Tremor is a common movement disorder that can be induced by medications, including valproate, which is used for the treatment of epilepsy. However, the clinical and neurophysiological features of ...valproate-induced tremor are still under-investigated. We performed a clinical and kinematic assessment of valproate-induced tremor by considering tremor body distribution and activation conditions. We investigated possible correlations between demographic and clinical data and kinematic features. Valproate-induced tremor results were also compared with those collected in a large sample of patients with essential tremor. Sixteen valproate-induced tremor patients and 93 essential tremor patients were enrolled. All participants underwent a standardised neurological examination and video recording. Patients also underwent an objective assessment of postural, kinetic and rest tremor of the upper limbs and head tremor through kinematic analysis. Nonparametric tests were used for statistical comparisons between the two groups. Clinical evaluation showed a higher occurrence of rest tremor as well as head or voice, and lower limb involvement in patients with valproate-induced tremor. Kinematic analysis showed a substantial variability in the tremor features of patients with valproate-induced tremor. Compared to essential tremor, we found a higher occurrence of rest tremor of the upper limbs and the involvement of more body segments in valproate-induced tremor patients. Valproate-induced tremor has distinctive clinical and kinematic features, which may suggest that valproate interferes with the cerebellar functions.
The increasing use of nanomaterials in a variety of industrial, commercial, medical products, and their environmental spreading has raised concerns regarding their potential toxicity on human health. ...Titanium dioxide nanoparticles (TiO
NPs) represent one of the most commonly used nanoparticles. Emerging evidence suggested that exposure to TiO
NPs induced reproductive toxicity in male animals. In this
study, porcine prepubertal Sertoli cells (SCs) have undergone acute (24 h) and chronic (from 1 up to 3 weeks) exposures at both subtoxic (5 µg/ml) and toxic (100 µg/ml) doses of TiO
NPs. After performing synthesis and characterization of nanoparticles, we focused on SCs morphological/ultrastructural analysis, apoptosis, and functionality (AMH, inhibin B), ROS production and oxidative DNA damage, gene expression of antioxidant enzymes, proinflammatory/immunomodulatory cytokines, and MAPK kinase signaling pathway. We found that 5 µg/ml TiO
NPs did not induce substantial morphological changes overtime, but ultrastructural alterations appeared at the third week. Conversely, SCs exposed to 100 µg/ml TiO
NPs throughout the whole experiment showed morphological and ultrastructural modifications. TiO
NPs exposure, at each concentration, induced the activation of caspase-3 at the first and second week. AMH and inhibin B gene expression significantly decreased up to the third week at both concentrations of nanoparticles. The toxic dose of TiO
NPs induced a marked increase of intracellular ROS and DNA damage at all exposure times. At both concentrations, the increased gene expression of antioxidant enzymes such as SOD and HO-1 was observed whereas, at the toxic dose, a clear proinflammatory stress was evaluated along with the steady increase in the gene expression of IL-1α and IL-6. At both concentrations, an increased phosphorylation ratio of p-ERK1/2 was observed up to the second week followed by the increased phosphorylation ratio of p-NF-kB in the chronic exposure. Although
, this pilot study highlights the adverse effects even of subtoxic dose of TiO
NPs on porcine prepubertal SCs functionality and viability and, more importantly, set the basis for further
studies, especially in chronic exposure at subtoxic dose of TiO
NPs, a condition closer to the human exposure to this nanoagent.
Over the past three decades, substantial advancements have occurred in non-invasive brain stimulation (NIBS). These developments encompass various non-invasive techniques aimed at modulating brain ...function. Among the most widely utilized methods today are transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES), which include direct- or alternating-current transcranial stimulation (tDCS/tACS). In addition to these established techniques, newer modalities have emerged, broadening the scope of non-invasive neuromodulation approaches available for research and clinical applications in movement disorders, particularly for Parkinson’s disease (PD) and, to a lesser extent, atypical Parkinsonism (AP). All NIBS techniques offer the opportunity to explore a wide range of neurophysiological mechanisms and exert influence over distinct brain regions implicated in the pathophysiology of Parkinsonism. This paper’s first aim is to provide a brief overview of the historical background and underlying physiological principles of primary NIBS techniques, focusing on their translational relevance. It aims to shed light on the potential identification of biomarkers for diagnostic and therapeutic purposes, by summarising available experimental data on individuals with Parkinsonism. To date, despite promising findings indicating the potential utility of NIBS techniques in Parkinsonism, their integration into clinical routine for diagnostic or therapeutic protocols remains a subject of ongoing investigation and scientific debate. In this context, this paper addresses current unsolved issues and methodological challenges concerning the use of NIBS, focusing on the importance of future research endeavours for maximizing the efficacy and relevance of NIBS strategies for individuals with Parkinsonism.
In this research, our primary objective was to explore the correlation between basal ganglia dopaminergic neurotransmission, assessed using 123I-FP-CIT (DAT-SPECT), and finger movements abnormalities ...in patients with essential tremor (ET) and Parkinson's disease (PD).
