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Sant'Ambrogio di Torino, Italy

Adenzato M.,University of Turin | Adenzato M.,Neuroscience Institute of Turin | Poletti M.,Child Neuropsychiatry Service
Clinical Neuropsychiatry | Year: 2013

There is fast-growing interest in the study of Theory of Mind (ToM) abilities in neurodegenerative diseases. In a previous work, we reviewed all the evidence of altered ToM abilities in patients with neurodegenerative diseases in the literature published until then. In the present paper, we extend that analysis by integrating our conclusions with the most updated evidence that is now available. This new analysis allows for a clarification of some pending questions, such as at which stage ToM deficits begin to appear in dementing disorders, what is the relationship between executive functioning and ToM abilities in patients with Parkinson's disease, and how can ToM tasks help clinicians to discriminate between different neurodegenerative disorders. Furthermore, we now provide the first review of all articles on ToM abilities in patients with multiple sclerosis. The data discussed here strongly suggest overall that a neuropsychological assessment of patients with neurodegenerative diseases should routinely include an accurate investigation of ToM abilities. Increasing evidence has shown that different ToM tasks may help clinicians in the diagnostic process and caregivers in understanding the behavioural problems that are often shown by their suffering relatives. © 2013 Giovanni Fioriti Editore s.r.l.

Poletti M.,Child Neuropsychiatry Service | Adenzato M.,University of Turin | Adenzato M.,Neuroscience Institute of Turin
Clinical Neuropsychiatry | Year: 2013

The presence of Theory of Mind (ToM) deficits in autistic children clearly shows that alterations of neurodevelopment may affect the normal development of ToM abilities. From this perspective, other clinical conditions of childhood and adolescence with less-severe alterations of neurodevelopment in comparison to autism could also be associated with ToM impairment. This hypothesis has been scarcely investigated, considering that apart from studies on autism and other pervasive developmental disorders, empirical research on ToM impairment is mostly focused on adult clinical populations. This paper reviews empirical studies on ToM abilities in non-autistic developmental psychiatric disorders. Preliminary findings derived from this weak empirical evidence suggest that in comparison to typically developing subjects, the following may have altered ToM: (1) patients with disorders with typical onset in childhood or adolescence, such as attention deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder, and (2) patients with psychiatric disorders typical of adult subjects but with childhood or adolescent onset, such as psychotic disorders, mood disorders, and personality disorders. Findings are discussed, and limitations of these studies as regards sample selection, controls, settings, and ToM assessment are identified. Directions for further studies on this topic are suggested. © 2013.

Cavallo M.,University of Turin | Cavallo M.,University of Piemonte Orientale | Adenzato M.,University of Turin | Adenzato M.,Neuroscience Institute of Turin | And 4 more authors.
PLoS ONE | Year: 2011

The present study aims at clarifying the nature of the Theory of Mind (ToM) deficits associated with Amyotrophic Lateral Sclerosis (ALS). ToM is the ability to attribute mental states such as intentions and beliefs to others in order to understand and predict their behaviour and to behave accordingly. Several neuroimaging studies reported the prefrontal cortices as the brain region underlying a key ToM ability, i.e. the comprehension of social intentions. Dysfunction of the prefrontal cortices in patients with ALS has been indicated by a range of neuroimaging studies. The frontal syndrome that appears to characterize up to 50% of ALS has been noted to be similar to the profile that characterizes patients with frontotemporal dementia (FTD), a neurodegenerative condition characterised by ToM deficits. In the present paper, we hypothesize that the performance of patients with ALS is significantly worse than healthy controls' performance on tasks requiring the comprehension of social contexts, whereas patients' performance is comparable to healthy controls' performance on tasks not requiring the comprehension of social contexts. To this end, we tested 15 patients with ALS with an experimental protocol that distinguishes between private (non-social) intentions and social intentions. The pattern of results followed the experimental hypothesis: the performance of patients with ALS and healthy controls significantly differed on the comprehension of social context only, with an impairment in patients with ALS. Single case analysis confirmed the findings at an individual level. The present study is the first which has examined and compared the understanding of social and non-social contexts in patients with ALS and shown a specific and selective deficit in the former only. The current findings further support the notion of a continuum of cognitive dysfunction ranging from ALS to FTD, with parallel cognitive profiles in both disorders. © 2011 Cavallo et al.

