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Huntington’s disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by involuntary choreatic movements, cognitive, behavioral, and psychiatric disturbances. Most HD suffer from dysphagia and aspiration pneumonia is the leading cause of death. However, little is known about dysphagia management in HD. A revision of the literature was conducted to depict the state of the art on the assessment and treatment of dysphagia in HD. Literature search of the last 10 years was performed using PubMed and EMBASE. Twenty-four studies were included: 16 cross-sectional studies, 2 case reports, 2 case series, 2 open-label trials, 1 pre-post study, and 1 randomized controlled trial. Based on the studies retrieved, dysphagia should be assessed from the early stage of the disease, especially when specific clinical markers occur. Timing for dysphagia re-assessment should be based on the recommendation of the swallowing experts on the individual case. Instrumental assessment of swallowing by videofluoroscopy or videoendoscopy is feasible and recommended to diagnose dysphagia in patients with HD. Clinical assessment tools and patient-reported outcome measures may be used to complete the swallowing examination, but not to replace instrumental assessment. The impact of pharmacological and rehabilitative treatments on dysphagia in HD has been little studied in literature. While the effect of tetrabenazine on swallowing is still controversial, compensatory strategies seem to be applicable and efficacious. To date, there are no well-proven rehabilitative strategies to improve swallowing function in patients with HD. The topic of dysphagia in HD remains poorly studied compared with its clinical relevance.

This study aimed at assessing the clinimetrics of the Montreal Cognitive Assessment (MoCA) in an Italian cohort of patients with adult-onset idiopathic focal dystonia (AOIFD). N  = 86 AOIFD patients and N  = 92 healthy controls (HCs) were administered the MoCA. Patients further underwent the Trail-Making Test (TMT) and Babcock Memory Test (BMT), being also screened via the Beck Depression Inventory-II (BDI-II) and the Dimensional Apathy Scale (DAS). Factorial structure and internal consistency were assessed. Construct validity was tested against TMT, BMT, BDI-II and DAS scores, whilst diagnostics against the co-occurrence of a defective performance on at least one TMT measure and on the BMT. Case–control discrimination was examined. The association between MoCA scores and motor-functional measures was explored. The MoCA was underpinned by a mono-component structure and acceptably reliable at an internal level. It converged towards TMT and BMT scores, as well as with the DAS, whilst diverging from the BDI-II. Its adjusted scores accurately detected cognitive impairment (AUC = .86) at a cut-off of < 17.212. The MoCA discriminated patients from HCs ( p  < .001). Finally, it was unrelated to disease duration and severity, as well as to motor phenotypes. The Italian MoCA is a valid, diagnostically sound and feasible cognitive screener in AOIFD patients.

Mutations in the gene cause early-onset Parkinson's disease (PD). Despite the high proportion of still missing phenotyping data in the literature devoted to early-onset PD, studies suggest that, as compared with late-onset PD, patients show dystonia at onset and extremely dose-sensitive levodopa-induced dyskinesia (LID). What pathophysiological mechanisms underpin such early and atypical dyskinesia in patients with mutations? Though the precise mechanisms underlying dystonia and LID are still unclear, evidence suggests that hyperkinetic disorders in PD are a behavioral expression of maladaptive functional and morphological changes at corticostriatal synapses induced by long-term dopamine (DA) depletion. However, since the dyskinesia in patients can also be present at onset, other mechanisms beside the well-established DA depletion may play a role in the development of dyskinesia in these patients. Because cortical and striatal neurons express parkin protein, and parkin modulates the function of ionotropic glutamatergic receptors (iGluRs), an intriguing explanation may rest on the potential role of parkin in directly controlling the glutamatergic corticostriatal synapse transmission. We discuss the novel theory that loss of parkin function can dysregulate transmission at the corticostriatal synapses where they cause early maladaptive changes that co-occur with the changes stemming from DA loss. This hypothesis suggests an early striatal synaptopathy; it could lay the groundwork for pharmacological treatment of dyskinesias and LID in patients with mutations.

Huntington disease (HD) is a progressive neurodegenerative monogenic disorder caused by expansion of a polyglutamine stretch in the huntingtin (Htt) protein. Mutant huntingtin triggers neural dysfunction and death, mainly in the corpus striatum and cerebral cortex, resulting in pathognomonic motor symptoms, as well as cognitive and psychiatric decline. Currently, there is no effective treatment for HD. We report that intraventricular infusion of ganglioside GM1 induces phosphorylation of mutant huntingtin at specific serine amino acid residues that attenuate huntingtin toxicity, and restores normal motor function in already symptomatic HD mice. Thus, our studies have identified a potential therapy for HD that targets a posttranslational modification of mutant huntingtin with critical effects on disease pathogenesis.

