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.

Clinical and MRI characterization of apraxic syndrome in corticobasal degeneration: A single-case study.

Objective: To identify the cortical and subcortical distribution of atrophy and the disorganization of white matter bundles underlying the apraxic disorders in a patient with corticobasal degeneration (CBD). Method: Patient underwent appropriate neuropsychological tasks aimed at identifying the nature of the apraxic disorder and morphometric structural MRI with whole-brain voxel-wise analysis. Results: Progressive limbkinetic apraxia (LKA) with onset in the right upper limb with subsequent extension to the limbs, trunk, orofacial district, and eye movements was documented, associated with element of ideomotor apraxia (IMA). The MRI study showed grey matter atrophy extending to much of the frontal cortex bilaterally, including the precentral cortex, and into the inferior parietal regions. Caudate and putamen were involved on the left. Significant clusters of white matter atrophy were found in the bilateral superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and corpus callosum (CC). Sensory evoked potentials (SEPs) and motor evoked potentials (MEPs) were normal. Conclusion: Previous observations in CBD indicate lack of inhibitory control from the sensory to the primary motor cortex with dysfunctional frontoparietal and cortico-motoneuron projections. Our neuroimaging data are partially consistent with these observations suggesting that the apraxic disorder in our patient might be produced by the disconnection of the primary motor cortex from the parietal areas that prevents selection and control of muscle movements, in the presence of preserved cortico-motoneuron as demonstrated by normal PEM. Apraxic disorders in CBD are high-level deficits of movement control that spare the motoneuron.

Functional Movement Disorders during COVID-19: Psychological Distress, Affective Temperament and Emotional Dysregulation.

Background and objective: Functional movement disorders (FMD) represent a spectrum of psychosomatic symptoms particularly sensitive to stress. The COVID-19 pandemic has increased psychological distress worldwide and may have worsened FMD. The study aimed to confirm this hypothesis and to test whether in FMD there is a relationship between affective temperament, emotional dysregulation and psychological distress due to the pandemic. Methods: We recruited individuals with FMD, diagnosed them according to validated criteria and matched them with healthy controls (HC). Psychological distress and temperament were obtained using the Kessler-10 and the Temperament Evaluation of Memphis, Pisa and San Diego Autoquestionnaire, respectively. We used bootstrapped mediation analysis to test the mediator role of emotional dysregulation on the effect of temperament on psychological distress. Results: The sample consisted of 96 individuals. During the pandemic, 31.3% of the patients reported the need for urgent neurological care, and 40.6% reported a subjective worsening neurological condition. Patients with FMD presented with more psychological distress during the COVID-19 pandemic (F = 30.15, df = 1, p ≤ 0.001) than HC. They also reported more emotional dysregulation (F = 15.80, df = 1, p ≤ 0.001) and more cyclothymic traits (F = 14.84, df = 1, p ≤ 0.001). Cyclothymic temperament showed an indirect effect on COVID-19-related psychological distress, mediated by deficits in emotion regulation mechanisms (Bootstrapped LLCI = 0.41, ULCI = 2.41). Conclusion: Our results suggest that emotional dysregulation may represent a dimension mediating cyclotimic temperament response to the stressful effect of the pandemic and provide insight for developing intervention policies.

Efficacy and safety of long-term botulinum toxin treatment for acquired cervical dystonia: a 25-year follow-up.

