstem oculomotor circuitry performance. Results Thirty patients had no oculomotor abnormalities compared to controls, all other presented a broad spectrum of impaired eye movement control including increased anti- and delayed saccades errors, a high prevalence of saccadic intrusions, gaze-palsy and a cerebellar type of smooth pursuit disturbance. Oculomotor deficits manifested sequentially witch permits a categorization of two stages: Stage 1, exclusively executive dysfunctions, and Stage 2, executive deficits plus impaired ,genuine‘ oculomotor control such as gaze-palsy or impaired pre-cereballary circuits. Conclusions Impaired executive eye movements appear as the initial manifestation, followed by disturbed infratentorial oculomotor control pathways. Key message Alterations in eye movement control in ALS follow a sequential pattern and may serve as a technical marker of the corticofugal axonal spread of the disease.