The ability to simulate alternatives to factual events is called counterfactual thinking (CFT) and it is involved both in emotional and behavioral regulation. CFT deficits have been reported in psychiatric and neurological conditions, possibly contributing to patients' difficulties in modulating behaviors and affections. Thus, acknowledging the presence and possible consequences of CFT impairments might be essential for optimal clinical management. This scoping review aims to summarize the previous evidence about CFT in psychiatric and neurological diseases to determine the extent of the previous research and what has been discovered so far, the variety of clinical conditions considered, the methodologies adopted, and the relevant issues to be addressed by future investigations. PsycInfo, PubMed, Scopus, and Web of Science were searched to identify articles published up to January 2020, written in English and focused on CFT in adults affected by psychiatric or neurological conditions. Twenty-nine studies have been included; most of them focused on psychiatric conditions, a minority considered neurological diseases. The generation of counterfactual thoughts related to a negative real-life or a fictional event and the counterfactual inference test were the most popular tasks adopted. CFT impairments were reported in both psychiatric and neurological conditions, likely associated with a fronto-executive dysfunction. Future research might further explore CFT in those psychiatric and neurological conditions in which CFT difficulties have been preliminary reported. Furthermore, it would be recommendable to extend this investigation to all the clinical conditions possibly at risk of fronto-executive dysfunction. In the end, we speculate that since CFT plays a role in driving everyday behaviors, it might be crucial also when medical decisions are involved; thus, future research might extend the investigation of CFT especially to those populations that implicate complex clinical management.

The presence of executive deficits in patients with Amyotrophic Lateral Sclerosis is well established, even if standardized measures are difficult to obtain due to progressive physical disability of the patients. We present clinical data concerning a newly developed measure of cognitive flexibility, administered by means of Eye-Tracking (ET) technology in order to bypass verbal-motor limitations. 21 ALS patients and 21 age-and education-matched healthy subjects participated in an ET-based cognitive assessment, including a newly developed test of cognitive flexibility (Arrows and Colors Cognitive Test-ACCT) and other oculomotor-driven measures of cognitive functions. A standard screening of frontal and working memory abilities and global cognitive efficiency was administered to all subjects, in addition to a psychological self-rated assessment. For ALS patients, a clinical examination was also performed. ACCT successfully discriminated between patients and healthy controls, mainly concerning execution times obtained at different subtests. A qualitative analysis performed on error distributions in patients highlighted a lower prevalence of perseverative errors, with respect to other type of errors. Correlations between ACCT and other ET-based frontal-executive measures were significant and involved different frontal sub-domains. Limited correlations were observed between ACCT and standard 'paper and pencil' cognitive tests. The newly developed ET-based measure of cognitive flexibility could be a useful tool to detect slight frontal impairments in non-demented ALS patients by bypassing verbal-motor limitations through the oculomotor-driven administration. The findings reported in the present study represent the first contribution towards the development of a full verbal-motor free executive test for ALS patients.

Reduced Brain-Derived Neurotrophic Factor (BDNF) levels have been described in a number of patho-physiological conditions, most notably, in Huntington's disease (HD), a progressive neurodegenerative disorder. Since BDNF is also produced in blood, we have undertaken the measurement of its peripheral levels in the attempt to identify a possible link with HD prognosis and/or its progression. Here we evaluated BDNF level in 398 blood samples including 138 controls, 56 preHD, and 204 HD subjects. We found that BDNF protein levels were not reliably different between groups, whether measured in plasma (52 controls, 26 preHD, 105 HD) or serum (39 controls, 5 preHD, 29 HD). Our experience, and a re-analysis of the literature highlighted that intra-group variability and methodological aspects affect this measurement, especially in serum. We also assessed BDNF mRNA levels in blood samples from 47 controls, 25 preHD, and 70 HD subjects, and found no differences among the groups. We concluded that levels of BDNF in human blood were not informative (mRNA levels or plasma protein level) nor reliable (serum protein levels) as HD biomarkers. We also wish to warn the scientific community in interpreting the significance of changes measured in BDNF protein levels in serum from patients suffering from different conditions.