Botulinum toxin A (BoNT/A) is the first-line treatment for idiopathic cervical dystonia (ICD) and is widely used in the clinical setting. To date, scanty data are available on the effectiveness of BoNT in treating acquired cervical dystonia (ACD). Here we present a long-term follow-up of ACD patients treated with BoNT/A that focused on safety and efficacy. The study included subjects who had received at least six treatments of three commercially available BoNT/A drugs [abobotulinumtoxinA (A/Abo), incobotulinumtoxinA (A/Inco) and onabotulinumtoxinA (A/Ona)]. Safety and efficacy were assessed based on patients' self-reports regarding adverse effects (AE), duration of improvement of dystonia and/or pain relief. Global clinical improvement was measured on a six-point scale. 23 patients with ACD were administered 739 treatments (A/Abo in 235, A/Inco in 72, A/Ona in 432) with a mean number of treatments of 31 ± 20 (range 6-76) and duration of 10 ± 6 weeks (range 2-25). The mean dose was 737 ± 292 U for A/Abo, 138 ± 108 U for A/Inco and 158 ± 80 U for A/Ona. The average benefit duration was 89 ± 26 (A/Abo), 88 ± 30 days (A/Inco), and 99 ± 55 days (A/Ona) (p = 0.011); global clinical improvement for all sessions was 4 ± 1. ANOVA one-way analysis indicated that A/Ona had the best profile in terms of duration (p < 0.05), whereas A/Abo had the best pain relief effect (p = 0.002). Side effects were reported in 9% of treatments (67/739), with ten treatments (1%) complicated by two side effects. Most side effects were rated mild to moderate; severe side effects occurred following three treatments with the three different BoNT; two required medical intervention. No allergic reactions were reported. Even after 25 years of repeated treatments, all serotypes of BoNT demonstrate positive effects in treating ACD with long-lasting efficacy and safety.

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.

STN-DBS does not increase the risk of sialorrhea in patients with advanced Parkinson's disease.

The aims of this study were to assess the incidence rate and risk factors for sialorrhea in the long-term follow-up in a cohort of 132 patients with advanced Parkinson's disease [88 with deep brain stimulation (DBS) and 44 on medical treatment]. The incidence rate of sialorrhea did not differ between the two groups; male sex, Hoehn and Yahr stage and dysphagia resulted risk factors for sialorrhea. These findings indicate that DBS does not increase the risk of developing sialorrhea.

Impaired processing of conspecifics in Parkinson's disease.

Experimental evidence indicates that the inferior frontal gyrus (IFG) processes emotional/affective features crucial to elaborate knowledge about social groups and that knowledge of social concepts is stored in the anterior temporal lobe (ATL).We investigated whether knowledge about social groups is impaired in Parkinson's disease (PD), in which dysfunctional connectivity between IFG and ATL has been demonstrated.PD patients (N = 20) and healthy controls (HC, N = 16) were given a lexical decision task in a semantic priming paradigm: the prime-targets included 144 words and 144 pseudowords, each preceded by three types of prime ("animals," "things," "persons"). Out of these 288 prime-targets, forty-eight were congruent (same category) and 96 incongruent (different category). Out of 48 congruent prime-targets, 24 denoted social items and 24 nonsocial items. Thus, four types of trials were obtained: congruent social; congruent nonsocial; incongruent social; incongruent nonsocial.Congruent target-words were recognized better than incongruent target-words by all groups. The semantic priming effect was preserved in PD; however, accuracy was significantly lower in PD than in HC in social items. No difference emerged between the two groups in nonsocial items.Impaired processing of words denoting social groups in PD may be due to impairment in accessing the affective/emotional features that characterize conceptual knowledge of social groups, for the functional disconnection between the IFG and the ATL.

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.

Theory of mind: A clue for the interpretation of functional movement disorders.

OBJECTIVES: Functional movement disorders (FMD) refer to a heterogeneous group of manifestations incongruent with known neurological diseases. Functional neuroimaging studies in FMD indicate the overlap between cerebral regions in which abnormal activation occurs and those considered crucial for theory of mind (ToM), the ability to attribute mental states. The aim of this study was to explore whether FMD might be related to ToM disorders to the extent that they reduce the ability to make inferences about the mental states underlying motor behaviour during social interaction. MATERIALS & METHODS: Eighteen subjects with FMD and 28 matched healthy controls (HC) were given a ToM battery. The severity of FMD was rated by the Simplified-FMD Rating Scale (S-FMDRS). Dissociative symptoms were evaluated by the Dissociative Experiences Scale (DES-II). RESULTS: FMD scored worse than the HC in most ToM tasks: second-order False Beliefs (p = .005), Faux-Pas Recognition Test (p < .001) and Reading the Mind in the Eyes Test (p = .020); control questions elicited normal scores. The DES-II indicated dissociative-borderline psychopathology and negatively correlated with accuracy on the second-order False Belief (Spearman's rho = -.444; p = .032); the positive correlation between DES-II and severity of motor symptoms (S-FMDRS) approached significance (Spearman's rho test = .392; p = .054). ToM disorders were not correlated with S-FMDRS, due to the typical variability in FMD over time with regard to the severity of symptoms and the district of body involved. CONCLUSIONS: Our results are consistent with the hypothesis that FMD are related to ToM deficits, and future studies are needed to define the specific nature of this relationship.

