This study presents the Italian validation of the recently developed Edinburgh Cognitive and Behavioural ALS Screen (ECAS), a short screen for cognitive/behavioural alterations in patients with amyotrophic lateral sclerosis (ALS). We evaluated the psychometric properties of the ECAS Italian version in terms of reliability and convergent validity for both cognitive and behavioural features. Furthermore, we investigated the relationship with affective and clinical variables, in addition to ECAS usability and patients' insight into cognitive/behaviour changes. Finally, correlations between genetic and cognitive/behavioural data were analysed. We recruited 107 patients with ALS. Normative data were collected on 248 healthy subjects. Participants were administered the ECAS and two standard cognitive screening tools (FAB, MoCA), two psychological questionnaires (BDI, STAI/Y) and an ad hoc usability questionnaire. The FBI was also carried out with caregivers. Results showed that the ECAS Italian version discriminated well between patients and controls. The most prevalent deficit occurred in executive functions and fluency. Correlations were observed between the ECAS and standard cognitive screening tools and between the ECAS carer interview and the FBI, supporting its full convergent validity. In conclusion, the ECAS Italian version provides clinicians with a rapid, feasible and sensitive tool, useful to identify different profiles of cognitive-behavioural impairment in ALS.

Systemic lupus erythematosus (SLE) and antiphospholipid syndrome have an increased risk to develop cognitive impairment. A possible role for antiphospholipid antibodies (aPL) and antiglutamate receptor (anti-NMDA) antibodies in the pathogenesis of neurological manifestations of these two conditions, have been suggested. In particular, the role of anti-NMDA antibodies in the pathogenesis of neuropsychiatric SLE is supported by several experimental studies in animal models and by the finding of a correlation between anti-NMDA positivity in cerebrospinal fluid and neurological manifestations of SLE. However, data from the literature are controversial, as several studies have reported a correlation of these antibodies with mild cognitive impairment in SLE, but more recent studies have not confirmed this finding. The synergism between anti-NMDA and other concomitant autoantibodies, such as aPL, can be hypothesized to play a role in inducing the tissue damage and eventually the functional abnormalities. In line with this hypothesis, we have found a high incidence of at least one impaired cognitive domain in a small cohort of patients with primary APS (PAPS) and SLE. Interestingly, aPL were associated with low scoring for language ability and attention while anti-NMDA titers and mini-mental state examination scoring were inversely correlated. However, when patients were stratified according to the presence/absence of aPL, the correlation was confirmed in aPL positive patients only. Should those findings be confirmed, the etiology of the prevalent defects found in PAPS patients as well as the synergism between aPL and anti-NMDA antibodies would need to be explored.

The significant improvement of some ECAS scores over time supports the presence of possible practice effects, particularly in the memory domain, highlighting the need to accommodate for these in longitudinal assessments, through healthy controls groups or alternate versions. This work represents the first Italian ECAS follow-up study and confirms ECAS feasibility in patients with increasing physical disability.