We enrolled 16 patients with ET, 17 with PD, and 18 healthy controls (HC). Each participant underwent comprehensive clinical evaluations, kinematic assessments of finger tapping. ET and PD patients underwent DAT-SPECT imaging. The DAT-SPECT scans were subjected to both visual and semi-quantitative analysis using DaTQUANT®. We then investigated the correlations between the clinical, kinematic, and DAT-SPECT data, in patients.
Our findings confirm that individuals with ET exhibited slower finger tapping than HC. Visual evaluation of radiotracer uptake in both striata demonstrated normal levels within the ET patient cohort, while PD patients displayed reduced uptake. However, there was notable heterogeneity in the quantification of uptake within the striata among ET patients. Additionally, we found a correlation between the amount of radiotracer uptake in the striatum and movement velocity during finger tapping in patients. Specifically, lower radioligand uptake corresponded to decreased movement velocity (ET: coef. = 0.53, p-adj = 0.03; PD: coef. = 0.59, p-adj = 0.01).
The study's findings suggest a potential link between subtle changes in central dopaminergic tone and altered voluntary movement execution, in ET. These results provide further insights into the pathophysiology of ET. However, longitudinal studies are essential to determine whether the slight reduction in dopaminergic tone observed in ET patients represents a distinct subtype of the disease or could serve as a predictor for the clinical progression into PD.
Background:
Bradykinesia has been reported in patients with dystonia. Despite this, the pathophysiological mechanisms of bradykinesia in dystonia remain largely unknown.
Methods:
We here performed a ...comprehensive literature search and reviewed clinical and experimental studies on bradykinesia in patients with dystonia.
Results:
Many studies have documented the presence of bradykinesia in patients with idiopathic and inherited isolated dystonia, regardless of the presence of parkinsonism. In addition, bradykinesia has been observed as a side effect in dystonic patients who have undergone deep brain stimulation, in those with functional dystonia as well as in those with combined dystonia, e.g., dystonia-parkinsonism. These clinical and experimental findings support the hypothesis that dysfunction in a brain network involving the basal ganglia, primary sensorimotor cortex, and cerebellum may play a key role in the pathophysiology of both bradykinesia and dystonia.
Conclusion:
Bradykinesia is frequently observed in dystonia. We may gain insights into the pathophysiological underpinnings of two distinct movement disorders by investigating this issue. Furthermore, a deeper understanding of bradykinesia in dystonia may have terminological implications in this field.
The management of cardiogenic shock (CS) after ACS has evolved over time, and the development of a multidisciplinary team-based approach has been shown to improve outcomes, although mortality remains ...high.
All consecutive patients with ACS-CS admitted at our CICU from March 2012 to July 2021 were included in this single-center retrospective study. In 2019, we established a "shock team" consisting of a cardiac intensivist, an interventional cardiologist, an anesthetist, and a cardiac surgeon. The primary outcome was in-hospital mortality.
We included 167 patients males 67%; age 71 (61-80) years with ischemic CS. The proportion of SCAI shock stages from A to E were 3.6%, 6.6%, 69.4%, 9.6%, and 10.8%, respectively, with a mean baseline serum lactate of 5.2 (3.1-8.8) mmol/L. Sixty-six percent of patients had severe LV dysfunction, and 76.1% needed ≥ 1 inotropic drug. Mechanical cardiac support (MCS) was pursued in 91.1% 65% IABP, 23% Impella CP, 4% VA-ECMO. From March 2012 to July 2021, we observed a significative temporal trend in mortality reduction from 57% to 29% (OR = 0.90,
= 0.0015). Over time, CS management has changed, with a significant increase in Impella catheter use (
= 0.0005) and a greater use of dobutamine and levosimendan (
= 0.015 and
= 0.0001) as inotropic support. In-hospital mortality varied across SCAI shock stages, and the SCAI E profile was associated with a poor prognosis regardless of patient age (OR 28.50,
= 0.039).
The temporal trend mortality reduction in CS patients is multifactorial, and it could be explained by the multidisciplinary care developed over the years.
Overweight (Ow) and obesity (Ob) influence blood pressure (BP) and left ventricular hypertrophy (LVH). It is unclear whether the presence of metabolic syndrome (MetS) independently affects ...echocardiographic parameters in hypertension.
380 Ow/Ob essential hypertensive patients (age ≤ 65 years) presenting for referred BP control-related problems. MetS was defined according to NCEP III/ATP with AHA modifications and LVH as LVM/h(2.7) ≥ 49.2 g/m(2.7) in males and ≥ 46.7 g/m(2.7) in females. Treatment intensity score (TIS) was used to control for BP treatment as previously reported.
Hypertensive patients with MetS had significantly higher BMI, systolic and mean BP, interventricular septum and relative wall thickness and lower ejection fraction than those without MetS. LVM/h(2.7) was significantly higher in MetS patients (59.14 ± 14.97 vs. 55.33 ± 14.69 g/m(2.7); p = 0.022). Hypertensive patients with MetS had a 2.3-fold higher risk to have LVH/h(2.7) after adjustment for age, SBP and TIS (OR 2.34; 95%CI 1.40-3.92; p = 0.001), but MetS lost its independent relationship with LVH when BMI was included in the model.
