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

Validation of a guideline to reduce variability in diagnosing cervical dystonia

Background: Cervical dystonia is characterized by a variable pattern of neck muscle involvement. Due to the lack of a diagnostic test, cervical dystonia diagnosis is based on clinical examination and is therefore subjective. The present work was designed to provide practical guidance for clinicians in confirming or refuting suspected cervical dystonia. Methods: Participants were video recorded according to a standardized protocol to assess 6 main clinical features possibly contributing to cervical dystonia diagnosis: presence of repetitive, patterned head/neck movements/postures inducing head/neck deviation from neutral position (item 1); sensory trick (item 2); and red flags related to conditions mimicking dystonia that should be absent in dystonia (items 3-6). Inter-/intra-rater agreement among three independent raters was assessed by k statistics. To estimate sensitivity and specificity, the gold standard was cervical dystonia diagnosis reviewed at each site by independent senior neurologists. Results: The validation sample included 43 idiopathic cervical dystonia patients and 41 control subjects (12 normal subjects, 6 patients with isolated head tremor, 4 with chorea, 6 with tics, 4 with head ptosis due to myasthenia or amyotrophic lateral sclerosis, 7 with orthopedic/rheumatologic neck diseases, and 2 with ocular torticollis). The best combination of sensitivity and specificity was observed considering all the items except for an item related to capability to voluntarily suppress spasms (sensitivity: 96.1%; specificity: 81%). Conclusions: An accurate diagnosis of cervical dystonia can be achieved if, in addition to the core motor features, we also consider some clinical features related to dystonia mimics that should be absent in dystonia

Clinical correlates of "pure" essential tremor: the TITAN study

BackgroundTo date, there are no large studies delineating the clinical correlates of "pure" essential tremor (ET) according to its new definition.MethodsFrom the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of "pure" ET and excluded those with other tremor classifications, including ET-plus, focal, and task-specific tremor, which were formerly considered parts of the ET spectrum.ResultsOut of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) "pure" ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options.DiscussionThe findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of "pure" ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of "pure" ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies

Clinical correlates of “pure” essential tremor: the TITAN study

BackgroundTo date, there are no large studies delineating the clinical correlates of “pure” essential tremor (ET) according to its new definition.MethodsFrom the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of “pure” ET and excluded those with other tremor classifications, including ET-plus, focal, and task-specific tremor, which were formerly considered parts of the ET spectrum.ResultsOut of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) “pure” ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options.DiscussionThe findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of “pure” ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of “pure” ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Disease modeling in functional movement disorders

Introduction: The mechanisms underlying functional movement disorders are poorly known. We examined whether experience of a movement disorder model in the family and/or the friendships contributes to functional movement disorders. Methods: The hypothesis was tested in a caseecontrol study including 33 patients with functional movement disorders and 66 age- and sex-matched patients with organic movement disorders and using a conditional logistic multivariable analysis (adjusted by age, education, disease duration, chronic medical illnesses and clinical phenotype). Results: Case-control comparison yielded a significant association between functional movement dis- orders and exposure to phenotypically congruent movement disorder models (Odds ratio, 3.9, p 1⁄4 0.01), mainly when disease model came from friendships (Odds ratio, 5.9, p 1⁄4 0.04). By contrast no association was found between functional movement disorders and phenotypically different neurological or non neurological disease models. A significant inverse relationship between exposure to a phenotypically concordant movement disorder model and age of disease onset was also observed. Conclusions: These findings support disease modeling as a factor contributing to the phenomenology of functional movement disorders

Assessment of voice and speech symptoms in early Parkinson's disease by the Robertson dysarthria profile

