Association of Clinically Evident Eye Movement Abnormalities With Motor and Cognitive Features in Patients With Motor
Barbara Poletti1, Federica Solca1, Laura Carelli1
1From the Department of Neurology (B.P., L.C., A.D., E.C., S.T., A.M., F.G., F.V., C.M., V.S., N.T.), Istituto Auxologico Italiano IRCCS; Department of Pathophysiology and Transplantation (F.S., F.V., V.S., N.T.), Dino Ferrari Center and Department of Health Sciences (R.F.), Aldo Ravelli Center for Neurotechnology and Experimental Brain Therapeutics, Universitá degli Studi di Milano; Neuromuscular Omnicenter (L.G., F.C., A.L., C.L.), Fondazione Serena Onlus; Department of Materials Science and COMiB Research Center (F.C.), Università degli Studi di Milano-Bicocca; ASST Santi Paolo e Carlo (R.F.), Neurology Clinic III; and IRCCS Ca Granda Foundation Maggiore Policlinico Hospital (R.F.), Milan, Italy.
Background And Objectives:
Although oculomotor abnormalities (OMAs) are not usually considered prominent features of amyotrophic lateral sclerosis (ALS), they may represent potential clinical markers of neurodegeneration, especially when investigated together with cognitive and behavioral alterations. The aim of our study was to identify patterns of clinically evident OMAs in patients with ALS and to correlate such findings with cognitive-behavioral data.
Methods:
Three consecutive inpatient cohorts of Italian patients with ALS and controls were retrospectively evaluated to assess the frequency of OMAs and cognitive-behavioral alterations. The ALS population was divided into a discovery cohort and a replication cohort. Controls included a cohort of cognitively impaired individuals and patients with Alzheimer disease (AD). Participants underwent bedside eye movement evaluation to determine the presence and pattern of OMAs. Cognitive assessment was performed with a standard neuropsychological battery (discovery ALS cohort and AD cohort) and the Italian Edinburgh Cognitive and Behavioural ALS Screen (ECAS) (replication ALS cohort).
Results:
We recruited 864 individuals with ALS (635 discovery, 229 replication), 798 who were cognitively unimpaired and 171 with AD. OMAs were detected in 10.5% of our ALS cohort vs 1.6% of cognitively unimpaired controls (p = 1.2 × 10-14) and 11.4% of patients with AD (p = NS). The most frequent deficits were smooth pursuit and saccadic abnormalities. OMA frequency was higher in patients with bulbar onset, prominent upper motor neuron signs, and advanced disease stages. Cognitive dysfunction was significantly more frequent in patients with OMAs in both ALS cohorts (p = 1.1 × 10-25). Furthermore, OMAs significantly correlated with the severity of cognitive impairment and with pathologic scores at the ECAS ALS-specific domains. Last, OMAs could be observed in 35.0% of cognitively impaired patients with ALS vs 11.4% of patients with AD (p = 6.4 × 10-7), suggesting a possible involvement of frontal oculomotor areas in ALS.
Conclusion:
Patients with ALS showed a range of clinically evident OMAs, and these alterations were significantly correlated with cognitive, but not behavioral, changes. OMAs may be a marker of neurodegeneration, and bedside assessment represents a rapid, highly specific tool for detecting cognitive impairment in ALS.
Related Concept Videos
01:37Neural Regulation
01:28Disorders of the Skeletal Muscle
Musculoskeletal disorders
Musculoskeletal disorders involve injuries and conditions affecting the skeletal muscles and associated connective tissues. These disorders can arise from acute biomechanical stresses or chronic overuse and can occur across different age groups. Common injuries include sprains, fractures, and muscular strains, often resulting from...