Social cognition in Parkinson's disease and functional movement disorders.

INTRODUCTION: Functional movement disorders (FMD) can overlap with Parkinson's disease (PD), and distinguishing between the two clinical conditions can be complex. Framing social cognition (theory of mind) (TOM) disorder, attention deficit, and psychodynamic features of FMD and PD may improve diagnosis. METHODS: Subjects with FMD and PD and healthy controls (HC) were administered tasks assessing TOM abilities and attention. The psychodynamic hypothesis of conversion disorder was explored by a questionnaire assessing dissociative symptoms. A comprehensive battery of neuropsychological tasks was also administered to FMD and PD. RESULTS: Although both FMD and PD scored lower than HC on all TOM tests, significant correlations between TOM and neuropsychological tasks were found only in PD but not in FMD. Only PD showed a reduction in attentional control. Dissociative symptoms occurred only in FMD. DISCUSSION: Cognitive-affective disturbances are real in FMD, whereas they are largely dependent on cognitive impairment in PD. Attentional control is preserved in FMD compared to PD, consistent with the hypothesis that overload of voluntary attentional orientation may be at the basis of the onset of functional motor symptoms. On a psychodynamic level, the confirmation of dissociative symptoms in FMD supports the conversion disorder hypothesis. CONCLUSION: FMD and PD can be distinguished on an affective and cognitive level. At the same time, however, the objective difficulty often encountered in distinguishing between the two pathologies draws attention to how blurred the boundary between 'organic' and 'functional' can be.

Beyond the CAG triplet number: exploring potential predictors of delayed age of onset in Huntington's disease.

OBJECTIVE: Huntington's disease (HD) is a genetic neurodegenerative disease characterized by cognitive, motor, and psychiatric dysfunction. It is caused by an expansion of the trinucleotide repeat sequence cytosine-adenine-guanine (CAG) in the Huntingtin gene on chromosome 4. Onset typically occurs in the fourth or fifth decade, ranging from childhood to late adulthood. The CAG triplet number is generally inversely proportional to the age of onset (AOO), but the repeat number only accounts for ∼70% of the variability in AOO. Several studies demonstrated the impact of genetic modifiers on age of disease onset. In addition to genetics, we also explored the demographic, anamnestic, and socio-environmental factors that can affect AOO, to help us understand the non-genetic variability of age of onset in HD. METHODS: We analyzed the retrospective data of the ENROLL-HD global registry study, particularly focusing on the continuum of ages, to include sociodemographic, genetic, and anamnestic psychobehavioral variables in a multivariate regression model aimed at identifying the potential predictors of age of motor onset (n = 5053). We ran the same regression model in the sample of subjects who had the same number of triplets (41 CAG, n = 593) and in the sample whose family history was absent/unknown (n = 630). RESULTS: Patients with delayed onset more frequently have unknown/missing family history, are married or widowed, live in larger urbanized contexts and have a lower educational level. Individuals with earlier onset more frequently develop psychobehavioral symptoms. CONCLUSIONS: In the past, the HD gene was considered the epitome of genetic determinism. Our results are consistent with recent evidence that other factors might modulate its impact. These findings allow characterizing the determinants of AOO beyond the CAG expansions and provide valuable information for stratifying patients for future clinical trial designs.

Clinical and genetic characteristics of late-onset Huntington's disease in a large European cohort.

BACKGROUND AND PURPOSE: Huntington's disease (HD) is an autosomal dominant condition caused by CAG-triplet repeat expansions. CAG-triplet repeat expansion is inversely correlated with age of onset in HD and largely determines the clinical features. The aim of this study was to examine the phenotypic and genotypic correlates of late-onset HD (LoHD) and to determine whether LoHD is a more benign expression of HD. METHODS: This was a retrospective observational study of 5053 White European HD patients from the ENROLL-HD database. Sociodemographic, genetic and phenotypic variables at baseline evaluation of subjects with LoHD, common-onset HD (CoHD) and young-onset HD (YoHD) were compared. LoHD subjects were compared with healthy subjects (HS) aged ≥60 years. Differences between the CoHD and LoHD groups were also explored in subjects with 41 CAG triplets, a repeat number in the lower pathological expansion range associated with wide variability in age at onset. RESULTS: Late-onset HD presented predominantly as motor-onset disease, with a lower prevalence of both psychiatric history and current symptomatology. Absent/unknown HD family history was significantly more common in the LoHD group (31.2%) than in the other groups. The LoHD group had more severe motor and cognitive deficits than the HS group. Subjects with LoHD and CoHD with 41 triplets in the larger allele were comparable with regard to cognitive impairment, but those with LoHD had more severe motor disorders, less problematic behaviors and more often an unknown HD family history. CONCLUSIONS: It is likely that cognitive disorders and motor symptoms of LoHD are at least partly age-related and not a direct expression of the disease. In addition to CAG-triplet repeat expansion, future studies should investigate the role of other genetic and environmental factors in determining age of onset.