Changes in voice and speech are thought to involve 75–90 % of people with PD, but the impact of PD progression on voice/speech parameters is not well defined. In this study, we assessed voice/speech symptoms in 48 parkinsonian patients staging <3 on the modified Hoehn and Yahr scale and 37 healthy subjects using the Robertson dysarthria profile (a clinical–perceptual method exploring all components potentially involved in speech difficulties), the Voice handicap index (a validated measure of the impact of voice symptoms on quality of life) and the speech evaluation parameter contained in the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III). Accuracy and metric properties of the Robertson dysarthria profile were also measured. On Robertson dysarthria profile, all parkinsonian patients yielded lower scores than healthy control subjects. Differently, the Voice Handicap Index and the speech evaluation parameter contained in the UPDRS-III could detect speech/voice disturbances in 10 and 75 % of PD patients, respectively. Validation procedure in Parkinson’s disease patients showed that the Robertson dysarthria profile has acceptable reliability, satisfactory internal consistency and scaling assumptions, lack of floor and ceiling effects, and partial correlations with UPDRS-III and Voice Handicap Index. We concluded that speech/voice disturbances are widely identified by the Robertson dysarthria profile in early parkinsonian patients, even when the disturbances do not carry a significant level of disability. Robertson dysarthria profile may be a valuable tool to detect speech/voice disturbances in Parkinson’s disease

Are Cognitive Symptoms Part of the Phenotypic Spectrum of Idiopathic Adult‐Onset Dystonia? Summary of Evidence from Controlled Studies

Background: Cognitive dysfunction has been reported in idiopathic adult-onset dystonia (IAOD), but whether this is a primary or secondary component of the disorder remains uncertain. Objective: Here, we aimed to analyze the key domains of abnormal cognitive performance in IAOD and whether this is associated with motor or mood changes. Methods: Article selection for our critical review was guided by PRISMA guidelines (mesh terms "dystonia" and "cognitive," publication period: 2000-2022). Only peer-reviewed, English-language original case-control studies involving patients with IAOD who were not exposed to dopamine- or acetylcholine-modulating agents and validated cognitive assessments were included. Results: Abstract screening ultimately yielded 22 articles for full-text review and data extraction. A greater proportion of studies (17 of 22, 82%) reported abnormal cognitive performance in IAOD. Most of these studies focused on blepharospasm (BSP) and cervical dystonia (10 and 14, respectively). Most studies reporting cognitive impairment (11 of 17) identified multidomain impairment in cognition. Executive functions were the domain most frequently explored (14 of 22 studies), 79% of which detected worse performance in people with dystonia. Results related to other domains were inconclusive. Cognitive abnormalities were independent of motor symptoms in most studies (7 of 12) that explored this relationship and independent of mood status in all 8 that investigated this. Conclusions: Within IAOD, cognitive dysfunction (in particular, executive dysfunction) has been documented mainly in BSP and cervical dystonia. More comprehensive testing is warranted to assess abnormalities in other domains and in other forms of IAOD, as well as to evaluate longitudinal progression of cognitive disturbances in this condition

Chronic coffee consumption and striatal DAT-SPECT findings in Parkinson's disease

Coffee may interfere with the dopaminergic transmission, and this action would possibly enhance motor activity and exert an antidyskinetic effect in Parkinsonâs disease (PD). This study aimed to see whether coffee habit could be associated with change in striatal dopamine active transporter (DAT)-single photon emission computed tomography (SPECT) imaging in PD. A total of 83 PD patients (71 current coffee drinkers and 12 never drinkers) underwent a DAT-SPECT study, using [123I]FP-CIT as radionuclide. Socio-demographic and clinical information as well as smoking habit was collected at the time of imaging acquisition. The Unified Parkinsonâs Disease Rating Scale part III was used to evaluate disease severity. On multivariable analysis, chronic coffee consumption was not associated with any significant change in striatal uptake of the radionuclide. However, the number of years patients drunk coffee was correlated with a significant increase in age at PD onset (p &lt; 0.001). Confirming a previous report, current cigarette smoking was associated with a reduction of radionuclide uptake in putamen and caudate (p &lt; 0.001)