Theory of Mind and Its Neuropsychological and Quality of Life Correlates in the Early Stages of Amyotrophic Lateral Sclerosis.

This study aims to explore the potential impairment of Theory of Mind (ToM; i.e., the ability to represent cognitive and affective mental states to both self and others) and the clinical, neuropsychological and Quality of Life (QoL) correlates of these cognitive abnormalities in the early stages of amyotrophic lateral sclerosis (ALS), a multisystem neurodegenerative disease recently recognized as a part of the same clinical and pathological spectrum of frontotemporal lobar degeneration. Twenty-two consecutive, cognitively intact ALS patients, and 15 healthy controls, underwent assessment of executive, verbal comprehension, visuospatial, behavioral, and QoL measures, as well as of the ToM abilities by Emotion Attribution Task (EAT), Advanced Test of ToM (ATT), and Eyes Task (ET). ALS patients obtained significantly lower scores than controls on EAT and ET. No significant difference was found between the two groups on ATT. As regard to type of ALS onset, patients with bulbar onset performed worse than those with spinal onset on ET. Correlation analysis revealed that EAT and ET were positively correlated with education, memory prose, visuo-spatial performances, and "Mental Health" scores among QoL items. Our results suggest that not only "cognitive" but also "affective" subcomponents of ToM may be impaired in the early stages of ALS, with significant linkage to disease onset and dysfunctions of less executively demanding conditions, causing potential impact on patients' "Mental Health."

Impact on children of a parent with ALS: a case-control study.

BACKGROUND: Numerous studies have explored how patients and their caregivers cope with amyotrophic lateral sclerosis (ALS), but the literature completely lacks research on the psychological impact of the disease on patients' children. The aim of our study was to investigate the emotional and psychological impact of a parent with ALS on school-age children and adolescents in terms of problem behavior, adjustment, and personality characteristics. METHODS: The study involved 23 children (mean age = 10.62 years, six females) with a parent suffering from ALS, and both their parents. Children were matched for age, gender, and birth-order with a control group of children with healthy parents. They were administered the Youth Self Report (YSR) questionnaire and the Rorschach Comprehensive System, and their healthy parent completed the Child Behavior Checklist (CBCL). RESULTS: Findings clearly showed that, compared with controls, children with a parent who had ALS had several clinically significant adverse emotional and behavioral consequences, with emotional and behavioral problems, internalizing problems, anxiety and depressive symptoms. Children of a parent with ALS scored higher than controls for the Total Problems, Internalizing Problems, Anxious/Depressed and Withdrawn/Depressed scales in the YSR. A relevant percentage of children fell within the clinical range (42.9%) and borderline range (28.6%) for Internalizing Problems. The Rorschach CS confirmed the substantial impact of ALS in a parent on their offspring in terms of internalizing behavior and depression, with adjustment difficulties, psychological pain, and thought problems. CONCLUSION: Our findings indicate that school-aged children and adolescents with a parent who has ALS are vulnerable and carry a substantially higher risk of internalizing behavior, depressive symptoms, and reactive problems than children with healthy parents. Families affected may need support to cope with such an overwhelming disease.

Dysfunctions within limbic-motor networks in amyotrophic lateral sclerosis.

Previous studies have shown that affective symptoms are part of the clinical picture in amyotrophic lateral sclerosis (ALS), the most common motor neuron disorder in elderly people. Diffuse neurodegeneration of limbic regions (e.g., prefrontal cortex [PFC], amygdala) was demonstrated in ALS post-mortem, although the mechanisms of emotional dysregulation in ALS in vivo remain unclear. Using functional imaging, we assessed the brain responses to emotional faces in 11 cognitively unimpaired ALS patients and 12 healthy controls (HCs). We tested whether regional activities and connectivity patterns in the limbic system differed between ALS patients and HCs and whether the variability in clinical measures modulated the neuroimaging data. Relative to HCs, ALS patients displayed greater activation in a series of PFC areas and altered left amygdala-PFC connectivity. Anxiety modulated the right amygdala-PFC connectivity in HCs but not in ALS patients. Reduced right premotor cortex activity and altered left amygdala-supplementary motor area connectivity were associated with longer disease duration and greater disease severity, respectively. Our findings demonstrate dysfunctions of the limbic system in ALS patients at early stages of the disease, and extend our knowledge about the interplay between emotional brain areas and the regions traditionally implicated in motor control.

Ataxin-1 and ataxin-2 intermediate-length PolyQ expansions in amyotrophic lateral sclerosis.

OBJECTIVE: Recent evidence suggests that intermediate-length polyglutamine (PolyQ) expansions in the ataxin-2 (ATXN-2) gene are a risk factor for amyotrophic lateral sclerosis (ALS). This work was undertaken with the aim to investigate the frequency of ataxin-1 (ATXN-1) and ATXN-2 PolyQ expansions in a cohort of patients with sporadic ALS (sALS) and patients with familial ALS (fALS) from southern Italy. METHODS: We assessed the PolyQ lengths of ATXN-1 and ATXN-2 in 405 patients with sALS, 13 patients with fALS, and 296 unrelated controls without history of neurodegenerative disorders. RESULTS: We found significantly higher intermediate PolyQ expansions ≥ 32 for ATXN-1 alleles and ≥ 28 for ATXN-2 alleles in the sALS cohort (ATXN-1: ALS, 7.07% vs controls, 2.38%; p = 0.0001; ATXN-2: ALS, 2.72% vs controls, 0.5%; p = 0.001). ATXN-1 CAT and ATXN-2 CAA interruptions were detected in patients with ALS only. Age at onset, site of onset, and sex were not significantly related to the ATXN-1 or ATXN-2 PolyQ repeat length expansions. CONCLUSIONS: Both ATXN-1 and ATXN-2 PolyQ intermediate expansions are independently associated with an increased risk for ALS.