In Ow/Ob hypertensive patients MetS maintains its role of risk factor for LVH independently of age, SBP, and TIS, resulting in a useful predictor of target organ damage in clinical practice. However, MetS loses its independent relationship when BMI is taken into account, suggesting that the effects on MetS on LV parameters are mainly driven by the degree of adiposity.
Blinking analysis contributes to the understanding of physiological mechanisms in healthy subjects as well as the pathophysiological mechanisms of neurological diseases. To date, blinking is assessed ...by various neurophysiological techniques, including electromyographic (EMG) recordings and optoelectronic motion analysis. We recorded eye-blink kinematics with a new portable device, the EyeStat (Generation 3, blinktbi, Inc., Charleston, SC, USA), and compared the measurements with data obtained using traditional laboratory-based techniques. Sixteen healthy adults underwent voluntary, spontaneous, and reflex blinking recordings using the EyeStat device and the SMART motion analysis system (BTS, Milan, Italy). During the blinking recordings, the EMG activity was recorded from the orbicularis oculi muscles using surface electrodes. The blinking data were analyzed through dedicated software and evaluated with repeated-measure analyses of variance. The Pearson’s product-moment correlation coefficient served to assess possible associations between the EyeStat device, the SMART motion system, and the EMG data. We found that the EMG data collected during the EyeStat and SMART system recordings did not differ. The blinking data recorded with the EyeStat showed a linear relationship with the results obtained with the SMART system (r ranging from 0.85 to 0.57; p ranging from <0.001 to 0.02). These results demonstrate a high accuracy and reliability of a blinking analysis through this portable device, compared with standard techniques. EyeStat may make it easier to record blinking in research activities and in daily clinical practice, thus allowing large-scale studies in healthy subjects and patients with neurological diseases in an outpatient clinic setting.
Abstract
The “interlimb transfer” phenomenon consists of improved performance of the trained and untrained contralateral limbs after unilateral motor practice. We here assessed whether a visuomotor ...learning task can be transferred from one hemisphere to the other, whether this occurs symmetrically, and the cortical neurophysiological correlates of this phenomenon, focusing on interhemispheric connectivity measures. We enrolled 33 healthy subjects (age range: 24–73 years). Participants underwent two randomized sessions, which investigated the transfer from the dominant to the nondominant hand and vice versa. Measures of cortical and intracortical excitability and interhemispheric inhibition were assessed through transcranial magnetic stimulation before and after a visuomotor task. The execution of the visuomotor task led to an improvement in motor performance with the dominant and nondominant hands and induced a decrease in intracortical inhibition in the trained hemisphere. Participants were also able to transfer the visuomotor learned skill. The interlimb transfer, however, only occurred from the dominant to the nondominant hand and positively correlated with individual learning-related changes in interhemispheric inhibition. We here demonstrated that the “interlimb transfer” of a visuomotor task occurs asymmetrically and relates to the modulation of specific inhibitory interhemispheric connections. The study results have pathophysiological, clinical, and neuro-rehabilitative implications.
•Cerebellar theta (θ)-tACS reduced movement regularity in a tapping task and prolonged the movement duration of a pointing task.•Cerebellar θ-tACS enhanced the effectiveness of CBI and the effect of ...θ-tACS on movement rhythm was correlated with changes in CBI.•tACS effects potentially involve the modulation of cerebellar neurons resonating with θ rhythm.
To evaluate the effects of cerebellar transcranial alternating current stimulation (tACS) delivered at cerebellar-resonant frequencies, i.e., theta (θ) and gamma (γ), on upper limb motor performance and cerebellum-primary motor cortex (M1) connectivity, as assessed by cerebellar-brain inhibition (CBI), in healthy subjects.
Participants underwent cerebellar-tACS while performing three cerebellar-dependent motor tasks: (i) rhythmic finger-tapping, (ii) arm reaching-to-grasp (‘grasping’) and (iii) arm reaching-to-point (‘pointing’) an object. Also, we evaluated possible changes in CBI during cerebellar-tACS.
θ-tACS decreased movement regularity during the tapping task and increased the duration of the pointing task compared to sham- and γ-tACS. Additionally, θ-tACS increased the CBI effectiveness (greater inhibition). The effect of θ-tACS on movement rhythm correlated with CBI changes and less tapping regularity corresponded to greater CBI.
Cerebellar-tACS delivered at the θ frequency modulates cerebellar-related motor behavior and this effect is, at least in part, mediated by changes in the cerebellar inhibitory output onto M1. The effects of θ-tACS may be due to the modulation of cerebellar neurons that resonate to the θ rhythm.
These findings contribute to a better understanding of the physiological mechanisms of motor control and provide new evidence on cerebellar non-invasive brain stimulation.
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