Objective: In order to evaluate Parkinson disease patients' response to therapeutic interventions, sources of information are mainly patient reports and clinicians' assessment of motor functions. ...However, these sources can suffer from patient's subjectivity and from inter/intra rater's score variability. Our work aimed at determining the impact of wearable electronics and data analysis in objectifying the effectiveness of levodopa treatment. Methods: Seven motor tasks performed by thirty-six patients were measured by wearable electronics and related data were analyzed. This was at the time of therapy initiation (T0), and repeated after six (T1) and 12 months (T2). Wearable electronics consisted of inertial measurement units each equipped with 3-axis accelerometer and 3-axis gyroscope, while data analysis of ANOVA and Pearson correlation algorithms, in addition to a support vector machine (SVM) classification. Results: According to our findings, levodopa-based therapy alters the patient's conditions in general, ameliorating something (e.g., bradykinesia), leaving unchanged others (e.g., tremor), but with poor correlation to the levodopa dose. Conclusion: A technology-based approach can objectively assess levodopa-based therapy effectiveness. Significance: Novel devices can improve the accuracy of the assessment of motor function, by integrating the clinical evaluation and patient reports.
Although the discovery of the critical role of α-synuclein (α-syn) in the pathogenesis of Parkinson's disease (PD) is now twenty-five years old, it still represents a milestone in PD research. ...Abnormal forms of α-syn trigger selective and progressive neuronal death through mitochondrial impairment, lysosomal dysfunction, and alteration of calcium homeostasis not only in PD but also in other α-syn-related neurodegenerative disorders such as dementia with Lewy bodies, multiple system atrophy, pure autonomic failure, and REM sleep behavior disorder. Furthermore, α-syn-dependent early synaptic and plastic alterations and the underlying mechanisms preceding overt neurodegeneration have attracted great interest. In particular, the presence of early inflammation in experimental models and PD patients, occurring before deposition and spreading of α-syn, suggests a mechanistic link between inflammation and synaptic dysfunction. The knowledge of these early mechanisms is of seminal importance to support the research on reliable biomarkers to precociously identify the disease and possible disease-modifying therapies targeting α-syn. In this review, we will discuss these critical issues, providing a state of the art of the role of this protein in early PD and other synucleinopathies.
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.
Because of COVID-19 outbreak, regular clinical services for Parkinson’s disease (PD) patients have been suddenly suspended, causing worries, confusion and unexpected needs in such frail population. ...Here, we reviewed the messages spontaneously sent by patients to an Italian PD clinic during the first two weeks of COVID-19 lockdown (9–21 March 2020), in order to highlight their main needs and then outline appropriate strategies of care for this critical period. One hundred sixty-two messages were analysed. Forty-six percent queried about clinical services; 28% communicated an acute clinical worsening for which a therapeutic change was done in 52% of cases; 17% (those patients with younger age and milder disease) asked about the relationship between PD and COVID-19; 8% informed about an intercurrent event. Our analysis suggests that PD patients’ needs during COVID-19 emergency include appropriate and complete information, a timely update on changes in clinical services, and the continuity of care, even in a remote mode. By addressing these issues, acute clinical worsening, complications and subsequent therapeutic changes could be prevented. In this perspective, telecommunication systems and virtual medicine should be implemented.
Neuroinflammation is one of the hallmarks of Parkinson's disease (PD) and may contribute to midbrain dopamine (DA) neuron degeneration. Recent studies link chronic inflammation with failure to ...resolve early inflammation, a process operated by specialized pro-resolving mediators, including resolvins. However, the effects of stimulating the resolution of inflammation in PD - to modulate disease progression - still remain unexplored. Here we show that rats overexpressing human α-synuclein (Syn) display altered DA neuron properties, reduced striatal DA outflow and motor deficits prior to nigral degeneration. These early alterations are coupled with microglia activation and perturbations of inflammatory and pro-resolving mediators, namely IFN-γ and resolvin D1 (RvD1). Chronic and early RvD1 administration in Syn rats prevents central and peripheral inflammation, as well as neuronal dysfunction and motor deficits. We also show that endogenous RvD1 is decreased in human patients with early-PD. Our results suggest there is an imbalance between neuroinflammatory and pro-resolving processes in PD.
Currently, clinical evaluation represents the primary outcome measure in Parkinson's disease (PD). However, clinical evaluation may underscore some subtle motor impairments, hidden from the visual ...inspection of examiners. Technology-based objective measures are more frequently utilized to assess motor performance and objectively measure motor dysfunction. Gait and balance impairments, frequent complications in later disease stages, are poorly responsive to classic dopamine-replacement therapy. Although recent findings suggest that transcranial direct current stimulation (tDCS) can have a role in improving motor skills, there is scarce evidence for this, especially considering the difficulty to objectively assess motor function. Therefore, we used wearable electronics to measure motor abilities, and further evaluated the gait and balance features of 10 PD patients, before and (three days and one month) after the tDCS. To assess patients' abilities, we adopted six motor tasks, obtaining 72 meaningful motor features. According to the obtained results, wearable electronics demonstrated to be a valuable tool to measure the treatment response. Meanwhile the improvements from tDCS on gait and balance abilities of PD patients demonstrated to be generally partial and selective.