Chio A.,University of Turin | Chio A.,Neuroscience Institute of Turin | Canosa A.,University of Turin | Gallo S.,University of Turin | And 5 more authors.
Neurology | Year: 2011

Objective: To assess the effect of eligibility criteria in amyotrophic lateral sclerosis (ALS) clinical trials on the representativeness of the enrolled population. Methods: Patients enrolled in 8 placebo-controlled clinical trials in our ALS center from 2003 to 2008 were compared 1) to the patients included a prospective epidemiologic register (Piemonte and Valle d'Aosta register for ALS, PARALS) in the same period and 2) the subset of PARALS patients who met the usual criteria for inclusion in clinical trials (PARALS-ct) (definite, probable, probable laboratory-supported ALS; age between 18 and 75 years; disease duration<36 months; vital capacity at diagnosis≥70%; score≥3 at the items swallowing and respiratory insufficiency at the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised scale; riluzole therapy). Results: A total of 164 patients were enrolled in 8 different clinical trials. The PARALS cohort included 813 patients, of whom 539 (66.3%) met the entry criteria for clinical trials. Patients enrolled in clinical trials were different from both epidemiologic cohorts, since they were younger, had a longer diagnostic delay, and were more likely to have a spinal onset, and to be men. Tracheostomy-free survival was significantly longer in the group of patients enrolled in clinical trials (median survival time, trial patients, 3.9 years [95% confidence interval (CI) 3.4-4.4]; PARALS, 2.6 [2.4-2.8]; PARALS-ct, 2.9 [2.7-3.1]). Conclusions: Patients enrolled in clinical trials do not satisfactorily represent the ALS population; consequently, the findings of ALS trials lack of external validity (generalizability). Efforts should be made to improve patients' recruitment in trials, particularly enrolling incident rather than prevalent cases. © 2011 by AAN Enterprises, Inc.

Pagani M.,CNR Institute of Neuroscience | Pagani M.,Karolinska University Hospital | Chio A.,University of Turin | Chio A.,Neuroscience Institute of Turin | And 11 more authors.
Neurology | Year: 2014

Objective: We investigated a large sample of patients with amyotrophic lateral sclerosis (ALS) at rest in order to assess the value of 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) PET as a biomarker to discriminate patients from controls. Methods: A total of 195 patients with ALS and 40 controls underwent brain 18F-FDG-PET, most within 5 months of diagnosis. Spinal and bulbar subgroups of ALS were also investigated. Twenty-five bilateral cortical and subcortical volumes of interest and cerebellum were taken into account, and 18F-FDG uptakes were individually normalized by whole-brain values. Group analyses investigated the ALS-related metabolic changes. Discriminant analysis investigating sensitivity and specificity was performed using the 51 volumes of interest as well as age and sex. Metabolic connectivity was explored by voxel-wise interregional correlation analysis. Results: Hypometabolismwas found in frontal, motor, and occipital cortex and hypermetabolismin midbrain, temporal pole, and hippocampus in patients with ALS compared to controls. A similar metabolic pattern was also found in the 2 subgroups. Discriminant analysis showed a sensitivity of 95% and a specificity of 83% in separating patients from controls. Connectivity analysis found a highly significant positive correlation between midbrain and white matter in corticospinal tracts in patients with ALS. Conclusions: 18F-FDG distribution changes in ALS showed a clear pattern of hypometabolism in frontal and occipital cortex and hypermetabolism in midbrain. The latter might be interpreted as the neurobiological correlate of diffuse subcortical gliosis. Discriminant analysis resulted in high sensitivity and specificity in differentiating patients with ALS from controls. Once validated by diseased-control studies, the present methodology might represent a potentially useful biomarker for ALS diagnosis. Classificaton of evidence: This study provides Class III evidence that 18F-FDG-PET accurately distinguishes patients with ALS from normal controls (sensitivity 95.4%, specificity 82.5%). © 2014 American Academy of Neurology.

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