Writing errors in primary progressive aphasia.

Peripheral errors in writing, that is errors produced download the spelling, have been occasionally described in primary progressive aphasia (PPA), but the possibility that these errors might be a marker of parkinsonism associated to some subtypes of PPA has not been explored. We investigated whether errors of peripheral nature characterize the writing disorder in PPA when associated with parkinsonian signs (PSs). Subgroups of PPA without PSs and with PSs were studied. The proportion of the central and peripheral errors in writing words and pseudowords was calculated in each group. In writing words, central errors significantly exceeded peripheral errors in subgroups without PSs. The higher the number of peripheral errors, the higher the probability of presenting PSs. No relation emerged between any error and the Unified Parkinson's Disease Rating Scale, but both types of errors correlated with measures of cognitive ability. Peripheral errors emerge when PSs are associated with PPA and may be linked to a decay of the cognitive control on movement, possibly involving the right hemisphere. Peripheral errors have clinical relevance in PPA, to the extent that they may assume the significance of a marker of specific subtypes and can help to outline the specific clinical picture of individual patients.

What about the caregiver? A journey into Parkinson's disease following the burden tracks.

OBJECTIVES: To investigate caregivers and patients characteristics related to different dimensions of burden in Parkinson's disease (PD). METHODS: 55 pairs of PD patients and caregivers were recruited. The burden was evaluated with the Caregiver Burden Inventory (CBI). Multivariate analysis was applied to evaluate the impact of caregivers' and patients' characteristics on the varying aspects of burden. RESULTS: ADL score was the dominant predictor for the total score and all dimensions of CBI, except for the social burden, which is strongly predicted by the motor severity of PD. As one can easily imagine, the Total CBI decreases as the ADL score increases. DISCUSSION: An increased appreciation for characteristics of caregiver burden is a fundamental aspect of the patient's global evaluation. Clinicians may need to directly probe for these factors in the caregiver as they may not be elicited routinely.

Should face masks be worn to contain the spread of COVID-19 in the postlockdown phase?

BACKGROUND: In East Asia, face masks are commonly worn to reduce viral spread. In Euope and North America, however, their use has been stigmatised for a long time, although this view has radically changed during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Notwithstanding this, it is still unclear whether face masks worn by COVID-19 carriers may indeed prevent viral transmission and environmental contamination. The objective of this study was to evaluate the effectiveness of surgical face masks in filtering SARS-CoV-2. METHODS: Four male patients with COVID-19 were recruited for the study. Two patients wore a surgical mask for 5 h, while two others did not. The spread of the virus in the environment was evaluated through the approved Allplex 2019-nCoV assay. RESULTS: In the room with the two patients without surgical masks, the swab performed on the headboard and sides of the beds was positive for SARS-CoV-2 contamination. In the other room, where two patients were wearing surgical masks, all of the swabs obtained after 5 h tested negative. CONCLUSIONS: The results of the current study add to the growing body of literature supporting the use of face masks as a measure to contain the spread of SARS-CoV-2 by retaining potentially contagious droplets that can infect other people and/or contaminate surfaces. Based on the current evidence, face masks should therefore be considered a useful and low-cost device in addition to social distancing and hand hygiene during the postlockdown phase.

Predictive Factors for a New Positive Nasopharyngeal Swab Among Patients Recovered From COVID-19.

