Oculomotor dysfunction in amyotrophic lateral sclerosis: a comprehensive review.

Although traditionally regarded as spared, a range of oculomotor dysfunction has been recorded in patients with amyotrophic lateral sclerosis (ALS). Most frequent is ophthalmoparesis, particularly in patients with prolonged survival; however, pursuit, nystagmus, and saccadic impairments have also been reported. The apparent resistance to pathologic involvement of oculomotor (and sphincter) control pathways in most patients with ALS has prompted comparative study to establish the key pathways that underlie motor neuronal vulnerability, with the hope of generating novel therapeutic strategies. Developments in the assessment of oculomotor function, including portable eye-tracking devices, have revealed more subtle impairments in ALS in relation to phenotype, which can now be better understood through parallel elucidation of the normal cerebral oculomotor control network. Given the clinicopathologic overlap between ALS and some types of frontotemporal dementia, the study of oculomotor function has particular value in probing the variable but consistent cognitive impairment seen in ALS and that reflects frontotemporal extramotor cerebral abnormalities. By transcending the requirement to write or speak, loss of which precludes standard neuropsychological testing in some patients with advanced ALS, cognitive tests performed using only oculomotor functions offer additional potential, allowing the study of patients much later in their disease course. The study of oculomotor dysfunction holds significant promise as an additional source of much needed prognostic, monitoring, and mechanistic biomarkers for ALS.