An Italian Neurology Outpatient Clinic Facing SARS-CoV-2 Pandemic: Data From 2,167 Patients.

Objective: Neurological sequelae of SARS-CoV-2 infection have already been reported, but there is insufficient data about the impact of the pandemic on the management of the patients with chronic neurological diseases. We aim to analyze the effect of COVID-19 pandemic and social restriction rules on these fragile patients. Methods: Patients with chronic neurologic diseases routinely followed at the outpatient clinic of Gemelli University Hospital, Rome, were assessed for symptoms suggestive of SARS-CoV-2 infection in the pandemic period, consequences of social restrictions, and neurological disease features, concomitant medical conditions, current medical and disease-specific treatments. Data source: a dedicated telephone survey designed to encompass questions on COVID-19 symptoms and on pandemic effects in chronic neurologic conditions. Results: Overall, 2,167 individuals were analyzed: 63 patients reported contact with COVID-19 positive cases, 41 performed the swab, and 2 symptomatic patients tested positive for COVID-19 (0.09%). One hundred fifty-eight individuals (7%) needed urgent neurological care, deferred due to the pandemic; 641 patients (30%) suspended hospital treatments, physiotherapy or other support interventions; 405 individuals (19%) reported a subjective worsening of neurological symptoms. Conclusions: In our population, the presence of neurological chronic diseases did not increase the prevalence of COVID-19 infection. Nevertheless, the burden of neurological disorders has been worsened by the lockdown.

The long-term effect of tetrabenazine in the management of Huntington disease.

OBJECTIVES: To enhance the knowledge on the long-term efficacy and safety of tetrabenazine (TBZ) in managing chorea. METHODS: We analyzed 68 Huntington disease patients (mean disease duration, 55.8 +/- 34.7 months) who had been treated with TBZ for a mean period of 34.4 +/- 25.2 months (median, 34 months; mode, 48 months; range, 3-104 months). We measured the variation from pretreatment of the motor score of Unified Huntington's Disease Rating Scale at the first follow-up visit and at the latest. RESULTS: Mean Unified Huntington's Disease Rating Scale-chorea underscore at the time of the pretreatment visit was 10.4 +/- 4.1 (range, 0-28). At the first follow-up, 9.7 +/- 7.8 months after the prescription of TBZ (mean dose, 35.3 +/- 14.7 mg), mean score of chorea was 8.2 +/- 4.1 (-21% compared with baseline), whereas at the latest follow-up visit (mean dose, 57.5 +/- 14.7 mg), it was 9.5 +/- 5.0 (9%). During the follow-up, the clinical benefit persisted, but the magnitude was reduced despite a progressive increase of the doses (up to 60%). Motor improvement was not influenced by sex, or doses or duration of therapy; age at onset was the only predictor of a good outcome. Five patients (7%) did not gain any improvement, and TBZ was discontinued. There were 2 withdrawals because of side effects; 34 patients reported at least 1 side effect. CONCLUSIONS: Tetrabenazine was well tolerated and produced long-term improvement of motor symptoms in Huntington disease patients, although a slight reduction of benefit occurred during the course of treatment.

Effects of an intensive rehabilitation programme on patients with Huntington's disease: a pilot study.

OBJECTIVE: To investigate the effects of an intensive, inpatient rehabilitation programme on individuals affected by Huntington's disease. DESIGN: A pilot study. Within-subjects design. SETTING: Inpatient rehabilitation home of the Italian welfare system. SUBJECTS: Forty patients, early and middle stage of the disease, were recruited to an intensive, inpatient rehabilitation protocol. INTERVENTIONS: The treatment programme included respiratory exercises and speech therapy, physical and occupational therapy and cognitive rehabilitation exercises. The programme involved three-week admission periods of intensive treatment that could be repeated three times a year. MAIN MEASURES: A standard clinical assessment was performed at the beginning of each admission using the Zung Depression Scale, Mini-Mental State Examination (MMSE), Barthel Index, Tinetti Scale and Physical Performance Test (PPT). Tinetti and PPT were also used at the end of each admission to assess the outcomes in terms of motor and functional performance. RESULTS: Each three-week period of treatment resulted in highly significant (P < 0.001) improvements of motor performance and daily life activities. The average increase was 4.7 for Tinetti and 5.21 for PPT scores. No carry-over effect from one admission to the next was apparent but at the same time, no motor decline was detected over two years, indicating that patients maintained a constant level of functional, cognitive as well as motor performance. CONCLUSIONS: Intensive rehabilitation treatments may positively influence the maintenance of functional and motor performance in patients with Huntington's disease.