Cross-sectional evaluation of clinical neuro-ophthalmic abnormalities in an amyotrophic lateral sclerosis population

Objective: Ocular motility abnormalities may be a marker of neuro-degeneration beyond motor neurons in amyotrophic lateral sclerosis (ALS). We formally compared clinical neuro-ophthalmic abnormalities in ALS patients and a control population. Methods: Patients attending a multidisciplinary ALS clinic (n = 63, age 60.8 +/- 16.4 years) and their caregivers serving as controls (n = 37, ages 55.0 +/- 12.7 years) participated in this cross-sectional study. Visual acuity was assessed. Video recordings of a standardized ocular motility exam including gaze fixation, voluntary saccades, reflex saccades, smooth pursuit, eyelid opening and Bell's phenomenon were rated by two senior neuro-ophthalmologists who were masked to subject group. Results: Visual acuity was lower in ALS patients versus control subjects (OR 0.81 (0.71-0.93), p = 0.003, logistic regression). Inter- and intra-rater reliability for ocular motility examination ratings were good (Cohen's Kappa > 0.6). Findings observed only in ALS subjects included gaze impersistence (14%, p = 0.01), moderately or severely restricted voluntary upgaze (13%, p = 0.01), and moderate or severe eyelid opening apraxia (27%, p = 0.0002). Accounting for age, moderately or severely saccadic horizontal smooth pursuits distinguished ALS from control subjects (OR 3.6 (1.2-10.9), p = 0.02, logistic regression). Conclusions: Clinical findings of decreased visual acuity, gaze impersistence, voluntary upgaze restriction, eyelid opening apraxia, and saccadic horizontal smooth pursuits are more frequent in patients with ALS than in similar-aged controls. These findings are potential clinical markers of neurodegeneration beyond upper and lower motor neuron disease in ALS. Further study is warranted regarding their application to disease categorization and outcomes assessment.