Neurodegeneration and neuroinflammation are two intertwined mechanisms contributing to the pathophysiology of Parkinson's disease. Whether circulating biomarkers reflecting those two processes differ ...according to disease duration remains to be established. The present study was conducted to characterize the biomarkers individuals with PD with short (≤5 years) or long disease duration (>5 years).
We consecutively enrolled 104 patients with Parkinson's disease and evaluated them using validated clinical scales (MDS-UPDRS, Hoehn and Yahr staging, MMSE). Serum samples were assayed for the following biomarkers: neurofilament light chain (NfL), brain-derived neurotrophic factor (BDNF), interleukin (IL-) 1β, 4, 5, 6, 10, 17, interferon-γ, and tumor necrosis factor α.
Mean age of participants was 66.0 ± 9.6 years and 45 (34%) were women. The average disease duration was 8 ± 5 years (range 1 to 19 years). Patients with short disease duration (≤ 5 years) showed a pro-inflammatory profile, with significantly higher levels of pro-inflammatory IL-1β and lower concentrations of IL-5, IL-10 and IL-17 (p < 0.05). NfL serum levels showed a positive correlation with disease duration and age (respectively rho = 0.248, p = 0.014 and rho = 0.559, p < 0.001) while an opposite pattern was detected for BDNF (respectively rho -0,187, p = 0.034 and rho = -0.245, p = 0.014).
Our findings suggest that a pro-inflammatory status may be observed in PD patients in the early phases of the disease, independently from age.
Abstract
Early noninvasive reliable biomarkers are among the major unmet needs in Parkinson’s disease (PD) to monitor therapy response and disease progression. Objective measures of motor ...performances could allow phenotyping of subtle, undetectable, early stage motor impairments of PD patients. This work aims at identifying prognostic biomarkers in newly diagnosed PD patients and quantifying therapy-response. Forty de novo PD patients underwent clinical and technology-based kinematic assessments performing motor tasks (MDS-UPDRS part III) to assess tremor, bradykinesia, gait, and postural stability (T0). A visit after 6 months (T1) and a clinical and kinematic assessment after 12 months (T2) where scheduled. A clinical follow-up was provided between 30 and 36 months after the diagnosis (T3). We performed an ANOVA for repeated measures to compare patients’ kinematic features at baseline and at T2 to assess therapy response. Pearson correlation test was run between baseline kinematic features and UPDRS III score variation between T0 and T3, to select candidate kinematic prognostic biomarkers. A multiple linear regression model was created to predict the long-term motor outcome using T0 kinematic measures. All motor tasks significantly improved after the dopamine replacement therapy. A significant correlation was found between UPDRS scores variation and some baseline bradykinesia (toe tapping amplitude decrement,
p
= 0.009) and gait features (velocity of arms and legs, sit-to-stand time,
p
= 0.007;
p
= 0.009;
p
= 0.01, respectively). A linear regression model including four baseline kinematic features could significantly predict the motor outcome (
p
= 0.000214). Technology-based objective measures represent possible early and reproducible therapy-response and prognostic biomarkers.
Attention-deficit/hyperactivity disorder (ADHD) is characterized by an inappropriate, pervasive and persistent pattern of inattention, hyperactivity, and/or impulsivity and associated with ...substantial functional impairment. Despite considerable advances in the understanding and management of ADHD, some patients do not respond well to methylphenidate (MPH), the first-choice pharmacological treatment. Over the past decades, among non-invasive brain stimulation techniques, transcranial direct current stimulation (tDCS) has proven to be an effective and safe technique to improve behavior and cognition in children with neurodevelopmental disorders, including ADHD, by modifying cortical excitability. However, the effect of tDCS has never been directly compared with that of the MPH. The present randomized sham-controlled trial evaluated the effect of a single session of anodal tDCS compared with the administration of a single dose of MPH in children and adolescents with ADHD.
After completing baseline assessment (T0), 26 children and adolescents with ADHD were exposed to 3 conditions with a 24-h interval-sessions: (A) a single session of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC); (B) a single session of sham tDCS over the left DLPFC; (C) a single dose of MPH.
Our results showed that after administering a single dose of MPH, children and adolescents with ADHD improved inhibitory control and visual-spatial WM compared with baseline, anodal, and sham tDCS. However, a single session of active tDCS over the left DLPFC was not effective compared with either baseline or sham tDCS.
In conclusion, our protocol in ADHD involving a single tDCS session did not demonstrate consistent improvements in neurocognitive features compared with baseline, sham tDCS, or single MPH administration. Different protocols need to be developed to further test the effectiveness of tDCS in improving ADHD symptoms.
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