NEUROLOGICAL REVIEW Oculomotor Dysfunction in Amyotrophic Lateral Sclerosis A Comprehensive Review Rakesh Sharma, MBBS; Stephen Hicks, PhD; Claire M. Berna, MSc; Christopher Kennard, PhD, FRCP, FMedSci; Kevin Talbot, DPhil, FRCP; Martin R. Turner, PhD, MRCP A lthough traditionally regarded as spared, a range of oculomotor dysfunction has been recorded in patients with amyotrophic lateral sclerosis (ALS). Most frequent is oph- thalmoparesis, particularly in patients with prolonged survival; however, pursuit, nys- tagmus, 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 as- sessment 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 par- allel elucidation of the normal cerebral oculomotor control network. Given the clinicopathologic overlap between ALS and some types of frontotemporal dementia, the study of oculomotor func- tion has particular value in probing the variable but consistent cognitive impairment seen in ALS and that reflects frontotemporal extramotor cerebral abnormalities. By transcending the require- ment to write or speak, loss of which precludes standard neuropsychological testing in some pa- tients with advanced ALS, cognitive tests performed using only oculomotor functions offer addi- tional 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 prog- nostic, monitoring, and mechanistic biomarkers for ALS. Arch Neurol. 2011;68(7):857-861 Eye movements are traditionally regarded as spared from involvement in most cases of amyotrophic lateral sclerosis (ALS), de- spite progressive weakness of limb, respi- ratory, and bulbar musculature. The cen- tral diagnostic criterion for ALS (as the most common form of motor neuron disease) is the combined degeneration of upper mo- tor neurons of the corticospinal tract and lower motor neurons in brainstem nuclei and spinal anterior horns. It has been long established, however, that ALS is a neuro- degenerative disorder of a third compart- ment comprising widespread areas of the extramotor brain. Neuroimaging and neu- ropsychological studies 1-3 have demon- strated particular involvement of frontal, es- pecially dorsolateral prefrontal, regions. Although the exact nature and cause of the observed variability in the region of onset and spread of abnormality in ALS remain uncertain, the recognition of clinicopatho- logic overlap with frontotemporal demen- tia (FTD) clearly points to more wide- spread central nervous system involvement. Frank dementia affects only a small minor- ity of patients with ALS, but the true ex- tent of diffuse central nervous system in- volvement in ALS may be masked because life-span is so drastically reduced as a re- sult of respiratory failure. Recognition of this confounding factor challenges simplistic concepts of intellectual sparing in ALS, and it is estimated that up to half of patients with ALS may have detectable cognitive impair- ment on rigorous neuropsychological test- ing. 4 Oculomotor function, sphincter con- Author Affiliations: Oxford University Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, United Kingdom. ARCH NEUROL / VOL 68 (NO. 7), JULY 2011 WWW.ARCHNEUROL.COM 857 ©2011 American Medical Association. All rights reserved. at HINARI, on July 11, 2011 www.archneurol.com Downloaded from