Rest tremor in Parkinson's disease: body distribution and time of appearance

Objective To assess body distribution and timing of appearance of rest tremor in Parkinson's disease. Methods Information was obtained by a computerized database containing historical information collected at the first visit and data collected during the subsequent follow-up visits. Information on rest tremor developed during the follow-up could be therefore obtained by our own observation in a proportion of patients. Results Among 289 patients, rest tremor was reported at disease onset in 65.4% of cases and detected at last follow-up examination in 74.4% of patients. Analysis of patients who did not report rest tremor at disease onset indicated that 26% of such patients (9% in the overall population) manifested rest tremor over the disease course. Rest tremor spread to new sites in 39% of patients who manifested rest tremor at disease onset. Regardless of tremor presentation at disease onset or during the follow-up, upper limb was the most frequent tremor localization. Over the follow-up, rest tremor developed faster in the upper limb than in other body sites. The risk of developing rest tremor during the follow-up was not affected by sex, side of motor symptom onset and site of tremor presentation. However, age of disease onset > 63 years was associated with an increased risk of rest tremor spread. Conclusions This study provides new information about body distribution and timing of rest tremor appearance during the course of early stages of Parkinson's disease that may help clinicians in patients' counselling

Relationship between Temperament, Depression, Anxiety, and Hopelessness in Adolescents: A Structural Equation Model

The purpose of this study was to test the validity of affective temperaments for predicting psychiatric morbidity and suicide risk, using a two-factor model to explain the relationships between temperament, anxiety, depression, and hopelessness. We investigated 210 high school students, 103 males and 107 females, 18-19 years old, who were administered self-report questionnaires to assess temperament (TEMPS-A), depression (BDI-II), anxiety (STAI) and hopelessness (BHS). The final structural model had a good fit with the data, with two factors significantly correlated, the first labeled unstable cyclothymic temperament including Dysthymic/Cyclothymic/Anxious temperament, Irritable temperament and Depression, and the second labeled Demoralization including Anxiety (State/Trait) and Hopelessness. Depression, anxiety and hopelessness are in a complex relationship partly mediated by temperament

Executive functions, impulsivity, and inhibitory control in adolescents: a structural equation model

Background. Adolescence represents a critical period for brain development, addressed by neurodevelopmental models to frontal, subcortical-limbic, and striatal activation, a pattern associated with rise of impulsivity and deficits in inhibitory control. The present study aimed at studying the association between self-report measures of impulsivity and inhibitory control with executive function in adolescents, employing structural equation modeling. Method. Tests were administered to 434 high school students. Acting without thinking was measured through the Barratt Impulsiveness Scale and the Dickman Impulsivity Inventory, reward sensitivity through the Behavioral Activation System, and sensation seeking through the Zuckerman–Kuhlman–Aluja Personality Questionnaire. Inhibitory control was assessed through the Behavioral Inhibition System. The performance at the Wisconsin Card Sorting Task indicated executive function. Three models were specified using Sample Covariance Matrix, and the estimated parameters using Maximum Likelihood. Results. In the final model, impulsivity and inhibitory control predicted executive function, but sensation seeking did not. The fit of the model to data was excellent. Conclusions. The hypothesis that inhibitory control and impulsivity are predictors of executive function was supported. Our results appear informative of the validity of self-report measures to examine the relation between impulsivity traits rather than others to regulatory function of cognition and behavior

Ventricular arrhythmias in young competitive athletes: Prevalence, determinants, and underlying substrate

Whether ventricular arrhythmias (VAs) represent a feature of the adaptive changes of the athlete's heart remains elusive. We aimed to assess the prevalence, determinants, and underlying substrates of VAs in young competitive athletes.Background--Whether ventricular arrhythmias (VAs) represent a feature of the adaptive changes of the athlete's heart remains elusive. We aimed to assess the prevalence, determinants, and underlying substrates of VAs in young competitive athletes. Method and Results--We studied 288 competitive athletes (age range, 16-35 years; median age, 21 years) and 144 sedentary individuals matched for age and sex who underwent 12-lead 24-hour ambulatory electrocardiographic monitoring. VAs were evaluated in terms of number, complexity (ie, couplet, triplet, or nonsustained ventricular tachycardia), exercise inducibility, and morphologic features. Twenty-eight athletes (10%) and 13 sedentary individuals (11%) showed > 10 isolated premature ventricular beats (PVBs) or 651 complex VA (P=0.81). Athletes with > 10 isolated PVBs or 651 complex VA were older (median age, 26 versus 20 years; P=0.008) but did not differ with regard to type of sport, hours of training, and years of activity compared with the remaining athletes. All athletes with > 10 isolated PVBs or 651 complex VA had a normal echocardiographic examination; 17 of them showing > 500 isolated PVBs, exercise-induced PVBs, and/or complex VA underwent additional cardiac magnetic resonance, which demonstrated nonischemic left ventricular late gadolinium enhancement in 3 athletes with right bundle branch block PVBs morphologic features. Conclusions--The prevalence of > 10 isolated PVBs or 651 complex VA at 24-hour ambulatory electrocardiographic monitoring did not differ between young competitive athletes and sedentary individuals and was unrelated to type, intensity, and years of sports practice. An underlying myocardial substrate was uncommon and distinctively associated with right bundle branch block VA morphologic features

Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: The L-carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial

