Different saccadic profile in bulbar versus spinal-onset amyotrophic lateral sclerosis

Abstract

Two clinical phenotypes characterize the onset of amyotrophic lateral sclerosis (ALS): the spinal variant, with symptoms beginning in the limbs, and the bulbar variant, affecting firstly speech and swallowing. The two variants show some distinct features in the histopathology, localization and prognosis, but to which extent they really differ clinically and pathologically remains to be clarified. Recent neuropathological and neuroimaging studies have suggested a broader spreading of the neurodegenerative process in ALS, extending beyond the motor areas, toward other cortical and deep grey matter regions, many of which are involved in visual processing and saccadic control. Indeed, a wide range of eye movement deficits have been reported in ALS, but they have never been used to distinguish the two ALS variants. Since quantifying eye movements is a very sensitive and specific method for the study of brain networks, we compared different saccadic and visual search behaviours across spinal ALS patients (n = 12), bulbar ALS patients (n = 6) and healthy control subjects (n = 13), along with cognitive and MRI measures, with the aim to define more accurately the two patients subgroups and possibly clarify a different underlying neural impairment. We found separate profiles of visually-guided saccades between spinal (short saccades) and bulbar (slow saccades) ALS, which could result from the pathologic involvement of different pathways. We suggest an early involvement of the parieto-collicular-cerebellar network in spinal ALS and the fronto-brainstem circuit in bulbar ALS. Overall, our data confirm the diagnostic value of the eye movements analysis in ALS and add new insight on the involved neural networks.

Keywords: cognitive dysfunction; executive functions; eye movements; motor neuron disease; quantitative neuroimaging.