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.

Background Malnutrition and weight loss are negative prognostic factors for survival in patients with amyotrophic lateral sclerosis (ALS). However, energy expenditure at rest (REE) is still not included in clinical practice, and no data are available concerning hypometabolic state in ALS. Objective To evaluate in a referral cohort of patients with ALS the prevalence of hypometabolic state as compared with normometabolic and hypermetabolic states, and to correlate it with clinical phenotype, rate of progression and survival. Design We conducted a retrospective study examining REE measured by indirect calorimetry in patients with ALS referred to Milan, Limoges and Tours referral centres between January 2011 and December 2017. Hypometabolism and hypermetabolism states were defined when REE difference between measured and predictive values was ≤−10% and ≥10%, respectively. We evaluated the relationship between these metabolic alterations and measures of body composition, clinical characteristics and survival. Results Eight hundred forty-seven patients with ALS were recruited. The median age at onset was 63.79 years (IQR 55.00–71.17). The male/female ratio was 1.26 (M/F: 472/375). Ten per cent of patients with ALS were hypometabolic whereas 40% were hypermetabolic. Hypometabolism was significantly associated with later need for gastrostomy, non-invasive ventilation and tracheostomy placement. Furthermore, hypometabolic patients with ALS significantly outlived normometabolic (HR=1.901 (95% CI 1.080 to 3.345), p=0.0259) and hypermetabolic (HR=2.138 (95% CI 1.154 to 3.958), p=0.0157) patients. Conclusion Hypometabolism in ALS is not uncommon and is associated with slower disease progression and better survival than normometabolic and hypermetabolic subjects. Indirect calorimetry should be performed at least at time of diagnosis because alterations in metabolism are correlated with prognosis.

The main aim of this Human Centred Design project was to develop the Environment COntrol in Amyotrophic Lateral Sclerosis (ECO-ALS) System, a new device which could improve ALS patient’s autonomy i...

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease involving both upper and lower motor neurons and resulting in increasing disability and death 3–5 years after ...