Objectives. This study was performed to evaluate the effects of l-carnitine administration on long-term left ventricular dilation in patients with acute anterior myocardial infarction. Background. Carnitine is a physiologic compound that performs an essential role in myocardial energy production at the mitochondrial level. Myocardial carnitine deprivation occurs during ischemia, acute myocardial infarction and cardiac failure. Experimental studies have suggested that exogenous carnitine administration during these events has a beneficial effect on function. Methods. The l-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial was a randomized, double-blind, placebo-controlled, multicenter trial in which 472 patients with a first acute myocardial infarction and high quality two-dimensional echocardiograms received either placebo (239 patients) or l-carnitine (233 patients) within 24 h of onset of chest pain. Placebo or l-carnitine was given at a dose of 9 g/day intravenously for the first 5 days and then 6 g/day orally for the next 12 months. Left ventricular volumes and ejection fraction were evaluated on admission, at discharge from hospital and at 3, 6 and 12 months after acute myocardial infarction. Results. A significant attenuation of left ventricular dilation in the first year after acute myocardial infarction was observed in patients treated with l-carnitine compared with those receiving placebo. The percent increase in both end-diastolic and endsystolic volumes from admission to 3-, 6- and 12-mouth evaluation was significantly reduced in the l-carnitine group. No significant differences were observed in left ventricular ejection fraction changes over time in the two groups. Although not designed to demonstrate differences in clinical end points, the combined incidence of death and congestive heart failure after discharge was 14 (6%) in the l-carnitine treatment group versus 23 (9.6%) in the placebo group (p = NS). Incidence of ischemic events during follow-up was similar in the two groups of patients. Conclusions. l-Carnitine treatment initiated early after acute myocardial infarction and continued for 12 months can attenuate left ventricular dilation during the first year after an acute myocardial infarction, resulting in smaller left ventricular volumes at 3, 6 and 12 months after the emergent event

Psychometric properties of the Italian versions of the Gambling Urge Scale (GUS) and the Gambling Refusal Self-Efficacy Questionnaire (GRSEQ)

Gambling urges and gambling refusal self-efficacy beliefs play a major role in the development and maintenance of problem gambling. This study aimed to translate the Gambling Urge Scale (GUS) and the Gambling Refusal Self-Efficacy Questionnaire (GRSEQ) from English to Italian (GUS-I, GRSEQ-I) and to test their factor structure, internal consistency, construct validity, concurrent validity, and gender differences in 513 individuals from the Italian community. Factor structure and construct validity were tested through Confirmatory Factor Analysis, internal consistency through Cronbach’s alpha, concurrent validity through correlations with gambling-related cognitions (GRCS-I), probable pathological gambling (SOGS-I), and gambling functioning (GFA-R-I). Results confirmed that the 6 items of the GUS-I load highly on one dimension of Gambling Urge, and each of the 26 items of the GRSEQ-I load highly on their relevant sub-dimension, among the following: situations/thoughts, drugs, positive emotions, negative emotions. Both scales are internally consistent and show concurrent validity with gambling-related cognitions, probable pathological gambling, and gambling functioning. Males score higher than females at the GUS-I; females score higher than males at the GRSEQ-I. The findings from the present study suggest that the GUS-I and the GRSEQ-I are internally consistent and valid scales for the assessment of gambling urges and gambling refusal self-efficacy in Italian individuals from the community, with significant repercussions in terms of assessment, prevention, and intervention

Unique diagnostic signatures of concussion in the saliva of male athletes: the Study of Concussion in Rugby Union through MicroRNAs (SCRUM)

Funder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272Funder: Marker DiagnosticsFunder: Rugby Football UnionFunder: Midland Neuroscience Teaching and Research FundObjective: To investigate the role of salivary small non-coding RNAs (sncRNAs) in the diagnosis of sport-related concussion. Methods: Saliva was obtained from male professional players in the top two tiers of England’s elite rugby union competition across two seasons (2017–2019). Samples were collected preseason from 1028 players, and during standardised head injury assessments (HIAs) at three time points (in-game, post-game, and 36–48 hours post-game) from 156 of these. Samples were also collected from controls (102 uninjured players and 66 players sustaining a musculoskeletal injury). Diagnostic sncRNAs were identified with next generation sequencing and validated using quantitative PCR in 702 samples. A predictive logistic regression model was built on 2017–2018 data (training dataset) and prospectively validated the following season (test dataset). Results: The HIA process confirmed concussion in 106 players (HIA+) and excluded this in 50 (HIA−). 32 sncRNAs were significantly differentially expressed across these two groups, with let-7f-5p showing the highest area under the curve (AUC) at 36–48 hours. Additionally, a combined panel of 14 sncRNAs (let-7a-5p, miR-143-3p, miR-103a-3p, miR-34b-3p, RNU6-7, RNU6-45, Snora57, snoU13.120, tRNA18Arg-CCT, U6-168, U6-428, U6-1249, Uco22cjg1,YRNA_255) could differentiate concussed subjects from all other groups, including players who were HIA− and controls, immediately after the game (AUC 0.91, 95% CI 0.81 to 1) and 36–48 hours later (AUC 0.94, 95% CI 0.86 to 1). When prospectively tested, the panel confirmed high predictive accuracy (AUC 0.96, 95% CI 0.92 to 1 post-game and AUC 0.93, 95% CI 0.86 to 1 at 36–48 hours). Conclusions: SCRUM, a large prospective observational study of non-invasive concussion biomarkers, has identified unique signatures of concussion in saliva of male athletes diagnosed with concussion

PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability

The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster. We first identified a homozygous PTPA variant, c.893T&gt;G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C&gt;A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus. In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment. We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.</p