INTRODUCTION: As an emerging infectious disease, the clinical and virologic course of COVID-19 requires better investigation. The aim of this study is to identify the potential risk factors associated with persistent positive nasopharyngeal swab real-time reverse transcription‒polymerase chain reaction tests in a large sample of patients who recovered from COVID-19. METHODS: After the acute phase of SARS-CoV-2 epidemic infection, the Fondazione Policlinico A. Gemelli IRCSS of Rome established a post-acute care service for patients discharged from the hospital and recovered from COVID-19. Between April 21 and May 21, 2020, a total of 137 individuals who officially recovered from COVID-19 were enrolled in this study. All patients were tested for the SARS-CoV-2 virus with nucleic acid RT-PCR tests. Analysis was conducted in June 2020. RESULTS: Of the 131 patients who repeated the nasopharyngeal swab, 22 patients (16.7%) tested positive again. Some symptoms such as fatigue (51%), dyspnea (44%), and coughing (17%) were still present in a significant percentage of the patients, with no difference between patients with a negative test and those who tested positive. The likelihood of testing positive for SARS-CoV-2 infection was significantly higher among participants with persistent sore throat (prevalence ratio=6.50, 95% CI=1.38, 30.6) and symptoms of rhinitis (prevalence ratio=3.72, 95% CI=1.10, 12.5). CONCLUSIONS: This study is the first to provide a given rate of patients (16.7%) who test positive on RT-PCR test for SARS-CoV-2 nucleic acid after recovering from COVID-19. These findings suggest that a significant proportion of patients who have recovered from COVID-19 still could be potential carriers of the virus. In particular, if patients continue to have symptoms related to COVID-19, such as sore throat and rhinitis, it is reasonable to be cautious by avoiding close contact, wearing a face mask, and possibly repeating a nasopharyngeal swab.

The Geriatrician: The Frontline Specialist in the Treatment of COVID-19 Patients.

On February 20, 2020, a man living in the north of Italy was admitted to the emergency room with an atypical pneumonia that later proved to be COVID-19. This was the trigger of one of the most serious clusters of COVID-19 in the world, outside of China. Despite aggressive restraint and inhibition efforts, COVID-19 continues to increase, and the total number of infected patients in Italy is growing daily. After 6 weeks, the total number of patients reached 128,948 cases (April 5, 2020), with the higher case-fatality rate (15,887 deaths) dominated by old and very old patients. This sudden health emergency severely challenged the Italian Health System, in particular acute care hospitals and intensive care units. In 1 hospital, geriatric observation units were created, the experience of which can be extremely useful for European countries, the United States, and all countries that in the coming days will face a similar situation.

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 "develOpment of metabolic and functional markers of Dementia IN Older people" (ODINO) Study: Rationale, Design and Methods.

Mild cognitive impairment (MCI), also termed mild neurocognitive disorder, includes a heterogeneous group of conditions characterized by declines in one or more cognitive domains greater than that expected during "normal" aging but not severe enough to impair functional abilities. MCI has been associated with an increased risk of developing dementia and even considered an early stage of it. Therefore, noninvasively accessible biomarkers of MCI are highly sought after for early identification of the condition. Systemic inflammation, metabolic perturbations, and declining physical performance have been described in people with MCI. However, whether biological and functional parameters differ across MCI neuropsychological subtypes is presently debated. Likewise, the predictive value of existing biomarkers toward MCI conversion into dementia is unclear. The "develOpment of metabolic and functional markers of Dementia IN Older people" (ODINO) study was conceived as a multi-dimensional investigation in which multi-marker discovery will be coupled with innovative statistical approaches to characterize patterns of systemic inflammation, metabolic perturbations, and physical performance in older adults with MCI. The ultimate aim of ODINO is to identify potential biomarkers specific for MCI subtypes and predictive of MCI conversion into Alzheimer's disease or other forms of dementia over a three-year follow-up. Here, we describe the rationale, design, and methods of ODINO.